A role for the RISK pathway and K ATP channels in pre‐ and post‐conditioning induced by levosimendan in the isolated guinea pig heart

• Published in: British journal of pharmacology 2009-01, Vol.154 (1), p.41-50
• Main Authors: Du Toit, E F, Genis, A, Opie, L H, Pollesello, P, Lochner, A
• Format: Article
• Language: English
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/bjp.2008.52

Background and purpose: Myocardial reperfusion injury prevents optimal salvage of the ischaemic myocardium, and adjunct therapy that would significantly reduce reperfusion injury is still lacking. We investigated whether (1) the heart could be pre‐ and/or post‐conditioned using levosimendan (levosimendan pre‐conditioning (LPC) and levosimendan post‐conditioning (LPostC)) and (2) the prosurvival kinases and/or the sarcolemmal or mitochondrial K ATP channels are involved. Experimental approach: Isolated guinea pig hearts were treated with two 5 min cycles of levosimendan (0.1 μ M ) interspersed with vehicle perfusion, or two 5 min cycles of ischaemia/reperfusion, before coronary artery ligation (CAL) for 40 min at 36.5 °C. Hearts were treated with mitochondrial or sarcolemmal K ATP channel blockers before LPC or LPostC. For post‐conditioning, hearts received three 30 s cycles of ischaemia/reperfusion or levosimendan/vehicle. Hearts were pretreated with levosimendan immediately before CAL (without washout). Cardiac function, infarct size and reperfusion injury salvage kinase activity was assessed. Key results: LPC and LPostC halved the infarct size compared with controls ( P