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

Jay H Traverse1, YingJie Chen, MingXiao Hou

  • 1Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. trave004@umn.edu

Circulation Research
|May 5, 2007
PubMed

Insights

In congestive heart failure (CHF), ATP-sensitive potassium channels (K(ATP)) regulate resting coronary blood flow (CBF). Adenosine may inhibit oxygen consumption in failing hearts.

Area of Science:

  • Cardiovascular Physiology
  • Metabolic Regulation
  • Heart Failure Pathophysiology

Background:

  • K(ATP) channels are key metabolic regulators of coronary blood flow (CBF), activated by low ATP or perfusion pressure.
  • In normal hearts, K(ATP) channel blockade reduces resting CBF, while adenosine receptor blockade has minimal effect.
  • Congestive heart failure (CHF) exhibits reduced CBF matched by decreased myocardial oxygen consumption (MVO(2)).

Purpose of the Study:

  • To investigate the role of K(ATP) channels and adenosine in regulating CBF and MVO(2) in dogs with pacing-induced CHF.
  • To determine if K(ATP) channel activity is altered in the failing heart.
  • To assess the interaction between adenosine and K(ATP) channels in CHF.

Main Methods:

  • Pacing-induced CHF model in dogs.
  • Measurement of myocardial blood flow (MBF) and MVO(2) at rest and during exercise.
  • Pharmacological blockade of K(ATP) channels using glibenclamide.
  • Pharmacological blockade of adenosine receptors using 8-phenyltheophylline (8-PT).

Main Results:

  • K(ATP) channel inhibition decreased both resting and exercise CBF and MVO(2) in CHF dogs, without altering their relationship.
  • Adenosine receptor blockade significantly increased CBF in CHF dogs, secondary to increased MVO(2).
  • These results suggest K(ATP) channels are crucial for maintaining resting MBF in CHF.

Conclusions:

  • Coronary K(ATP) channel activity is essential for regulating resting myocardial blood flow in congestive heart failure.
  • Endogenous adenosine appears to play a role in inhibiting myocardial oxygen consumption in the failing heart.
  • Findings highlight distinct roles for K(ATP) channels and adenosine in cardiovascular regulation during heart failure.

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