Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Effects of a new adrenergic β-blocking agent, Kö 1400 on the canine heart-lung preparation supported by a donor dog and the perfused hindlimb preparation of the dog
Yoshito NAKAGAWAKeisuke TAKEDAYumi KATANOTokumasa TSUKADAIssei MATSUBARAHiroshi SAKURAIShoichi IMAITakeshi OTORII
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1977 Volume 73 Issue 4 Pages 411-421

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Abstract
Using the canine heart-lung preparation supported by a donor, effects of a new adrenergic β-blocking agent, dl-1-(tert. butylamino)-3-[(2-propinyloxy) phenoxy]-2-propanol hydrochloride (Kö 1400), on cardiac function, myocardial metabolism, and coronary circulation were studied and compared with those of propranolol. Effects of this substance on the peripheral vascular bed were also studied in the perfused hindlimb preparation of the dog. Kö 1400 produced a positive inotropic and chronotropic effect. Mechanical efficiency of the heart improved after Kö 1400, while it lessened after propranolol. A decrease in the coronary flow was observed in association with a slight increase in myocardial O2 consumption, indicating that the substance exerted a direct constrictive effect on the coronary vasculature. As a β-blocker, Kö 1400 was found to be 2-3 times more effective than propranolol. The uptake of the free fatty acid (FFA) by the heart was increased by Kö 1400 and the myocardial redox potential improved. In the perfused hindlimb preparation, intraarterial injection of Kö 1400 resulted in a transient increase of the femcral blood flow for a decrease in the flow followed by a sustained decrease. With repeated administration a marked tachyphylaxis was observed.
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