ACUTE AND CHRONIC EFFECTS OF DEXFENFLURAMINE ON THE PORCINE CORONARY-ARTERY

Experiments were designed to verify whether or not acute or chronic ex posure to dexfenfluramine favors the occurrence of coronary vasospasm in vivo or in vitro. Rings of left anterior and left circumflex porcin e coronary artery, with and without endothelium, were studied in conve ntional organ chambers for the measurement of isometric force. The don or pigs were divided into two groups: controls and animals fed for 4 w eeks with dexfenfluramine. In each group, one-half of the animals unde rwent balloon denudation of the left anterior descending coronary arte ry at the beginning of the study. Coronary angiography was performed a t the time of denudation and, in all animals, during the 3rd week of t he study. Acutely, dexfenfluramine at concentrations higher than 10(-5 ) M caused contractions which were blunted by the presence of the endo thelium and inhibited by indomethacin (an inhibitor of cyclooxygenase) . Chronic treatment with dexfenfluramine did not affect coronary diame ter and did not alter the response to intracoronary infusion of seroto nin. Chronic treatment with dexfenfluramine reduced the contractions o f rings without endothelium to serotonin, but not those to norepinephr ine or endothelin. It did not affect endothelium-dependent relaxations in the absence or presence of pertussis toxin to serotonin, UK14304 ( alpha-2 adrenergic agonist), adenosine diphosphate or aggregating plat elets. Chronic treatment with dexfenfluramine did not modify relaxatio ns of rings without endothelium to SIN-1 (nitric oxide donor; the acti ve metabolite of molsidomine) or adenosine diphosphate. These findings do not support the hypothesis that acute or chronic exposure to dexfe nfluramine favors the occurrence of coronary vasospasm.