PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
33839989-9	2022	In conclusion, intermittent LEVO infusions in ambulatory patients with end-stage HF is associated with less frequent cardiovascular death alongside with improved NYHA class, quality of life, BNP levels, and LV function.	Simendan	28-32	natriuretic peptide B	Homo sapiens	191-194
33662980-0	2021	Pharmacological Pre- and Postconditioning With Levosimendan Protect H9c2 Cardiomyoblasts From Anoxia/Reoxygenation-induced Cell Death via PI3K/Akt Signaling.	Simendan	47-59	AKT serine/threonine kinase 1	Rattus norvegicus	143-146
33710108-11	2021	CONCLUSIONS: Levosimendan significantly reduced the cardiac injury and corrected the metabolic status in an experimental rat model of ventricular fibrillation (VF) induced CA and CPR.	Simendan	13-25	cytochrome p450 oxidoreductase	Rattus norvegicus	179-182
32462455-0	2021	Levosimendan Can Improve the Level of B-Type Natriuretic Peptide and the Left Ventricular Ejection Fraction of Patients with Advanced Heart Failure: A Meta-analysis of Randomized Controlled Trials.	Simendan	0-12	natriuretic peptide B	Homo sapiens	38-64
32462455-9	2021	Compared with other agents (placebo, dobutamine, furosemide, and prostaglandin E1), levosimendan significantly reduced the BNP level (SMD - 0.91; 95% CI - 1.44 to - 0.39; p = 0.001; I2 = 74.3%) and improved the LVEF (SMD 0.74; 95% CI 0.22-1.25; p = 0.005; I2 = 79.7%).	Simendan	84-96	natriuretic peptide B	Homo sapiens	123-126
32462455-12	2021	CONCLUSION: Our meta-analysis suggests that intravenous levosimendan can reduce BNP level and increase LVEF in patients with advanced heart failure to reduce the mortality at the shortest follow-up available.	Simendan	56-68	natriuretic peptide B	Homo sapiens	80-83
33269816-9	2020	RESULTS: Levosimendan therapy was associated with reduced HF symptoms and signs, New York Heart Association (NYHA) class and level of B-type natriuretic peptide (BNP) at discharge.	Simendan	9-21	natriuretic peptide B	Homo sapiens	134-160
33103204-12	2020	Compared to other inotropes, levosimendan appears to have a better safety profile and is associated with decreased mortality in CS, particularly when combined with a vasopressor.	Simendan	29-41	citrate synthase	Homo sapiens	128-130
33103204-13	2020	Our literature review suggests that treatment combination of the inotrope levosimendan with the vasopressor noradrenaline may be the most effective management option in CS.	Simendan	74-86	citrate synthase	Homo sapiens	169-171
33269816-9	2020	RESULTS: Levosimendan therapy was associated with reduced HF symptoms and signs, New York Heart Association (NYHA) class and level of B-type natriuretic peptide (BNP) at discharge.	Simendan	9-21	natriuretic peptide B	Homo sapiens	162-165
33269816-14	2020	CONCLUSIONS: The use of levosimendan was safe and associated with clinical improvement and reduction in BNP level in AdvHF patients hospitalized due to HF decompensation, although the mortality and re-hospitalization rate during the one-year follow-up remains high.	Simendan	24-36	natriuretic peptide B	Homo sapiens	104-107
32421724-7	2020	MATERIAL AND METHODS: In IPL, levosimendan (10 muM) was perfused in untreated and endothelin-1 pre-contracted lungs.	Simendan	30-42	endothelin 1	Homo sapiens	82-94
32596387-9	2020	Levosimendan also inhibited the activation of phosphatase and tensin homolog (PTEN) and upregulated P-Akt expression both in vivo and in vitro.	Simendan	0-12	phosphatase and tensin homolog	Mus musculus	46-76
32596387-9	2020	Levosimendan also inhibited the activation of phosphatase and tensin homolog (PTEN) and upregulated P-Akt expression both in vivo and in vitro.	Simendan	0-12	phosphatase and tensin homolog	Mus musculus	78-82
32596387-10	2020	And inhibition of Akt abolished the cardioprotection of levosimendan in vitro.	Simendan	56-68	thymoma viral proto-oncogene 1	Mus musculus	18-21
32596387-11	2020	Conclusion: Levosimendan may protect against DOX-induced cardiotoxicity via modulation of the PTEN/Akt signaling pathway.	Simendan	12-24	phosphatase and tensin homolog	Mus musculus	94-98
32596387-11	2020	Conclusion: Levosimendan may protect against DOX-induced cardiotoxicity via modulation of the PTEN/Akt signaling pathway.	Simendan	12-24	thymoma viral proto-oncogene 1	Mus musculus	99-102
32596387-0	2020	Levosimendan Protects against Doxorubicin-Induced Cardiotoxicity by Regulating the PTEN/Akt Pathway.	Simendan	0-12	phosphatase and tensin homolog	Mus musculus	83-87
32596387-0	2020	Levosimendan Protects against Doxorubicin-Induced Cardiotoxicity by Regulating the PTEN/Akt Pathway.	Simendan	0-12	thymoma viral proto-oncogene 1	Mus musculus	88-91
32596387-7	2020	And an Akt inhibitor was utilized to verify the cardioprotection of levosimendan.	Simendan	68-80	thymoma viral proto-oncogene 1	Mus musculus	7-10
32421724-11	2020	Levosimendan-induced relaxation was studied in naive and endothelin-1 pre-contracted PAs and PVs.	Simendan	0-12	endothelin 1	Homo sapiens	57-69
32421724-16	2020	In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost.	Simendan	8-20	endothelin 1	Homo sapiens	36-48
32421724-20	2020	DISCUSSION: Levosimendan reduces rats" segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1.	Simendan	12-24	endothelin 1	Homo sapiens	129-141
31155645-4	2020	Levosimendan infusion was started at a dose of 0.1 microg kg-1 min-1 for a maximum of 48 h without a bolus.	Simendan	0-12	CD59 molecule (CD59 blood group)	Homo sapiens	63-68
31228183-10	2020	Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN-/- mice.	Simendan	31-43	thymoma viral proto-oncogene 1	Mus musculus	95-98
31228183-10	2020	Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN-/- mice.	Simendan	31-43	nitric oxide synthase 3, endothelial cell	Mus musculus	99-103
31228183-10	2020	Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN-/- mice.	Simendan	31-43	phospholamban	Mus musculus	126-129
31228183-10	2020	Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN-/- mice.	Simendan	31-43	phospholamban	Mus musculus	179-182
31228183-13	2020	CONCLUSION: Single dose levosimendan prevented doxorubicin cardiotoxicity through a cAMP-PKA-PLN pathway, highlighting the role of inotropy in doxorubicin cardiotoxicity.	Simendan	24-36	phospholamban	Mus musculus	93-96
29637229-8	2019	CONCLUSION: In the present meta-analysis, levosimendan infusion in patients with ADHF appeared to reduce BNP regardless of the comparator (except for dopamine), and also improve LVEF and increase HR in after vs. before use comparisons but not compared to controls.	Simendan	42-54	natriuretic peptide B	Homo sapiens	105-108
31889123-5	2019	Cardiac index significantly increased in the levosimendan group by 0.74 (0.24 to 1.23) [standardized mean difference (95% CI); p = 0.003] from baseline to postoperative day (POD) 1, and by 0.75 (0.25 to 1.25; p = 0.003) from baseline to POD 7, when corrected for the standardized mean difference at baseline by a multivariate mixed effects meta-analysis model.	Simendan	45-57	coronin 7	Homo sapiens	155-180
31730560-1	2019	Levosimendan is a calcium sensitizer that promotes myocyte contractility through its calcium-dependent interaction with cardiac troponin C.	Simendan	0-12	troponin C1, slow skeletal and cardiac type	Homo sapiens	120-138
31272201-7	2019	Levosimendan at 1 and 10 microM protected against LPS-induced endothelial cell death and reduced TLR4 expression (p < .05).	Simendan	0-12	toll like receptor 4	Homo sapiens	97-101
30489437-1	2019	Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels.	Simendan	0-12	troponin C1, slow skeletal and cardiac type	Homo sapiens	109-127
31527618-0	2019	Levosimendan pretreatment improves survival of septic rats after partial hepatectomy and suppresses iNOS induction in cytokine-stimulated hepatocytes.	Simendan	0-12	nitric oxide synthase 2	Rattus norvegicus	100-104
31527618-6	2019	In serum, levosimendan decreased the level of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and nitric oxide (NO).	Simendan	10-22	interleukin 1 beta	Rattus norvegicus	76-98
31527618-6	2019	In serum, levosimendan decreased the level of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and nitric oxide (NO).	Simendan	10-22	interleukin 6	Rattus norvegicus	100-104
31527618-7	2019	In remnant livers, levosimendan inhibited inducible nitric oxide synthase (iNOS) gene expression.	Simendan	19-31	nitric oxide synthase 2	Rattus norvegicus	42-73
31527618-7	2019	In remnant livers, levosimendan inhibited inducible nitric oxide synthase (iNOS) gene expression.	Simendan	19-31	nitric oxide synthase 2	Rattus norvegicus	75-79
31527618-8	2019	In primary cultured rat hepatocytes stimulated by IL-1beta, levosimendan suppressed NO production by inhibiting iNOS promoter activity and stability of its mRNA.	Simendan	60-72	interleukin 1 beta	Rattus norvegicus	50-58
31527618-8	2019	In primary cultured rat hepatocytes stimulated by IL-1beta, levosimendan suppressed NO production by inhibiting iNOS promoter activity and stability of its mRNA.	Simendan	60-72	nitric oxide synthase 2	Rattus norvegicus	112-116
31206508-10	2019	We predict that levosimendan, a PDE inhibitor for heart failure, inhibits serine/threonine-protein kinase RIOK1 and other kinases.	Simendan	16-28	RIO kinase 1	Homo sapiens	106-111
31206508-11	2019	Subsequent experiments and systems biology analyses confirm this prediction, and suggest that levosimendan is active against multiple cancers, notably lymphoma, through the direct inhibition of RIOK1 and RNA processing pathway.	Simendan	94-106	RIO kinase 1	Homo sapiens	194-199
30958071-4	2019	This review also elaborates on the pathogenesis of levosimendan, including the mechanisms of its anti-inflammatory effects, improvement of myocardial ischaemia, increased synthesis of nitric oxide, vascular endothelial cell protection, increased myocardial contractility, improved diastolic function, and inhibition of hypoxia-inducible factor-1alpha expression.	Simendan	51-63	hypoxia inducible factor 1 subunit alpha	Homo sapiens	319-350
31356552-5	2019	The same effect elicited by the known inodilator levosimendan was less pronounced at a concentration of 3.7 microM: -1.82 +- 0.44 mV, N = 22 (P < 0.05 vs. CNP).	Simendan	49-61	natriuretic peptide C	Homo sapiens	158-161
30732532-6	2019	RGECO-TnT/TnI revealed changes to localized Ca2+ handling conferred by MYK-461 and levosimendan, including an increase in Ca2+ binding rates with both levosimendan and MYK-461 not detected by an unrestricted protein sensor.	Simendan	83-95	troponin T1, slow skeletal type	Homo sapiens	6-9
30732532-6	2019	RGECO-TnT/TnI revealed changes to localized Ca2+ handling conferred by MYK-461 and levosimendan, including an increase in Ca2+ binding rates with both levosimendan and MYK-461 not detected by an unrestricted protein sensor.	Simendan	151-163	troponin T1, slow skeletal type	Homo sapiens	6-9
30886824-10	2019	Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance.	Simendan	0-12	lipocalin 2	Rattus norvegicus	83-125
30886824-10	2019	Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance.	Simendan	0-12	lipocalin 2	Rattus norvegicus	127-131
30886824-11	2019	Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1).	Simendan	0-12	O-GlcNAcase	Rattus norvegicus	89-120
30886824-11	2019	Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1).	Simendan	0-12	O-GlcNAcase	Rattus norvegicus	122-125
30886824-11	2019	Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1).	Simendan	0-12	hepatitis A virus cellular receptor 1	Rattus norvegicus	131-155
30886824-11	2019	Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1).	Simendan	0-12	hepatitis A virus cellular receptor 1	Rattus norvegicus	157-162
30886824-12	2019	Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor-alpha (TNF-alpha), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation.	Simendan	0-12	tumor necrosis factor	Rattus norvegicus	90-117
30886824-12	2019	Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor-alpha (TNF-alpha), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation.	Simendan	0-12	tumor necrosis factor	Rattus norvegicus	119-128
30446219-9	2018	Further, levosimendan pretreatment upregulated the expression of Bcl-2 and downregulated the expression of Bax.	Simendan	9-21	BCL2, apoptosis regulator	Rattus norvegicus	65-70
30446219-9	2018	Further, levosimendan pretreatment upregulated the expression of Bcl-2 and downregulated the expression of Bax.	Simendan	9-21	BCL2 associated X, apoptosis regulator	Rattus norvegicus	107-110
30446219-10	2018	The experiments also demonstrated that levosimendan could decrease the expression and activity of caspase-3, which is a key factor in regulating apoptosis.	Simendan	39-51	caspase 3	Rattus norvegicus	98-107
30376637-7	2018	Ser84 (replacing the unique Cys84 in cTnC reported to make a reversible covalent bond with levosimendan) also contacts W7.	Simendan	91-103	troponin C, cardiac/slow skeletal	Mus musculus	37-41
29548887-5	2018	Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO2 increase and VE/VCO2 slope reduction.	Simendan	0-12	natriuretic peptide B	Homo sapiens	43-46
29653089-0	2018	Modification of levosimendan-induced suppression of atrial natriuretic peptide secretion in hypertrophied rat atria.	Simendan	16-28	natriuretic peptide A	Rattus norvegicus	52-78
29653089-1	2018	This study aimed to determine the effects of levosimendan, a calcium sensitizer, on atrial contractility and atrial natriuretic peptide (ANP) secretion and its modification in hypertrophied atria.	Simendan	45-57	natriuretic peptide A	Rattus norvegicus	109-135
