Adenosene and K_ATP channels are not required for control of coronary blood flow during local metabolic vasodilation

Electrical paired pulse stimulation of the heart was used to increase myocardial oxygen consumption (MVO₂) without catecholamines in anesthetized closed-chest dogs. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous values with a previously validated mathematical model. Paired stimulation increased the heart rate from 59 to 120 b/min, and MV̇O₂ increased 83%. Coronary flow increased 76% without interstitial adenosine concentration reaching vasoactive levels. Following K_ATP channel and adenosine blockade with glibenclamide (1 mg/kg iv), unstimulated flow was reduced 12% and coronary venous P_O2 decreased from 19 to 13 mm Hg with a 5% increase in MV̇O₂. After glibenclamide, paired stimulation increased the heart rate from 59 to 120 b/min, and MV̇O₂ increased 81%. Coronary blood flow increased 74%. Although interstitial adenosine concentration increased modestly, it was not enough to overcome the 10-fold shift in the adenosine response curve due to glibenclamide blockade. In conclusion, adenosine and K_ATP channel blockade reduced basal coronary blood flow and coronary venous P_O2 but did not alter the increase in blood flow during paired pacing. This indicates that neither adenosine nor K_ATP channels are required for control of coronary blood flow during local metabolic vasodilation.