Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats
AbstractAim:To examine whether the protective effect of remifentanil preconditioning (RPC) on postischemic hearts is mediated by protein kinase (PKC) activation in comparison with ischemic preconditioning (IPC).Methods:Male Sprague-Dawley rats were anesthetized and their chests were opened. The experiment was performed with chelerythrine (CHE, 2 mg/kg), GF109203X (0.05 mg/kg) protein kinase C (PKC) inhibitors administered before RPC (remifentanil 6 μg.kg-1·min−1× 3 cycle) or IPC, respectively. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining.Results:In groups subjected to IPC and RPC the IS/AAR were significantly reduced (IS/AAR from 52.7%± 5.5% to 12.9%± 3.4%, P<0.01 vs CON and 16.2%± 6.4%, P>0.01 vs CON), respectively. CHE and GF, both PKC inhibitors, administered 5 min before RPC or IPC completely abolished the cardioprotective effect of RPC (IS/AAR: CHE+RPC 51.2%± 5.0%, GF+RPC 53.6%± 6.1%, P>0.05 vs CON) or IPC (CHE+IPC 53.7%± 4.3%, GF+IPC 54.1%± 6.2%, P>0.05 vs CON). The difference was not significant in any of the hemodynamic parameters between control and treatment groups during ischemia and reperfusion.Conclusion:Remifentanil confers myocardial protection against ischemic injury through a mechanism that is similar to IPC and involves PKC activation.