29653089-4	2018	Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4 inhibitor also suppressed ANP secretion.	Simendan	11-23	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	39-58
29653089-5	2018	Suppression of ANP secretion by 1 microM levosimendan was abolished by PDE3 inhibitor, but reversed by PDE4 inhibitor.	Simendan	41-53	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	71-75
29653089-8	2018	The stimulation of ANP secretion induced by levosimendan combined with PDE4 inhibitor was blocked by the protein kinase A (PKA) inhibitor.	Simendan	44-56	protein kinase cAMP-activated catalytic subunit alpha	Rattus norvegicus	105-121
29653089-8	2018	The stimulation of ANP secretion induced by levosimendan combined with PDE4 inhibitor was blocked by the protein kinase A (PKA) inhibitor.	Simendan	44-56	protein kinase cAMP-activated catalytic subunit alpha	Rattus norvegicus	123-126
29653089-10	2018	These results suggests that levosimendan suppresses ANP secretion by both inhibiting PDE3 and opening KATP channels and that levosimendan combined with PDE4 inhibitor stimulates ANP secretion by activating the cAMP-PKA pathway.	Simendan	28-40	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	85-89
29653089-10	2018	These results suggests that levosimendan suppresses ANP secretion by both inhibiting PDE3 and opening KATP channels and that levosimendan combined with PDE4 inhibitor stimulates ANP secretion by activating the cAMP-PKA pathway.	Simendan	125-137	protein kinase cAMP-activated catalytic subunit alpha	Rattus norvegicus	215-218
29685053-0	2018	Cardioprotective and Anti-Aggregatory Effects of Levosimendan on Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to Cilostazol.	Simendan	49-61	AKT serine/threonine kinase 1	Rattus norvegicus	154-157
29685053-0	2018	Cardioprotective and Anti-Aggregatory Effects of Levosimendan on Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to Cilostazol.	Simendan	49-61	mechanistic target of rapamycin kinase	Rattus norvegicus	158-162
30052230-9	2018	There was a significant reduction in PASP and significant improvement in RV-FAC with both intravenous and inhalational levosimendan.	Simendan	119-131	FA complementation group C	Homo sapiens	76-79
27614436-7	2016	It was reviewed whether levosimendan has a beneficial influence on endothelin(A) and/or endothelin(B1) receptors (ET-(A) and ET-(B1) receptors) in cerebral vessels after SAH.	Simendan	24-36	endothelin receptor type A	Homo sapiens	114-120
29558109-0	2018	Reversible Covalent Reaction of Levosimendan with Cardiac Troponin C in Vitro and in Situ.	Simendan	32-44	troponin C1, slow skeletal and cardiac type	Homo sapiens	50-68
29558109-6	2018	In this study, we use mass spectrometry to show that the in vitro mechanism of action of levosimendan is consistent with an allosteric, reversible covalent inhibitor; to determine whether the presence of the cTnI switch peptide or changes in either Ca2+ concentration or pH modify the reaction kinetics; and to determine whether the reaction can occur with cTnC in situ in cardiac myofibrils.	Simendan	89-101	troponin I3, cardiac type	Homo sapiens	208-212
27594341-6	2018	This raises the possibility that levosimendan may interact with smooth muscle proteins, such as, calmodulin, and regulatory myosin light chains.	Simendan	33-45	myosin heavy chain 14	Homo sapiens	124-130
29145424-10	2017	RESULTS: Administration of levosimendan during reperfusion increases the metabolic activity of human hepatocytes and decreases AST levels.	Simendan	27-39	solute carrier family 17 member 5	Homo sapiens	127-130
29145424-11	2017	Moreover, apoptosis after IRI is reduced in treated vs. untreated hepatocytes, and levosimendan prevents down-regulation of the anti-apoptotic protein Bcl-2 as well as up-regulation of the pro-apoptotic protein BAX.	Simendan	83-95	BCL2 apoptosis regulator	Homo sapiens	151-156
29145424-11	2017	Moreover, apoptosis after IRI is reduced in treated vs. untreated hepatocytes, and levosimendan prevents down-regulation of the anti-apoptotic protein Bcl-2 as well as up-regulation of the pro-apoptotic protein BAX.	Simendan	83-95	BCL2 associated X, apoptosis regulator	Homo sapiens	211-214
29145424-13	2017	Our findings suggest that treatment with levosimendan during reperfusion attenuates apoptosis of human hepatocytes by influencing BAX and Bcl-2 levels.	Simendan	41-53	BCL2 associated X, apoptosis regulator	Homo sapiens	130-133
29145424-13	2017	Our findings suggest that treatment with levosimendan during reperfusion attenuates apoptosis of human hepatocytes by influencing BAX and Bcl-2 levels.	Simendan	41-53	BCL2 apoptosis regulator	Homo sapiens	138-143
28479018-6	2017	RESULTS: The administration of levosimendan significantly attenuated (i) consumptive coagulopathy displayed by thromboelastography, (ii) the decreases of platelet count and plasma fibrinogen level, (iii) injury in the lung, liver and kidney, and (iv) the rise in plasma interleukin-6 in rats treated with LPS.	Simendan	31-43	interleukin 6	Rattus norvegicus	270-283
28192257-9	2017	Co-treatment with levosimendan strongly attenuated the effects of IL-1beta and thrombin on PAI-1 and TF mRNA by up to 50% and 45%, in a dose- and time-dependent manner.	Simendan	18-30	interleukin 1 beta	Homo sapiens	66-74
28192257-9	2017	Co-treatment with levosimendan strongly attenuated the effects of IL-1beta and thrombin on PAI-1 and TF mRNA by up to 50% and 45%, in a dose- and time-dependent manner.	Simendan	18-30	coagulation factor II, thrombin	Homo sapiens	79-87
28192257-9	2017	Co-treatment with levosimendan strongly attenuated the effects of IL-1beta and thrombin on PAI-1 and TF mRNA by up to 50% and 45%, in a dose- and time-dependent manner.	Simendan	18-30	serpin family E member 1	Homo sapiens	91-96
28192257-9	2017	Co-treatment with levosimendan strongly attenuated the effects of IL-1beta and thrombin on PAI-1 and TF mRNA by up to 50% and 45%, in a dose- and time-dependent manner.	Simendan	18-30	coagulation factor III, tissue factor	Homo sapiens	101-103
28192257-11	2017	Furthermore, co-treatment with levosimendan dampened the antigen production of PAI-1 and the surface expression of TF by 35% and 45%, respectively.	Simendan	31-43	serpin family E member 1	Homo sapiens	79-84
28192257-12	2017	Additionally, levosimendan diminished both TF and PAI-1 activity.	Simendan	14-26	serpin family E member 1	Homo sapiens	50-55
28192257-13	2017	CONCLUSION: Levosimendan down-regulates the expression of the pro-thrombotic and anti-fibrinolytic biomolecules TF and PAI-1 in activated human endothelial cells.	Simendan	12-24	serpin family E member 1	Homo sapiens	119-124
27914501-3	2016	METHODS: LEVO-CTS is a phase 3 randomized, controlled, multicenter study evaluating the efficacy, safety, and cost-effectiveness of levosimendan in reducing morbidity and mortality in high-risk patients with reduced left ventricular ejection fraction (<=35%) undergoing cardiac surgery on CPB.	Simendan	132-144	transthyretin	Homo sapiens	14-17
27914501-4	2016	Patients will be randomly assigned to receive either intravenous levosimendan (0.2 mug kg-1 min-1 for the first hour followed by 0.1 mug/kg for 23hours) or matching placebo initiated within 8hours of surgery.	Simendan	65-77	CD59 molecule (CD59 blood group)	Homo sapiens	92-97
27914501-9	2016	CONCLUSION: LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB.	Simendan	131-143	transthyretin	Homo sapiens	17-20
29861626-14	2018	Conclusion: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ.	Simendan	72-84	caspase 3	Rattus norvegicus	127-136
29861626-14	2018	Conclusion: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ.	Simendan	72-84	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	138-141
29861626-14	2018	Conclusion: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ.	Simendan	72-84	BCL2 associated X, apoptosis regulator	Rattus norvegicus	147-150
29052821-9	2017	Both high and low doses of levosimendan reduced serum IL-1ss levels, and high doses of levosimendan reduced IL-6 and NO levels.	Simendan	87-99	interleukin 6	Rattus norvegicus	108-112
29052821-11	2017	CONCLUSION: In conclusion, the results showed that in a rat model of PC, the experimental agent levosimendan could reduce neutrophil cell infiltration to damaged pulmonary tissues and the systemic expressions of some cytokines (IL-1ss, IL-6, and NO), thereby partially reducing and/or correcting pulmonary damage.	Simendan	96-108	interleukin 6	Rattus norvegicus	236-240
28214866-8	2017	Interestingly, levosimendan could markedly attenuate PTEN expression and inhibit myocardial apoptosis, therefore partially reverse cardiac dysfunction.	Simendan	15-27	phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Sus scrofa	53-57
28214866-9	2017	CONCLUSION: Modulation of PTEN was probably as a potential mechanism involved in the beneficial effects of pretreatment of levosimendan to cardiac function and apoptosis in animal models of CME.	Simendan	123-135	phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Sus scrofa	26-30
27851890-0	2017	Levosimendan exerts anticonvulsant properties against PTZ-induced seizures in mice through activation of nNOS/NO pathway: Role for KATP channel.	Simendan	0-12	nitric oxide synthase 1, neuronal	Mus musculus	105-109
27851890-10	2017	SIGNIFICANCE: Levosimendan has anticonvulsant effects possibly via KATP/nNOS/NO pathway activation in the hippocampus and temporal cortex.	Simendan	14-26	nitric oxide synthase 1, neuronal	Mus musculus	72-76
27673371-0	2016	Reversible Covalent Binding to Cardiac Troponin C by the Ca2+-Sensitizer Levosimendan.	Simendan	73-85	troponin C1, slow skeletal and cardiac type	Homo sapiens	31-49
27673371-5	2016	While the primary target of levosimendan is thought to be cTnC, the molecular details of this interaction are not well understood.	Simendan	28-40	troponin C1, slow skeletal and cardiac type	Homo sapiens	58-62
27673371-6	2016	In this study, we used mass spectrometry, computational chemistry, and nuclear magnetic resonance spectroscopy to demonstrate that levosimendan reacts specifically with cysteine 84 of cTnC to form a reversible thioimidate bond.	Simendan	131-143	troponin C1, slow skeletal and cardiac type	Homo sapiens	184-188
27673371-7	2016	We also showed that levosimendan only reacts with the active, Ca2+-bound conformation of cTnC.	Simendan	20-32	troponin C1, slow skeletal and cardiac type	Homo sapiens	89-93
27673371-8	2016	Finally, we propose a structural model of levosimendan bound to cTnC, which suggests that the Ca2+-sensitizing function of levosimendan is due to stabilization of the Ca2+-bound conformation of cTnC.	Simendan	42-54	troponin C1, slow skeletal and cardiac type	Homo sapiens	64-68
27673371-8	2016	Finally, we propose a structural model of levosimendan bound to cTnC, which suggests that the Ca2+-sensitizing function of levosimendan is due to stabilization of the Ca2+-bound conformation of cTnC.	Simendan	42-54	troponin C1, slow skeletal and cardiac type	Homo sapiens	194-198
27673371-8	2016	Finally, we propose a structural model of levosimendan bound to cTnC, which suggests that the Ca2+-sensitizing function of levosimendan is due to stabilization of the Ca2+-bound conformation of cTnC.	Simendan	123-135	troponin C1, slow skeletal and cardiac type	Homo sapiens	64-68
27673371-8	2016	Finally, we propose a structural model of levosimendan bound to cTnC, which suggests that the Ca2+-sensitizing function of levosimendan is due to stabilization of the Ca2+-bound conformation of cTnC.	Simendan	123-135	troponin C1, slow skeletal and cardiac type	Homo sapiens	194-198
27684548-13	2016	TNF-alpha levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion.	Simendan	57-69	tumor necrosis factor	Rattus norvegicus	0-9
26207881-6	2016	LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment.	Simendan	0-4	C-reactive protein	Rattus norvegicus	343-361
27232927-10	2016	Levosimendan should be preferred over adrenergic inotropes as a first line therapy for all ACS-AHF patients who are under beta-blockade and/or when urinary output is insufficient after diuretics.	Simendan	0-12	1-aminocyclopropane-1-carboxylate synthase homolog (inactive)	Homo sapiens	91-94
27058979-0	2016	Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway.	Simendan	0-12	solute carrier family 8 member A1	Rattus norvegicus	129-133
27138236-8	2016	HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group (p<0.05).	Simendan	27-39	fatty acid binding protein 3	Homo sapiens	0-5
27138236-8	2016	HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group (p<0.05).	Simendan	27-39	natriuretic peptide B	Homo sapiens	16-19
27143905-1	2016	PURPOSE: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase.	Simendan	59-71	lipocalin 2	Homo sapiens	315-357
27143905-1	2016	PURPOSE: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase.	Simendan	59-71	lipocalin 2	Homo sapiens	359-364
26375298-9	2016	Levosimendan, bepridil, and pimobendan were found to elevate the Ca(2+) -sensitivity of cTnT(T204E) containing samples in this context.	Simendan	0-12	troponin T2, cardiac type	Homo sapiens	88-92
26207881-6	2016	LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment.	Simendan	0-4	caspase 3	Rattus norvegicus	367-376
25949787-8	2015	As slow skeletal/cardiac troponin C is also the dominant troponin C isoform in slow-twitch skeletal muscle fibers, we hypothesized that levosimendan improves slow-twitch muscle fiber strength at submaximal levels of activation in patients with NEB-NM.	Simendan	136-148	troponin C1, slow skeletal and cardiac type	Homo sapiens	17-35
