Cardiotoxicity of a new inotrope/vasodilator drug (SK&F 94120) in the dog |
| |
Authors: | J. H. Harleman E. C. Joseph R. J. Eden T. F. Walker I. R. Major M. S. Lamb |
| |
Affiliation: | (1) SK&F Research Ltd., AL6 9AR The Frythe, Welwyn, Great Britain;(2) Present address: Asta Werke AG, Postbox 140129, D-4800 Bielefeld 14, Federal Republic of Germany |
| |
Abstract: | The cardiotoxicity and haemodynamic changes induced by IV administration of high doses of SK&F 94120, a novel positive inotrope/vasodilator, were studied in the dog. Inotropism was observed at a dose of 0.375 mg/kg. Mean blood pressure was reduced in a dose-related manner, reaching a nadir of 43.7 mm Hg at 24 mg/ kg. Heart rate was increased at doses of 1.5 mg/kg and above. ECG examination revealed a shortening of PR interval and an increase in T-wave amplitude. At doses of 15 mg/kg and above, occasional AV dissociation with accrochage were sometimes seen shortly after the start of the infusion. Ventricular extrasystoles were only seen at doses of 120 mg/kg and above. A dose-related increase in severity and incidence of haemorrhages, deposition of haemosiderin and fibroplasia were seen in the left ventricular endocardium and atrioventricular valves at doses of 15 mg/ kg and above. Focal myocardial necrosis, predominantly of the left ventricular papillary muscle, and mild periarteritis of medium-sized extramural arteries, mostly in the right atrium, were seen at doses of 45 mg/kg and above. Intimai proliferation of intra- and extramural coronary vessels was observed. A necrotising peri/panarteritis of these arteries was noted at doses of 200 and 400 mg/kg. The cardiotoxicity observed was considered to be due to the exaggerated pharmacologic effects seen at these high dose levels. |
| |
Keywords: | Toxicity Heart Dog |
本文献已被 SpringerLink 等数据库收录! |
|