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(Circulation Research. 2007;100:1643.)
© 2007 American Heart Association, Inc.

Integrative Physiology

Effect of K⁺_ATP Channel and Adenosine Receptor Blockade During Rest and Exercise in Congestive Heart Failure

Jay H. Traverse, YingJie Chen, MingXiao Hou, Yunfang Li, Robert J. Bache

From the Department of Medicine (J.H.T., Y.C., M.H., Y.L., R.J.B.), Division of Cardiology, University of Minnesota Medical School and the Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital (J.H.T.), Minneapolis, Minn.

Correspondence Jay H Traverse, MD, Division of Cardiology, University of Minnesota, MMC 508 UMHC, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail trave004{at}umn.edu

K⁺_ATP channels are important metabolic regulators of coronary blood flow (CBF) that are activated in the setting of reduced levels of ATP or perfusion pressure. In the normal heart, blockade of K⁺_ATP channels results in a 20% reduction in resting CBF but does not impair the increase in CBF that occurs during exercise. In contrast, adenosine receptor blockade fails to alter CBF or myocardial oxygen consumption (MVO₂) in the normal heart but contributes to the increase in CBF during exercise when vascular K⁺_ATP channels are blocked. Congestive heart failure (CHF) is associated with a decrease in CBF that is matched to a decrease in MVO₂ suggesting downregulation of myocardial energy utilization. Because myocardial ATP levels and coronary perfusion pressure are reduced in CHF, this study was undertaken to examine the role of K⁺_ATP channels and adenosine in dogs with pacing-induced CHF. Myocardial blood flow (MBF) and MVO₂ were measured during rest and treadmill exercise before and after K⁺_ATP channel blockade with glibenclamide (50 µg/kg/min ic) or adenosine receptor blockade with 8-phenyltheophylline (8-PT; 5 mg/kg iv). Inhibition of K⁺_ATP channels resulted in a decrease in CBF and MVO₂ at rest and during exercise without a change in the relationship between CBF and MVO₂. In contrast, adenosine receptor blockade caused a significant increase in CBF that occurred secondary to an increase of MVO₂. These findings demonstrate that coronary K⁺_ATP channel activity contribute to the regulation of resting MBF in CHF, and that endogenous adenosine may act to inhibit MVO₂ in the failing heart.

Key Words: heart failure • K⁺_ATP channels • coronary blood flow • exercise • myocardial oxygen consumption

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