Exercise Preconditioning of Myocardial Infarct Size in Dogs Is Triggered by Calcium

Abstract

We showed that exercise induces early and late myocardial preconditioning in dogs and that these effects are mediated through nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activation. As the intracoronary administration of calcium induces preconditioning and exercise enhances the calcium inflow to the cell, we studied if this effect of exercise triggers exercise preconditioning independently of its hemodynamic effects. We analyzed in 81 dogs the effect of blocking sarcolemmal L-type Ca channels with a low dose of verapamil on early and late preconditioning by exercise, and in other 50 dogs, we studied the effect of verapamil on NADPH oxidase activation in early exercise preconditioning. Exercise reduced myocardial infarct size by 76% and 52% (early and late windows respectively; P < 0.001 both), and these effects were abolished by a single low dose of verapamil given before exercise. This dose of verapamil did not modify the effect of exercise on metabolic and hemodynamic parameters. In addition, verapamil blocked the activation of NADPH oxidase during early preconditioning. The protective effect of exercise preconditioning on myocardial infarct size is triggered, at least in part, by calcium inflow increase to the cell during exercise and, during the early window, is mediated by NADPH oxidase activation.

Changes in Autophagy Levels in Rat Myocardium During Exercise Preconditioning-Initiated Cardioprotective Effects

“…49 5 minute periods of rest before a coronary occlusion can initiate a significant protective effect with respect to the cardiac infarct size in dogs. [2][3][4] Pretreatment of EP established by an acute bout of high-intensity intermittent exercise which strenuously and repeatedly stimulates cardiac work was also found to initiate cardioprotective effects against isoproterenol injection or exhaustive exerciseinduced ischemia-hypoxia injury in rat myocardium. 5,6,9,51) In this study, pretreatment of EP at 0.5 hours before exhaustive exercise attenuated the ischemia-hypoxia injury in rat myocardium and decreased the release of cTnI.…”

“…Group EP (Exercise preconditioning group): an EP protocol was designed with minor modifications from previous studies. 2,4) The rats were kept on the animal treadmill. After a warm-up protocol of 15 m/minute, 0% grade for 5 minutes, the speed of the treadmill was increased gradually to 30 m/minute within a 5 minute period.…”

“…1) Exercise preconditioning (EP) established by an acute bout of highintensity intermittent exercise before a severe, sustained myocardial ischemia episode could initiate remarkable intrinsic cardioprotective effects for strenuous and repetitive stimulations to cardiovascular systems. [2][3][4][5][6][7] EP can be divided into EP-initiated cardioprotective effects and cardioprotective phase. Although the EP-initiated cardioprotective effects have been widely recognized, 2,8,9) and the evidences show the cardioprotective phase can last a long time, 10,11) the potential mechanisms during EP-initiated cardioprotective effects and phase still need to be investigated.…”

Association of Exercise Preconditioning With Immediate Cardioprotection

“…29 In a series of studies, Domenech and co-workers explored if intermittent exercise resulted in early and late cardiac precondition. 30 They found that exercise prior to coronary occlusion induces early and late precondition, leading to a reduction in infarct size of 46-52 30,31 and 56-78%, [30][31][32] respectively.…”

Alterations of Cardiac K_ATP Channels and Autophagy Contribute in the Late Cardioprotective Phase of Exercise Preconditioning

“…The late cardioprotection of EP has been observed by other researchers in myocardial infarction animal models. In a study by Domenech, et al, 16,17) dogs ran on a treadmill for 5 periods of 5 minutes each at 6 km/hour along with 5minute periods of rest as a preconditioning protocol. Results revealed that infarct size induced by I/R injury in EP group significantly decreased in the late preconditioned phase, but the decline in the cardiac function was not significantly improved.…”