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Research ArticleArticle

DROMOTROPIC EFFECTS OF OPTICAL ISOMERS OF BETA BLOCKERS ON THE CROSS-CIRCULATED CANINE ATRIOVENTRICULAR NODE PREPARATION

TOSHIHIKO IIJIMA, KEITARO HASHIMOTO, NORIO TAIRA and KOROKU HASHIMOTO
Journal of Pharmacology and Experimental Therapeutics July 1973, 186 (1) 145-151;
TOSHIHIKO IIJIMA
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KEITARO HASHIMOTO
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NORIO TAIRA
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KOROKU HASHIMOTO
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Abstract

The effects of l-norepinephrine (l-NE) and both optical isomers of propranolol and alprenolol on atrioventricular (A-V) conduction were studied in the isolated and cross-circulated A-V node preparation of the dog (consisting of the right atrium and the ventricular septum). The A-V conduction time was measured by an A-V interval graph to which atrial and ventricular electrograms were provided. The right atrium was paced at 2.5 Hz, at which the A-V conduction time was about 125 msec. All drugs were injected into the posterior septal (A-V node) artery. l-NE (0.01-3 nmol) caused does-dependent decreases in the A-V conduction time down to 80 msec and in higher doses caused A-V nodal tachycardia. The l-isomers of propranolol and alprenolol fully antagonized the positive dromotropic effect of l-NE at an antagonist/agonist ratio of 30, while their d-isomers antagonized only about 10% of the positive dromotropic effect at that ratio. When compared at the dose level causing 50% antagonism, the d-isomers were 100 to 300 times less potent than the l-isomers. In doses above 100 nmol, all of these compounds caused an increase in the A-V conduction time, which was reversible. In this dose range, there were no significant differences in negative dromotropic action between the l- and the d-isomers or between propranolol and alprenolol. This indicates that the negative dromotropic action does not relate to beta adrenergic blockade.

Footnotes

    • Received September 6, 1972.
    • Accepted March 19, 1973.
  • © 1972 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 186, Issue 1
1 Jul 1973
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Research ArticleArticle

DROMOTROPIC EFFECTS OF OPTICAL ISOMERS OF BETA BLOCKERS ON THE CROSS-CIRCULATED CANINE ATRIOVENTRICULAR NODE PREPARATION

TOSHIHIKO IIJIMA, KEITARO HASHIMOTO, NORIO TAIRA and KOROKU HASHIMOTO
Journal of Pharmacology and Experimental Therapeutics July 1, 1973, 186 (1) 145-151;

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Research ArticleArticle

DROMOTROPIC EFFECTS OF OPTICAL ISOMERS OF BETA BLOCKERS ON THE CROSS-CIRCULATED CANINE ATRIOVENTRICULAR NODE PREPARATION

TOSHIHIKO IIJIMA, KEITARO HASHIMOTO, NORIO TAIRA and KOROKU HASHIMOTO
Journal of Pharmacology and Experimental Therapeutics July 1, 1973, 186 (1) 145-151;
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