Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model.

Abstract

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.

• Authors: István Leprán, Piero Pollesello, Szilvia Vajda, András Varró, Julius Gy Papp
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 48 Issue 4 Pg. 148-52 (Oct 2006) ISSN: 0160-2446 [Print] United States
• PMID: 17086092 (Publication Type: Journal Article)

Chemical References

• Hydrazones
• Pyridazines
• Simendan

Topics

• Animals
• Diastole (drug effects)
• Hydrazones (pharmacology)
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Infarction (drug therapy)
• Myocardial Reperfusion Injury (prevention & control)
• Pyridazines (pharmacology)
• Rabbits
• Simendan
• Ventricular Function, Left (drug effects)