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.
This study tested the hypothesis that intrinsic negative inotropic effects of a 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. To test this hypothesis, studies were conducted in eight 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 oxygen consumption were made (1) under control conditions, (2) after 10 min of intracoronary infusion of a vasodilator distal to the stenosis, and (3) under repeat control conditions. Each animal received both intracoronary adenosine (400 micrograms/min) and nifedipine (50 micrograms/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 X 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 X g-1; p less than .05). Regional myocardial oxygen consumption (MVO2) declined in comparison with control in response to nifedipine (14.0 +/- 4.2 to 11.1 +/- 5.0 ml/min X 100 g-1; p less than .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 X g-1; p less than .05), while epicardial flow increased (1.31 +/- 0.55 to 2.26 +/- 0.59 ml/min X g-1; p less than .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 X 100 g-1) and was significantly (p less than .05) reduced in comparison with postintervention control (14.6 +/- 4.2 ml/min X 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 less than .01). Thus, administration of nifedipine, a negative inotropic agent, resulted in (1) a decline in regional MVO2, (2) increased epicardial blood flow with variable effects on endocardial flow distal to the stenosis, and (3) no evidence of de novo or worsening ischemia, even in animals in which endocardial flow decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003251:Constriction, Pathologic; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology*; D010101:Oxygen Consumption; D051381:Rats; D013552:Swine
D009543:Nifedipine; D000241:Adenosine