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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 May;82(1):191–197. doi: 10.1111/j.1476-5381.1984.tb16458.x

Alterations to the electrical activity of atrial muscle isolated from the rat heart, produced by exposure in vitro to amiodarone.

B J Northover
PMCID: PMC1987237  PMID: 6329388

Abstract

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of the left atrial free wall of rat hearts during superfusion and electrical stimulation in vitro at 37 degrees C. Availability of the fast sodium channel for current flow was inferred from the maximum rate of rise of membrane potential during phase O of the action potential (Vmax). Muscle exposed to polysorbate 80 (10 to 80 micrograms ml-1) showed a concentration-dependent lengthening of action potential duration (APD) but no detectable change in Vmax. Amiodarone (1 to 20 micrograms ml-1) was dissolved in physiological salt solution with the aid of polysorbate 80 (50 micrograms ml-1) and caused a concentration-dependent prolongation of APD and a decrease in Vmax, both of which were slow to develop and extremely slow to wash-out. The speed of onset of action of amiodarone varied with drug concentration and ranged from a few minutes with high concentrations to many hours with low concentrations.

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Selected References

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  1. Andreasen F., Agerbaek H., Bjerregaard P., Gøtzsche H. Pharmacokinetics of amiodarone after intravenous and oral administration. Eur J Clin Pharmacol. 1981 Mar;19(4):293–299. doi: 10.1007/BF00562807. [DOI] [PubMed] [Google Scholar]
  2. CHARLIER R., DELTOUR G., TONDEUR R., BINON F. [Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran]. Arch Int Pharmacodyn Ther. 1962 Sep 1;139:255–264. [PubMed] [Google Scholar]
  3. Chen C. M., Gettes L. S., Katzung B. G. Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium. Circ Res. 1975 Jul;37(1):20–29. doi: 10.1161/01.res.37.1.20. [DOI] [PubMed] [Google Scholar]
  4. Coutte R., Fontaine G., Frank R., Dragodanne C., Phan-Thuc H., Facquet J. Etude électrocardiologique des effets de l'amiodarone sur la conduction intracardiaque chez l'homme. Comparaison entre les voies intraveineuse et orale. Ann Cardiol Angeiol (Paris) 1976 Dec;25(6):543–548. [PubMed] [Google Scholar]
  5. Debbas N. M., Du Cailar C., Sassine A., Derancourt J., Demaille J. G., Puech P. Determination of cardiac and plasma drug levels during long-term amiodarone therapy. Eur J Clin Invest. 1983 Apr;13(2):123–127. doi: 10.1111/j.1365-2362.1983.tb00076.x. [DOI] [PubMed] [Google Scholar]
  6. Demoulin J. C., Legrand V. Place de l'amiodarone en 1979 dans l'arsenal thérapeutique d'une unité de soins intensifs cardiologiques. Rev Med Liege. 1979 Dec 1;34(23):963–968. [PubMed] [Google Scholar]
  7. Finerman W. B., Jr, Hamer A., Peter T., Weiss D., Mandel W. J. Electrophysiologic effects of chronic amiodarone therapy in patients with ventricular arrhythmias. Am Heart J. 1982 Nov;104(5 Pt 1):987–996. doi: 10.1016/0002-8703(82)90430-6. [DOI] [PubMed] [Google Scholar]
  8. Fogoros R. N., Anderson K. P., Winkle R. A., Swerdlow C. D., Mason J. W. Amiodarone: clinical efficacy and toxicity in 96 patients with recurrent, drug-refractory arrhythmias. Circulation. 1983 Jul;68(1):88–94. doi: 10.1161/01.cir.68.1.88. [DOI] [PubMed] [Google Scholar]