26528797-0	2015	Levosimendan inhibits interleukin-1beta-induced apoptosis through activation of Akt and inhibition of inducible nitric oxide synthase in rat cardiac fibroblasts.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	22-39
26528797-0	2015	Levosimendan inhibits interleukin-1beta-induced apoptosis through activation of Akt and inhibition of inducible nitric oxide synthase in rat cardiac fibroblasts.	Simendan	0-12	AKT serine/threonine kinase 1	Rattus norvegicus	80-83
26528797-3	2015	The aim of this study was to examine whether levosimendan modulates interleukin (IL)-1beta-induced apoptosis in adult rat cardiac fibroblast.	Simendan	45-57	interleukin 1 beta	Rattus norvegicus	68-90
26528797-9	2015	Levosimendan (3-100muM) concentration-dependently inhibited IL-1beta (4ng/ml, 24h)-induced apoptotic changes in cardiac fibroblasts, such as cellular shrinkage, nuclear condensation and the increase of TUNEL-positive cells.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	60-68
26528797-10	2015	Levosimendan inhibited IL-1beta-induced iNOS expression and subsequent NO production.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	23-31
26528797-10	2015	Levosimendan inhibited IL-1beta-induced iNOS expression and subsequent NO production.	Simendan	0-12	nitric oxide synthase 2	Rattus norvegicus	40-44
26528797-12	2015	Levosimendan alone-treatment concentration-dependently increased phosphorylation of Akt (Ser473).	Simendan	0-12	AKT serine/threonine kinase 1	Rattus norvegicus	84-87
26528797-13	2015	LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, reversed the protective effect of levosimendan on IL-1beta-induced apoptosis in TUNEL assay.	Simendan	94-106	interleukin 1 beta	Rattus norvegicus	110-118
26528797-14	2015	In addition, levosimendan and 1400W inhibited the IL-1beta-induced cytosolic translocation of cytochrome-c. LY294002 reversed the suppressive effects of levosimendan.	Simendan	13-25	interleukin 1 beta	Rattus norvegicus	50-58
26528797-14	2015	In addition, levosimendan and 1400W inhibited the IL-1beta-induced cytosolic translocation of cytochrome-c. LY294002 reversed the suppressive effects of levosimendan.	Simendan	153-165	interleukin 1 beta	Rattus norvegicus	50-58
26528797-15	2015	The present study for the first time demonstrated that levosimendan inhibits IL-1beta-induced apoptosis via the activation of PI3K/Akt pathway and the inhibition of iNOS expression in adult rat cardiac fibroblasts.	Simendan	55-67	interleukin 1 beta	Rattus norvegicus	77-85
26528797-15	2015	The present study for the first time demonstrated that levosimendan inhibits IL-1beta-induced apoptosis via the activation of PI3K/Akt pathway and the inhibition of iNOS expression in adult rat cardiac fibroblasts.	Simendan	55-67	AKT serine/threonine kinase 1	Rattus norvegicus	131-134
26528797-15	2015	The present study for the first time demonstrated that levosimendan inhibits IL-1beta-induced apoptosis via the activation of PI3K/Akt pathway and the inhibition of iNOS expression in adult rat cardiac fibroblasts.	Simendan	55-67	nitric oxide synthase 2	Rattus norvegicus	165-169
26468714-13	2015	Instead, levosimendan and pimobendan prevented high mobility group box 1 release from the nucleus to the extracellular space in macrophages.	Simendan	9-21	high mobility group box 1	Mus musculus	47-72
26468714-15	2015	The elevated serum high mobility group box 1 levels in cecal ligation and puncture-induced septic mice were also inhibited by continued administration of levosimendan and pimobendan.	Simendan	154-166	high mobility group box 1	Mus musculus	19-44
27708855-7	2015	BNP showed no change with placebo (1042 +- 811 to 1043 +- 867 pg/mL), but it was decreased with levosimendan (1163 +- 897 to 509 +- 543 pg/mL, P < 0.001).	Simendan	96-108	natriuretic peptide B	Homo sapiens	0-3
27708855-12	2015	CONCLUSION: Levosimendan treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in patients with ADHF.	Simendan	12-24	natriuretic peptide B	Homo sapiens	97-100
25880552-7	2015	Pre-treatment of hepatocytes with levosimendan dose-dependently counteracted the injuries caused by oxidative stress and reduced NO release by modulating eNOS/iNOS activation.	Simendan	34-46	nitric oxide synthase 3	Rattus norvegicus	154-158
25880552-7	2015	Pre-treatment of hepatocytes with levosimendan dose-dependently counteracted the injuries caused by oxidative stress and reduced NO release by modulating eNOS/iNOS activation.	Simendan	34-46	nitric oxide synthase 2	Rattus norvegicus	159-163
25738589-0	2015	The inotropic effect of the active metabolite of levosimendan, OR-1896, is mediated through inhibition of PDE3 in rat ventricular myocardium.	Simendan	49-61	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	106-110
25867530-0	2015	Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure.	Simendan	0-12	myeloperoxidase	Homo sapiens	62-65
25867530-3	2015	We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course.	Simendan	28-40	myeloperoxidase	Homo sapiens	54-57
25867530-4	2015	Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 +- 31.1 pmol/l at baseline to 215.02 +- 27.96 pmol/l at 6 h, p < 0.05).	Simendan	53-65	myeloperoxidase	Homo sapiens	7-10
25867530-5	2015	Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 +- 1.4-fold increase at baseline vs. 6.0 +- 1.1-fold increase with levosimendan).	Simendan	39-51	myeloperoxidase	Homo sapiens	62-65
25867530-9	2015	We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients.	Simendan	40-52	myeloperoxidase	Homo sapiens	72-75
26082815-8	2015	RESULTS: Levosimendan induced an increase in cerebral blood flow velocities and a decrease in NT-pro-BNP compared with placebo.	Simendan	9-21	natriuretic peptide B	Homo sapiens	101-104
25273157-7	2015	Treatment with levosimendan strongly attenuated IL-1beta-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs.	Simendan	15-27	interleukin 1 beta	Homo sapiens	48-56
25888356-8	2015	Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05).	Simendan	0-12	nitric oxide synthase 2, inducible	Mus musculus	162-166
25273157-7	2015	Treatment with levosimendan strongly attenuated IL-1beta-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs.	Simendan	15-27	interleukin 6	Homo sapiens	79-83
25273157-7	2015	Treatment with levosimendan strongly attenuated IL-1beta-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs.	Simendan	15-27	C-X-C motif chemokine ligand 8	Homo sapiens	88-92
25273157-7	2015	Treatment with levosimendan strongly attenuated IL-1beta-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs.	Simendan	15-27	selectin E	Homo sapiens	112-122
25273157-7	2015	Treatment with levosimendan strongly attenuated IL-1beta-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs.	Simendan	15-27	intercellular adhesion molecule 1	Homo sapiens	127-133
25273157-10	2015	Additionally, levosimendan strongly diminished IL-1beta-induced reactive oxygen species and nuclear factor-kappaB (NF-kappaB) activity through inhibition of S536 phosphorylation.	Simendan	14-26	interleukin 1 beta	Homo sapiens	47-55
26082815-12	2015	CONCLUSIONS: Oral levosimendan increases cerebral blood flow velocities and diminishes NT-pro-BNP levels in patients with earlier ischemic cerebrovascular event.	Simendan	18-30	natriuretic peptide B	Homo sapiens	94-97
24657218-8	2014	Our results show that patients treated with levosimendan had a significant reduction of glutathionylated proteins and an increase in the amount of the antioxidant enzyme MnSOD, underlining its antioxidant properties.	Simendan	44-56	superoxide dismutase 2	Homo sapiens	170-175
25280932-2	2014	We therefore wanted to test whether levosimendan, a calcium sensitizer and dose-dependent phosphodiesterase 3 (PDE3) inhibitor, is able to elevate stroke volume during rewarming from experimental hypothermia.	Simendan	36-48	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	90-109
25280932-2	2014	We therefore wanted to test whether levosimendan, a calcium sensitizer and dose-dependent phosphodiesterase 3 (PDE3) inhibitor, is able to elevate stroke volume during rewarming from experimental hypothermia.	Simendan	36-48	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	111-115
25280932-9	2014	CONCLUSION: The present data shows that levosimendan ameliorates hypothermia-induced systolic dysfunction by elevating SV during rewarming from 15 C. Inotropic treatment during rewarming from hypothermia in the present rat model is therefore better achieved through calcium sensitizing and PDE3 inhibition, than beta-receptor stimulation.	Simendan	40-52	phosphodiesterase 4D, cAMP-specific-like 1	Rattus norvegicus	290-294
25432865-4	2014	Plasma interleukin-1beta, nitric oxide and organ superoxide levels in the levosimendan-treated CLP group were less than those in CLP rats treated with vehicle (P < 0.05).	Simendan	74-86	interleukin 1 beta	Rattus norvegicus	7-24
25432865-5	2014	In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05).	Simendan	132-144	nitric oxide synthase 2	Rattus norvegicus	17-48
25432865-5	2014	In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05).	Simendan	132-144	nitric oxide synthase 2	Rattus norvegicus	50-54
25432865-5	2014	In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05).	Simendan	132-144	caspase 3	Rattus norvegicus	68-77
25094034-9	2014	The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-alpha, iNOS, eNOS, and caspase-3.	Simendan	25-37	tumor necrosis factor	Rattus norvegicus	90-99
25094034-9	2014	The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-alpha, iNOS, eNOS, and caspase-3.	Simendan	25-37	nitric oxide synthase 2	Rattus norvegicus	101-105
25094034-9	2014	The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-alpha, iNOS, eNOS, and caspase-3.	Simendan	25-37	caspase 3	Rattus norvegicus	117-126
25094034-10	2014	The hepatoprotective effect of levosimendan was partially attenuated by pretreatment by either nonselective COX inhibitor, NOS inhibitor, or K-ATP channel blocker; indicating that the hepatoprotective effect of levosimendan was attributed, at least in part to activation of COX-1, modulation of NO, and opening of K-ATP channel.	Simendan	31-43	cytochrome c oxidase I, mitochondrial	Rattus norvegicus	274-279
24547784-7	2014	During treatment with a PDE4 inhibitor and a supra-threshold concentration of isoprenaline, levosimendan generated an amplified inotropic response.	Simendan	92-104	phosphodiesterase 4A	Homo sapiens	24-28
25053182-4	2014	While there were no differences in serum creatinine (sCr) or eGFR between groups at baseline, patients in the LS group had a greater increase in their relative eGFR (62% vs. 12%, p = 0.002) and a lower incidence of acute kidney injury (AKI) (28% vs. 6%, p = 0.01) during the first post-transplant week.	Simendan	110-112	epidermal growth factor receptor	Homo sapiens	160-164
24785343-6	2014	Levosimendan inhibited the hypothermic preservation-induced calpain activation and cleavage of Bid.	Simendan	0-12	BH3 interacting domain death agonist	Rattus norvegicus	95-98
24464960-9	2014	Specifically, the levosimendan and placebo group exhibited significantly different changes over time in GFR (P = 0.037), renal blood flow (P = 0.037), and renal artery diameter (P = 0.033), with ensuing improvements in serum levels of BUN (P = 0.014), creatinine (P = 0.042), and cystatin C (P = 0.05).	Simendan	18-30	cystatin C	Homo sapiens	280-290
24699010-6	2014	ICG detected the Levosimendan-induced recovery of the hemodynamic status, associated with improved systolic and diastolic function and reduction in BNP levels.	Simendan	17-29	natriuretic peptide B	Homo sapiens	148-151
24138817-9	2013	In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold.	Simendan	55-67	troponin I3, cardiac type	Rattus norvegicus	78-82
24351506-11	2014	The protein expression of HIF-1alpha was increased both by levosimendan (0.563 +- 0.175 IDV vs 0.142 +- 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 +- 0.222 IDV; P < 0.0001) pretreatment.	Simendan	59-71	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	26-36
22722773-7	2014	The protective enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase and antioxidant glutathione level were significantly (p < 0.001) higher in levosimendan group than in controls.	Simendan	178-190	catalase	Rattus norvegicus	63-71
24050857-7	2013	MEASUREMENTS AND MAIN RESULTS: PubMed, EMBASE, the Cochrane database of clinical trials, and conference proceedings were searched for clinical trials of perioperative levosimendan in patients undergoing cardiac surgery through May 1, 2012.	Simendan	167-179	protein kinase C delta	Homo sapiens	227-232
24273004-10	2014	Levosimendan administration was able to counteract oxidative damage and apoptosis in a dose-dependent way and to increase GSH, Akt, and eNOS activation.	Simendan	0-12	AKT serine/threonine kinase 1	Rattus norvegicus	127-130
23957729-5	2013	The serum levels of TNF-alpha, IL-6, and IL-1beta were found to have decreased as a result of the administration of both doses of levosimendan in the IR.	Simendan	130-142	tumor necrosis factor	Rattus norvegicus	20-29
23957729-5	2013	The serum levels of TNF-alpha, IL-6, and IL-1beta were found to have decreased as a result of the administration of both doses of levosimendan in the IR.	Simendan	130-142	interleukin 6	Rattus norvegicus	31-35
23957729-5	2013	The serum levels of TNF-alpha, IL-6, and IL-1beta were found to have decreased as a result of the administration of both doses of levosimendan in the IR.	Simendan	130-142	interleukin 1 beta	Rattus norvegicus	41-49
