Role of K(ATP)/⁺ channels in local metabolic coronary vasodilation

ATP-sensitive potassium (K(ATP)/⁺) channels have been shown to play a role in the maintenance of basal coronary vascular tone in vivo. K(ATP)/⁺ channels are also involved in the coronary vasodilator response to adenosine. The aim of this study was to determine the role of K(ATP)/⁺ channels in local metabolically mediated increases in coronary blood flow during cardiac electrical paired pacing without catecholamine effects. In 10 anesthetized closed-chest dogs, coronary blood flow was measured in the left circumflex coronary artery, and myocardial O₂ consumption was calculated using the arteriovenous O₂ difference. Cardiac interstitial adenosine concentration was estimated from coronary venous and arterial plasma adenosine measurements using a previously described, multicompartmental, axially distributed, mathematical model. Paired stimulation increased heart rate from 57 to 120 beats/min, myocardial O₂ consumption 88%, and coronary blood flow 76%. During K(ATP)/⁺ channel blockade with glibenclamide, baseline coronary blood flow decreased in relation to myocardial O₂ consumption and thus coronary sinus O₂ tension fell. Paired-pulse pacing with glibenclamide resulted in increases in myocardial O₂ consumption and coronary blood flow similar to those during control pacing. Coronary venous and estimated interstitial adenosine concentration did not increase sufficiently to overcome the glibenclamide blockade. In conclusion, K(ATP)/⁺ channels are not required for locally mediated metabolic increases in coronary blood flow that accompany myocardial O₂ consumption during pacing tachycardia without catecholamines, and adenosine levels do not increase sufficiently to overcome the glibenclamide blockade.