Exercise Training Decreases Arrhythmias But Is Not Associated With Improved Mitochondrial Calcium Retention Capacity

Abstract

PURPOSE: To determine if 10 days of exercise training decreases cardiac arrhythmias in the isolated female rat heart, and to determine if mitochondrial adaptations are involved. We hypothesized that exercise would promote an anti-arrhythmic phenotype characterized by improved calcium tolerance, improved ROS scavenging by superoxide dismutase (SOD), and delayed mitochondrial permeability transition pore opening. METHODS: Female Sprague-Dawley rats were randomly assigned to either the sedentary handling control (Sed) or the exercise trained (Ex) group. Animals in the Ex group were placed on a motorized treadmill at speeds of 15/30/15 meters per minute for 15/30/15 minutes respectively. Animals in the Sed group were handled and placed on the treadmill each day. Exercise duration was 10 days. Twenty-four hours after the last session hearts were excised via thoracotomy and either instrumented for isolated heart experiments or used for mitochondrial isolations. Isolated hearts were exposed to global ischemia for 30 minutes, followed by 30 minutes of reperfusion. RESULTS: Ex led to a significant decrease in the severity of arrhythmias by: 1) reducing the arrhythmia score (5.7 ± 0.9 and 3.0 ± 0.6, for Sed and Ex group respectively, P < 0.05) and 2) decreasing the time spent in a ventricular arrhythmia (11 ± 3 and 2 ± 1 minutes, for Sed and Ex group respectively, P 0.05). However, during reperfusion coronary flow was significantly preserved in the Ex group (P < 0.05, RM ANOVA). Western blots for both SOD isoforms showed that neither SOD1 nor SOD2 protein levels were increased following Ex. In isolated mitochondria, the calcium retention capacity in Ex animals was significantly lower than Sed counterparts (433 ± 33 and 343 ± 10 nmoles of calcium, for Sed and Ex respectively, P < 0.05). CONCLUSIONS: Our results suggest that Ex causes intrinsic changes in the female heart that decrease the severity of arrhythmias without increases in protein expression of SOD1 or SOD2. Surprisingly, mitochondria of trained animals were more sensitive to calcium-induced opening of the mitochondrial permeability transition pore. Future experiments investigating the kinetics of calcium uptake and extrusion in isolated mitochondria will improve our understanding of how mitochondrial calcium handling influences the propensity for arrhythmias.