23957729-6	2013	Relative TNF-alpha and NFkappaB mRNA levels was decreased by administration of both doses of levosimendan in the IR.	Simendan	93-105	tumor necrosis factor	Rattus norvegicus	9-18
24072410-0	2013	Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene.	Simendan	10-22	ATPase, Ca++ transporting, cardiac muscle, slow twitch 2	Mus musculus	140-146
24072410-5	2013	SERCA2 knockout (SERCA2KO) mice were treated with levosimendan or vehicle from the time of KO induction.	Simendan	50-62	ATPase, Ca++ transporting, cardiac muscle, slow twitch 2	Mus musculus	0-6
24138817-11	2013	CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.	Simendan	13-25	troponin I3, cardiac type	Rattus norvegicus	74-78
24012928-0	2013	Levosimendan inhibits interleukin-1beta-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	22-39
24012928-0	2013	Levosimendan inhibits interleukin-1beta-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts.	Simendan	0-12	matrix metallopeptidase 9	Rattus norvegicus	67-72
24012928-3	2013	Therefore, we investigated the effects of levosimendan on interleukin (IL)-1beta-induced MMP-9 secretion and migration in adult rat cardiac fibroblasts.	Simendan	42-54	interleukin 1 beta	Rattus norvegicus	58-80
24012928-9	2013	Levosimendan (3-100 muM) concentration-dependently inhibited IL-1beta (4 ng/ml)-induced MMP-9 secretion, activity and mRNA expression.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	61-69
24012928-9	2013	Levosimendan (3-100 muM) concentration-dependently inhibited IL-1beta (4 ng/ml)-induced MMP-9 secretion, activity and mRNA expression.	Simendan	0-12	matrix metallopeptidase 9	Rattus norvegicus	88-93
24012928-10	2013	Levosimendan inhibited IL-1beta (4 ng/ml)-induced ERK phosphorylation.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	23-31
24012928-10	2013	Levosimendan inhibited IL-1beta (4 ng/ml)-induced ERK phosphorylation.	Simendan	0-12	Eph receptor B1	Rattus norvegicus	50-53
24012928-11	2013	Levosimendan (10 and 100 muM) inhibited IL-1beta-induced migration, and CTTHWGFTLC peptide (10 muM), an MMP inhibitor, or PD98059 (50 muM), an ERK inhibitor, also suppressed it.	Simendan	0-12	interleukin 1 beta	Rattus norvegicus	40-48
24012928-12	2013	The present study for the first time demonstrated in adult rat cardiac fibroblasts that levosimendan inhibits IL-1beta-induced migration at least partly through the inhibition of MMP-9 secretion via suppressing ERK phosphorylation.	Simendan	88-100	interleukin 1 beta	Rattus norvegicus	110-118
24012928-12	2013	The present study for the first time demonstrated in adult rat cardiac fibroblasts that levosimendan inhibits IL-1beta-induced migration at least partly through the inhibition of MMP-9 secretion via suppressing ERK phosphorylation.	Simendan	88-100	matrix metallopeptidase 9	Rattus norvegicus	179-184
24012928-12	2013	The present study for the first time demonstrated in adult rat cardiac fibroblasts that levosimendan inhibits IL-1beta-induced migration at least partly through the inhibition of MMP-9 secretion via suppressing ERK phosphorylation.	Simendan	88-100	Eph receptor B1	Rattus norvegicus	211-214
24364085-10	2013	Our research showed that C-reactive protein was higher postoperatively in the control group than in the levosimendan group (P < 0.05).	Simendan	104-116	C-reactive protein	Homo sapiens	25-43
23824760-9	2013	In both PAs and PVs, levosimendan increased intracellular cAMP- and cGMP-levels, whereas NO end products remained unchanged.	Simendan	21-33	cathelicidin antimicrobial peptide	Cavia porcellus	58-72
22362016-5	2013	Superoxide dismutase, glutathione peroxidase, catalase and carbonic anhydrase enzyme activities were lower in levosimendan injected group than controls.	Simendan	110-122	catalase	Rattus norvegicus	46-54
22938184-4	2013	LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-alpha, IL-1 and IL-6 at doses of 2 and 3 mg/kg.	Simendan	0-4	tumor necrosis factor	Rattus norvegicus	71-80
23490237-8	2013	In addition, levosimendan resulted in a distinct decrease in BNP levels in comparison with placebo, and the beneficial effect returned to baseline by day 14 and remained so at day 30 postinfusion.	Simendan	13-25	natriuretic peptide B	Homo sapiens	61-64
23469954-2	2013	In coronary vessels, levosimendan has a vasorelaxant, endothelium-independent effect and an antagonistic effect on endothelin-1 (ET-1).	Simendan	21-33	endothelin 1	Homo sapiens	115-127
23469954-2	2013	In coronary vessels, levosimendan has a vasorelaxant, endothelium-independent effect and an antagonistic effect on endothelin-1 (ET-1).	Simendan	21-33	endothelin 1	Homo sapiens	129-133
22938184-4	2013	LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-alpha, IL-1 and IL-6 at doses of 2 and 3 mg/kg.	Simendan	0-4	interleukin 6	Rattus norvegicus	91-95
22932705-5	2012	In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01).	Simendan	7-11	natriuretic peptide B	Homo sapiens	111-114
22843162-7	2012	It was found that MDA, GSH and CAT enzyme levels increased in thoracic aortae of rats after levosimendan administration.	Simendan	92-104	catalase	Rattus norvegicus	31-34
22928945-9	2012	Similar decreases in systolic and diastolic blood pressure, pulmonary capillary wedge pressure and BNP, and similar survival and adverse event profiles were seen in sulfonylurea users and non-users exposed to levosimendan.	Simendan	209-221	natriuretic peptide B	Homo sapiens	99-102
21932058-2	2012	The study was tested in a fecal peritonitis-induced septic shock model, we observed that levosimendan combined with arginine vasopressin supplemented with norepinephrine therapy resulted in lower mean pulmonary artery pressure, lactate concentrations, arterial total nitrate/nitrite, and high-mobility group box 1 levels; decreased lung wet/dry ratio, and pulmonary levels of interleukin-6, total histological scores, and improved pulmonary gas exchange when compared with norepinephrine group.	Simendan	89-101	high mobility group box 1	Homo sapiens	288-313
22870740-5	2012	RESULTS: In both groups statistically significant improvement was observed in NYHA class, plasma BNP levels and left ventricular end-systolic diameter after the levosimendan infusion compared to baseline (P < 0.025).	Simendan	161-173	natriuretic peptide B	Homo sapiens	97-100
21932058-2	2012	The study was tested in a fecal peritonitis-induced septic shock model, we observed that levosimendan combined with arginine vasopressin supplemented with norepinephrine therapy resulted in lower mean pulmonary artery pressure, lactate concentrations, arterial total nitrate/nitrite, and high-mobility group box 1 levels; decreased lung wet/dry ratio, and pulmonary levels of interleukin-6, total histological scores, and improved pulmonary gas exchange when compared with norepinephrine group.	Simendan	89-101	interleukin 6	Homo sapiens	376-389
22239823-8	2012	CONCLUSION: Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening.	Simendan	26-38	protein tyrosine phosphatase, receptor type, U	Mus musculus	88-92
22240915-5	2012	Compared with hypoxia baseline, levosimendan decreased MPAP and PVR (P < 0.05), by approximately 9% and 19%, respectively, plateauing between 10 and 90 minutes.	Simendan	32-44	PVR cell adhesion molecule	Sus scrofa	64-67
21749676-9	2011	RESULTS: In vitro, levosimendan suppressed respiratory burst activity in fMLP or PMA stimulated PMN in a dose dependent manner by 30 +- 11% (P < 0.001) at 100 ng/mL and by 27 +- 17% (P < 0.001) at 1000 ng/mL respectively.	Simendan	19-31	formyl peptide receptor 1	Homo sapiens	73-77
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	angiotensin II receptor, type 1b	Rattus norvegicus	75-97
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	angiotensin II receptor, type 1b	Rattus norvegicus	99-104
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	chymase 1	Rattus norvegicus	107-116
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	chymase 1	Rattus norvegicus	118-122
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	thimet oligopeptidase 1	Rattus norvegicus	128-151
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	thimet oligopeptidase 1	Rattus norvegicus	153-158
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	diacylglycerol kinase, gamma	Rattus norvegicus	228-255
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	diacylglycerol kinase, gamma	Rattus norvegicus	257-261
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	carboxyl ester lipase	Rattus norvegicus	264-285
21699655-10	2011	Levosimendan up-regulated 3 genes in the renin-angiotensin system pathway [angiotensin receptor 1 (Agtr1), chymase 1 (Cma1) and thimet oligopeptidase 1 (Thop1)] and down-regulated 3 genes in the glycerolipid metabolism pathway [diacylglycerol kinase gamma (Dgkg), carboxyl ester lipase (Cel) and Diacylglycerol kinase iota].	Simendan	0-12	carboxyl ester lipase	Rattus norvegicus	287-290
21699655-11	2011	Levosimendan induced opposite effects on the gene expression of pleckstrin homology (PH) domain containing family f (Plekhf1), carboxymethylenebutenolidase homologue (Cmbl) (up-regulation) and hydroxyprostaglandin dehydrogenase 15 (Hpgd) (down-regulation) as compared with MI.	Simendan	0-12	pleckstrin homology and FYVE domain containing 1	Rattus norvegicus	117-124
21699655-11	2011	Levosimendan induced opposite effects on the gene expression of pleckstrin homology (PH) domain containing family f (Plekhf1), carboxymethylenebutenolidase homologue (Cmbl) (up-regulation) and hydroxyprostaglandin dehydrogenase 15 (Hpgd) (down-regulation) as compared with MI.	Simendan	0-12	carboxymethylenebutenolidase homolog	Rattus norvegicus	167-171
21699655-11	2011	Levosimendan induced opposite effects on the gene expression of pleckstrin homology (PH) domain containing family f (Plekhf1), carboxymethylenebutenolidase homologue (Cmbl) (up-regulation) and hydroxyprostaglandin dehydrogenase 15 (Hpgd) (down-regulation) as compared with MI.	Simendan	0-12	15-hydroxyprostaglandin dehydrogenase	Rattus norvegicus	193-230
21699655-11	2011	Levosimendan induced opposite effects on the gene expression of pleckstrin homology (PH) domain containing family f (Plekhf1), carboxymethylenebutenolidase homologue (Cmbl) (up-regulation) and hydroxyprostaglandin dehydrogenase 15 (Hpgd) (down-regulation) as compared with MI.	Simendan	0-12	15-hydroxyprostaglandin dehydrogenase	Rattus norvegicus	232-236
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	tumor necrosis factor	Homo sapiens	137-164
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	tumor necrosis factor	Homo sapiens	166-175
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	selectin E	Homo sapiens	212-222
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	intercellular adhesion molecule 1	Homo sapiens	224-257
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	intercellular adhesion molecule 1	Homo sapiens	259-265
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	prostaglandin-endoperoxide synthase 2	Homo sapiens	268-284
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	prostaglandin-endoperoxide synthase 2	Homo sapiens	286-291
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	C-C motif chemokine ligand 2	Homo sapiens	298-328
21626431-9	2011	Indeed, levosimendan increased cyclic guanosine monophosphate (cGMP) in human umbilical vein endothelial cells (HUVECs) and impaired the tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and monocyte chemotactic protein-1 (MCP-1).	Simendan	8-20	C-C motif chemokine ligand 2	Homo sapiens	330-335
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	tumor necrosis factor	Homo sapiens	91-100
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	162-181
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	JunB proto-oncogene, AP-1 transcription factor subunit	Homo sapiens	183-186
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	hypoxia inducible factor 1 subunit alpha	Homo sapiens	189-220
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	hypoxia inducible factor 1 subunit alpha	Homo sapiens	222-232
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	nuclear factor kappa B subunit 1	Homo sapiens	239-260
21626431-10	2011	In luciferase reporter gene assays in HUVECs, levosimendan dose-dependently attenuated the TNF-alpha-stimulated increase of proinflammatory transcription factors activator protein 1 (AP1), hypoxia-inducible factor-1alpha (HIF-1alpha), and nuclear factor-kappaB (NF-kappaB).	Simendan	46-58	nuclear factor kappa B subunit 1	Homo sapiens	262-271
21664904-4	2011	Pretreatment with levosimendan reversed the effects of ischaemia and ischaemia/reperfusion on cell viability and enhanced phosphorylation of Akt, p38-mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2).	Simendan	18-30	AKT serine/threonine kinase 1	Homo sapiens	141-144
21664904-4	2011	Pretreatment with levosimendan reversed the effects of ischaemia and ischaemia/reperfusion on cell viability and enhanced phosphorylation of Akt, p38-mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2).	Simendan	18-30	mitogen-activated protein kinase 14	Homo sapiens	146-182
21664904-4	2011	Pretreatment with levosimendan reversed the effects of ischaemia and ischaemia/reperfusion on cell viability and enhanced phosphorylation of Akt, p38-mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2).	Simendan	18-30	mitogen-activated protein kinase 14	Homo sapiens	184-188
