INHIBITION OF ADENOSINE-MEDIATED CORONARY VASODILATION EXACERBATES MYOCARDIAL-ISCHEMIA DURING EXERCISE

Persisting coronary vasoconstrictor tone that is responsive to exogeno us adenosine administration has been demonstrated during myocardial is chemia. Therefore, the role and extent of endogenous adenosine-mediate d coronary vasodilation in opposing coronary vasoconstriction within r egions of ischemic myocardium was investigated in 10 chronically instr umented exercising dogs. Studies were performed on dogs with left circ umflex coronary artery stenosis during treadmill exercise (6.5 km/h, 6 % grade), while myocardial blood flow was measured with radioactive mi crospheres. Blood flow was measured before and again after inhibition of the effects of endogenously produced adenosine through combined ina ctivation of adenosine and adenosine receptor antagonism by the admini stration of intracoronary adenosine deaminase (ADA) (5 mug . kg-1 . mi n-1 X 10 min) plus 8-phenyltheophylline (8-PT) (5 mg/kg iv), respectiv ely. Coronary perfusion pressure was held equal during both conditions at approximately 41 mmHg with a hydraulic occluder. During exercise i n the presence of a coronary stenosis, blood flow was reduced in all l ayers of myocardium in regions supplied by the stenosed left circumfle x coronary artery compared with blood flow in regions of myocardium su pplied by the nonstenotic left anterior descending coronary artery. Af ter ADA plus 8-PT, myocardial blood flow (in ml . min-1 . g-1) was fur ther reduced in all layers of myocardium in regions supplied by the st enotic left circumflex coronary artery compared with baseline (subendo cardial layer 0.44 +/- 0.09 vs. 0.67 +/- 0.13 ml . min-1 . g-1, mean t ransmural flow 0.92 +/- 0.13 vs. 1.25 +/- 0.2 ml . min-1 . g-1, both P < 0.05). Blood flow in regions of myocardium supplied by the nonsteno tic left anterior descending coronary artery were unchanged following ADA plus 8-PT. These results demonstrate that endogenous adenosine con tributes significantly to coronary vasodilation during exercise-induce d ischemia.