INTERSTITIAL PURINE METABOLITES AND LACTATE DURING REGIONAL MYOCARDIAL HYPOXIA

Objective: Adenosine is a well known vasodilator believed to contribut e to metabolic adjustments of the coronary circulation. The purpose of this study was to assess changes in interstitial fluid adenosine, ade nosine metabolites, and lactate during prolonged regional, non-ischaem ic myocardial hypoxia. Methods: To induce regional hypoxia, the left a nterior descending coronary artery of anaesthetised dogs (n=9) was per fused at constant pressure (100 mm Hg) with deoxygenated blood (PO2 al most-equal-to 2.6 kPa) for 60 min via an extracorporeal shunt. Cardiac interstitial fluid was sampled by cardiac microdialysis, using dialys ate metabolite levels as indices of interstitial fluid concentrations. Results: During hypoxia, coronary blood flow increased 3.9-fold, whil e myocardial oxygen consumption was maintained relatively constant. Th ere were no changes in global cardiac function, systemic arterial pres sure, or heart rate during regional hypoxia, indicating that the hypox ic stimulus did not augment sympathetic nervous system activity. Dialy sate adenosine was not increased at any point of the hypoxic period, b ut was decreased by 25 min hypoxia. Dialysate levels of inosine, hypox anthine, and xanthine were increased transiently during the first 10 m in of hypoxia while there was a sustained increase in dialysate lactat e. In the presence of erythro-9-(2-hydroxy-3-nonyl) adenine, an adenos ine deaminase inhibitor, adenosine was the predominant purine metaboli te and increased transiently during hypoxia. Conclusions: Flux through the adenosine production and degradation pathways is transiently incr eased during hypoxia. However, the lack of an increase in interstitial fluid adenosine does not support a role for adenosine in the sustaine d hyperaemic response to regional myocardial hypoxia.