Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model.
The preconditioning effects of levosimendan were investigated on ischemia-reperfusion induced morphological and functional cardiac damage. Langendorff-perfused rabbit hearts were reserved as controls or subjected either to global myocardial ischemic preconditioning or to perfusion with levosimendan (0.1 micromol/l) for two 5-minute cycles. After a washout period, all hearts were then subjected to 30 minutes of global ischemia and 120 minutes of drug-free reperfusion. Intraventricular pressure and coronary flow were measured, and infarct size determined after nitroblue-tetrazolium staining on completion of the experiments. Levosimendan pretreatment resulted in a significantly smaller elevation from the preischemic level in left ventricular end-diastolic pressure during reperfusion (37 +/- 17 mm Hg) compared with controls (56 +/- 14 mm Hg) and ischemia-preconditioned hearts (53 +/- 34 mm Hg). The left ventricular developed pressure-representing the functional recovery of the heart after ischemia-that was significantly improved by levosimendan pretreatment (38 +/- 6% vs 16 +/- 5% in controls, P < 0.05). In addition, contractility and relaxability parameters (+dP/dt and -dP/dt, respectively) were better preserved in the levosimendan hearts. The volume of infarcted myocardium after global ischemia-reperfusion was significantly (P < 0.05) decreased by both ischemic preconditioning (38 +/- 2%) or levosimendan pretreatment (45 +/- 2%) versus controls (52 +/- 2%). The results of this study suggest that levosimendan pretreatment is capable of decreasing infarct size in an ischemia-reperfusion model and improving recovery of cardiac function following ex vivo global ischemia.
Leprán
István
I
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, University of Szeged, Szeged, Hungary.
Pollesello
Piero
P
Vajda
Szilvia
S
Varró
András
A
Papp
Julius Gy
JG
D000818:Animals; D003971:Diastole / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D000077464:Simendan; D016277:Ventricular Function, Left / Q000187:drug effects
D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan