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Inhibition of adenosine-mediated coronary vasodilation exacerbates myocardial ischemia during exercise
D D Laxson1, D C Homans, R J Bache
1Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Insights
Endogenous adenosine plays a crucial role in maintaining coronary blood flow during myocardial ischemia. Inhibiting adenosine
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia Research
- Adenosine Signaling Pathways
Background:
- Coronary vasoconstrictor tone persists during myocardial ischemia.
- Exogenous adenosine administration can alleviate this tone.
- The role of endogenous adenosine in vasodilation during ischemia is not fully understood.
Purpose of the Study:
- To investigate the role of endogenous adenosine-mediated coronary vasodilation.
- To determine the extent to which adenosine opposes vasoconstriction in ischemic myocardium.
- To quantify the impact of adenosine inhibition on myocardial blood flow during exercise-induced ischemia.
Main Methods:
- Utilized chronically instrumented exercising dogs with induced left circumflex coronary artery stenosis.
- Measured myocardial blood flow using radioactive microspheres.
- Inhibited endogenous adenosine effects via adenosine deaminase (ADA) and 8-phenyltheophylline (8-PT).
Main Results:
- Exercise with coronary stenosis reduced blood flow in the stenosed region compared to the non-stenosed region.
- Inhibition of endogenous adenosine (ADA + 8-PT) significantly further reduced myocardial blood flow in the stenosed region.
- Blood flow in the non-stenosed region remained unchanged after adenosine inhibition.
Conclusions:
- Endogenous adenosine significantly contributes to maintaining coronary blood flow during ischemia.
- Inhibition of endogenous adenosine exacerbates the reduction in blood flow during exercise-induced myocardial ischemia.
- Adenosine-mediated vasodilation is a critical compensatory mechanism opposing vasoconstriction in ischemic myocardium.
Abstract:
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 micrograms.kg-1 x min-1 x 10 min) plus 8-phenyltheophylline (8-PT) (5 mg/kg i.v.), respectively. Coronary perfusion pressure was held equal during both conditions at approximately 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 x 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 x g-1, mean transmural flow 0.92 +/- 0.13 vs. 1.25 +/- 0.2 ml.min-1 x 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.(ABSTRACT TRUNCATED AT 250 WORDS)