Abstract
Data from our laboratory indicate that the heart reacts as a target organ in systemic hypersensitivity reactions (Capurro and Levi, 1975; Graver et al., 1983). Cardiac dysfunction observed during anaphylaxis in the guinea pig (Capurro and Levi, 1975; Zavecz and Levi, 1977) resembles that reported in humans (Bernreiter, 1959; Both and Patterson, 1970; Criep and Woehler, 1971; Petsas and Kotier, 1973; Sullivan, 1982) and is caused by mediators released intracardially and reaching the heart from the lung (Zavecz and Levi, 1977). “Cardiac anaphylaxis” (Feigen and Prager, 1969) is characterized by tachycardia, arrhythmias, contractile failure, coronary constriction, and mediator release (Capurro and Levi, 1975; Levi and Allan, 1980; Levi et al., 1982). Tachycardia and arrhythmias are caused by the release of endogenous cardiac histamine, since they are reproduced by the intracardiac administration of histamine and abolished by antihistamines (Levi and Allan, 1980; Levi et al., 1982). On the other hand, anaphylactic coronary constriction is markedly reduced by cyclooxygenase inhibitors such as indomethacin or aspirin or by thromboxane syn-thetase inhibitors such as 1-(2-isopropylphenyl)imidazole (Allan and Levi, 1981). Furthermore, the intracardiac administration of U 46619, a stable thromboxane analogue, causes coronary constriction (Allan and Levi, 1980a). Thus, prostanoate compounds, particularly thromboxane, contribute to the fall in coronary flow rate that characterizes cardiac anaphylaxis (Levi et al., 1982). Other potent coronary-constricting agents, such as platelet-activating factor (PAF, AGEPC), are also likely to contribute to anaphylactic coronary constriction (Levi et al., 1984).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Aehringhaus, U., Peskar, B.A., Wittenberg, H.R., and Wolbling, R.H., 1983, Effect of inhibition of synthesis and receptor antagonism of SRS-A in cardiac anaphylaxis, Br. J. Pharmacol. 80:73–80.
Aehringhaus, U., Dembinska-Kiéc, A., and Peskar, B. A., 1984, Effects of exogenous prostaglandins on the release of leukotriene C4-like immunoreactivity and on coronary flow in indomethacin-treated anaphylactic guinea-pig hearts, Naunyn Schmiedebergs Arch. Pharmacol. 326:368–374.
Allan, G., and Levi, R., 1980a, The cardiac effects of prostaglandins and their modification by the prostaglandin antagonist N-0164, J. Pharmacol. Exp. Ther. 214:45–49.
Allan, G., and Levi, R., 1980b, Pharmacological studies on the role of prostaglandins in cardiac hypersensitivity reactions, in: Prostaglandins in Cardiovascular and Renal Function (A. Scriabine, A. M. Lefer, and F. A. Keuhl, Jr., eds.), Spectrum, New York, pp. 223–237.
Allan, G., and Levi, R., 1981, Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro, J. Pharmacol. Exp. Ther. 217:157–161.
Anhut, H., Peskar, B.A., and Bernauer, W., 1978, Release of 15-keto-13,14-dihydro-thromboxane B2 and prostaglandin D2 during anaphylaxis as measured by radioimmunoassay, Naunyn Schmiedebergs Arch. Pharmacol. 305:247–252.
Augstein, J., Farmer, J.B., Lee, T.B., Sheard, P., and Tattersall, M.L., 1973, Selective inhibitor of slow reacting substance of anaphylaxis, Nature 245:216–217.
Bernreiter, M., 1959, Electrocardiogram of patient in anaphylactic shock, JAM.A. 170:1628–1630.
Bessin, P., Bonnet, J., Apffel, D., Soulard, C, Desgroux, L., Pelas, I., and Benveniste, J., 1983, Acute circulatory collapse caused by platelet-activating factor (PAF-Aether) in dogs, Eur. J. Pharmacol. 86:403–413.
Booth, B.H., and Patterson, R., 1970, Electrocardiographic changes during human anaphylaxis, J.AM.A. 211:627–631.
Burke, J.A., and Levi, R., 1980, Slow reacting substance of anaphylaxis (SRS-A): Direct and indirect cardiac effects, Fed. Proc. 39:389.
Burke, J.A., Levi, R., and Corey, E.J., 1981, Cardiovascular effects of pure synthetic leukotrienes C and D, Fed. Proc. 40:1015.
Burke, J.A., Levi, R., Guo, Z.-G., and Corey, E.J., 1981, Leukotrienes C4, D4 and E4: Effects on human and guinea-pig cardiac preparations in vitro. J. Pharmacol. Exp. Ther. 221:235–241.
