Search tips
Search criteria 


Logo of heartHeartVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Heart. 1996 December; 76(6): 513–519.
PMCID: PMC484605

Effects of blockade of fast and slow inward current channels on ventricular fibrillation in the pig heart.


OBJECTIVE: To determine the contribution of fast and slow inward channels to the electrocardiogram (ECG) of ventricular fibrillation. METHODS: Ventricular fibrillation was induced by endocardial electrical stimulation in pigs anaesthetised with pentobarbitone sodium (30 mg/kg intravenously). ECGs simultaneously recorded from the body surface (lead II) and from the endocardium were studied by power spectrum analysis (0-40 Hz). RESULTS: The mean (SEM) dominant frequency of fibrillation (9.0 (1.1) Hz in lead II at 0-40 s) did not change significantly with time in pigs given intravenous saline. However, the dominant frequency was significantly reduced by intravenous pretreatment with the class I antiarrhythmic drugs, lignocaine (3 mg/kg, 6.5 (0.5) Hz; 10 mg/kg, 4.2 (0.6) Hz), mexiletine (3 mg/kg, 6.2 (0.4) Hz; 10 mg/kg, 5.5 (0.4) Hz), and disopyramide (2.5 mg/kg, 5.4 (0.6) Hz). After flecainide (3 mg/kg, 6.9 (0.5) Hz) the reduction in frequency was not significant. Similar data were obtained with endocardial recordings. In contrast pre-treatment with verapamil (0.2 mg/kg, 11.7 (0.8) Hz; and 1.0 mg/kg, 12.9 (1.6) Hz) produced a significantly higher dominant frequency of fibrillation than saline and widened the bandwidth of frequencies around the dominant frequency. CONCLUSIONS: These results indicate that voltage-dependent sodium channel currents contribute to the rapid frequencies of ventricular fibrillation. Blockade of L-type inward calcium channel activity increases the fibrillation frequency and fractionates the frequencies of the fibrillation wavefronts.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Janse MJ, van Capelle FJ, Morsink H, Kléber AG, Wilms-Schopman F, Cardinal R, d'Alnoncourt CN, Durrer D. Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms. Circ Res. 1980 Aug;47(2):151–165. [PubMed]
  • Pogwizd SM, Corr PB. Mechanisms underlying ventricular tachycardia and fibrillation in the ischemic heart: relation to nonlinear dynamics. Ann N Y Acad Sci. 1990;591:278–300. [PubMed]
  • Ideker RE, Klein GJ, Harrison L, Smith WM, Kasell J, Reimer KA, Wallace AG, Gallagher JJ. The transition to ventricular fibrillation induced by reperfusion after acute ischemia in the dog: a period of organized epicardial activation. Circulation. 1981 Jun;63(6):1371–1379. [PubMed]
  • Carlisle EJ, Allen JD, Kernohan WG, Anderson J, Adgey AA. Fourier analysis of ventricular fibrillation of varied aetiology. Eur Heart J. 1990 Feb;11(2):173–181. [PubMed]
  • Stewart AJ, Allen JD, Adgey AA. Frequency analysis of ventricular fibrillation and resuscitation success. Q J Med. 1992 Oct;85(306):761–769. [PubMed]
  • Clayton RH, Murray A, Campbell RW. Changes in the surface electrocardiogram during the onset of spontaneous ventricular fibrillation in man. Eur Heart J. 1994 Feb;15(2):184–188. [PubMed]
  • Clayton RH, Murray A, Campbell RW. Analysis of the body surface ECG measured in independent leads during ventricular fibrillation in humans. Pacing Clin Electrophysiol. 1995 Oct;18(10):1876–1881. [PubMed]
  • Davis J, Matsubara T, Scheinman MM, Katzung B, Hondeghem LH. Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo. Circulation. 1986 Jul;74(1):205–214. [PubMed]
  • Pallandi RT, Campbell TJ. Selective depression of conduction of premature action potentials in canine Purkinje fibres by class Ib antiarrhythmic drugs: comparison with Ia and Ic drugs. Cardiovasc Res. 1988 Mar;22(3):171–178. [PubMed]
  • Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984 Apr;24(4):129–147. [PubMed]
  • Merillat JC, Lakatta EG, Hano O, Guarnieri T. Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. Circ Res. 1990 Nov;67(5):1115–1123. [PubMed]
  • Kojima S, Wikman-Coffelt J, Wu ST, Parmley WW. Nature of [Ca2+]i transients during ventricular fibrillation and quinidine treatment in perfused rat hearts. Am J Physiol. 1994 Apr;266(4 Pt 2):H1473–H1484. [PubMed]
  • Koretsune Y, Marban E. Cell calcium in the pathophysiology of ventricular fibrillation and in the pathogenesis of postarrhythmic contractile dysfunction. Circulation. 1989 Aug;80(2):369–379. [PubMed]
