Myocardial Oxygen Consumption Modulates Adenosine Formation by Canine Right Ventricle in Absence of Hypoxia

Abstract

Myocardial adenosine formation varies with myocardial oxygen consumption (MVO2), but whether concurrent hypoxia is required for adenosine formation is uncertain. Changes in right coronary (RC) perfusion pressure (RCP) produce directionally similar alterations in right ventricular (RV) MVO2and in RC venous PO2 (PvO2), an index of myocardial P O2. RCP was varied in 10 anesthetized, open chest dogs to determine if, under these conditions, RV formation of adenosine would increase with MVO2in absence of myocardial hypoxia. Dialysis probes were implanted in the mid myocardium of RV free wall for collecting dialysate samples for HPLC analyses to estimate interstitial adenosine and other purines. Coronary venous blood was sampled from a superficial vein draining the RC artery (RCA) perfusion territory. At 115±3 mmHg baseline RCP, RC blood flow (RCBF)=0.51±0.04 ml/min/g, MVO2=4.6±0.5 ml/min/100 g, PvO2=34±1.5 mmHg, and dialysate adenosine=0.27±0.03μM. When RCP was lowered to 61±1 mmHg by adjusting an occluder on the proximal RCA, RCBF decreased to 0.36±0.03 ml/min/g, MVO2fell to 3.7±0.4 ml/min/100 g, lactate uptake remained positive, PvO2fell to 30±1.7 mmHg, and dialysate adenosine decreased to 0.20±0.03μM. Reactive hyperemia of 1.25±0.13 ml/min/g was observed when the RCA constriction was released, although dialysate adenosine had fallen. When RCP was elevated to 164±2 mmHg by inflating a balloon catheter in the descending aorta, RCBF increased to 0.70±0.06 ml/min/g, MVO2increased to 5.8±1.0 ml/min/100 g, PvO2rose to 39±2.3 mmHg, and dialysate adenosine increased to 0.33±0.04μM. These data indicate that (1) RV oxygen demand varies with RCP; (2) if RV ischemia is absent, myocardial adenosine formation is modulated by MVO2, with no requirement for hypoxia; (3) pressure–flow autoregulation is relatively ineffective in the RC circulation, where adenosine does not mediate and may even blunt autoregulation.