Summary
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1.
In the guinea pig heart-lung-preparation (HLP) anaphylactic bronchospasm was not greatly affected by mepyramine (2–40 μg/ml blood), adrenaline (0.1 and 1 μg/ml), noradrenaline (0.1 μg/ml) or papaverine (100 μg/ml) but was completely abolished by combining mepyramine with the lower dose of adrenaline. A partial antagonism was achieved by the combined action of mepyramine and papaverine which became complete when adrenaline was added.
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2.
Bronchospasm due to histamine was completely prevented by mepyramine, but only partially antagonized by both adrenaline doses used.
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3.
The increase of pulmonary vascular resistance in anaphylaxis was not inhibited by the highest tolerated amounts of mepyramine or papaverine, no matter whether the drugs were given alone or in combination. Adrenaline, in contrast to noradrenaline, was partially effective at the lower dose (0.1 μg/ml). The higher concentration did not act more strongly. It became fully effective when mepyramine was added either alone or combined with papaverine.
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4.
The increase of pulmonary vascular resistance induced by histamine was strongly and significantly antagonized by mepyramine alone as well as by the lower concentration of adrenaline (0.1 μg/ml). Noradrenaline had no significant effect in either amount given (0.1 and 1 μg/ml).
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5.
Antigen increased heart rate in sensitized HLPs, probably due to histamine release. This effect was resistant to mepyramine.
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6.
The present findings are discussed
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a)
with respect to the refractoriness of the anaphylactic bronchospasm to mepyramine, an effect displayed in isolated lung preparations but not in intact animals.
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b)
with respect to the mechanism of the so-called protracted shock which is mainly due to heart failure.
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References
Alberty, J.: Versuche über den Anteil von Histamin am anaphylaktischen Asthma sowie Beobachtungen über Auslösung und Verhalten der Asthma- und Kreislauf-symptome anaphylaktischer Schockfragmente des Meerschweinchens. Int. Arch. Allergy14, 162–204 (1959).
Bernauer, W., Gossow, U., Hahn, F.: Role of catecholamines in mepyramine resi-stance of anaphylactic bronchospasm in vitro. Int. Arch. Allergy37, 311–324 (1970).
—, Hahn, F.: Studies on heart anaphylaxis. II. Effect of histamine and antigen on heart failure in heart-lung-preparation of guinea-pigs. Arch. int. Pharmacodyn.181, 232–251 (1969).
— —, Giertz, H.: Comparison of the antilethal, broncholytic and antiemphysematous activities of mepyramine in anaphylactic, histamine, and anaphylatoxin shock of guinea-pigs. Arch. int. Pharmacodyn.178, 137–151 (1969).
—, Seseke, G., Hahn, F., Schmutzler, W., Giertz, H.: Über die anaphylaktische Histaminfreisetzung am Herzlungenpräparat des Meerschweinchens. Arch. int. Pharmacodyn.162, 319–329 (1966).
Burrage, W. S., Irwin, J. W.: Microscopic observations of the pulmonary arteriols, capillaries, and venules of living mammals before and during anaphylaxis. J. Allergy24, 289–296 (1953).
Castillo, C. J.: The tracheal chain. II. The anaphylactic guinea pig trachea and its response to antihistamine and bronchodilator drugs. J. Pharmacol. exp. Ther.94, 412–415 (1948).
Collier, H. O. J., James, O. W. L.: Humoral factors affecting pulmonary inflation during acute anaphylaxis in the guinea pig in vivo. Brit. J. Pharmacol.30, 283–301 (1967).
Daly, J. de Burgh, Peat, S., Schild, H.: The release of histamine-like substance. from the lungs of guinea pigs during anaphylactic shock. Quart. J. exp. Physiol.25, 33–59 (1935).
Engelhardt, G., Hahn, G.: Pharmakologische Beeinflussung anaphylaktischer Reaktionen an Gefäßpräparaten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.231, 507–525 (1957).
Ettinger, G. H.: An investigation of the pulmonary circulation of the guinea-pig. Preliminary report. J. Physiol. (Lond.)67, 42–43 (1929).
Feinberg, S. M.: The antihistaminic drugs. Pharmacology and therapeutic effects. Amer. J. Med.3, 560–570 (1947).
