Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats
Abstract
Aim: 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 mug.kg-1dotmin-1times 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%plusminus 5.5% to 12.9%plusminus 3.4%, P<0.01 vs CON and 16.2%plusminus 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%plusminus 5.0%, GF+RPC 53.6%plusminus 6.1%, P>0.05 vs CON) or IPC (CHE+IPC 53.7%plusminus 4.3%, GF+IPC 54.1%plusminus 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.
Keywords:
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 mug.kg-1dotmin-1times 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%plusminus 5.5% to 12.9%plusminus 3.4%, P<0.01 vs CON and 16.2%plusminus 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%plusminus 5.0%, GF+RPC 53.6%plusminus 6.1%, P>0.05 vs CON) or IPC (CHE+IPC 53.7%plusminus 4.3%, GF+IPC 54.1%plusminus 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.