21664904-4	2011	Pretreatment with levosimendan reversed the effects of ischaemia and ischaemia/reperfusion on cell viability and enhanced phosphorylation of Akt, p38-mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2).	Simendan	18-30	mitogen-activated protein kinase 1	Homo sapiens	194-236
21664904-4	2011	Pretreatment with levosimendan reversed the effects of ischaemia and ischaemia/reperfusion on cell viability and enhanced phosphorylation of Akt, p38-mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinases 1/2 (ERK1/2).	Simendan	18-30	mitogen-activated protein kinase 3	Homo sapiens	238-244
21664904-6	2011	Levosimendan stimulated the phosphorylation of Akt, ERK1/2 and p38-MAPK with different kinetics and the activation of these pathways was dependent on the opening of the mitochondrial K(ATP) channels and the production of oxygen free radicals.	Simendan	0-12	AKT serine/threonine kinase 1	Homo sapiens	47-50
21664904-6	2011	Levosimendan stimulated the phosphorylation of Akt, ERK1/2 and p38-MAPK with different kinetics and the activation of these pathways was dependent on the opening of the mitochondrial K(ATP) channels and the production of oxygen free radicals.	Simendan	0-12	mitogen-activated protein kinase 3	Homo sapiens	52-58
21664904-6	2011	Levosimendan stimulated the phosphorylation of Akt, ERK1/2 and p38-MAPK with different kinetics and the activation of these pathways was dependent on the opening of the mitochondrial K(ATP) channels and the production of oxygen free radicals.	Simendan	0-12	mitogen-activated protein kinase 1	Homo sapiens	63-66
21664904-6	2011	Levosimendan stimulated the phosphorylation of Akt, ERK1/2 and p38-MAPK with different kinetics and the activation of these pathways was dependent on the opening of the mitochondrial K(ATP) channels and the production of oxygen free radicals.	Simendan	0-12	mitogen-activated protein kinase 14	Homo sapiens	67-71
21664904-7	2011	The levosimendan-induced phosphorylation of ERK1/2 and Akt was reduced by inhibitors of epidermal growth factor receptor and Src.	Simendan	4-16	mitogen-activated protein kinase 3	Homo sapiens	44-50
21664904-7	2011	The levosimendan-induced phosphorylation of ERK1/2 and Akt was reduced by inhibitors of epidermal growth factor receptor and Src.	Simendan	4-16	AKT serine/threonine kinase 1	Homo sapiens	55-58
21664904-7	2011	The levosimendan-induced phosphorylation of ERK1/2 and Akt was reduced by inhibitors of epidermal growth factor receptor and Src.	Simendan	4-16	epidermal growth factor receptor	Homo sapiens	88-120
21664904-7	2011	The levosimendan-induced phosphorylation of ERK1/2 and Akt was reduced by inhibitors of epidermal growth factor receptor and Src.	Simendan	4-16	SRC proto-oncogene, non-receptor tyrosine kinase	Homo sapiens	125-128
21821501-0	2011	Value of IGF-I levels in the evaluation of response to treatment with levosimendan in patients with severe heart failure.	Simendan	70-82	insulin like growth factor 1	Homo sapiens	9-14
21821501-3	2011	The aim of this study was to determine the value of baseline insulin-like growth factor 1 (IGF-I) measurements in predicting response to levosimendan treatment.	Simendan	137-149	insulin like growth factor 1	Homo sapiens	61-89
21821501-3	2011	The aim of this study was to determine the value of baseline insulin-like growth factor 1 (IGF-I) measurements in predicting response to levosimendan treatment.	Simendan	137-149	insulin like growth factor 1	Homo sapiens	91-96
21821501-13	2011	CONCLUSION: Baseline IGF-I levels may be used to predict response to levosimendan treatment in patients hospitalized for decompensated HF.	Simendan	69-81	insulin like growth factor 1	Homo sapiens	21-26
21749676-11	2011	In patients suffering from septic shock levosimendan treatment decreased oxidative burst activity in unstimulated, fMLP and PMA stimulated PMN by 48% (P < 0.05), 46% (P < 0.01) and 43% (P < 0.01) respectively.	Simendan	40-52	formyl peptide receptor 1	Homo sapiens	115-119
21749676-10	2011	Markers of apoptosis and PMN cell adhesion molecule expression remained unaffected by levosimendan treatment.In vivo, levosimendan treatment for two hours resulted in a significant reduction of PMA stimulated oxidative burst by 45% (P < 0.01) and fMLP stimulated oxidative burst by 49% (P < 0.05) in patients with acute heart failure.	Simendan	118-130	formyl peptide receptor 1	Homo sapiens	250-254
19875306-11	2010	Levosimendan significantly reduced the proportion of TUNEL-positive cardiomyocytes (3 +/- 1 v 20 +/- 4, respectively; p < 0.001) and increased Bcl-2 expression compared with control hearts (44% +/- 3% v 31% +/- 3%, respectively; p = 0.01).	Simendan	0-12	BCL2, apoptosis regulator	Rattus norvegicus	146-151
21247774-10	2011	In addition, after intracoronary levosimendan, the inhibition of apoptosis and activation of autophagy and a dose-related increase of the level of phosphorylation of ERK and Akt were observed.	Simendan	33-45	AKT serine/threonine kinase 1	Sus scrofa	174-177
21358614-0	2011	Effects of levosimendan/furosemide infusion on plasma brain natriuretic peptide, echocardiographic parameters and cardiac output in end-stage heart failure patients.	Simendan	11-23	natriuretic peptide B	Homo sapiens	54-79
21358614-6	2011	At the end of levosimendan therapy, BNP decreased (from 679.7 +- 512.1 pg/ml to 554.2 +- 407.6 pg/ml p = 0.03), and 6 MWT and LVEF improved (from 217.6 +- 97.7 m to 372.2 +- 90.4 m p = 0.0001; from 22.8 +- 9.1% to 25.4 +- 9.8% p = 0.05).	Simendan	14-26	natriuretic peptide B	Homo sapiens	36-39
21358614-10	2011	CONCLUSIONS: Treating end-stage CHF patients with levosimendan improved BNP and LVEF, but this effect disappeared after 1 week.	Simendan	50-62	natriuretic peptide B	Homo sapiens	72-75
20811386-0	2010	Levosimendan improves cardiac function and survival in rats with angiotensin II-induced hypertensive heart failure.	Simendan	0-12	angiotensinogen	Rattus norvegicus	65-79
20811386-2	2010	We tested the hypothesis that levosimendan, an inodilator that acts through calcium sensitization, opening of ATP-dependent potassium channels and phosphodiesterase III inhibition, improves cardiac function and survival in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin II (Ang II)-induced hypertensive heart failure.	Simendan	30-42	renin	Homo sapiens	262-267
20811386-2	2010	We tested the hypothesis that levosimendan, an inodilator that acts through calcium sensitization, opening of ATP-dependent potassium channels and phosphodiesterase III inhibition, improves cardiac function and survival in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin II (Ang II)-induced hypertensive heart failure.	Simendan	30-42	angiotensinogen	Homo sapiens	314-328
20811386-2	2010	We tested the hypothesis that levosimendan, an inodilator that acts through calcium sensitization, opening of ATP-dependent potassium channels and phosphodiesterase III inhibition, improves cardiac function and survival in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin II (Ang II)-induced hypertensive heart failure.	Simendan	30-42	angiotensinogen	Homo sapiens	330-336
20811386-6	2010	However, levosimendan improved systolic function, decreased cardiac atrial natriuretic peptide mRNA expression, ameliorated Ang II-induced cardiac damage and decreased mortality.	Simendan	9-21	angiotensinogen	Rattus norvegicus	124-130
20811386-9	2010	Our findings suggest that levosimendan ameliorates Ang II-induced hypertensive heart failure and reduces mortality.	Simendan	26-38	angiotensinogen	Rattus norvegicus	51-57
20811386-10	2010	The results also support the notion that the effects of levosimendan in dTGRs are mediated by blood pressure-independent mechanisms and include improved systolic function and amelioration of Ang II-induced coronary and cardiomyocyte damage.	Simendan	56-68	angiotensinogen	Rattus norvegicus	191-197
19997054-11	2010	Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap.	Simendan	0-12	PCO2	Sus scrofa	224-228
21237146-0	2011	Levosimendan preserves the contractile responsiveness of hypoxic human myocardium via mitochondrial K(ATP) channel and potential pERK 1/2 activation.	Simendan	0-12	eukaryotic translation initiation factor 2 alpha kinase 3	Homo sapiens	129-133
21237146-10	2011	Cytochrome c was detected at 60min post reoxygenation, in both levosimendan treated and untreated tissue.	Simendan	63-75	cytochrome c, somatic	Homo sapiens	0-12
21237146-13	2011	The significant increase in the activity of prosurvival mediators ERK 1/2 and P38 following hypoxia indicates a potential mechanism of action for levosimendan-induced cardioprotection.	Simendan	146-158	mitogen-activated protein kinase 3	Homo sapiens	66-73
21237146-13	2011	The significant increase in the activity of prosurvival mediators ERK 1/2 and P38 following hypoxia indicates a potential mechanism of action for levosimendan-induced cardioprotection.	Simendan	146-158	mitogen-activated protein kinase 1	Homo sapiens	78-81
20162343-8	2010	Moreover, levosimendan prevented the down-regulation of the anti-apoptotic gene, Bcl-2, and the up-regulation of the apoptotic markers Bax and cytochrome c, which resulted in a reduced expression of TUNEL fragmented nuclei (p < 0.05).	Simendan	10-22	apoptosis regulator Bcl-2	Sus scrofa	81-86
20335355-8	2010	Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03).	Simendan	77-89	natriuretic peptide B	Homo sapiens	13-39
20335355-8	2010	Reduction in B-type natriuretic peptide (BNP) was significantly greater with levosimendan at 48 h (P = 0.03).	Simendan	77-89	natriuretic peptide B	Homo sapiens	41-44
18973957-0	2010	Plasma B-type natriuretic peptide reduction predicts long-term response to levosimendan therapy in acutely decompensated chronic heart failure.	Simendan	75-87	natriuretic peptide B	Homo sapiens	7-33
18973957-7	2010	In the levosimendan group, treatment-induced percent BNP change was the best predictor of events (OR=0.970, 95% CI=0.954-0.986, p<0.001).	Simendan	7-19	natriuretic peptide B	Homo sapiens	53-56
18973957-10	2010	CONCLUSION: Treatment-induced BNP reduction is an independent predictor of 6-month outcome following levosimendan therapy in ADHF.	Simendan	101-113	natriuretic peptide B	Homo sapiens	30-33
20849043-1	2010	BACKGROUND: This prospective, controlled experimental study was planned to investigate the effects of levosimendan on transforming growth factor (TGF)-beta3 and Smad1, Smad2 and Smad3 expression in the early stages of sepsis.	Simendan	102-114	SMAD family member 1	Rattus norvegicus	161-166
20849043-8	2010	Smad1, Smad2 and Smad3 were found moderately increased only in group levosimendan.	Simendan	69-81	SMAD family member 1	Rattus norvegicus	0-5
20849043-8	2010	Smad1, Smad2 and Smad3 were found moderately increased only in group levosimendan.	Simendan	69-81	SMAD family member 2	Rattus norvegicus	7-12
20849043-8	2010	Smad1, Smad2 and Smad3 were found moderately increased only in group levosimendan.	Simendan	69-81	SMAD family member 3	Rattus norvegicus	17-22
19842009-14	2010	Postconditioning with levosimendan significantly increased the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3beta (GSK-3beta) at 5 min of reperfusion, an effect which could be blocked completely by the additional administration of wortmannin.	Simendan	22-34	AKT serine/threonine kinase 1	Homo sapiens	100-103
19842009-14	2010	Postconditioning with levosimendan significantly increased the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3beta (GSK-3beta) at 5 min of reperfusion, an effect which could be blocked completely by the additional administration of wortmannin.	Simendan	22-34	glycogen synthase kinase 3 beta	Homo sapiens	109-139
19842009-14	2010	Postconditioning with levosimendan significantly increased the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3beta (GSK-3beta) at 5 min of reperfusion, an effect which could be blocked completely by the additional administration of wortmannin.	Simendan	22-34	glycogen synthase kinase 3 beta	Homo sapiens	141-150
20162343-8	2010	Moreover, levosimendan prevented the down-regulation of the anti-apoptotic gene, Bcl-2, and the up-regulation of the apoptotic markers Bax and cytochrome c, which resulted in a reduced expression of TUNEL fragmented nuclei (p < 0.05).	Simendan	10-22	apoptosis regulator BAX	Sus scrofa	135-138
20162343-8	2010	Moreover, levosimendan prevented the down-regulation of the anti-apoptotic gene, Bcl-2, and the up-regulation of the apoptotic markers Bax and cytochrome c, which resulted in a reduced expression of TUNEL fragmented nuclei (p < 0.05).	Simendan	10-22	cytochrome c	Sus scrofa	143-155
20162343-9	2010	Furthermore, levosimendan maintained Beclin 1 at 4 h and potentiated LC3 II expression, these results being consistent with autophagy activation.	Simendan	13-25	beclin 1	Sus scrofa	37-45
19812809-6	2009	The levosimendan group had a greater decrease in BNP and a greater increase in active emptying fraction at 24 h compared with the dobutamine group.	Simendan	4-16	natriuretic peptide B	Homo sapiens	49-52
19681782-0	2010	Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs.	Simendan	0-12	adrenoceptor beta 1	Sus scrofa	41-67
19812809-8	2009	Levosimendan- induced percentage change of BNP was significantly correlated with the percentage change of E/e and PEF (r=0.48 [P<0.005] and r=-0.38 [P<0.05], respectively).	Simendan	0-12	natriuretic peptide B	Homo sapiens	43-46
19861257-2	2009	METHODS: A meta-analysis was performed on the selected data to analyze the effect of levosimendan on BNP levels.	Simendan	85-97	natriuretic peptide B	Homo sapiens	101-104
