Effect of levosimendan on balance between ATP production and consumption in isolated perfused guinea-pig heart before ischemia or after reperfusion.
Levosimendan is a novel drug developed for treatment of decompensated heart failure. Levosimendan is a calcium sensitizer that increases contractile force of the myocardium by enhancing the sensitivity of myofilaments to calcium without increasing intracellular calcium concentration. The present study was carried out to investigate whether levosimendan induces any changes in the phosphorylation potential (ie, the balance between ATP production and consumption) in the normal heart and in the post-ischemic heart while exerting its positive inotropic effect. We show that 0.1 microM levosimendan increased the left ventricle developed pressure in the pre-ischemic and in the post ischemic hearts by 16 and 18% respectively, and the +dP/dt by 16 and 19%, respectively. At that concentration levosimendan did not cause any effect on the phosphorylation potential (1 x 10(5) M(-1) and 0.2 x 10(5) M(-1) in the pre-ischemic and post-ischemic heart, respectively) as assessed by P-NMR, although an increased beating rate (13%) and oxygen consumption (10%) was observed when adding the drug post-ischemically. Our findings are consistent with the results of a recent clinical trial (RUSSLAN), which showed that levosimendan does not induce ischemia and reduces the risk of worsening heart failure and death, in patients with left ventricular failure complicating acute myocardial infarction.
Institute of Biomedicine/Biochemistry, Biomedicum, University of Helsinki, Helsinki, Finland.
Ove
O
Eriksson
Piero
P
Pollesello
Heimo
H
Haikala
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006333:Heart Failure / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion / Q000379:methods; D010758:Phosphorus / Q000737:chemistry / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D000077464:Simendan; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D002247:Carbon Isotopes; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D010758:Phosphorus; D000077464:Simendan; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate