Effect of K+ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure

Jay H. Traverse, Yingjie Chen, Ming Xiao Hou, Yunfang Li, Robert J Bache

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

KATP 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 KATP 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 KATP 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 KATP 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 KATP channel blockade with glibenclamide (50 μg/kg/min ic) or adenosine receptor blockade with 8-phenyltheophylline (8-PT; 5 mg/kg iv). Inhibition of KATP 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 KATP channel activity contribute to the regulation of resting MBF in CHF, and that endogenous adenosine may act to inhibit MVO2 in the failing heart.

Original languageEnglish (US)
Pages (from-to)1643-1649
Number of pages7
JournalCirculation research
Volume100
Issue number11
DOIs
StatePublished - Jun 2007

Keywords

  • Coronary blood flow
  • Exercise
  • Heart failure
  • K channels
  • Myocardial oxygen consumption

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