19730126-11	2009	Levosimendan also ameliorated MI-induced atrial natriuretic peptide, IL-6, and connective tissue growth factor overexpression as well as MI-induced disturbances in calcium-handling proteins (SERCA2, Na-Ca exchanger) without changes in diabetic status or systemic blood pressure.	Simendan	0-12	interleukin 6	Rattus norvegicus	69-73
19730126-11	2009	Levosimendan also ameliorated MI-induced atrial natriuretic peptide, IL-6, and connective tissue growth factor overexpression as well as MI-induced disturbances in calcium-handling proteins (SERCA2, Na-Ca exchanger) without changes in diabetic status or systemic blood pressure.	Simendan	0-12	cellular communication network factor 2	Rattus norvegicus	79-110
19730126-11	2009	Levosimendan also ameliorated MI-induced atrial natriuretic peptide, IL-6, and connective tissue growth factor overexpression as well as MI-induced disturbances in calcium-handling proteins (SERCA2, Na-Ca exchanger) without changes in diabetic status or systemic blood pressure.	Simendan	0-12	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2	Rattus norvegicus	191-197
19730126-11	2009	Levosimendan also ameliorated MI-induced atrial natriuretic peptide, IL-6, and connective tissue growth factor overexpression as well as MI-induced disturbances in calcium-handling proteins (SERCA2, Na-Ca exchanger) without changes in diabetic status or systemic blood pressure.	Simendan	0-12	solute carrier family 8 member A1	Rattus norvegicus	199-214
19861257-0	2009	[Effect of levosimendan on B-type natriuretic peptide levels in patients with advanced heart failure: a meta-analysis].	Simendan	11-23	natriuretic peptide B	Homo sapiens	27-53
19861257-3	2009	RESULTS: Levosimendan decreased BNP by a mean of 337.66 [95%CI (-296.30, -379.02)] pg/ml 24 h after the administration, and by 259.92 [95%CI (-195.76, -324.08)] pg/ml at 48 h, and by 123.09 [95%CI(-53.32,-195.86)] pg/ml at 1 week.	Simendan	9-21	natriuretic peptide B	Homo sapiens	32-35
19861257-1	2009	OBJECTIVE: To conduct a meta-analysis of the effect of levosimendan on B-type natriuretic peptide (BNP) levels and evaluate the therapeutic effect of levosimendan on advanced heart failure.	Simendan	55-67	natriuretic peptide B	Homo sapiens	71-97
19861257-1	2009	OBJECTIVE: To conduct a meta-analysis of the effect of levosimendan on B-type natriuretic peptide (BNP) levels and evaluate the therapeutic effect of levosimendan on advanced heart failure.	Simendan	55-67	natriuretic peptide B	Homo sapiens	99-102
19861257-5	2009	CONCLUSION: Levosimendan produces favorable effects on the cardiac functions and BNP levels.	Simendan	12-24	natriuretic peptide B	Homo sapiens	81-84
19426242-11	2009	Increased levels of tumor necrosis factor alpha during reperfusion were only abated by milrinone and levosimendan.	Simendan	101-113	tumor necrosis factor	Homo sapiens	20-47
18501448-0	2008	The prolonged lowering effect of levosimendan on brain natriuretic peptide levels in patients with decompansated heart failure: clinical implications.	Simendan	33-45	natriuretic peptide B	Homo sapiens	49-74
19539144-0	2009	Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure.	Simendan	50-62	natriuretic peptide B	Homo sapiens	8-34
19027145-4	2009	TNF-alpha immunolabelling was negative in both the sham and levosimendan groups, but moderate and weak immunoreactivities were observed in the dobutamine and control groups, respectively.	Simendan	60-72	tumor necrosis factor	Rattus norvegicus	0-9
19027145-8	2009	In addition, iNOS immunoreactivity was strongly detected in the control group; this immunoreactivity was less in the levosimendan group than the dobutamine group.	Simendan	117-129	nitric oxide synthase 2	Rattus norvegicus	13-17
19154424-0	2009	Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial K(ATP) channel.	Simendan	0-12	AKT serine/threonine kinase 1	Sus scrofa	61-64
19154424-2	2009	Moreover, the coronary vasodilatation caused by levosimendan in anaesthetized pigs has recently been found to be abolished by the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the vascular effects of levosimendan.	Simendan	48-60	nitric oxide synthase 2	Sus scrofa	130-151
19154424-2	2009	Moreover, the coronary vasodilatation caused by levosimendan in anaesthetized pigs has recently been found to be abolished by the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester, indicating that nitric oxide (NO) has a role in the vascular effects of levosimendan.	Simendan	280-292	nitric oxide synthase 2	Sus scrofa	130-151
19154424-9	2009	The response of CEC to levosimendan was prevented by the K(ATP) channel blockers, the adenylyl cyclase inhibitor and the Akt, ERK, p38 inhibitors.	Simendan	23-35	AKT serine/threonine kinase 1	Sus scrofa	121-124
19154424-11	2009	CONCLUSIONS AND IMPLICATIONS: In CEC levosimendan induced eNOS-dependent NO production through Akt, ERK and p38.	Simendan	37-49	AKT serine/threonine kinase 1	Sus scrofa	95-98
16713737-6	2006	In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion.	Simendan	30-42	interleukin 6	Homo sapiens	59-63
18570382-0	2008	Defining the binding site of levosimendan and its analogues in a regulatory cardiac troponin C-troponin I complex.	Simendan	29-41	troponin C1, slow skeletal and cardiac type	Homo sapiens	76-94
18570382-2	2008	As such, the cTnC-cTnI interface is a logical target for cardiotonic agents such as levosimendan that can modulate the Ca (2+) sensitivity of the myofilaments.	Simendan	84-96	troponin I3, cardiac type	Homo sapiens	18-22
18570382-4	2008	In this study, we utilized two-dimensional (1)H- (15)N HSQC NMR spectroscopy to monitor the binding of levosimendan and its analogues, CMDP, AMDP, CI-930, imazodan, and MPDP, to cNTnC.Ca (2+) in complex with two versions of the switch region of cTnI (cTnI 147-163 and cTnI 144-163).	Simendan	103-115	troponin I3, cardiac type	Homo sapiens	245-249
18570382-4	2008	In this study, we utilized two-dimensional (1)H- (15)N HSQC NMR spectroscopy to monitor the binding of levosimendan and its analogues, CMDP, AMDP, CI-930, imazodan, and MPDP, to cNTnC.Ca (2+) in complex with two versions of the switch region of cTnI (cTnI 147-163 and cTnI 144-163).	Simendan	103-115	troponin I3, cardiac type	Homo sapiens	251-255
18570382-4	2008	In this study, we utilized two-dimensional (1)H- (15)N HSQC NMR spectroscopy to monitor the binding of levosimendan and its analogues, CMDP, AMDP, CI-930, imazodan, and MPDP, to cNTnC.Ca (2+) in complex with two versions of the switch region of cTnI (cTnI 147-163 and cTnI 144-163).	Simendan	103-115	troponin I3, cardiac type	Homo sapiens	251-255
18570382-5	2008	Levosimendan, CMDP, AMDP, and CI-930 were found to bind to both cNTnC.Ca (2+).cTnI 147-163 and cNTnC.Ca (2+).cTnI 144-163 complexes.	Simendan	0-12	troponin I3, cardiac type	Homo sapiens	78-82
18570382-5	2008	Levosimendan, CMDP, AMDP, and CI-930 were found to bind to both cNTnC.Ca (2+).cTnI 147-163 and cNTnC.Ca (2+).cTnI 144-163 complexes.	Simendan	0-12	troponin I3, cardiac type	Homo sapiens	109-113
18496375-13	2008	Additionally, inhalation of 240 microg and infusion of 24 microg/kg levosimendan significantly reduced the release of interleukin-1beta, the nitric oxide release from alveolar macrophages, macrophage inflammatory protein-2 in plasma, and the macrophage inflammatory protein-2 and matrix metalloproteinase-9 content in bronchoalveolar lavage fluid compared with VILI only.	Simendan	68-80	interleukin 1 beta	Rattus norvegicus	118-135
18496375-13	2008	Additionally, inhalation of 240 microg and infusion of 24 microg/kg levosimendan significantly reduced the release of interleukin-1beta, the nitric oxide release from alveolar macrophages, macrophage inflammatory protein-2 in plasma, and the macrophage inflammatory protein-2 and matrix metalloproteinase-9 content in bronchoalveolar lavage fluid compared with VILI only.	Simendan	68-80	C-X-C motif chemokine ligand 2	Rattus norvegicus	189-222
18496375-13	2008	Additionally, inhalation of 240 microg and infusion of 24 microg/kg levosimendan significantly reduced the release of interleukin-1beta, the nitric oxide release from alveolar macrophages, macrophage inflammatory protein-2 in plasma, and the macrophage inflammatory protein-2 and matrix metalloproteinase-9 content in bronchoalveolar lavage fluid compared with VILI only.	Simendan	68-80	C-X-C motif chemokine ligand 2	Rattus norvegicus	242-275
18496375-13	2008	Additionally, inhalation of 240 microg and infusion of 24 microg/kg levosimendan significantly reduced the release of interleukin-1beta, the nitric oxide release from alveolar macrophages, macrophage inflammatory protein-2 in plasma, and the macrophage inflammatory protein-2 and matrix metalloproteinase-9 content in bronchoalveolar lavage fluid compared with VILI only.	Simendan	68-80	matrix metallopeptidase 9	Rattus norvegicus	280-306
18424862-11	2008	Levosimendan resulted in a significant increase in LVEF,VTI, P(max), P(min), V(max), and V(min) (p<0.01) and, moreover, a significant reduction in PEP, ET, and PEP/ET (p=0.04) on day 7 compared with day 0 values.	Simendan	0-12	progestagen associated endometrial protein	Homo sapiens	150-153
18424862-11	2008	Levosimendan resulted in a significant increase in LVEF,VTI, P(max), P(min), V(max), and V(min) (p<0.01) and, moreover, a significant reduction in PEP, ET, and PEP/ET (p=0.04) on day 7 compared with day 0 values.	Simendan	0-12	progestagen associated endometrial protein	Homo sapiens	163-169
17892613-11	2008	Tissue myeloperoxidase (MPO) enzyme activity was significantly higher in the non-treated group than in the levosimendan-treated group (P = 0.004).	Simendan	107-119	myeloperoxidase	Rattus norvegicus	7-22
17892613-11	2008	Tissue myeloperoxidase (MPO) enzyme activity was significantly higher in the non-treated group than in the levosimendan-treated group (P = 0.004).	Simendan	107-119	myeloperoxidase	Rattus norvegicus	24-27
18290886-8	2008	MPO level was also found statistically significant when we compared levosimendan group with the control group.	Simendan	68-80	myeloperoxidase	Oryctolagus cuniculus	0-3
17620456-7	2007	Levosimendan [(-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile] and dextrosimendan reversed interleukin (IL)-5-afforded survival of human eosinophils by inducing apoptosis in vitro.	Simendan	0-12	interleukin 5	Homo sapiens	134-152
17620456-9	2007	Dextrosimendan further enhanced spontaneous apoptosis as well as that induced by CD95 ligation, without inducing primary necrosis.	Simendan	0-14	Fas cell surface death receptor	Homo sapiens	81-85
17610056-8	2007	Levosimendan-induced BNP reduction was significantly correlated with concomitant increase in 6MWT (r = 0.643, p < 0.001) as well as with the decrease of BDI (r = 0.30, p < 0.05) and Zung SDS (r = 0.25, p = 0.05).	Simendan	0-12	natriuretic peptide B	Homo sapiens	21-24
17325658-11	2007	Levosimendan also corrected salt-induced decreases in myocardial SERCA2a protein expression and myocardial SERCA2a/NCX-ratio.	Simendan	0-12	solute carrier family 8 member A1	Rattus norvegicus	115-118
17596101-13	2007	Levosimendan reduces plasma brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels substantially, and a decrease in plasma endothelin-1 has been observed.	Simendan	0-12	natriuretic peptide B	Homo sapiens	28-53
17596101-13	2007	Levosimendan reduces plasma brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels substantially, and a decrease in plasma endothelin-1 has been observed.	Simendan	0-12	natriuretic peptide B	Homo sapiens	55-58
17596101-13	2007	Levosimendan reduces plasma brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels substantially, and a decrease in plasma endothelin-1 has been observed.	Simendan	0-12	natriuretic peptide B	Homo sapiens	79-82
17596101-15	2007	The effects of a 24-hour levosimendan infusion on filling pressure, ventricular function and BNP, as well as NT-proBNP, last for at least 7 days.	Simendan	25-37	natriuretic peptide B	Homo sapiens	93-96
18570382-10	2008	These results will help in the delineation of the mode of action of levosimendan on the important functional unit of cardiac troponin that constitutes the regulatory domain of cTnC and the switch region of cTnI.	Simendan	68-80	troponin I3, cardiac type	Homo sapiens	206-210
18242130-13	2008	CONCLUSION: The majority of repeated levosimendan infusions were well tolerated, reduced BNP and improved NYHA functional class.	Simendan	37-49	natriuretic peptide B	Homo sapiens	89-92
18062901-6	2007	Compared to baseline, the percent changes in CF-VTI were related to the concomitant changes in EF, E/E?, and BNP after treatment with levosimendan (r=0.69, r=?0.51 and r=?0.80, p<0.05 respectively).	Simendan	134-146	natriuretic peptide B	Homo sapiens	109-112
17126656-8	2006	Levosimendan beneficially modulated neurohormonal and inflammatory status by decreasing B-type natriuretic peptide levels (p <0.05) and by altering the ratio of interleukin-6 to interleukin-10 in favor of the latter (p <0.05).	Simendan	0-12	interleukin 6	Homo sapiens	164-177
17126656-8	2006	Levosimendan beneficially modulated neurohormonal and inflammatory status by decreasing B-type natriuretic peptide levels (p <0.05) and by altering the ratio of interleukin-6 to interleukin-10 in favor of the latter (p <0.05).	Simendan	0-12	interleukin 10	Homo sapiens	181-195
17105880-6	2006	A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion.	Simendan	133-145	C-reactive protein	Homo sapiens	66-69
17105880-6	2006	A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion.	Simendan	133-145	interleukin 6	Homo sapiens	93-96
