Regulation of Coronary Blood Flow During Exercise in Failing Heart

Abstract

PURPOSE: Myocardial ischemia is one of the most common causes of exercise associated cardiac arrest in adults. The purpose of this study was to explore the pathophysiological mechanism of exercise associated cardiac arrest by investigating the regulation of coronary blood flow (CBF) during exercise in failing heart. METHODS: Studies were performed in 11 adult mongrel dogs trained to run on a treadmill. A Doppler velocity probe was positioned on the left anterior descending coronary artery for the measurement of CBF. CBF and the endothelium dependent vasodilator response to acetylcholine were studied in dogs in which congestive heart failure (CHF) was produced by rapid ventricular pacing for 4 weeks. Tissue homogenates of left ventricular myocardium from normal dogs and dogs with pacing-induced CHF were investigated by routine Western blot analysis. RESULTS: The CBF at rest and during treadmill exercise were significantly decreased after development of CHF (36.7±2.44 vs 20.1±2.87 ml/min at rest, 49.9±3.88 vs 24.2±3.48 ml/min during exercise). The CBF responses to exercise were gradually decreased at different stages of pacing. The effect of acetylcholine-induced coronary vasodilatation was significantly suppressed by nitric oxide synthase (NOS) blocker L-NNA (p<0.05). Western blot analysis showed that endothelial NOS (eNOS) protein was increased by 43±12 % significantly in failing heart. CONCLUSIONS: Our findings of the decreased CBF response to exercise and the increased eNOS expression in the failing heart may suggest that NO signaling play an important role in the regulation of CBF during exercise and this may be a novel approach to protect heart from exercise associated cardiac arrest.