Serotonin S2 and thromboxane A2-prostaglandin H2 receptor blockade provide protection against epinephrine-induced cyclic flow variations in severely narrowed canine coronary arteries.
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)
Ashton
J H
JH
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Golino
P
P
McNatt
J M
JM
Buja
L M
LM
Willerson
J T
JT
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000139:chemically induced / Q000188:drug therapy*; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000097:blood; D004873:Ergolines / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D012702:Serotonin Antagonists / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004873:Ergolines; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D012702:Serotonin Antagonists; D015016:Yohimbine; C045749:SQ 29548; C032663:LY 53857; D004837:Epinephrine