The object of this study was to test the hypothesis that administration of both
serotonin S2 and
thromboxane A2-prostaglandin H2 (
PGH2) receptor antagonists provides significant protection against
epinephrine-induced cyclic coronary artery flow variations in open chest, anesthetized dogs with severe proximal
coronary artery stenosis and endothelial injury. Three groups of dogs were studied. In Group 1 (n = 7) and Group 2 (n = 6), cyclic coronary flow variations were initiated after placement of a concentric constrictor around the left anterior descending coronary artery and were abolished by administration of either a
thromboxane A2-prostaglandin H2 receptor antagonist, SQ29,548 (SQ) (Group 1), or a
serotonin S2 receptor antagonist, LY53,857 (LY) (Group 2). Cyclic flow variations were restored with an
epinephrine infusion and the second antagonist (LY for Group 1; SQ for Group 2) was administered to abolish
epinephrine-induced cyclic flow variations. The rate of
epinephrine infusion was increased until cyclic coronary flow variations returned (n = 8) or significant hemodynamic changes occurred. Plasma
epinephrine concentrations were determined during a control period of cyclic coronary flow variations, after
epinephrine restored cyclic flow variations in the presence of either SQ or LY, and again after
epinephrine restored cyclic flow variations in the presence of both SQ and LY. A third group of dogs (Group 3, n = 9) required both SQ and LY to eliminate the initial cyclic coronary flow variations and infused
epinephrine restored cyclic flow variations (n = 8). Plasma
epinephrine concentrations were determined during a control period and after cyclic coronary flow variation restoration with
epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)