Inhibition of adenosine-mediated coronary vasodilation exacerbates myocardial ischemia during exercise

Persisting coronary vasoconstrictor tone that is responsive to exogenous adenosine administration has been demonstrated during myocardial ischemia. Therefore, the role and extent of endogenous adenosine-mediated coronary vasodilation in opposing coronary vasoconstriction within regions of ischemic myocardium was investigated in 10 chronically instrumented exercising dogs. Studies were performed on dogs with left circumflex coronary artery stenosis during treadmill exercise (6.5 km/h, 6% grade), while myocardial blood flow was measured with radioactive microspheres. Blood flow was measured before and again after inhibition of the effects of endogenously produced adenosine through combined inactivation of adenosine and adenosine receptor antagonism by the administration of intracoronary adenosine deaminase (ADA) (5 μg · kg^-1 · min^-1 x 10 min) plus 8-phenyltheophylline (8-PT) (5 mg/kg iv), respectively. Coronary perfusion pressure was held equal during both conditions at ~41 mmHg with a hydraulic occluder. During exercise in the presence of a coronary stenosis, blood flow was reduced in all layers of myocardium in regions supplied by the stenosed left circumflex coronary artery compared with blood flow in regions of myocardium supplied by the nonstenotic left anterior descending coronary artery. After ADA plus 8-PT, myocardial blood flow (in ml · min^-1 · g^-1) was further reduced in all layers of myocardium in regions supplied by the stenotic left circumflex coronary artery compared with baseline (subendocardial layer 0.44 ± 0.09 vs. 0.67 ± 0.13 ml · min^-1 · g^-1, mean transmural 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 nonstenotic left anterior descending coronary artery were unchanged following ADA plus 8-PT. These results demonstrate that endogenous adenosine contributes significantly to coronary vasodilation during exercise-induced ischemia.