Interstitial purine metabolites and lactate during regional myocardial hypoxia

Objective: Adenosine is a well known vasodilator believed to contribute to metabolic adjustments of the coronary circulation. The purpose of this study was to assess changes in interstitial fluid adenosine, adenosine metabolites, and lactate during prolonged regional, non-ischaemic myocardial hypoxia. Methods: To induce regional hypoxia, the left anterior descending coronary artery of anaesthetised dogs (n=9) was perfused at constant pressure (100 mm Hg) with deoxygenated blood (PO2≍2.6 kPa) for 60 min via an extracorporeal shunt. Cardiac interstitial fluid was sampled by cardiac microdialysis, using dialysate metabolite levels as indices of interstitial fluid concentrations. Results: During hypoxia, coronary blood flow increased 3.9-fold, while myocardial oxygen consumption was maintained relatively constant. There were no changes in global cardiac function, systemic arterial pressure, or heart rate during regional hypoxia, indicating that the hypoxic stimulus did not augment sympathetic nervous system activity. Dialysate adenosine was not increased at any point of the hypoxic period, but was decreased by 25 min hypoxia. Dialysate levels of inosine, hypoxanthine, and xanthine were increased transiently during the first 10 min of hypoxia while there was a sustained increase in dialysate lactate. In the presence of erythro-9-(2-hydroxy-3-nonyl) adenine, an adenosine deaminase inhibitor, adenosine was the predominant purine metabolite and increased transiently during hypoxia. Conclusions: Flux through the adenosine production and degradation pathways is transiently increased during hypoxia. However, the lack of an increase in interstitial fluid adenosine does not support a role for adenosine in the sustained hyperaemic response to regional myocardial hypoxia. Cardiovascular Research 1993; 27:1498-1503