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

  • Allergy, Histamine and Kinins
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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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References

  1. J. P. Trzeciakowski and R. Levi,Reduction of ventricular fibrillation threshold by histamine: resolution into separate H 1-and H 2-mediated components. J. Pharmacol. Exp. Ther.223, 774–783 (1982).

    Google Scholar 

  2. R. Levi, D. A. A. Owen and J. Trzeciakowski,Actions of histamine on the heart and vasculature. InPharmacology of histamine receptors. (Eds. C. R. Ganellin and M. E. Parsons) pp. 236–297. Wright PSG, London 1982.

    Google Scholar 

  3. R. W. Gristwood, D. A. A. Owen, P. Romanec and K. A. Sampford,Histamine and myocardial dysfunction. InFrontiers in histamine research. (Eds. C. R. Ganellin and J. C. Schwartz) pp. 309–315. Pergamon Press, Oxford 1985.

    Google Scholar 

  4. S. Dai,Effects of ranitidine and cimetidine on experimentally induced ventricular arrhythmias in anaesthetized rats. Agents and Actions17, 460–465 (1986).

    Google Scholar 

  5. S. Dai,Ventricular histamine concentrations and arrhythmias during acute myocardial ischaemia in rats. Agents and Actions21, 66–71 (1987).

    Google Scholar 

  6. S. Dai and C. W. Ogle,Ventricular histamine concentrations and mast cell counts in the rat heart during acute ischaemia. Agents and Actions29, 138–143 (1990).

    Google Scholar 

  7. S. Dai,Histamine enhances hypoxia-induced ventricular arrhythmias in isolated rat hearts. Clin. Exp. Pharmacol. Physiol.16, 925–931 (1989).

    Google Scholar 

  8. F. L. Pearce, H. Ali, K. E. Barrett, A. D. Befus, J. Bienenstock, J. Brostoff, M. Ennis, K. C. Flint, N. McI. Johnson, K. B. P. Leung and P. T. Peachell,Mast cell heterogeneity differential responsitivity to histamine liberators and anti-allergic drugs. InFrontiers in histamine research. (Eds. C. R. Ganellin and J. C. Schwartz) pp. 411–421. Pergamon Press, Oxford 1985.

    Google Scholar 

  9. T. I. Florjanc and F. Erjavec,Alterations in histamine levels in the rat induced by compound 48/80. Agents and Actions20, 194–197 (1987).

    Google Scholar 

  10. F. L. Pearce,Mast cell heterogeneity. Trends Pharmacol. Sci.44, 165–167 (1983).

    Google Scholar 

  11. D. M. Philbin, J. Moss, C. E. Rosow, C. W. Akins and J. L. Rosenberger,Histamine release with intravenous narcotics: Protective effects of H 1-and H 2-receptor antagonists. Klin. Wochenschr.60, 1056–1059 (1982).

    Google Scholar 

  12. W. Lorenz and A. Doenicke,H 1 and H 2 blockade: A prophylactic principle in anesthesia and surgery against histamine-release responses of any degree of severity: Part I New Engl. Reg. Allergy Proc.6, 37–57 (1985).

    Google Scholar 

  13. E. Inada, D. M. Philbin, V. Machaj, J. Moss, M. N. D'Ambra, C. E. Rosow and C. W. Akins,Histamine antagonists and d-tubocurarine-induced hypotension in cardiac surgical patients. Clin. Pharmac. Ther.40, 575–580 (1986).

    Google Scholar 

  14. M. Tryba, F. Zevounou and M. Zenz,Prevention of histamine-induced cardiovascular reactions during the induction of anaesthesia following premedication with H 1-+H 2-antagonists I. M. Br. J. Anaesth.58, 478–482 (1986).

    Google Scholar 

  15. W. Lorenz and A. Doenicke,H 1 and H 2 blockade: A prophylactic principle in anaesthesia and surgery against histamine-release responses of any degree of severity: Part II. New Engl. Allergy Proc.6, 174–193 (1985).

    Google Scholar 

  16. R. W. Brimblecombe, D. A. A. Owen and M. E. Parsons,The cardiovascular effects of histamine in laboratory animals. Agents and Actions4, 191–192 (1974).

    Google Scholar 

  17. C. A. Papacostas, E. R. Loew and G. B. West,Studies on the toxicology of a histamine liberator, compound 48/80. Arch. Int. Pharmacodyn.120, 353–362 (1959).

    Google Scholar 

  18. E. Angaard and K. Strandberg,Efflux of prostaglandin E 2 from cat paws perfused with compound 48/80. Acta Physicol. Scand.,82, 333–344 (1971).

    Google Scholar 

  19. K. Strandberg and B. Uvnas,Purification and properties of the slow reacting substance formed in the cat paw perfused with compound 48/80. Acta Physiol. Scand.82, 358–374 (1971).

    Google Scholar 

  20. S. Dai,A study of the actions of histamine on the isolated rat heart. Clin. Exp. Pharmacol. Physiol.3, 359–367 (1976).

    Google Scholar 

  21. A. J. Lewis and P. Eyre,Some cardiorespiratory effects of histamine, 5-hydroxytryptamine, and compound 48/80 in the calf. Can. J. Physiol. Pharmacol.50, 545–553 (1972).

    Google Scholar 

  22. R. Levi, M. A. Beaven, R. D. Luskind, C.-H. Lee, J. Trzeciakowski and W. A. Gay Jr.,Release of cardiac histamine by chemicals and drugs: Effects and complications. Fed. Proc.39, A642 (1980).

    Google Scholar 

  23. H. Ali and F. L. Pearce,Isolation and properties of cardiac and other mast cells from the rat and guinea-pig. Agents and Actions16, 138–140 (1985).

    Google Scholar 

  24. P. F. Mannaioni,Physiology and pharmacology of cardiac histamine, revisited. InFrontiers in histamine research. (Eds. C. R. Ganellin and J. C. Schwartz) pp. 301–304. Pergamon Press, Oxford 1985.

    Google Scholar 

  25. P. Eyre and N. Chand,Histamine receptor mechanisms of the lung. InPharmacology of histamine receptors. (Eds. C. R. Ganellin and M. E. Parsons) pp. 298–322. Wright PSG, London 1982.

    Google Scholar 

  26. H. Y. A. Lau and F. L. Pearce,Dual effect of antihistamines on rat peritoneal mast cells: induction and inhibition of histamine release. Agents and Actions16, 176–178 (1985).

    Google Scholar 

  27. H. Y. A. Lau and F. L. Pearce,Effects of antihistamines on isolated mast cells from the rat, guinea pig and man. Agents and Actions18, 107–109 (1986).

    Google Scholar 

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  1. S. Dai

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

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

    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

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