Myocardial stunning following no flow ischaemia is diminished by levosimendan or cariporide, without benefits of combined administration

Aim of the study: Levosimendan, a calcium sensitiser, and cariporide, a blocker of the Na+/H+ exchanger, decrease necrosis and improve function following myocardial ischaemia. However, their role in myocardial stunning is unclear. We tested the hypothesis that levosimendan, cariporide, or their combination reduce stunning after global myocardial ischaemia. Methods: In a prospective, controlled, randomised laboratory study isolated guinea pig hearts (n = 48) were perfused in a Langendorff apparatus. Stunning was induced by 20 min of global no-flow ischaemia. Levosimendan (0.1 mu mol/l) or cariporide (1 mu mol/l) were given either before or after ischaemia, and effects of both drugs combined were also assessed. Left ventricular developed pressure (LVdp) was assessed continuously before ischaemia and for 45min after reperfusion. Results: Levosimendan (24 +/- 7%) and the combination of levosimendan and cariporide (38.7 +/- 4%) increased LVdp from baseline values before ischaemia, without differences between groups. In contrast, cariporide alone decreased LVdp (-11 +/- 2%) from baseline. Ischaemia/reperfusion decreased LVdp by about 70% in vehicle treated hearts compared to baseline. Treatment with cariporide, levosimendan, or their combination both before and after ischaemia, and treatment with cariporide after ischaemia caused a 25% greater recovery of LVdp than in control hearts. There were no differences between these groups and no enhanced effect with levosimendan/cariporide combined. In contrast, levosimendan only given after ischaemia did not improve LVdp. Conclusions: Cariporide diminished stunning when given before or after ischaemia, while Levosimendan was only effective if given before ischaemia. Thus, levosimendan or cariporide may be useful in settings where ischaemia/reperfusion is to be expected. (c) 2007 Elsevier Ireland Ltd. ALL rights reserved.