Observations in Conscious Domestic Swine

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior discending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 ± 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 ± 0.38, P < 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 ± 0.36 vs. circumflex zone = 1.45 ± 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distakcircumflex epicardial flow ratio declined vs. control 1 (0.98 ± 0.14) during adenosine deaminase infusion (0.87 ± 0.17, P < 0.05). The distakcircumflex endocardial flow ratio during adenosine deaminase (0.72 ± 0.20) was unchanged vs. control 1 (0.76 ± 0.22) but was less than control 2 (0.80 ± 0.18, P < 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s). (Circ Res 53: 42-51, 1983)