704-6 Chronic Exercise Training Restores Endothelium-mediated Control of Epicardial Coronary Artery During Development of Heart Failure in Awake Dogs

The beneficial effects of exercise training (EX) in patients with heart failure have been reported but the underlying mechanisms are still unknown. The objective of this study was to determine the potential beneficial effects of chronic EX on endothelium-mediated dilation of epicardial coronary artery in awake dogs during development of heart failure. Dogs were chronically instrumented for measurements of left ventricular pressure, aortic pressure, and epicardial coronary artery diameter (CD, sonomicrometer) and for chronic pacing. The dogs were allowed to recover and experiments were performed in conscious state. Dogs were cardiac paced (210 b/min for 3 weeks and 240 b/min for the 4th week), and were trained to run on a treadmill two hours/day at speed of 5,8 ± 2.2 kms/hour (one hour in the morning and one hour in the afternoon) during this 4 week pacing period. Experiments were performed before and after this 4 wk period. Following release of 5, 10, 15, 20 and 30 second coronary artery occlusion, CD dilated 4.2 ± 1.0%, 5.63 ± 1.4%,5.94 ± 1.5%, 6.74 ± 1.0% and 7.04 ± 1.2% vs 4.35 ± 1.0%,5.55 ± 1.3%, 5.85 ± 0.82%, 6.23 ± 0.61% and 6.36 ± 0.61% (p g 0.05) before and after EX plus pacing, respectively. The responses of CD to acetylcholine at doses of 0.25, 0.5, 1,5, 10 and 20 μg/kg were also preserved: 2.22 ± 1.3%, 2.76 ± 1.8%,4.26 ± 1.7%,6.59 ± 1.32%, 7.15 ± 1.21%, 7.64 ± 1.15% vs 257 ± 1.6%, 2.28 ± 0.99%, 4.37 ± 1.89%, 6.37 ± 0.85%, 6.72 ± 0.97%, 6.82 ± 0.51%, respectively (p g 0.05). Nitroglycerin-induced dilation of CD was not altered. In contrast, endothelium-mediated vasodilation is enhanced after chronic EX in normal dogs and is eliminated in dogs with pacing-induced heart failure. Thus, chronic EX protected endothelium-mediated dilation of epicardial coronary artery during development of heart failure. This might be due to EX normalized production of endothelial-derived relaxing factor.