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. 1989 Sep;98(1):192–196. doi: 10.1111/j.1476-5381.1989.tb16881.x

Cardiac electrophysiological actions of captopril: lack of direct antiarrhythmic effects.

P D Hemsworth 1, R T Pallandi 1, T J Campbell 1
PMCID: PMC1854648  PMID: 2679956

Abstract

1. Standard microelectrode techniques were used to study the effects of captopril (1, 10 and 100 microM) on action potentials recorded from guinea-pig ventricular cells and sinoatrial node cells. 2. Captopril had no effect on the maximum rate of depolarization (Vmax) of ventricular action potentials in cells exposed to either normal Locke solution or 'simulated ischaemic' solution (K1 11.2 mM; pH-6.4; PO2 less than 80 mmHg), nor was there any augmentation of the normal small decline in Vmax with increasing stimulation rate (range of interstimulus intervals = 2400 ms to 300 ms). 3. Captopril had no effect on the duration of ventricular action potentials, nor did it alter the shortening seen on exposure to simulated ischaemia. 4. Captopril did not alter spontaneous sinus cycle length or any recorded parameter of sinus node action potentials. 5. It is concluded that any antiarrhythmic effects observed during clinical use of captopril are most unlikely to be due to direct actions of the drug on cardiac cell membrane properties.

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Selected References

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  1. Bernier M., Hearse D. J., Manning A. S. Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with "anti-free radical" interventions and a free radical-generating system in the isolated perfused rat heart. Circ Res. 1986 Mar;58(3):331–340. doi: 10.1161/01.res.58.3.331. [DOI] [PubMed] [Google Scholar]
  2. Campbell T. J. Cellular electrophysiological effects of D- and DL-sotalol in guinea-pig sinoatrial node, atrium and ventricle and human atrium: differential tissue sensitivity. Br J Pharmacol. 1987 Mar;90(3):593–599. doi: 10.1111/j.1476-5381.1987.tb11210.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell T. J. Resting and rate-dependent depression of maximum rate of depolarisation (Vmax) in guinea pig ventricular action potentials by mexiletine, disopyramide, and encainide. J Cardiovasc Pharmacol. 1983 Mar-Apr;5(2):291–296. doi: 10.1097/00005344-198303000-00021. [DOI] [PubMed] [Google Scholar]
  4. Cleland J. G., Dargie H. J., Hodsman G. P., Ball S. G., Robertson J. I., Morton J. J., East B. W., Robertson I., Murray G. D., Gillen G. Captopril in heart failure. A double blind controlled trial. Br Heart J. 1984 Nov;52(5):530–535. doi: 10.1136/hrt.52.5.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cleland J. G., Dargie H. J., Robertson J. I., Ball S. G., Hodsman G. P. The use of captopril in the management of cardiac failure. Scott Med J. 1984 Apr;29(2):129–130. [PubMed] [Google Scholar]
  6. Dzau V. J. Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation. 1988 Jun;77(6 Pt 2):I4–13. [PubMed] [Google Scholar]
  7. Edwards C. R., Padfield P. L. Angiotensin-converting enzyme inhibitors: past, present, and bright future. Lancet. 1985 Jan 5;1(8419):30–34. doi: 10.1016/s0140-6736(85)90975-4. [DOI] [PubMed] [Google Scholar]
  8. Frederick W. R., Delapenha R., Gray G., Greaves W. L., Saxinger C. HIV testing of surrogate mothers. N Engl J Med. 1987 Nov 19;317(21):1351–1352. doi: 10.1056/NEJM198711193172113. [DOI] [PubMed] [Google Scholar]
  9. Kripalani K. J., McKinstry D. N., Singhvi S. M., Willard D. A., Vukovich R. A., Migdalof B. H. Disposition of captopril in normal subjects. Clin Pharmacol Ther. 1980 May;27(5):636–641. doi: 10.1038/clpt.1980.90. [DOI] [PubMed] [Google Scholar]
  10. Morganroth J. Computer recognition of cardiac arrhythmias and statistical approaches to arrhythmia analysis. Ann N Y Acad Sci. 1984;432:117–128. doi: 10.1111/j.1749-6632.1984.tb14514.x. [DOI] [PubMed] [Google Scholar]
  11. Neri R., Mestroni L., Salvi A., Pandullo C., Camerini F. Ventricular arrhythmias in dilated cardiomyopathy: efficacy of amiodarone. Am Heart J. 1987 Mar;113(3):707–715. doi: 10.1016/0002-8703(87)90711-3. [DOI] [PubMed] [Google Scholar]
  12. Pallandi R. T., Perry M. A., Campbell T. J. Proarrhythmic effects of an oxygen-derived free radical generating system on action potentials recorded from guinea pig ventricular myocardium: a possible cause of reperfusion-induced arrhythmias. Circ Res. 1987 Jul;61(1):50–54. doi: 10.1161/01.res.61.1.50. [DOI] [PubMed] [Google Scholar]
  13. Podrid P. J. Aggravation of ventricular arrhythmia. A drug-induced complication. Drugs. 1985;29 (Suppl 4):33–44. doi: 10.2165/00003495-198500294-00009. [DOI] [PubMed] [Google Scholar]
  14. Rochette L., Ribuot C., Belichard P., Bril A., Devissaguet M. Protective effect of angiotensin converting enzyme inhibitors (CEI): captopril and perindopril on vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion in rat. Clin Exp Hypertens A. 1987;9(2-3):365–368. doi: 10.3109/10641968709164198. [DOI] [PubMed] [Google Scholar]
  15. Singhvi S. M., McKinstry D. N., Shaw J. M., Willard D. A., Migdalof B. H. Effect of food on the bioavailability of captopril in healthy subjects. J Clin Pharmacol. 1982 Feb-Mar;22(2-3):135–140. doi: 10.1002/j.1552-4604.1982.tb02661.x. [DOI] [PubMed] [Google Scholar]
  16. Van Gilst W. H., De Graeff P. A., Kingma J. H., Wesseling H., De Langen C. D. Captopril reduces purine loss and reperfusion arrhythmias in the rat heart after coronary artery occlusion. Eur J Pharmacol. 1984 Apr 13;100(1):113–117. doi: 10.1016/0014-2999(84)90323-6. [DOI] [PubMed] [Google Scholar]
  17. Vaughan Williams E. M. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984 Apr;24(4):129–147. doi: 10.1002/j.1552-4604.1984.tb01822.x. [DOI] [PubMed] [Google Scholar]
  18. Walton M., Fozzard H. A. The relation of Vmax to INa, GNa, and h infinity in a model of the cardiac Purkinje fiber. Biophys J. 1979 Mar;25(3):407–420. doi: 10.1016/S0006-3495(79)85312-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Webster M. W., Fitzpatrick M. A., Nicholls M. G., Ikram H., Wells J. E. Effect of enalapril on ventricular arrhythmias in congestive heart failure. Am J Cardiol. 1985 Sep 15;56(8):566–569. doi: 10.1016/0002-9149(85)91186-5. [DOI] [PubMed] [Google Scholar]
  20. van Gilst W. H., de Graeff P. A., Wesseling H., de Langen C. D. Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498. J Cardiovasc Pharmacol. 1986 Jul-Aug;8(4):722–728. [PubMed] [Google Scholar]

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