Antiarrhythmic Actions of Clemizole as Pharmacologic Evidence for a Circus Movement Mechanism in Atrial Flutter
The antihistaminic clemizole was studied as an antiarrhythmic in a preparation in which two arrhythmias of different nature and mechanism were produced in the right atrium of anesthetized dogs. One of the arrhythmias was a circus movement flutter induced by the method of Rosenblueth and Garcia Ramos; the other, an ectopic focus induced by local application of aconitine in the auricular appendage, electrically isolated from the rest of the atrium. Clemizole selectively converted the flutter to sinus rhythm with little action on the coexistent aconitine dysrhythmia. It did not modify arterial pressure. In effective doses the wave length of the impulse was increased by prolongation of the refractory period without significant reduction in conduction velocity. Similarly, in subendocardial cells of isolated rat atria, clemizole in appropriate concentrations retards repolarization with little effect on the rate of depolarization. These results afford pharmacological evidence for the existence of atrial circus movement arrhythmias which can respond to prolongation of the refractory period unaccompanied by effects on other properties of the tissue. Other arrhythmias, self-sustained by the discharge of an ectopic focus, such as the tachysystole produced by aconitine, are not suppressed by similar increase in the refractory period.
Key-WordsClemizole Arrhythmia Antihistaminics Cell Membrane
Unable to display preview. Download preview PDF.
- Cardenas, M., u F. Attie: Flutter auricular y potasio. Evidencia del movimiento circular y focos ectópicos en casos clinicos. Arch. Inst. Cardiol. Méx. 36, 137 (1966).Google Scholar
- Kabela, E., M. A. Mena, M. Martinez-López, and R. Mendez: The action of the antihistaminic agents antazoline and meclizine on experimental arrhythmias. Acta cardiol. (Brux.) 22, 113 (1967).Google Scholar
- Mendez, R., J. Aceves, and E. Kabela: Differences among quinidine, atropine and potassium in their action on experimental arrhythmias. Acta cardiol. (Brux.) 20, 1 (1965).Google Scholar
- Prinzmetal, M., E. Corday, I. C. Brill, R. W. Oblath, and H. E. Kruger: The auricular arrhythmias. Springfield, Ill.: Ch. C. Thomas 1952.Google Scholar
- Rosen, M. R., R. Lisak, and I. L. Rubin: Diphenylhydantoin in cardiac arrhythmias. Circulation. Suplement III, 33, 201 (1966).Google Scholar
- Rosenblueth, A., y J. García Ramos: Estudios sobre el flutter y la fibrilación; la influencia de los obstáculos artificiales en el flutter auricular experimental. Arch. Inst, Cardiol. Méx. 17, 1 (1947).Google Scholar
- Sherf, D., and A. Schott: Extrasystoles and allied arrhythmias. London: Heinemarm 1953.Google Scholar
- Surawicz, B.: Antiarrhythmic properties of potassium salts. In Cardiovascular drug therapy. Ed. by Brest, A. M., and J. H. Moyer. New York: Grune and Stratton 1965.Google Scholar
- Takayasu, M., Y. Tateishi, M. Osawa, M. Fujiwara, and S. Ikuta: Experimental studies on the auricular flutter and fibrillation. Jap. Circulat. J. 21, 477 (1958).Google Scholar
- Vaughan Williams, E. M.: Some observations concerning the mode of action of acetylcholine in isolated rabbit atria. J. Physiol. (Lond.) 140, 327 (1958).Google Scholar