Role of Calcium Channel Blockers in Myocardial Preconditioning

Coronary heart disease is the leading cause of mortality and morbidity worldwide. The effects of coronary heart disease are usually attributable to the detrimental effects of acute myocardial ischaemia-reperfusion injury. Newer strategies such as ischaemic or pharmacological preconditioning have been shown to condition the myocardium to ischaemia-reperfusion injury and thus reduce the final infarct size. This review investigates the role of calcium channel blockers in myocardial preconditioning. Additionally, special attention is given to nicorandil whose mechanism of action may be associated with the cardioprotective effects of preconditioning. There are still many uncertainties in understanding the role of these agents in preconditioning, but future research in this direction will certainly help reduce coronary heart disease.

Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury

Interleukin-6 (IL-6) is a pleiotropic cytokine that protects against cardiac ischemia-reperfusion (I/R) injury following pharmacological and ischemic preconditioning (IPC), but the affiliated role in exercise preconditioning is unknown. Our study purpose was to characterize exercise-induced IL-6 cardiac signaling ( aim 1) and evaluate myocardial preconditioning ( aim 2). In aim 1, C57 and IL-6−/− mice underwent 3 days of treadmill exercise for 60 min/day at 18 m/min. Serum, gastrocnemius, and heart were collected preexercise, immediately postxercise, and 30 and 60 min following the final exercise session and analyzed for indexes of IL-6 signaling. For aim 2, a separate cohort of exercise-preconditioned (C57 EX and IL-6−/− EX) and sedentary (C57 SED and IL-6−/− SED) mice received surgical I/R injury (30 min I, 120 min R) or a time-matched sham operation. Ischemic and perfused tissues were examined for necrosis, apoptosis, and autophagy. In aim 1, serum IL-6 and IL-6 receptor (IL-6R), gastrocnemius, and myocardial IL-6R were increased following exercise in C57 mice only. Phosphorylated (p) signal transducer and activator of transcription 3 was increased in gastrocnemius and heart in C57 and IL-6−/− mice postexercise, whereas myocardial iNOS and cyclooxygenase-2 were unchanged in the exercised myocardium. Exercise protected C57 EX mice against I/R-induced arrhythmias and necrosis, whereas arrhythmia score and infarct outcomes were higher in C57 SED, IL-6−/− SED, and IL-6−/− EX mice compared with SH. C57 EX mice expressed increased p-p44/42 MAPK (Thr202/Tyr204) and p-p38 MAPK (Thr180/Tyr182) compared with IL-6−/− EX mice, suggesting pathway involvement in exercise preconditioning. Findings indicate exercise exerts cardioprotection via IL-6 and strongly implicates protective signaling originating from the exercised skeletal muscle.