  9. Gettes L. S., Reuter H. Slow recovery from inactivation of inward currents in mammalian myocardial fibres. J Physiol. 1974 Aug;240(3):703–724. doi: 10.1113/jphysiol.1974.sp010630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gough W. B., Zeiler R. H., Barreca P., El-Sherif N. Hypotensive action of commercial intravenous amiodarone and polysorbate 80 in dogs. J Cardiovasc Pharmacol. 1982 May-Jun;4(3):375–380. doi: 10.1097/00005344-198205000-00006. [DOI] [PubMed] [Google Scholar]
  11. Lubbe W. F., McFadyen M. L., Muller C. A., Worthington M., Opie L. H. Protective action of amiodarone against ventricular fibrillation in the isolated perfused rat heart. Am J Cardiol. 1979 Mar;43(3):533–540. doi: 10.1016/0002-9149(79)90010-9. [DOI] [PubMed] [Google Scholar]
  12. Marcus F. I., Fontaine G. H., Frank R., Grosgogeat Y. Clinical pharmacology and therapeutic applications of the antiarrhythmic agent amiodarone. Am Heart J. 1981 Apr;101(4):480–493. doi: 10.1016/0002-8703(81)90140-x. [DOI] [PubMed] [Google Scholar]
  13. Mason J. W., Hondeghem L. M., Katzung B. G. Amiodarone blocks inactivated cardiac sodium channels. Pflugers Arch. 1983 Jan;396(1):79–81. doi: 10.1007/BF00584702. [DOI] [PubMed] [Google Scholar]
  14. Néliat G., Ducouret P., Moreau M., Gargouïl Y. M. Effects of butoprozine on ionic currents in frog atrial and ferret ventricular fibres. Comparison with amiodarone and verapamil. Arch Int Pharmacodyn Ther. 1982 Feb;255(2):237–255. [PubMed] [Google Scholar]
  15. Néliat G., Moreau M., Ducouret P., Gargouïl Y. M. Electrophysiological effects of butoprozine on isolated heart preparations. Comparison with amiodarone and verapamil. Arch Int Pharmacodyn Ther. 1982 Feb;255(2):220–236. [PubMed] [Google Scholar]
  16. Rosenbaum M. B., Chiale P. A., Halpern M. S., Nau G. J., Przybylski J., Levi R. J., Lázzari J. O., Elizari M. V. Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol. 1976 Dec;38(7):934–944. doi: 10.1016/0002-9149(76)90807-9. [DOI] [PubMed] [Google Scholar]
  17. Saksena S., Rothbart S. T., Cappello G. Chronic effects of amiodarone in patients with refractory ventricular tachycardia. Int J Cardiol. 1983 Jun;3(3):339–352. doi: 10.1016/0167-5273(83)90177-8. [DOI] [PubMed] [Google Scholar]
  18. Sarel O., Hasin Y., Rogel S. Myocardial conduction time and antiarrhythmic drugs. J Electrocardiol. 1981 Jul;14(3):261–266. doi: 10.1016/s0022-0736(81)80007-6. [DOI] [PubMed] [Google Scholar]
  19. Singh B. N., Vaughan Williams E. M. The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657–667. doi: 10.1111/j.1476-5381.1970.tb09891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Touboul P., Atallah G., Gressard A., Kirkorian G. Effects of amiodarone on sinus node in man. Br Heart J. 1979 Nov;42(5):573–578. doi: 10.1136/hrt.42.5.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Touboul P., Atallah G., Kirkorian G. Effect of intravenous amiodarone in patients with intraventricular conduction disorders. Eur Heart J. 1982 Dec;3(6):546–552. doi: 10.1093/oxfordjournals.eurheartj.a061351. [DOI] [PubMed] [Google Scholar]
  22. Touboul P., Huerta F., Porte J., Delahaye J. P. Bases électrophysiologiques de l'action antiarythmique de l'amiodarone chez l'homme. Arch Mal Coeur Vaiss. 1976 Aug;69(8):845–853. [PubMed] [Google Scholar]
  23. Touboul P., Porte J., Huerta F., Delahaye J. P. Effets électrophysiologiques de l'amiodarone dans le syndrome de Wolff-Parkinson-White. Arch Mal Coeur Vaiss. 1976 Aug;69(8):855–863. [PubMed] [Google Scholar]
  24. Waleffe A., Bruninx P., Kulbertus H. E. Effects of amiodarone studied by programmed electrical stimulation of the heart in patients with paroxysmal re-entrant supraventricular tachycardia. J Electrocardiol. 1978 Jul;11(3):253–260. doi: 10.1016/s0022-0736(78)80125-3. [DOI] [PubMed] [Google Scholar]

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