Giertz, H.: Über die Rolle des Histamins bei der Meerschweinchenanaphylaxie. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.250, 150–163 (1965).
—, Hahn, F.: Über die Wirkung von Mepyramin und Papaverin auf den anaphylaktischen Schock des Meerschweinchens mit besonderer Berücksichtigung des protrahierten Schocks. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.258, 11–23 (1967).
— —, Hahn, F., Jurna, I., Schmutzler, W.: Vergleichende Untersuchungen über den anaphylaktischen Schock und den Anaphylatoxinschock am intakten Meerschweinchen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.242, 65–75 (1961).
— —, Hahn, F., Opferkuch, W., Schmutzler, W.: Vergleichende Untersuchungen über den anaphylaktischen Schock und den Anaphylatoxinschock an der isolierten Meerschweinchenlunge. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.242, 42–64 (1961).
— —, Schmutzler, W.: Untersuchungen über die Beziehungen zwischen der Intensität der anaphylaktischen Reaktionen des Meerschweinchens und dem Zeitintervall zwischen Erst- und Re-Injektion des Antigens. Int. Arch. Allergy19, 178–191 (1961).
Über die Wirkung von Theophyllin, Isoproterenol, Orciprenalin und Dexamethason auf den protrahierten anaphylaktischen Schock des Meerschweinchens. Arzneimittel-Forsch, (im Druck).
Grove, E. F.: Studies in anaphylaxis in the rabbit. I. A study of the factors concerned in the establishment of maximal hypersensitiveness in rabbits to egg white and horse serum. J. Immunol.23, 101–123 (1932).
Hahn, F., Bernauer, W.: Studies on heart anaphylaxis. I. Effect of antigen and histamine on the guinea pig heart-lung-preparation. Int. Arch. Allergy35, 476–494 (1969).
— —: Studies on heart anaphylaxis. III. Effect of antigen and histamine on perfused guinea-pig heart. Arch. int. Pharmacodyn.184, 129–157 (1970).
—, Giertz, H.: Die theoretischen Grundlagen der Allergie. Arch. Ohr.-, Nas.-u. Kehlk.-Heilk.176, 1–81 (1960).
Halpern, B. N.: Die synthetischen Antihistaminica. In: Pathogenese und Therapie allergischer Reaktionen, S. 517–565. Stuttgart: Ferd. Enke 1966.
Konzett, H., Rössler, R.: Versuchsanordnung zu Untersuchungen an der Bronchialmuskulatur. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.195, 71–74 (1940).
Meier, R., Bucher, K.: Pharmakologie der Antihistaminica. Progr. Allergy2, 290–328 (1949).
Piper, P. J., Collier, H. O. J., Vane, J. R.: Release of catecholamines in the guinea pig by substances involved in anaphylaxis. Nature (Lond.)213, 838–840 (1967).
Reuse, J. J.: Antihistamine drugs and histamine release especially in anaphylaxis. Ciba Foundation Symposion on Histamine, pp. 150–154. London: Churchill 1956.
Rose, J. M., Feinberg, A. R., Friedlaender, S., Feinberg, S. M.: Histamine antagonists. VII. Comparative antianaphylactic activity of some new antihistaminic drugs. J. Allergy18, 149–155 (1947).
Staub, A. M., Bovet, D.: Action de la thymoxyéthyldiéthylamine (929 F) et des ethers phénoliques sur le choc anaphylactique du cobaye. C. R. Soc. Biol. (Paris)125, 818–821 (1937).
Yonkman, F. F., Oppenheimer, E., Rennick, B., Pellet, E.: Pharmacodynamic studies of a new antihistaminic agent, pyribenzamine (N,N-dimethyl-N′-benzylN′-(α-pyridyl)-ethylene diamine hydrochloride). II. Effects on smooth muscle of the guinea pig and dog lung. J. Pharmacol. exp. Ther.89, 31–41 (1947).
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Hahn, F., Bernauer, W., Mahlstedt, J. et al. Synergistic effects of adrenaline and mepyramine on the anaphylactic reactions of the bronchi and pulmonary vessels in the guinea pig heart-lung-preparation. Naunyn-Schmiedebergs Arch. Pharmak. 267, 224–240 (1970). https://doi.org/10.1007/BF00997094
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DOI: https://doi.org/10.1007/BF00997094