Role of morphine and sufentanil in myocardial ischemia/reperfusion induced ventricular arrhythmias

In this study, we investigated the preconditioning effects of the classical opioid morphine and the novel opioid receptor agonist sufentanil on myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias and their possible modes of action. Rats were divided into six groups: sham operation (C), I/R model (I/R), morphine (M) and sufentanil (S) preconditioned, and morphine (MPA) and sufentanil (SPA) preconditioned plus the p38 MAPK inhibitor SB203580. All groups (except C) received I/R, with morphine and sufentanil administered intravenously before left coronary artery ligation, and SB203580 administered before preconditioning. Hemodynamic indices (heart rate, mean arterial blood pressure and rate pressure product) were decreased in all groups compared to C (P < 0.05) but increased significantly in M, S, MPA and SPA (P < 0.05) compared with I/R; there were no significant differences between M and S, and between MPA and SPA. Analysis of arrhythmias by electrocardiography showed a similar trend. Western blotting and/or immunohistochemistry revealed that myocardiocytes in I/R expressed high levels of p38 MAPK and phosphorylated p38 MAPK, with decreased levels in M, S, MPA and SPA compared to C, while expression of Cx43 and p-Cx43 showed opposing patterns to that of p38 MAPK. Morphine and sufentanil may protect against myocardial I/R injury via Cx43 phosphorylation, but not via p38 MAPK.