  • Vincent JL, Goldstein J, Dufaye P, Domb M. Electromechanical dissociation after ventricular fibrillation: prevention with calcium-entry blockers. J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1124–1131. [PubMed]
  • Martin G, Cosin J, Such M, Hernandez A, Llamas P. Relation between power spectrum time course during ventricular fibrillation and electromechanical dissociation. Effects of coronary perfusion and nifedipine. Eur Heart J. 1986 Jul;7(7):560–569. [PubMed]
  • Muller CA, Opie LH, Hamm CW, Peisach M, Pineda CA, Thandroyen FT. Verapamil and tiapamil in prevention of ventricular fibrillation in pigs with coronary ligation. Comparative effects on left ventricular function. Circulation. 1988 Jul;78(1):227–232. [PubMed]
  • Jenkins MG, Johnson TA, Engle C, Gettes LS. Metabolic protection by verapamil during graded coronary flow reduction independent of effect on baseline systolic function. Separation of mechanical and ionic markers of ischemia. Circulation. 1989 Dec;80(6):1870–1877. [PubMed]
  • Brown CG, Dzwonczyk R, Werman HA, Hamlin RL. Estimating the duration of ventricular fibrillation. Ann Emerg Med. 1989 Nov;18(11):1181–1185. [PubMed]
  • Pedersen LE, Hermansen K, Olesen HP, Rasmussen SN. The pharmacokinetics and protein binding of disopyramide in pigs. Acta Pharmacol Toxicol (Copenh) 1986 Apr;58(4):282–288. [PubMed]
  • Vogt B, Martin C, Meesmann W. Prophylactic lidocaine: concentrations in plasma and myocardial tissue and antifibrillatoric efficacy during early ischemia in dogs and pigs. J Cardiovasc Pharmacol. 1988;12(5):571–578. [PubMed]
  • Verdouw PD, Deckers JW, Conrad GJ. Antiarrhythmic and hemodynamic actions of flecainide acetate (R-818) in the ischemic porcine heart. J Cardiovasc Pharmacol. 1979 Jul-Aug;1(4):473–486. [PubMed]
  • Kaplan DT, Cohen RJ. Is fibrillation chaos? Circ Res. 1990 Oct;67(4):886–892. [PubMed]
  • Rosen MR, Hoffman BF, Wit AL. Electrophysiology and pharmacology of cardiac arrhythmias. V. Cardiac antiarrhythmic effects of lidocaine. Am Heart J. 1975 Apr;89(4):526–536. [PubMed]
  • Echt DS, Black JN, Barbey JT, Coxe DR, Cato E. Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation. Circulation. 1989 May;79(5):1106–1117. [PubMed]
  • Echt DS, Mason JW. Management of serious cardiac arrhythmias with drugs. Cardiovasc Clin. 1984;14(3):191–209. [PubMed]
  • Marshall RJ, Parratt JR. The effects of disopyramide phosphate on early post-coronary artery ligation dysrhythmias and on epicardial ST-segment elevation in anaesthetized dogs. Br J Pharmacol. 1979 Jun;66(2):241–250. [PubMed]
  • Scamps F, Undrovinas A, Vassort G. Inhibition of ICa in single frog cardiac cells by quinidine, flecainide, ethmozin, and ethacizin. Am J Physiol. 1989 Mar;256(3 Pt 1):C549–C559. [PubMed]
  • Carlisle EJ, Allen JD, Kernohan WG, Leahey W, Adgey AA. Pharmacological analysis of established ventricular fibrillation. Br J Pharmacol. 1990 Jul;100(3):530–534. [PubMed]
  • Hirata Y, Kodama I, Iwamura N, Shimizu T, Toyama J, Yamada K. Effects of verapamil on canine Purkinje fibres and ventricular muscle fibres with particular reference to the alternation of action potential duration after a sudden increase in driving rate. Cardiovasc Res. 1979 Jan;13(1):1–8. [PubMed]
  • Elharrar V, Gaum WE, Zipes DP. Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs. Am J Cardiol. 1977 Apr;39(4):544–549. [PubMed]
  • Fondacaro JD, Han J, Yoon MS. Effects of verapamil on ventricular rhythm during acute coronary occlusion. Am Heart J. 1978 Jul;96(1):81–86. [PubMed]
  • Fleet WF, Johnson TA, Graebner CA, Engle CL, Gettes LS. Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig. Circulation. 1986 Apr;73(4):837–846. [PubMed]
  • Sherman LG, Liang C, Boden WE, Hood WB., Jr The effect of verapamil on mechanical performance of acutely ischemic and reperfused myocardium in the conscious dog. Circ Res. 1981 Feb;48(2):224–232. [PubMed]
  • Auffermann W, Wagner S, Wu S, Buser P, Parmley WW, Wikman-Coffelt J. Calcium inhibition of glycolysis contributes to ischaemic injury. Cardiovasc Res. 1990 Jun;24(6):510–520. [PubMed]
  • Dahl G, Isenberg G. Decoupling of heart muscle cells: correlation with increased cytoplasmic calcium activity and with changes of nexus ultrastructure. J Membr Biol. 1980 Mar 31;53(1):63–75. [PubMed]
  • Schräder R, Brooks M, Echt DS. Effects of verapamil and Bay K 8644 on defibrillation energy requirements in dogs. J Cardiovasc Pharmacol. 1992 Jun;19(6):839–850. [PubMed]

Articles from Heart are provided here courtesy of BMJ Publishing Group