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The role of histamine in cardiac anaphylaxis; characterization of histaminergic H1-and H2-receptor effects

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Summary

Histamine is known to act as a direct stimulator. In the heart, two types of histamine receptors are present: H1- and H2-receptors. H2-receptors cause an increase in heart rate and contractility as well as coronary vasodilatation, whereas H1-receptors mediate chronotropic effects and coronary vasoconstriction. During anaphylactic states, histamine is released from cardiac tissue where it is stored in large amounts.

The present study was designed to ascertain the role of cardiac histamine release during cardiac anaphylaxis. In guinea pigs, sensitization was produced by intraperitoneal administration of ovalbumin (O). 14 days after sensitization, the effects of an intracoronary infusion of O (1.1×10−8 moles/min) were tested in the isolated perfused heart preparation. The response of the sensitized hearts to O was characterized by a rapid increase in contractile force (dp/dtmax 120% above baseline after 30 s), followed by a decrease reaching a minimum of 30% below bascline after 10 min. Over the same time range, the heart rate first increased (+24%), then decreased, concurrent with the appearance of arrhythmias, before reaching baseline level. Coronary flow decreased (−40% after 1 min) and finally stabilized at a new steady state (−20% below baseline).

It is concluded that histamine might be an important mediator of these effects, since in the presence of H2-receptor blockade with cimetidine 96.2×10−7 moles/min), the positive inotropic and chronotropic effects were completely antagonized. Furthermore, a decrease in heart rate and contractility occurred (−25% and −50% after 2 min, respectively). Finally, coronary constriction was intensified and resulted in coronary spasm with flow rates approaching zero after 1 min. On the other hand, additional H1-receptor blockade with dimetinden (2.5×10−9 moles/min) did not antagonize the development of coronary spasm significantly and did not influence the decrease in contractility and the occurrence of bradycardia. The results obtained therefore suggest that besides histamine, other mediators are involved in the development of cardiac anaphylaxis. The cardiodepressant actions of these anaphylactic mediators were revealed by the H2-receptor blockade.

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References

  1. Achringhaus U, Peskar BA, Wittenberg HR, Wölbling RH (1983) Effect of inhibition of synthesis and receptor antagonism of SRS-A in cardiac anaphylaxis. Br J Pharmacol 80:73–80

    PubMed  Google Scholar 

  2. Allan G, Zavez JH, Levi R (1977) Release of prostaglandins and SRS-A during cardiac anaphylaxis. Bull NY Acad Med 53:304

    Google Scholar 

  3. Allan G, Levi R (1980) Pharmacological studies on the role of prostaglandins in cardiac hypersensitivity reactions. In: Scriabine A, Lefer AM, Kuehl Jr (eds) Prostaglandins in cardiovascular and renal function. Spectrum Press, New York, pp 223–237

    Google Scholar 

  4. Allan G, Levi R (1981) Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro. J Pharmacol Ther 217:157–161

    Google Scholar 

  5. Anhut H, Bernauer W, Peskar BA (1977) Radioimmunological determination of thromboxane release in cardiac anaphylaxis. Europ J Pharmacol 44:85–88

    Google Scholar 

  6. Assem ES, Machado FR, Ghanem NS (1986) Cardiac mast cells: Partial purification of guinea pig atrial mast cells and release from them of histamine and leukotriene C4 by immune and nonimmune stimuli. Agents Actions 18:167–171

    PubMed  Google Scholar 

  7. Baumann G, Schrader J, Gerlach E (1981) Inhibitory actions of adenosine on histamine- and dopamine-stimulated cardiac contractility and adenylate cyclase in guinea pigs. Circ Res 48:259–266

    PubMed  Google Scholar 

  8. Baumann G, Felix SB, Schrader J, heidecke CD, Riess G, Erhardt WD, Ludwig L, Loher U, Sebening F, Blömer H (1981) Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system. Res Exp Med 179:81–98

    Google Scholar 

  9. Baumann G, Felix SB, Riess G, Loher U, Ludwig L, Blömer H (1982) Effective stimulation of cardiac contractility and myocardial metabolism by Impromidine and Dimaprit-two new H2-agonistic compounds-in the surviving, catecholamine-insensitive myocardium after coronary occlusion. J Cardiovasc Pharmacol 4:542–553

    PubMed  Google Scholar 

  10. Baumann G, Loher U, Felix SB, Heidecke CD, Riess G, Ludwig L, Blömer H (1982) Deleterious effects of Cimetidine in the presence of histamine on coronary circulation. Possible clinical implications in anaphylactic states in individuals with coronary heart disease. Res Exp Med 180:209–213

    Google Scholar 

  11. Baumann G, Felix SB, Heidecke CD, Ricss G, Loher U, Ludwig L, Blömer H (1982) Apparent superiority of H2-receptor stimulation and simultaneous β-blockade over conventional treatment with β-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of Impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium. Agents Actions 15:216–228