16713737-6	2006	In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion.	Simendan	30-42	tumor necrosis factor	Homo sapiens	175-184
16713737-8	2006	CONCLUSIONS: These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-alpha receptors and sFAS, immediately after infusion, an effect which persists for 7-30 d.	Simendan	42-54	tumor necrosis factor	Homo sapiens	110-119
16084762-7	2005	Both drugs produced a comparable reduction in PCP and pulmonary artery pressure after 24 and 48 h. Levosimendan decreased BNP by 28% after 24 h and 22% after 48 h, but effects disappeared after 1 week.	Simendan	99-111	natriuretic peptide B	Homo sapiens	122-125
16784930-7	2006	Plasma N-terminal-pro-B-type natriuretic peptide, tumor necrosis factor-alpha, and soluble Fas ligand levels were significantly decreased only in the levosimendan group (from 1,900 +/- 223 to 1,378 +/- 170 pg/ml, 13.4 +/- 1.0 to 12.3 +/- 1.2 pg/ml, and 68.2 +/- 3.7 to 59.8 +/- 3.6 pg/ml, respectively; p <0.05 for all); interleukin-6 was also borderline reduced (p = 0.051).	Simendan	150-162	tumor necrosis factor	Homo sapiens	50-77
16784930-7	2006	Plasma N-terminal-pro-B-type natriuretic peptide, tumor necrosis factor-alpha, and soluble Fas ligand levels were significantly decreased only in the levosimendan group (from 1,900 +/- 223 to 1,378 +/- 170 pg/ml, 13.4 +/- 1.0 to 12.3 +/- 1.2 pg/ml, and 68.2 +/- 3.7 to 59.8 +/- 3.6 pg/ml, respectively; p <0.05 for all); interleukin-6 was also borderline reduced (p = 0.051).	Simendan	150-162	Fas ligand	Homo sapiens	91-101
16784930-7	2006	Plasma N-terminal-pro-B-type natriuretic peptide, tumor necrosis factor-alpha, and soluble Fas ligand levels were significantly decreased only in the levosimendan group (from 1,900 +/- 223 to 1,378 +/- 170 pg/ml, 13.4 +/- 1.0 to 12.3 +/- 1.2 pg/ml, and 68.2 +/- 3.7 to 59.8 +/- 3.6 pg/ml, respectively; p <0.05 for all); interleukin-6 was also borderline reduced (p = 0.051).	Simendan	150-162	interleukin 6	Homo sapiens	324-337
16784930-8	2006	Levosimendan-induced reduction in end-systolic wall stress was significantly correlated with respective decreases in N-terminal-pro-B-type natriuretic peptide (r = 0.671, p <0.01), tumor necrosis factor-alpha (r = 0.586, p <0.01), soluble Fas (r = 0.441, p <0.05), and soluble Fas ligand (r = 0.614, p <0.01).	Simendan	0-12	tumor necrosis factor	Homo sapiens	184-211
16784930-8	2006	Levosimendan-induced reduction in end-systolic wall stress was significantly correlated with respective decreases in N-terminal-pro-B-type natriuretic peptide (r = 0.671, p <0.01), tumor necrosis factor-alpha (r = 0.586, p <0.01), soluble Fas (r = 0.441, p <0.05), and soluble Fas ligand (r = 0.614, p <0.01).	Simendan	0-12	Fas ligand	Homo sapiens	286-296
16418300-11	2006	LS completely blocked ANG II-induced MC contraction, an action likely to increase K(f).	Simendan	0-2	angiotensinogen	Rattus norvegicus	22-28
16435069-3	2005	We investigated the effect of levosimendan, a novel calcium sensitizer, on serum levels of MMP-2.	Simendan	30-42	matrix metallopeptidase 2	Homo sapiens	91-96
16435069-7	2005	RESULTS: Serum levels of MMP-2 were reduced from 427 ng/ml 95%CI 372-484 to 371 ng/ml 95%CI 329-413 in the levosimendan treated group and from 433 ng/ml 95%CI 422-444 to 425 ng/ml 95%CI 414-436 in the placebo group.	Simendan	107-119	matrix metallopeptidase 2	Homo sapiens	25-30
16435069-8	2005	Repeated measurements ANOVA showed that treatment with levosimendan significantly affected levels of MMP-2 (p = 0.019).	Simendan	55-67	matrix metallopeptidase 2	Homo sapiens	101-106
16084762-9	2005	CONCLUSIONS: The differential beneficial effects of levosimendan (greater increase in CO) and PGE1 (sustained decrease in BNP) may have a potential impact on clinical outcome.	Simendan	52-64	natriuretic peptide B	Homo sapiens	122-125
16054474-1	2005	In this randomized, placebo-controlled study, it was found that a 24-hour levosimendan infusion improves echocardiographic markers of abnormal left ventricular diastolic function (transmitral flow patterns and mitral annulus velocities, as assessed by transthoracic pulse-wave Doppler and tissue Doppler imaging, respectively) and reduces substances of excessive neurohormonal activation (plasma B-type natriuretic peptide and interleukin-6) in patients with advanced heart failure.	Simendan	74-86	interleukin 6	Homo sapiens	427-440
16306809-0	2005	Duration of the beneficial effects of levosimendan in decompensated heart failure as measured by echocardiographic indices and B-type natriuretic peptide.	Simendan	38-50	natriuretic peptide B	Homo sapiens	127-153
16129976-6	2005	Furthermore, low doses of arginine vasopressin markedly deteriorated cardiac function via an afterload-independent mechanism, even when animals were pretreated with levosimendan, whereas norepinephrine showed no detrimental effects on cardiac function.	Simendan	165-177	arginine vasopressin	Homo sapiens	35-46
16181825-5	2005	Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels.	Simendan	0-12	troponin C1, slow skeletal and cardiac type	Homo sapiens	22-40
15921958-0	2005	The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine.	Simendan	20-32	natriuretic peptide B	Homo sapiens	60-63
15921958-4	2005	Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01).	Simendan	0-12	natriuretic peptide B	Homo sapiens	49-52
15921958-4	2005	Levosimendan produced a significant reduction in BNP compared to baseline, at both 48 h (744.1+/-100 vs 1136.3+/-93.7 pg/ml, p=0.04) and 5 days (446+/-119.3 vs 1136.3+/-93.7 pg/ml, p=0.03), while IL-6 values decreased after 5 days (4.8+/-1.3 vs 8.6+/-1.5 pg/ml, p=0.01).	Simendan	0-12	interleukin 6	Homo sapiens	196-200
15771921-0	2005	Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.	Simendan	0-12	natriuretic peptide B	Homo sapiens	28-54
15974888-6	2005	Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand.	Simendan	0-12	tumor necrosis factor	Homo sapiens	186-195
15974888-6	2005	Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand.	Simendan	0-12	interleukin 6	Homo sapiens	197-201
15974888-6	2005	Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand.	Simendan	0-12	Fas ligand	Homo sapiens	249-259
15771921-0	2005	Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.	Simendan	0-12	interleukin 6	Homo sapiens	59-72
15771921-3	2005	This study investigates whether levosimendan-induced hemodynamic improvement of CHF patients is related to the respective changes of NT-proBNP and IL-6 levels.	Simendan	32-44	interleukin 6	Homo sapiens	147-151
15771921-6	2005	RESULTS: NT-proBNP and IL-6 levels were significantly reduced in severe CHF patients within 72 h after the initiation of levosimendan treatment (p<0.01 and p<0.05, respectively).	Simendan	121-133	interleukin 6	Homo sapiens	23-27
15771921-9	2005	CONCLUSIONS: Our results indicate that changes of NT-pro BNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.	Simendan	128-140	natriuretic peptide B	Homo sapiens	57-60
15771921-9	2005	CONCLUSIONS: Our results indicate that changes of NT-pro BNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.	Simendan	128-140	interleukin 6	Homo sapiens	65-69
11113122-0	2001	Binding of levosimendan, a calcium sensitizer, to cardiac troponin C.	Simendan	11-23	troponin C1, slow skeletal and cardiac type	Homo sapiens	50-68
15646030-0	2004	The contractile apparatus as a target for drugs against heart failure: interaction of levosimendan, a calcium sensitiser, with cardiac troponin c.	Simendan	86-98	troponin C1, slow skeletal and cardiac type	Homo sapiens	127-145
15646030-6	2004	Levosimendan is a novel calcium sensitiser which has been discovered by using cardiac troponin C (cTnC) as target protein.	Simendan	0-12	troponin C1, slow skeletal and cardiac type	Homo sapiens	78-96
15646030-6	2004	Levosimendan is a novel calcium sensitiser which has been discovered by using cardiac troponin C (cTnC) as target protein.	Simendan	0-12	troponin C1, slow skeletal and cardiac type	Homo sapiens	98-102
15646030-11	2004	Finally, the binding of levosimendan to cTnC and its mechanism of action are described and the results discussed under the light of the action of this drug in vitro and in vivo.	Simendan	24-36	troponin C1, slow skeletal and cardiac type	Homo sapiens	40-44
15135713-1	2004	This randomized, placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators, such as soluble Fas and Fas ligand in patients with decompensated heart failure.	Simendan	54-66	interleukin 6	Homo sapiens	153-166
15135713-1	2004	This randomized, placebo-controlled trial showed that levosimendan administration causes a significant reduction of circulating proinflammatory cytokine interleukin-6 and soluble apoptosis mediators, such as soluble Fas and Fas ligand in patients with decompensated heart failure.	Simendan	54-66	Fas ligand	Homo sapiens	224-234
12967628-0	2003	Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides.	Simendan	15-27	troponin C1, slow skeletal and cardiac type	Homo sapiens	33-51
12967628-9	2003	It was clear that based on chemical shift changes, cTnI(32-79) blocked the levosimendan interaction sites on the C-domain, whereas cTnI(128-180) did not compete with levosimendan for the binding site on the N-domain.	Simendan	75-87	troponin I3, cardiac type	Homo sapiens	51-55
12208222-3	2002	METHODS AND RESULTS: Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) or placebo were administered intravenously for 6h to 504 patients in a randomised, placebo-controlled, double-blind study.	Simendan	21-33	CD59 molecule (CD59 blood group)	Homo sapiens	80-86
12208222-10	2002	CONCLUSION: s Levosimendan at doses 0.1-0.2 microg x kg(-1) x min(-1) did not induce hypotension or ischaemia and reduced the risk of worsening heart failure and death in patients with left ventricular failure complicating acute myocardial infarction.	Simendan	14-26	CD59 molecule (CD59 blood group)	Homo sapiens	62-68
11113122-3	2001	In the current work, we have studied the interaction of levosimendan with Ca(2+)-saturated cTnC by heteronuclear NMR and small angle x-ray scattering.	Simendan	56-68	troponin C1, slow skeletal and cardiac type	Homo sapiens	91-95
11113122-4	2001	A specific interaction between levosimendan and the Ca(2+)-loaded regulatory domain of recombinant cTnC(C35S) was observed.	Simendan	31-43	troponin C1, slow skeletal and cardiac type	Homo sapiens	99-103
11113122-5	2001	The changes in the NMR spectra of the N-domain of full-length cTnC(C35S), due to the binding of levosimendan to the primary site, were indicative of a slow conformational exchange.	Simendan	96-108	troponin C1, slow skeletal and cardiac type	Homo sapiens	62-66
11113122-7	2001	Moreover, it was shown that levosimendan was in fast exchange on the NMR time scale with a secondary binding site in the C-domain of both cTnC(C35S) and cTnC(A-Cys).	Simendan	28-40	troponin C1, slow skeletal and cardiac type	Homo sapiens	138-142
11113122-7	2001	Moreover, it was shown that levosimendan was in fast exchange on the NMR time scale with a secondary binding site in the C-domain of both cTnC(C35S) and cTnC(A-Cys).	Simendan	28-40	troponin C1, slow skeletal and cardiac type	Homo sapiens	153-157
11113122-8	2001	The small angle x-ray scattering experiments confirm the binding of levosimendan to Ca(2+)-saturated cTnC but show no domain-domain closure.	Simendan	68-80	troponin C1, slow skeletal and cardiac type	Homo sapiens	101-105
10446160-2	1999	Two putative Ca(2+) sensitizers, EMD 57033 and levosimendan, are reported to bind to cardiac troponin C (cTnC).	Simendan	47-59	troponin C1, slow skeletal and cardiac type	Homo sapiens	85-103
10935149-3	2000	The aim of this study was to assess the efficacy of the Ca2+ sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca2+ and beta-blockers.	Simendan	73-85	carbonic anhydrase 2	Homo sapiens	56-59
10935149-3	2000	The aim of this study was to assess the efficacy of the Ca2+ sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca2+ and beta-blockers.	Simendan	73-85	carbonic anhydrase 2	Homo sapiens	225-228
10731446-0	2000	Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan.	Simendan	78-90	troponin C1, slow skeletal and cardiac type	Homo sapiens	25-43
10731446-0	2000	Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan.	Simendan	148-160	troponin C1, slow skeletal and cardiac type	Homo sapiens	25-43
10731446-2	2000	The aim of this study was to give further evidence that levosimendan binds to cardiac troponin C and that the binding involves amino acid residues on helixepsilon of the N-terminal domain of this calcium-binding protein.	Simendan	56-68	troponin C1, slow skeletal and cardiac type	Homo sapiens	78-96
10731446-4	2000	A good correlation between the calcium sensitization and the calcium-dependent binding to troponin complex (r=0.90) and to cardiac troponin C (r=0.91) for the analogs of levosimendan was shown.	Simendan	170-182	troponin C1, slow skeletal and cardiac type	Homo sapiens	123-141
10446160-2	1999	Two putative Ca(2+) sensitizers, EMD 57033 and levosimendan, are reported to bind to cardiac troponin C (cTnC).	Simendan	47-59	troponin C1, slow skeletal and cardiac type	Homo sapiens	105-109
10446160-9	1999	However, levosimendan covalently bound to a small percentage of free cTnC after prolonged incubation with the protein.	Simendan	9-21	troponin C1, slow skeletal and cardiac type	Homo sapiens	69-73
9876999-1	1998	BACKGROUND: Levosimendan is a new calcium sensitizer, acting calcium-dependently on cardiac troponin C.	Simendan	12-24	troponin C1, slow skeletal and cardiac type	Homo sapiens	84-102
