Exercise Protects The Heart Against Arrhythmias Induced By Thiol Oxidation

Abstract

The ability of exercise to confer resistance against cardiac ischemia/reperfusion injury is well known, although the mechanisms underlying exercise-induced cardioprotection have not been fully characterized. Previous work by our group has shown that oxidizing myocardial thiols can induce ventricular arrhythmias by overwhelming mitochondrial anti-oxidant defenses, collapsing mitochondrial membrane potential, and activating energy-sensitive potassium channels in the sarcolemma. PURPOSE: The following study was conducted to see if prior exercise could attenuate the extent of electrical dysfunction in hearts receiving the thiol-oxidant diamide. METHODS: Female Sprague-Dawley rats (3-4 months old) were placed in two groups: sedentary (Sed; n=10) or exercise (Ex; n=8). Animals in the Ex group were run for 10 consecutive days on a motorized treadmill, and Sed counterparts were placed on the non-moving treadmill each day as handling controls. Each exercise bout consisted of 15/30/15 minutes at a treadmill speed of 15/30/15 meters per minute (10% incline). Twenty-four hours after the last exercise bout hearts were excised and placed on a modified Langendorff apparatus for continuous monitoring of volume-conducted electrocardiogram, left ventricular function, and coronary flow. Following a 15 minute baseline period, hearts were switched to a buffer containing 200 μM diamide for 35 minutes, followed by a 25 minute washout period. RESULTS: The training protocol did not elicit markers of systemic stress such as adrenal hypertrophy (adrenal weights were 38 ± 3 and 39 ± 2 mg for Sed and Ex, respectively; P > 0.05) or splenic atrophy (spleen weights were 573 ± 27 and 624 ± 32 mg for Sed and Ex, respectively; P > 0.05). Exercise protected hearts against arrhythmias induced by diamide, as evidenced by: 1) lower incidence of non-reverting ventricular arrhythmia (70% of Sed hearts and 38% of Ex hearts experienced non-reverting arrhythmia), and 2) delayed time to non-reverting arrhythmia (12 ± 3 min and 20 ± 3 min in Sed and Ex, respectively; P < 0.05). Arrhythmia scores were significantly lower in the Ex group (5.8 ± 0.5) compared to Sed (7.2 ± 0.5; P < 0.05). Coronary flow rates during diamide washout were not different between the Sed (7.7 ± 1.1 mL/min*g heart wt) and Ex (8.4 ± 1.8 mL/min*g heart wt) groups (P > 0.05). CONCLUSIONS: Our results show that exercise training protects the heart from arrhythmias when challenged with an oxidizing agent, supporting the hypothesis that exercise-induced protection against arrhythmias involves maintenance of bioenergetics secondary to heightened oxidant buffering capacity.