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Circulatory depression and ventricular arrhythmias induced by compound 48/80 in anaesthetized rats

Agents and Actions volume 34, pages 316–323 (1991)Cite this article

Abstract

The effects of graded doses of compound 48/80 on various cardiovascular and respiratory parameters were studied in pentobarbitone-anaesthetized rats. Following intravenous injections, this compound significantly depressed the mean blood pressure (MBP), left ventricular pressure (LVP) and dLVP/dtmax, and caused ventricular tachycardia (VT) or fibrillation (VF) and death. Heart rate (HR) response were variable, and there were no marked changes in airway resistance or blood gases. Pretreatment of the animals with either cimetidine or diphenhydramine significantly prolonged the time of onset of VT/VF but failed to alter the changes in other circulatory variables. A combination of cimetidine and diphenhydramine significantly alleviated the decreases in MBP and LVP and prevented the occurrence of VT/VF. It is suggested that the circulatory depression and the occurrence of ventricular arrhythmias following the administration of compound 48/80 result from activation of H1- and H2-receptors by elevated blood histamine levels due to release of the amine from tissues.

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Author notes

  1. S. Dai

    Present address: Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, V6T 1W5, Vancouver, B. C., Canada

Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Hong Kong, 5 Sassoon Road, Hong Kong

    S. Dai

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  1. S. Dai
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Dai, S. Circulatory depression and ventricular arrhythmias induced by compound 48/80 in anaesthetized rats. Agents and Actions 34, 316–323 (1991). https://doi.org/10.1007/BF01988722

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  • DOI: https://doi.org/10.1007/BF01988722

Keywords

  • Histamine
  • Cimetidine
  • Ventricular Tachycardia
  • Ventricular Arrhythmia
  • Marked Change