Combined Heat-acclimation And Exercise-training Improves Cardiac Mechanical And Metabolic Performance And Enhances Cardioprotection.

Abstract

Heat acclimation (AC) and exercise training (EX) each improve mechanical and metabolic cardiac performance and protect against injury from ischemic reperfusion (I/R) insults. We hypothesize that these seemingly similar adaptations are achieved by different mechanisms. Purpose: To determine the impact of combined AC and EX on the heart. METHODS: Groups: AC (sedentary, 34°C), EX (swimming or treadmill training, normothermic), EXAC (34°C, swimming or treadmill training). Mechanical performance was assessed using isolated hearts (Langendorff perfusion) and cardiomyocytes. I/R injury severity was evaluated using ischemic contracture threshold, time to peak contracture and the infarct size, determined by triphenyl tetrazolium chloride (TTC) staining. Cellular contractile and metabolic mechanisms were evaluated by measuring Ca2+ transients, glucose transporter (GLUT 1 and 4) levels and PKC δ and levels in inner and outer cell membrane fractions. RESULTS AND DISCUSSION: All treatment groups showed enhanced pressure generation, with AC and EX showing similar changes whereas EXAC caused an additive effect. Nevertheless, only isolated cardiomyocytes from the AC group demonstrated significantly greater shortening and greater Ca2+ transient amplitudes. Ca2+ responsiveness of the contractile elements of the two heat treated groups (AC, EXAC) decreased as did the velocities of pressure generation and relaxation. AC increased GLUT1 and GLUT4 levels in the inner and outer membranes before and after ischemia and decreased the PKC δ/ PKC ratio during the ischemic episode. The exercise trained groups (EX, EXAC) had elevated GLUT1 levels. GLUT4 was only elevated in the inner cell membranes. Ischemia did not affect the PKC δ/ PKC ratio in these groups. The infarct size was significantly reduced in all treatment groups, with an infarct area of 4.3%, 15%, 8% in AC, EX and EXAC respectively, versus 29% in controls. Importantly, ischemic thresholds were markedly delayed compared to controls and peak contractures were lower in the exercise groups. We show that heat impacts predominantly on contractile parameters under normoperfusion and on glucose transporters both under normo and ischemic conditions. In the AC group, protection was also enhanced via attenuation of the deleterious effects of PKC δ. Despite the fact that the infarct size was similar in the treatment groups, only exercise significantly delayed the onset of ischemic contracture. Our published gene profiles of these groups are congruent with the current findings. These findings also lend support to our concept that AC and EX induce similar outcomes by using different pathways. Kodesh address: Haifa University