CHANGES IN INTERSTITIAL ADENOSINE DURING HYPOXIA - RELATIONSHIP TO OXYGEN SUPPLY-DEMAND IMBALANCE, AND EFFECTS OF ADENOSINE-DEAMINASE

Objective: The aim was to determine the changes in coronary blood flow and intramyocardial interstitial fluid (ISF) adenosine and adenosine metabolites during systemic hypoxia, and to evaluate (1) whether the increase in ISF adenosine during hypoxia is augmented if the hypoxic hyperaemia is prevented, and (2) the effects of adenosine deaminase on ISF adenosine and coronary blood flow during sustained hypoxia. Methods: Anaesthetised dogs were instrumented with a flow probe around the left anterior descending coronary artery to measure coronary blood flow and with a microdialysis probe in the myocardium perfused by this artery to sample intramyocardial ISF. Dialysate purine metabolite levels were used as indices of ISF levels. Systemic hypoxia was induced by a reduction in the F1O2. Results: Acute systemic hypoxia (P(a)o(2) approximate to 3.9 kPa) resulted in a 60% increase in dialysate adenosine, along with increases in dialysate levels of the adenosine metabolites inosine (74%), hypoxanthine (33%), and xanthine (32%). If the hypoxic hyperaemia was prevented, dialysate adenosine increased by 180% during hypoxia, and the increases in adenosine metabolites were augmented as well. During sustained hypoxia, intracoronary administration of adenosine deaminase decreased dialysate adenosine below prehypoxia levels, but did not alter the hypoxic hyperaemia. Conclusions: While ISF adenosine is increased during acute systemic hypoxia and is increased in relation to the oxygen supply: demand imbalance, consistent with a role of adenosine in hypoxic hyperaemia in the heart, adenosine is not necessary for the maintenance of a sustained increase in coronary blood flow during hypoxia.