Capurro, N., and Levi, R., 1975, The heart as a target organ in systemic allergic reactions, Circ. Res. 36:520–528.
Criep, L.H., and Woehler, T.R., 1971, The heart in human anaphylaxis, Ann. Allergy 29:399–109.
Ezeamuzie, I.C, and Assem, E.S.K., 1983, Effects of leukotrienes C4 and D4 on guinea-pig heart and the participation of SRS-A in the manifestations of guinea-pig cardiac anaphylaxis, Agents Actions 13:182–187.
Ezra, D., Boyd, L.M., Feuerstein, G., and Goldstein, R.E., 1983, Coronary constriction by leukotriene C4, D4, and E4 in the intact pig heart, Am. J. Cardiol. 51:1451–1454.
Feigen, G. A., and Prager, D. J., 1969, Experimental cardiac anaphylaxis: physiologic, pharmacologic and biochemical aspects of immune reactions in the isolated heart, Am. J. Cardiol. 24:474–491.
Feuerstein, G., Boyd, L. M., Ezra, D., and Goldstein, R. E., 1984, Effect of platelet-activating factor on coronary circulation of the domestic pig, Am. J. Physiol. 246:H466–H471.
Gateau, O., Arnoux, B., Deriaz, H., Viars, P., and Benveniste, J., 1984, Acute effects of intratracheal administration of PAF-acether (platelet-activating factor) in humans, Am. Rev. Respir. Dis. 129:A3.
Graver, L. M., Levi, R., Chenouda, A. A., Becker, C. G., and Gay, W. A., 1983, IgE-mediated hypersensitivity in human heart tissue, Circulation 68(III):322.
Guo, Z.-G., Levi, R., Graver, L.M., Robertson, D.A., and Gay, Jr., W.A., 1984, Inotropic effects of histamine in human myocardium: Differentiation between positive and negative components, J. Cardiovasc. Pharmacol. 6:1210–1215.
Hattori, Y., and Levi, R., 1984, Negative inotropic effect of leukotrienes: Leukotrienes C4 and D4inhibit calcium-dependent contractile responses in potassium-depolarized guinea-pig myocardium, J. Pharmacol. Exp. Ther. 230:646–651.
Hogaboom, G.K., Mong, S., Clark, M., and Crooke, S.T., 1983, Identification of specific leukotriene-D4 binding sites in guinea-pig heart, Pharmacologist 25:201.
Houki, S., 1973, Restoration effects of histamine on action potential in potassium-depolarized guinea-pig papillary muscle, Arch. Int. Pharmacodyn. Ther. 206:113–120.
Inui, J., and Imamura, H., 1976, Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium, Naunyn Schmiedebergs Arch. Pharmacol. 294:261–269.
Levi, R., and Allan, G., 1980, Histamine-mediated cardiac effects, in: Drug-Induced Heart Disease (M. Bristow, ed.), Elsevier/North-Holland Biomedical Press, Amsterdam, pp. 377–395.
Levi, R., and Burke, J.A., 1980, Cardiac anaphylaxis: SRS-A potentiates and extends the effects of released histamine, Eur. J. Phamacol. 62:41–49.
Levi, R., and Capurro, N., 1973, Histamine H2-receptor antagonism and cardiac anaphylaxis, in: Proceedings International Symposium on Histamine H 2-Receptor Antagonists (C. J. Wood and M. A. Simkins, eds.), S.K.&F., London, pp. 175–184.
Levi, R, and Hattori, Y.. 1985, Prostaglandin D2 and cardiac contractility: a negative inotropism secondary to coronary vasoconstriction conceals a primary positive inotropic ation, Fed. Proc. 44:6191.
Levi, R. Allan, G., and Zavecz, J.H., 1976, Prostaglandins and cardiac anaphylaxis, Life Sci. 18:1255–1264.
Levi, R. Burke, J. A., and Corey, E. J., 1982, SRS-A, leukotrienes, and immediate hypersensitivity reactions of the heart, in: Leukotrienes and Other Lipoxygenase Products, Advances in Prostaglandin, Thromboxane, and Leukotriene Research, Vol. 9 (B. Samuelsson and R. Paoletti, eds.). Raven Press. New York, pp. 215–222.
Levi, R., Burke, J.A., Guo, Z.-G., Hattori, Y., Hoppens, C.M., McManus, L.M., Hanahan, D.J., and Pinckard, R.N., 1984, Acetyl glyceryl ether phosphorylcholine (AGEPC): A putative mediator of cardiac anaphylaxis in the guinea pig, Circ. Res. 54:117–124.
