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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/H1306    most recent 00631.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Merkus, D. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Merkus, D. Articles by Duncker, D. J.

Contribution of K_ATP⁺ channels to coronary vasomotor tone regulation is enhanced in exercising swine with a recent myocardial infarction

Experimental Cardiology, Thoraxcenter, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

Submitted 24 June 2004 ; accepted in final form 9 November 2004

Previous studies demonstrated a decreased flow reserve in the hypertrophied myocardium early after myocardial infarction (MI). Previously, we reported that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise caused slight impairment of myocardial O₂ supply in swine with a recent MI. We hypothesized that increased metabolic coronary vasodilation [via ATP-sensitive K⁺ (K_ATP⁺) channels and adenosine] may have partially compensated for the increased extravascular compressive forces and increased vasoconstrictor neurohormones, thereby preventing a more severe impairment of myocardial O₂ balance. Chronically instrumented swine were exercised on a treadmill up to 85% of maximum heart rate. Under resting conditions, adenosine receptor blockade [8-phenyltheophylline (8-PT), 5 mg/kg iv] and K_ATP⁺ channel blockade (glibenclamide, 3 mg/kg iv) produced similar decreases in myocardial O₂ supply in normal and MI swine. However, while glibenclamide's effect waned in normal swine during exercise (P < 0.05), it was maintained in MI swine. 8-PT's effect was maintained during exercise and was not different between normal and MI swine. Finally, in normal swine combined treatment with 8-PT and glibenclamide produced a vasoconstrictor response that equaled the sum of the responses to blockade of the individual pathways. In contrast, in MI swine the vasoconstrictor response to 8-PT and glibenclamide was similar to that produced by glibenclamide alone. In conclusion, despite significant hemodynamic abnormalities in swine with a recent MI, myocardial O₂ supply and O₂ consumption in remodeled myocardium are still closely matched during exercise. This close matching is supported by increased K_ATP⁺ channel-mediated coronary vasodilation. Although the net vasodilator influence of adenosine was unchanged in remodeled myocardium, it became exclusively dependent on K_ATP⁺ channel opening.

heart failure; hypertrophy; myocardial oxygen balance; adenosine

This article has been cited by other articles:

				D. Merkus, O. Sorop, B. Houweling, B. A. Hoogteijling, and D. J. Duncker KCa+ channels contribute to exercise-induced coronary vasodilation in swine Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2090 - H2097. [Abstract] [Full Text] [PDF]