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Pathogenesis of coronary artery spasm induced by histamine in miniature pigs was studied angiographically in in vivo and in vitro conditions. Endothelial balloon denudation was performed and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. Regional hypercontraction of the coronary artery was documented by selective coronary arteriography, and the resulting myocardial ischemia was confirmed by ECG-ST changes. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of histamine-induced coronary constriction in the coronary spasm, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mm Hg. Histamine (10(-5) M) reduced the diameter of the coronary artery of the isolated heart by 29 +/- 4 and 67 +/- 3% (p less than 0.001) in nondenuded and denuded areas, respectively. These figures were similar to data obtained angiographically in vivo after the administration of histamine 10 micrograms/kg. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. The degree of focal constriction induced by histamine, defined as a percent of stenoses from the mean diameter of the areas of proximal and distal to the spastic site, was similar in in vivo (10 micrograms/kg i.c.) and in vitro (10(-5) M) conditions. KCl (40 mM) reduced both the denuded and nondenuded coronary artery diameter by 67 +/- 3% and 68 +/- 3% (NS), respectively. The dose-response relation of the coronary diameter to histamine was not influenced by pretreatment with the nerve transmitter blockers guanethidine (3 X 10(-6) M), atropine (10(-6) M), and tetrodotoxin (3 X 10(-7) M). Phenylephrine (10(-5) M) did not potentiate constriction of the denuded areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation.