Acute effects of amiodarone on membrane properties, refractoriness, and conduction in guinea pig papillary muscles

Springer Science and Business Media LLC - Tập 10 - Trang 78-86 - 1995
Toru Maruyama1, Lisa C. Richardson1, Weili Sun1, James J. McCarthy1, Leonard S. Gettes1
1Division of Cardiology, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, USA

Tóm tắt

Amiodarone has potent and complex antiarrhythmic effects associated with a rare incidence of proarrhythmia. For a comprehensive understanding of its antiarrhythmic mechanisms in the same preparations, amiodarone (50 µM) was employed as it would be in the clinical setting and applied to guinea pig papillary muscles impaled by microelectrodes, paced at different rates, and superfused with various concentrations of potassium ([K]e). Amiodarone exerted complex actions, as follows: (1) The maximum rate of rise (Vmax) of the fast action potential (i.e., [K]e = 5.4−9.0mM) as well as that of the slow action potential (i.e., [K]e = 15.0mM in the presence of 1.0µM isoproterenol) was suppressed in a rate-dependent manner. (2) Amiodarone exhibited a rate- and [K]e-dependent increase in the ratio of effective refractory period vs action potential duration at 90% repolarization (ERP/APD90), disclosing post-repolarization refractoriness. (3) Amiodarone had no effect on passive cable factors, such as threshold current and tissue resistance, during propagation. These versatile electrophysiological effects of amiodarone may contribute to its unique antiarrhythmic effects, as well as the low incidence of proarrhythmia with this drug.

Tài liệu tham khảo

Helmy I, Herre JM, Gee G, Sharkey H, Malone P, Sauve MJ, Griffin JC, Scheinman MM (1988) Use of intravenous amiodarone for emergency treatment of life-threatening ventricular arrhythmias. J Am Coll Cardiol 12:1015–1022 Klein RC, Machell C, Rushforth N, Standefur J (1988) Efficacy of intravenous amiodarone as short-term treatment for refractory ventricular tachycardia. Am Heart J 115:96–101 Kadish A, Morady F (1989) The use of intravenous amiodarone in the acute therapy of life-threatening tachyarrhythmias. Prog Cardiovasc Dis 31:281–294 Herre JM, Sauve MJ, Malone P, Scheinman MM (1989) Long-term results of amiodarone therapy in patients with recurrent sustained ventricular tachycardia or ventricular fibrillation. J Am Coll Cardiol 12:442–449 Burkart F, Pfisterer M, Kiowski W, Follath F, Burckhardt D (1990) Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 16:1711–1718 Cairns JA, Connolly SJ, Gent M, Roberts R (1991) Post-myocardial infarction mortality in patients with ventricular premature depolarization: Canadian amiodarone myocardial infarction arrhythmia trial pilot study. Circulation 84:550–557 Saksena S, Rothbart ST, Shah Y, Cappello G (1984) Clinical efficacy and electropharmacology of continuous intravenous amiodarone infusion and chronic oral amiodarone in refractory ventricular tachycardia. Am J Cardiol 54:347–352 Morady F, DiCarlo LA Jr, Krol RB, Baerman JM, DeBuitleir M (1986) Acute and chronic effects of amiodarone on ventricular refractoriness, intraventricular conduction and ventricular tachycardia induction. J Am Coll Cardiol 7:148–157 Cascio WE, Woelfel A, Knisley SB, Buchanan JW Jr, Foster JR, Gettes LS (1988) Use dependence of amiodarone during the sinus tachycardia of exercise in coronary artery disease. Am J Cardiol 61:1042–1045 Touboul P, Atallah G, Gressard A, Kirkorian G (1979) Effects of amiodarone on sinus node in man. Br Heart J 42:573–578 Ikeda N, Nademanee K, Kannan R, Singh BN (1984) Electrophysiologic effects of amiodarone: Experimental and clinical observations relative to serum and tissue drug concentrations. Am Heart J 108:890–898 Singh BN (1989) Controlling cardiac arrhythmias: To delay conduction or to prolong refractoriness? Cardiovasc Drugs Ther 3:671–674 Singh BN, Sarma JSM, Zhang ZH, Takanaka C (1992) Controlling cardiac arrhythmias by lengthening repolarization: Rationale from experimental findings and clinical considerations. Ann New York Acad Sci 644:187–209 Nademanee K, Singh BN, Stevenson WG, Weiss JN (1993) Amiodarone and post-MI patients. Circulation 88:764–774 Warren RJ, Stedman RJ, Shami EG, Rattie ES, Ravin LJ (1970) Observation on the micelle formation of 2-butyl-3-benzofurany1-4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride (SK & F 33134-A) by NMR spectroscopy. J Pharm Sci 59:1357–1358 Arita M, Kiyosue T, Aomine M, Imanishi S (1983) Nature of “residual fast channel” dependent action potentials and slow conduction in guinea pig ventricular muscle and its modification by isoproterenol. Am J Cardiol 51:1433–1440 Weidmann S (1970) Electrical constants of trabecular muscle from mammalian heart. J Physiol (Lond) 210:1041–1054 Buchanan JW, Oshita S, Fujino T, Gettes LS (1986) A method for measurement of internal longitudinal resistance in papillary muscle. Am J Physiol 251:H210-H217 Hochberg Y (1988) A sharper Bonferroni procedure for multiple tests of significance. Biometrika 74:800–802 Mason JW, Hondeghem LM, Katzung BG (1984) Block of inactivated sodium channels and of depolarizationinduced automaticity in guinea pig papillary muscle by amiodarone. Circ Res 66:277–285 Pallandi RT, Campbell TJ (1987) Resting, and ratedependent depression of Vmax of guinea pig ventricular action potentials by amiodarone and desethylamiodarone. Br J Pharmacol 92:97–103 Nishimura M, Follmer CH, Singer DH (1989) Amiodarone blocks calcium current in single guinea pig ventricular myocytes. J Pharmacol Exp Ther 251:650–659 Nattel S, Talajic M, Quantz M, DeRoode M (1987) Frequency-dependent effects of amiodarone on atrioventricular nodal function and slow-channel action potentials: Evidence for calcium channel-blocking activity. Circulation 76:442–449 Arnsdorf MF, Bigger JT (1975) The effect of lidocaine on compartments of excitability in long mammalian cardiac Purkinje fibers. J Pharmacol Exp Ther 195:206–215 Arnsdorf MF, Bigger JT (1976) The effect of procaine amide on compartments of excitability in long mannalian cardiac Purkinje fibers. Circ Res 38:115–122 Arnsdorf MF, Schmitt GA, Sawicki GJ (1985) Effects of encainide on the determinants of cardiac excitability in sheep Purkinje fibers. J Pharmacol Exp Ther 232:40–48 Quinteiro RA, Biagetti MO, de Forteza E (1990) Relationship between Vmax and conduction velocity in uniform anisotropic canine ventricular muscle: Differences between the effects of lidocaine and amiodarone. J Cardiovasc Pharmacol 16:931–939 Noma A, Tsuboi N (1987) Dependence of junctional conductance on proton, calcium, and magnesium ions in cardiac paired cells of guinea pig. J Physiol (Lond) 382:192–211 Levine JH, Moore EN, Kadish AH, Weisman HF, Balke CW, Hanich RF, Spear JF (1988) Mechanisms of depressed conduction from long-term amiodarone therapy in canine myocardium. Circulation 78:684–691 Latini R, Connolly SJ, Kates RE (1983) Myocardial disposition of amiodarone in the dog. J Pharmacol Exp Ther 224:603–608 Chatelain P, Ferreira J, Laruel R, Ruysschaert JM (1986) Amiodarone-induced modification of the phospholipid physical state. Biochem Pharmacol 35:3007–3013 Aomine M (1988) Does acute exposure to amiodarone prolong cardiac action potential duration? Gen Pharmacol 19:615–619 Varró A, Nakaya Y, Elharrar V, Surawicz B (1988) The effects of amiodarone on repolarization and refractoriness of cardiac fibers. Eur J Pharmacol 154:11–18 Gettes LS, Reuter H (1974) Slow recovery from inactivation of inward currents in mammalian myocardial fibres. J Physiol (Lond) 240:703–724 Gettes LS, Buchanan JW, Saito T, Kagiyama Y, Oshita S, Fujino T (1985) Studies concerned with slow conduction. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology and arrhythmias. Grune and Stratton, Orlando, pp 81–87 Brown RH Jr, Noble D (1978) Displacement of activation threshold in cardiac muscle by protons and calcium ions. J Physiol (Lond) 282:333–343 Hunter PJ, McNaughton PA, Noble D (1975) Analytical models of propagation in excitable cells. Prog Biophys Mol Biol 30:99–144 Chiamvimonvat N, Mitchell LB, Gillis AM, Wyse DG, Sheldon RS, Duff HJ (1992) Use-dependent electrophysiologic effects of amiodarone in coronary artery disease and inducible ventricular tachycardia. Am J Cardiol 70:598–604 Russell DC, Oliver MF (1978) Ventricular refractoriness during acute myocardial ischemia and its relationship to ventricular fibrillation. Cardiovasc Res 12:221–227 Janse MJ, Wit AL (1989) Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69:1049–1169 Hondeghem LM, Snyders DJ (1990) Class III antiarrhythmic agents have a lot of potential but a long way to go: Reduced effectiveness and dangers of reverse usedependence. Circulation 81:686–690 Hii JTY, Wyse DG, Gillis AM, Duff HJ, Solylo MA, Mitchell LB (1992) Precordial QT interval dispersion as a marker of Torsade de Pointes: Disparate effects of class Ia antiarrhythmic drugs and amiodarone. Circulation 86:1376–1382