    Google Scholar 

  12. Bristow MR, Ginsburg R, Harrison DC (1984) Histamine and the human heart: The other receptor system. Am J Cardiol 49:249–251

    Google Scholar 

  13. Feigen GA, Prager DJ (1969) Experimental cardiac anaphylaxis: Physiologic, pharmacologic and biochemical aspects of immune reactions in the isolated heart. Am J Cardiol 24:474–491

    PubMed  Google Scholar 

  14. Flynn SB, Johnston BM, Owen DAA (1977) The cardiovascular response to dimaprit, a selective histamine H2-receptor agonist. J Pharmacol 61:101

    Google Scholar 

  15. Ginsburg R, Bristow MR, Kantrowitz N, Baim DS, Harrison DC (1981) Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris. Am J Cardiol 102:819–822

    Google Scholar 

  16. Greeff K, Benfey BG, Bokelmann A (1959) Anaphylaktische Reaktionen am isolierten Herzvorhofpräparat des Meerschweinchens und ihre Becinflussung durch Antihistaminika, BOL, Dihydergotamin und Reserpin. Nauny-Schmiedeberg's Arch Path Pharmakol 236:421–434

    Google Scholar 

  17. Greeff K, Heeg E (1964) Die anaphylaktische Reaktion perfundierter Herzpräparate, isolierter Herzvorhofpräparate und isolierter Papillarmuskeln. Arch int Pharmacodyn 149, No 1-2:136–152

    PubMed  Google Scholar 

  18. Guidotti A, Zilletti L, Giotti A (1967) Correlation between mastcell population and histamine concentration of the guinea-pig heart. Sperimentale 117:113–123

    PubMed  Google Scholar 

  19. Levi R (1972) Effects of exogenous and immunologically released histamine on the isolated heart: A quantitative comparison. J Pharmacol Exp Ther 182:227–238

    PubMed  Google Scholar 

  20. Levi R, Kuye Jo (1974) Pharmacological characterization of cardiac histamine receptors: Sensitivity to H1-receptor anatogonists. Eur J Pharmacol 27:330–338

    PubMed  Google Scholar 

  21. Levi R, Burke J (1980) Cardiac anaphylaxis: SRS-A potentiates and extends the effects of the released histamine. Eur J Pharmacol 62:41–49

    PubMed  Google Scholar 

  22. Levi R, Burke J (1982) SRS-A, leukotrienes, and immediate hypersensitivity reactions of the heart. In: Samuelsson B, Paoletti R (eds) Leukotrienes and other lipoxygenase products. Raven Press. New York, pp 215–222

    Google Scholar 

  23. Levi R, Owen DAA, Trzeciakowsky J (1982) Actions of histamine on the heart and vasculature. In: Ganellin CR, Parsons M (eds) Pharmacology of histamine receptors. Wright and Sons Ltd. London, pp 236–297

    Google Scholar 

  24. Levi R, Burke JA, Guo ZG, Hattori Y, Hoppen CM, McManus LM, Hanahan DJ, Pinckard RN (1984) Acetyl Glyceryl Ether Phosphorylcholine (AGEPC) a putative mediator of cardiac anaphylaxis in guinea pig. Circ Res 54:117–124

    PubMed  Google Scholar 

  25. Liebig R, Bernauer W, Peskar BA (1975) Prostaglandin, slow-reacting substance, and histamine release from anaphylactic guinea pig hearts and its pharmacological modification. Arch Pharmacol 289:65–76

    Google Scholar 

  26. McNeil JH (1984) Histamine and the heart. Can J Physiol Pharmacol 62:720–726

    PubMed  Google Scholar 

  27. Schrader J, Gerlach E (1976) Compartmentation of cardiac adenine nucleotides and formation of adenosine. Pflügers Arch 367:129–135

    Google Scholar 

  28. Weinerowski P, Wittmann G, Achringhaus N, Peskar BA (1985) Pharmacological modification of leukotriene release and coronary constrictor effect in cardial anaphylaxis. Adv Prostagland Thrombox Leukotriene 13:47–50

    Google Scholar 

  29. Wolff AA, Levi R (1986) Histamine and cardiac arrhythmias. Circ Res 58:1–16

    PubMed  Google Scholar 

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This paper is dedicated to Prof. Blömer on the occasion of his 65th birthday

Data presented in this paper are part of the doctoral thesis by Dr. S. Helmus

Supported by grant Fe 250/1-1 from Deutsche Forschungsgemeinschaft (DFG)

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Felix, S.B., Baumann, G., Helmus, S. et al. The role of histamine in cardiac anaphylaxis; characterization of histaminergic H1-and H2-receptor effects. Basic Res Cardiol 83, 531–539 (1988). https://doi.org/10.1007/BF01906682

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  • DOI: https://doi.org/10.1007/BF01906682

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