Original ArticleExercise Preconditioning of Myocardial Infarct Size in Dogs Is Triggered by CalciumParra, Víctor M. MD; Macho, Pilar MD; Sánchez, Gina PhD; Donoso, Paulina PhD; Domenech, Raúl J. MDAuthor Information Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile. Reprints: Raúl J. Domenech, MD, Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Casilla 16038, Avenida Salvador 486 (Providencia), Santiago 9, Chile (e-mail: email@example.com). Supported by Fondo Nacional de Investigación Científica y Tecnológica (FONDECYT), grants 1030449 and 1030446, and by Fondo de Áreas Prioritarias (FONDAP), Center for Molecular Studies of the Cell, 15010006 from Chile. The authors report no conflicts of interest. Received July 27, 2014 Accepted November 04, 2014 Journal of Cardiovascular Pharmacology: March 2015 - Volume 65 - Issue 3 - p 276-281 doi: 10.1097/FJC.0000000000000191 Buy Metrics Abstract 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 Ca2+ 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. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.