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.