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 KATP channel and adenosine blockade with glibenclamide (1 mg/kg iv), unstimulated flow was reduced 12% and coronary venous PO2 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 KATP channel blockade reduced basal coronary blood flow and coronary venous PO2 but did not alter the increase in blood flow during paired pacing. This indicates that neither adenosine nor KATP channels are required for control of coronary blood flow during local metabolic vasodilation.
|State||Published - 20 Mar 1998|