Abstract
Coronary vasodilator responses were studied after bolus (0.2 ml) intracoronary injection of adenosine (1-5000 .mu.M), or after coronary artery occlusion (5-30 s) to determine if they are modified over a range from mild to severe hypoxia [outflow O2 tension (PO2v) = 119 .+-. 9 to 10 .+-. 2 (mean .+-. standard error of the mean) torr]. The vasculature of 10 isolated, paced (240 beats/min), nonworking guinea pig hearts was perfused by the Langendorff technique with a fortified Krebs-Ringer solution at 37.5.degree. C and at a constant pressure of 55 torr. Graded hypoxia was produced by randomly altering perfusate P[partial pressure]O2 to 1 of 5 predetermined levels. Individually maximal hypoxia, maximal adenosine injection and 30 s occlusion increased vascular conductance by 98, 100 and 98%, respectively. At constant myocardial O2 consumption (M.ovrhdot.VO2), PO2v was inversely proportional to baseline conductance (r = 0.42, P < 0.01); during normoxia (PO2v = 119 torr) log-dose adenosine concentration and occlusion period were directly proportional to peak conductance (r = 0.78, P < 0.01; r = 0.73, P < 0.01). Low doses of adenosine or short occlusions significantly shifted the conductance intercept to higher values but did not change individual PO2v vs. conductance slopes. Similar results were found in the relationship between PO2v and overflow volume after adenosine injection or occlusion. The excess volume flow with low doses of adenosine and the volume of reactive hyperemia were unaffected by PO2v when M.ovrhdot.VO2 was unchanged. As hypoxia became more severe and M.ovrhdot.VO2 decreased, reactive hyperemia decreased and the flow debt increased. Adenosine or coronary occlusion produces additive, noninteractive coronary vasodilation in the presence of tissue hypoxia. As conductance rises, the common receptors for endogenous and exogenous adenosine apparently become increasingly saturated.