Relationship between coronary flow and adenosine release during severe and mild hypoxia in the isolated perfused rat heart with special reference to time-course change

Summary The contribution of endogenous adenosine to coronary vasodilation induced by global myocardial hypoxia was examined. In isolated rat hearts perfused by means of Langendorff's technique, the relationship between chronological changes in coronary flow and adenosine release during hypoxia was analyzed. The oxygenation level of myoglobin (MbO₂), myocardial oxygen uptake, lactate release, and left ventricular pressure (LVP) was also measured. Adenosine was determined by radio-immunoassay, and the MbO₂ levels by the optical method. Severe hypoxia (20% O₂+75% N₂+5% CO₂) increased coronary flow, adenosine release, and lactate release and decreased both myocardial oxygen uptake and LVP. Mild hypoxia (50% O₂+45%N₂+5%CO₂) also increased coronary flow, adenosine release, and lactate release, while it affected neither myocardial oxygen uptake nor LVP. These results suggest that the oxygen supply is compensated by an increase in coronary flow in mild hypoxia, whereas this does not occur in severe hypoxia. Changes in MbO₂ were the reverse of those in coronary flow during severe hypoxia, confirming that a decrease in intracellular oxygen correlates well with an increase in coronary flow. The pattern of changes in adenosine release, however, was not identical with that in coronary flow in severe and mild hypoxia, indicating that there is no significant relationship between coronary flow and adenosine release in either severe or mild hypoxic hearts. These findings suggest that adenosine is not the only metabolic mediator of regulation of coronary flow in hypoxic hearts.