Contrasting effects of nifedipine and adenosine on regional myocardial flow distribution and metabolism distal to a severe coronary arterial stenosis: observations in sedated, closed-chest, domestic swine.

Publisher Website
Google Scholar
Abstract
The hypothesis that intrinsic negative inotropic effects of drug used to induce coronary vasodilation distal to a severe coronary arterial stenosis may influence the extent of redistribution of transmural flow and its metabolic consequences was tested. To test this hypothesis, studies were conducted in 8 closed-chest, sedated swine with severe (82% reduction in luminal diameter) coronary arterial stenoses. Measurement of hemodynamic parameters, regional myocardial blood flow (microsphere technique), lactate metabolism and O2 consumption were made under control conditions, after 10 min of intracoronary infusion of a vasodilator distal to the stenosis and under repeat control conditions. Each animal received both intracoronary adenosine (400 .mu.g/min) and nifedipine (50 .mu.g/min). The order of drug infusion was chosen at random and a control period separated administration of each. In response to nifedipine there was no significant change in the group mean (.+-. SD) value of endocardial flow (1.21 .+-. 0.34 to 1.29 .+-. 0.61 ml/min .cntdot. g-1) distal to the stenosis. In contrast, epicardial flow increased in comparison with control in response to nifedipine (1.30 .+-. 0.58 to 1.79 .+-. 0.74 ml/min .cntdot. g-1; P < 0.05). Regional myocardial O2 consumption (MVO2) declined in comparison with control in response to nifedipine (14.0 .+-. 4.2 to 11.1 .+-. 5.0 ml/min .cntdot. 100 g-1; P < .05). Regional lactate extraction did not change in comparison with control during infusion of nifedipine (18.2 .+-. 22.4 vs. 11.7 .+-. 16.8). In response to adenosine, endocardial blood flow distal to the stenosis declined in comparison with control (1.25 .+-. 0.53 to 1.07 .+-. 0.38 ml/min .cntdot. g-1; P < 0.05), while epicardial flow increased (1.31 .+-. 0.55 to 2.26 .+-. 0.59 ml/min .cntdot. g-1; P < 0.01). Regional MVO2 also tended to decline in comparison with control in response to adenosine (13.4 .+-. 4.9 to 11.7 .+-. 2.9 ml/min .cntdot. 100 g-1) and was significantly (P < 0.05) reduced in comparison with postintervention control (14.6 .+-. 4.2 ml/min .cntdot. 100 g-1). In contrast to nifedipine, adenosine caused a significant decline in regional lactate extraction in comparison with control (12.7 .+-. 23.2% to -40.6 .+-. 55.0%; P < 0.01). Thus, administration of nifedipine, a negative inotropic agent, resulted in a decline in regional MVO2, increased epicardial blood flow with variable effects on endocardial flow distal to the stenosis and no evidence of de novo or worsening ischemia, even in animals in which endocardial flow decreased. In contrast, coronary vasodilation induced by adenosine resulted in significant flow redistribution away from endocardial layers distal to the stenosis, with associated metabolic evidence of de novo or worsening myocardial ischemia. The results of the study support the proposed hypothesis.

This publication has 25 references indexed in Scilit: