Parra Víctor M, Macho Pilar, Sánchez Gina, Donoso Paulina, Domenech Raúl J
Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile.
J Cardiovasc Pharmacol. 2015 Mar;65(3):276-81. doi: 10.1097/FJC.0000000000000191.
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.
我们发现运动可诱导犬早期和晚期心肌预处理，且这些效应是通过还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶激活介导的。由于冠状动脉内注射钙可诱导预处理，且运动可增强钙流入细胞，我们研究了运动的这种效应是否独立于其血流动力学效应触发运动预处理。我们在81只犬中分析了低剂量维拉帕米阻断肌膜L型钙通道对运动诱导的早期和晚期预处理的影响，在另外50只犬中，我们研究了维拉帕米对早期运动预处理中NADPH氧化酶激活的影响。运动使心肌梗死面积分别减少76%和52%（分别为早期和晚期窗；两者P均<0.001），且运动前给予单次低剂量维拉帕米可消除这些效应。该剂量的维拉帕米未改变运动对代谢和血流动力学参数的影响。此外，维拉帕米在早期预处理期间阻断了NADPH氧化酶的激活。运动预处理对心肌梗死面积的保护作用至少部分是由运动期间钙流入细胞增加触发的，且在早期窗期间是由NADPH氧化酶激活介导的。