Lewis, R.A., Austen, K.F., Drazen, J.M., Clark, D.A., Marfat, A., and Corey, E.J., 1980, Slow reacting substances of anaphylaxis: Identification of leukotrienes C-l and D from human and rat sources, Proc. Natl. Acad. Sci. U.S.A. 77:3710–3714.
Liebig, R., Bernauer, W., and Peskar. B.A., 1975, Prostaglandin, slow-reacting substance, and histamine release from anaphylactic guinea-pig hearts, and its pharmacological modification, Naunyn Schmiedebergs Arch Pharmacol. 289:65–76.
Michelassi, F., Landa, L., Hill, R.D., Lowenstein, E., Watkins, W.D., Petkau, A.J., and Zapol, W.M., 1982, Leukotriene D4: A potent coronary artery vasoconstrictor associated with impaired ventricular contraction, Science 217:841–843.
Michelassi, F., Castorena, G., Hill, R.D., Lowenstein, E., Watkins, W.D., Petkau, A.J., and Zapol, W.M., 1983, Effects of leukotrienes B4 and C4 on coronary circulation and myocardial contractility, Surgery 94:267–275.
Morris, H.R., Taylor, G.W., Piper, P.J., and Tippins, J.R., 1980, Structure of slow-reacting substance of anaphylaxis from guinea-pig lung, Nature 285:104–106.
Murphy, R.C, Hammarström, S., and Samuelsson, B., 1979, Leukotriene C: A slow-reacting substance from murine mastocytoma cells, Proc. Natl. Acad. Sci. U.S.A. 76:4275–4279.
Panzenbeck, M.J., and Kaley, G., 1983, Leukotriene D4 reduces coronary blood flow in the anesthetized dog, Prostaglandins 25:661–670.
Petsas, A.A., and Kotier, M.N., 1973, Electrocardiographic changes associated with penicillin anaphylaxis, Chest 64:66–69.
Pfeffer, M. A., Pfeffer, J. M., Lewis, R. A., Braunwald, E., Corey, E. J., and Austen, K. F., 1983, Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat, Am. J. Physiol. 244:H628–H633.
Rouzer, C.A., Scott, W.A., Cohn, Z.A., Blackburn, P., and Manning, J.M., 1980, Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus, Proc. Natl. Acad. Sci. U.S.A. 77:4928–4932.
Samuelsson, B., Borgeat, P., Hammarström, S., and Murphy, R. C, 1980, Leukotrienes: A new group of biologically active compounds, in: Advances in Prostaglandin and Thromboxane Research, Vol. 6 (B. Samuelsson, P. W. Ramwell, and R. Paoletti, eds.), Raven Press, New York, pp. 1–18.
Shigenobu, K., Schneider, J.A., and Sperelakis, N., 1974, Verapamil blockade of slow Na+ and Ca++ responses in myocardial cells, J. Pharmacol. Exp. Ther. 190:280–288.
Smedegaard, G., Hedqvist, P., Dahlén, S.-E. Revenäs, B., Hammarström, S., and Samuelsson. B., 1982, Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey, Nature 295:327–329.
Sullivan, T.J., 1982, Cardiac disorders in penicillin-induced anaphylaxis, association with intravenous epinephrine therapy, JAMA. 248:2161–2162.
Thyrum, P.T., 1974, Inotropic stimuli and systolic transmembrane calcium flow in depolarized guinea-pig atria, J. Pharmacol. Exp. Ther. 188:166–179.
Tritthart, H., Volkmann, R., Weiss, R., and Eibach, H., 1976, The interrelationship of calcium-mediated action potentials and tension development in cat ventricular myocardium, J. Mol. Cell. Cardiol. 8:249–261.
Vemulapalli, S., Chiu, P.J.S., and Barnett, A., 1984, Cardiovascular and renal action of platelet-activating factor in anesthetized dogs, Hypertension 6:489–493.
Woodman, O.L., and Dusting, G.J., 1983, Coronary vasoconstriction induced by leukotrienes in the anaesthetized dog, Eur. J. Pharmacol. 86:125–128.
Zavecz, J.H., and Levi, R., 1977, Separation of primary and secondary cardiovascular events in systemic anaphylaxis, Circ. Res. 40:15–19.
Zavecz, J.H., and Levi, R., 1978, Histamine-induced negative inotropism: Mediation by H1-receptors, J. Pharmacol. Exp. Ther. 206:274–280.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer Science+Business Media New York
About this chapter
Cite this chapter
Levi, R. et al. (1985). Leukotriene C4 Is Released from the Anaphylactic Heart: A Case for Its Direct Negative Inotropic Effect. In: Bailey, J.M. (eds) Prostaglandins, Leukotrienes, and Lipoxins. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4946-4_27
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4946-4_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4948-8
Online ISBN: 978-1-4684-4946-4
eBook Packages: Springer Book Archive