Release of Adenosine by the Normal Myocardium in Dogs and Its Relationship to the Regulation of Coronary Resistance

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Abstract
The evidence supporting the hypothesis that adenosine is the mediator of metabolic regulation of coronary blood flow was obtained from experiments characterized by myocardial hypoxia. If adenosine serves the role of physiological regulator of coronary blood flow, it must also be released by the normal heart. Experiments designed to study this question were performed on 15 open-chest dogs in which adenosine was sought in perfusates of the epicardial surface of the well-oxygenated heart. The pericardial space was perfused with warm (37°C) Tyrode's or Krebs-Henseleit solutions (400 to 1200 ml over 1 to 3 hours), and the perfusates were analyzed for adenosine. With a normal myocardial oxygen supply, adenosine was present in the perfusates in a concentration of 3.1 ± 0.5 x 10>-8M. Partial asphyxia, induced by reducing pulmonary ventilation, significantly (P ≤ 0.02) increased the adenosine concentration of the perfusates to 5.4 ± 0.8 x 10-8M. In four dogs the normal pericardial fluid was found to contain adenosine in a concentration of 10.9 ± 2.9 x 10-7M, which probably represents the basal extracellular adenosine concentration in the myocardium. The results indicate that the normal myocardial cells release adenosine continuously into the surrounding interstitial fluid, and it is suggested that the level of the interstitial fluid concentration of adenosine probably regulates coronary blood flow to maintain the oxygen balance of the myocardium.