9659795-4	1998	In contrast, pimobendan, levosimendan, and MCI-154 accelerate left ventricular relaxation in heart failure, because Ca2+ sensitizing action of these agents may be prominent during the early phases of contraction.	Simendan	25-37	carbonic anhydrase 2	Homo sapiens	116-119
9593074-4	1998	Levosimendan (10(-7)-10(-3) M) completely relaxed arteries preconstricted by prostaglandin F2alpha (PGF2alpha) with a pD2 (-logEC50) value of 3.99 +/- 0.05 (n = 6-9 in all experiments).	Simendan	0-12	PAF1 homolog, Paf1/RNA polymerase II complex component	Homo sapiens	118-121
9593074-10	1998	However, levosimendan (10(-7)-3 x 10(-3) M) completely relaxed endothelin-1-induced contractions in this medium.	Simendan	9-21	endothelin 1	Homo sapiens	63-75
9597417-6	1998	Cardiac output increased by 0.7 and 1.61.min-1 (P < 0.05 for both) after 8 and 24 micrograms.kg-1 of levosimendan, respectively.	Simendan	104-116	CD59 molecule (CD59 blood group)	Homo sapiens	41-46
34786647-9	2021	Levosimendan significantly downregulated TNF-alpha (p = 0.022), NFK-ss (p = 0.008), and IL-6 (p = 0.033).	Simendan	0-12	tumor necrosis factor	Rattus norvegicus	41-50
8523447-4	1995	Only levosimendan showed calcium-dependent and to a lesser extent magnesium-dependent retention in the cTnC column.	Simendan	5-17	troponin C1, slow skeletal and cardiac type	Homo sapiens	103-107
8523447-5	1995	The findings indicate that levosimendan binds both to the N-terminal and C-terminal domains of cTnC.	Simendan	27-39	troponin C1, slow skeletal and cardiac type	Homo sapiens	95-99
8523447-6	1995	In agreement with this, only levosimendan shifted the calcium-induced fluorescence curve of dansylated cTnC to the left.	Simendan	29-41	troponin C1, slow skeletal and cardiac type	Homo sapiens	103-107
8523447-9	1995	In conclusion, it is suggested that the mechanism of calcium sensitizing effect of levosimendan, unlike that of the other calcium sensitizers, is based on calcium-dependent binding to the N-terminal domain of cTnC.	Simendan	83-95	troponin C1, slow skeletal and cardiac type	Homo sapiens	209-213
8907127-7	1995	By analyzing the velocity (dT/dt) of isometric tension development in paced papillary muscles, it was shown that levosimendan probably enhances the association rate but decreases the dissociation rate of myosin-actin crossbridges.	Simendan	113-125	myosin heavy chain 14	Homo sapiens	204-210
7961805-0	1994	Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C.	Simendan	34-46	troponin C1, slow skeletal and cardiac type	Homo sapiens	69-87
7961805-2	1994	The binding of a new calcium sensitizer, levosimendan, to human cardiac troponin C (cTnC) is described.	Simendan	41-53	troponin C1, slow skeletal and cardiac type	Homo sapiens	64-82
7961805-2	1994	The binding of a new calcium sensitizer, levosimendan, to human cardiac troponin C (cTnC) is described.	Simendan	41-53	troponin C1, slow skeletal and cardiac type	Homo sapiens	84-88
7961805-3	1994	Fluorescence studies done on dansylated recombinant human cTnC and a site-directed mutant showed that levosimendan modulated the calcium-induced conformational change in cTnC, and revealed the role of Asp-88 in the binding of the drug to the NH2-terminal domain of cTnC.	Simendan	102-114	troponin C1, slow skeletal and cardiac type	Homo sapiens	58-62
7961805-3	1994	Fluorescence studies done on dansylated recombinant human cTnC and a site-directed mutant showed that levosimendan modulated the calcium-induced conformational change in cTnC, and revealed the role of Asp-88 in the binding of the drug to the NH2-terminal domain of cTnC.	Simendan	102-114	troponin C1, slow skeletal and cardiac type	Homo sapiens	170-174
7961805-3	1994	Fluorescence studies done on dansylated recombinant human cTnC and a site-directed mutant showed that levosimendan modulated the calcium-induced conformational change in cTnC, and revealed the role of Asp-88 in the binding of the drug to the NH2-terminal domain of cTnC.	Simendan	102-114	troponin C1, slow skeletal and cardiac type	Homo sapiens	170-174
7961805-4	1994	Furthermore, NMR studies performed on the NH2-terminal fragment of cTnC showed a spatial proximity between levosimendan and Met81, Met85, and Phe77 in the drug-protein complex.	Simendan	107-119	troponin C1, slow skeletal and cardiac type	Homo sapiens	67-71
7961805-5	1994	These data were used to build an optimized model of the drug-protein complex, in which levosimendan binds cTnC at the hydrophobic pocket of the NH2-terminal domain.	Simendan	87-99	troponin C1, slow skeletal and cardiac type	Homo sapiens	106-110
7961805-6	1994	The role of the binding of levosimendan to cTnC in the pharmacological action of this drug in vivo is discussed.	Simendan	27-39	troponin C1, slow skeletal and cardiac type	Homo sapiens	43-47
8523447-0	1995	Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan.	Simendan	77-89	troponin C1, slow skeletal and cardiac type	Homo sapiens	0-18
8523447-1	1995	The role of cardiac troponin C (cTnC) as a target protein for the calcium sensitization by levosimendan, pimobendan, MCI-154 and EMD 53998 was evaluated using purified recombinant human cTnC.	Simendan	91-103	troponin C1, slow skeletal and cardiac type	Homo sapiens	12-30
8523447-1	1995	The role of cardiac troponin C (cTnC) as a target protein for the calcium sensitization by levosimendan, pimobendan, MCI-154 and EMD 53998 was evaluated using purified recombinant human cTnC.	Simendan	91-103	troponin C1, slow skeletal and cardiac type	Homo sapiens	32-36
19367398-3	2009	levosimendan (LEVO) on survival, inflammatory cytokines and the apoptotic mediator caspase-3 in a rat model of severe sepsis induced by cecal ligation and incision (CLI).	Simendan	0-12	caspase 3	Rattus norvegicus	83-92
19367398-25	2009	LEVO inhibited proinflammatory mediator release and reduced splenic caspase-3 expression.	Simendan	0-4	caspase 3	Rattus norvegicus	68-77
34788887-10	2022	LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels.	Simendan	0-3	myeloperoxidase	Rattus norvegicus	74-77
34786647-9	2021	Levosimendan significantly downregulated TNF-alpha (p = 0.022), NFK-ss (p = 0.008), and IL-6 (p = 0.033).	Simendan	0-12	interleukin 6	Rattus norvegicus	88-92
34588413-7	2021	RESULTS Cardiac output and LVEF of patients in the levosimendan group were significantly higher than those in the control group at different time points (P<0.05), and BNP level was lower than that of the control group (P<0.0001).	Simendan	51-63	natriuretic peptide B	Homo sapiens	167-170
34154760-4	2021	Levosimendan in comparison to dobutamine, increased cardiac output (0.76 vs. -0.38 at 48 h, 1.15 vs. -0.31 day 7, -2.02 vs. -1.51 day 30), cardiac index (0.89 vs.-0.13 at 48 h, 1.16 vs. -0.07 at day 7 and 1.05 vs. -0.25 at day 30) and eGFR (-1.4 vs. -0.75 at day 30) significantly.	Simendan	0-12	epidermal growth factor receptor	Homo sapiens	235-239
34213003-10	2021	Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage.	Simendan	170-182	myeloperoxidase	Rattus norvegicus	61-64
34213003-10	2021	Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage.	Simendan	170-182	myeloperoxidase	Rattus norvegicus	39-42
34213003-10	2021	Histopathological injury score, plasma MPO, AST, ALT, tissue MPO and tissue MDA values were statistically significantly lower in the treatment groups, prominently in the levosimendan and NAS combination group concerning liver histopathological damage.	Simendan	170-182	glutamic-oxaloacetic transaminase 2	Rattus norvegicus	44-47
34115930-0	2021	Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti-inflammation, anti-apoptosis and ERK activation.	Simendan	26-38	Eph receptor B1	Rattus norvegicus	129-132
34115930-9	2021	Levosimendan downregulated the expression of the apoptosis-related proteins Bax, cleaved caspase-3 and cleaved caspase-9, as well as upregulated Bcl-2 and p-ERK expression in vivo and in vitro.	Simendan	0-12	BCL2 associated X, apoptosis regulator	Rattus norvegicus	76-79
34115930-9	2021	Levosimendan downregulated the expression of the apoptosis-related proteins Bax, cleaved caspase-3 and cleaved caspase-9, as well as upregulated Bcl-2 and p-ERK expression in vivo and in vitro.	Simendan	0-12	caspase 3	Rattus norvegicus	89-98
34115930-9	2021	Levosimendan downregulated the expression of the apoptosis-related proteins Bax, cleaved caspase-3 and cleaved caspase-9, as well as upregulated Bcl-2 and p-ERK expression in vivo and in vitro.	Simendan	0-12	caspase 9	Rattus norvegicus	111-120
34115930-9	2021	Levosimendan downregulated the expression of the apoptosis-related proteins Bax, cleaved caspase-3 and cleaved caspase-9, as well as upregulated Bcl-2 and p-ERK expression in vivo and in vitro.	Simendan	0-12	BCL2, apoptosis regulator	Rattus norvegicus	145-150
34115930-9	2021	Levosimendan downregulated the expression of the apoptosis-related proteins Bax, cleaved caspase-3 and cleaved caspase-9, as well as upregulated Bcl-2 and p-ERK expression in vivo and in vitro.	Simendan	0-12	Eph receptor B1	Rattus norvegicus	157-160
34115930-10	2021	Thus, our data suggest that levosimendan reduces mortality and AKI following CA and CPR via suppression of inflammation and apoptosis, and activation of ERK signaling.	Simendan	28-40	Eph receptor B1	Rattus norvegicus	153-156
34900060-0	2021	Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model.	Simendan	174-186	NFE2 like bZIP transcription factor 2	Rattus norvegicus	28-71
34900060-8	2021	Conclusions: Cilostazol or levosimendan potentiates the renoprotective effect of Ipre against renal I/R injury, associated with upregulation of antioxidant genes Nrf2, HO-1, and NOQ-1 expression.	Simendan	27-39	NFE2 like bZIP transcription factor 2	Rattus norvegicus	162-166
34900060-8	2021	Conclusions: Cilostazol or levosimendan potentiates the renoprotective effect of Ipre against renal I/R injury, associated with upregulation of antioxidant genes Nrf2, HO-1, and NOQ-1 expression.	Simendan	27-39	heme oxygenase 1	Rattus norvegicus	168-172
35083882-9	2022	BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L (261-1035) to 719 ng/L (294-739), (P < 0.01).	Simendan	35-47	natriuretic peptide B	Homo sapiens	0-3
35083882-12	2022	CONCLUSIONS: In this small-scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.	Simendan	206-218	natriuretic peptide B	Homo sapiens	168-171
35126176-11	2021	Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036).	Simendan	0-12	caspase 3	Mus musculus	81-90
35350988-7	2022	Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001).	Simendan	85-97	natriuretic peptide B	Homo sapiens	0-25
35350988-7	2022	Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001).	Simendan	85-97	natriuretic peptide B	Homo sapiens	27-30
35350988-7	2022	Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001).	Simendan	114-126	natriuretic peptide B	Homo sapiens	0-25
35350988-7	2022	Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001).	Simendan	114-126	natriuretic peptide B	Homo sapiens	27-30
35280364-0	2022	Levosimendan protects from sepsis-inducing cardiac dysfunction by suppressing inflammation, oxidative stress and regulating cardiac mitophagy via the PINK-1-Parkin pathway in mice.	Simendan	0-12	PTEN induced putative kinase 1	Mus musculus	150-156
35280364-11	2022	In addition, our studies further confirmed the protection of levosimendan against LPS-induced myocardial injury and the mechanisms involving PINK-1-Parkin mediated mitophagy signaling.	Simendan	61-73	PTEN induced putative kinase 1	Mus musculus	141-147
35280364-12	2022	Conclusions: Levosimendan was able to rescue the LPS-induced cardiac dysfunction mice, supporting its mechanism of action by suppressing inflammation, oxidative stress, and directly targeting the PINK-1-Parkin pathway.	Simendan	13-25	PTEN induced putative kinase 1	Mus musculus	196-202
35132355-7	2022	Results: Levosimendan postconditioning inhibited H9c2 cell apoptosis in A/R models by elevating Bcl-2 while suppressing Caspase-3 and Bax at both mRNA and protein levels.	Simendan	9-21	BCL2, apoptosis regulator	Rattus norvegicus	96-101
35132355-7	2022	Results: Levosimendan postconditioning inhibited H9c2 cell apoptosis in A/R models by elevating Bcl-2 while suppressing Caspase-3 and Bax at both mRNA and protein levels.	Simendan	9-21	caspase 3	Rattus norvegicus	120-129
35132355-7	2022	Results: Levosimendan postconditioning inhibited H9c2 cell apoptosis in A/R models by elevating Bcl-2 while suppressing Caspase-3 and Bax at both mRNA and protein levels.	Simendan	9-21	BCL2 associated X, apoptosis regulator	Rattus norvegicus	134-137
35126176-11	2021	Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036).	Simendan	0-12	caspase 9	Mus musculus	112-121
35126176-11	2021	Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036).	Simendan	0-12	BCL2-associated X protein	Mus musculus	136-139
35126176-11	2021	Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036).	Simendan	0-12	B cell leukemia/lymphoma 2	Mus musculus	179-183
35126176-13	2021	IL-6, TNF-alpha expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan.	Simendan	180-192	interleukin 6	Mus musculus	0-4
35126176-13	2021	IL-6, TNF-alpha expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan.	Simendan	180-192	tumor necrosis factor	Mus musculus	6-15
35063963-4	2022	Thus, we will test the effect of a pre-emptive perioperative administration of levosimendan on postoperative NT-pro-BNP concentration as compared with the administration of a placebo in patients undergoing moderate-risk to high-risk major abdominal surgery.	Simendan	79-91	natriuretic peptide B	Homo sapiens	116-119