Circulation Research, Vol 69, 1402-1408, Copyright © 1991 by American Heart Association

ARTICLES

Endogenous adenosine inhibits platelet aggregation during myocardial ischemia in dogs

M Kitakaze, M Hori, H Sato, S Takashima, M Inoue, A Kitabatake and T Kamada
First Department of Medicine, Osaka University School of Medicine, Japan.

The goal of this study was to clarify that blockade of adenosine receptors during myocardial ischemia causes further reductions in coronary blood flow due to platelet aggregation. Coronary perfusion pressure in 47 open-chest dogs was reduced such that coronary blood flow decreased to one fifth of the control value; thereafter, coronary perfusion pressure was maintained at the low levels. During hypoperfusion, coronary flow was kept low but constant with a massive release of adenosine. When 8-phenyltheophylline, an adenosine receptor antagonist, was infused during coronary hypoperfusion, coronary blood flow (18 +/- 2 ml/100 g/min) gradually decreased at 5-10 minutes of ischemia and reached almost zero at 20 minutes. Three minutes after the onset of ischemia, before further reduction of coronary flow, the microscopic examination revealed the existence of thromboembolization in the small coronary arteries, and the number of platelets in the regional coronary venous blood were significantly decreased, indicating that a further reduction of coronary flow due to treatment with 8- phenyltheophylline is attributed to thromboembolism caused by platelet aggregations. This reduction of coronary flow and formation of thromboembolism were inhibited by the treatments with dibutyryl cAMP, forskolin, and yohimbine, indicating that this thromboembolization during a lack of adenosine activity is due to platelet aggregation and that platelet aggregation caused by 8-phenyltheophylline is triggered by stimulation of alpha 2-adrenoceptors by released norepinephrine during ischemia. We demonstrate that adenosine, generated endogenously in response to ischemia, inhibits platelet aggregation. The finding that adenosine is not merely a vasodilator but that it also regulates thrombosis has major implications for designing new strategies of myocardial salvage.

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