1. The effects of anti-arrhythmic drugs on the power spectrum of established ventricular fibrillation induced by endocardial electrical stimulation, have been studied in greyhounds anaesthetized with sodium pentobarbitone (35 mg kg-1, i.v.). 2. In dogs receiving no drug, initial recording of ventricular fibrillation showed a dominant frequency of 9.9 +/- 0.7 Hz (lead II) and 10.0 +/- 0.6 Hz (endocardium). After 3.3 min the frequency had fallen to 4.0 +/- 0.4 Hz in lead II, but remained high in the endocardium (10.7 +/- 0.5 Hz). 3. Lignocaine significantly reduced the dominant frequency for fibrillation recorded from lead II at (0-80 s), and for endocardial fibrillation at (0-200 s). 4. Pretreatment with propranolol or bretylium had little effect on the time course of the dominant frequency of fibrillation in lead II or the endocardium. 5. Verapamil prevented the fall in frequency seen in lead II after 80 s in the no drug group. A significantly higher frequency was maintained in both lead II (14.7 +/- 0.9 Hz) and the endocardium (14.8 +/- 0.9 Hz) for 3.3 min, compared with the no drug group (P less than 0.01). 6. Activation of fast sodium channels may determine the rapid frequency of the initial stages of ventricular fibrillation. The rapid fall in dominant frequency in lead II after fibrillation for 80 s can be prevented by calcium channel blockade and may be due to intracellular accumulation of calcium.
Reference text: ADGEY, A.A.J., ALLEN, J.D., CARLISLE, E.J.F., KERNOHAN, W.G. &
LEAHEY, W. (1987). Effects of anti-arrhythmic drugs on established
ventricular fibrillation in the anaesthetized dog. J. Physiol., 392,
ANDERSON, J.L., PATTERSON, E., CONLON, M., PASYK, S., PInT, B. &
LUCCHESI, B.R. (1980). Kinetics of antifibrillatory effects of bretylium:
correlation with myocardial drug concentrations. Am. J.
Cardiol., 46, 583-592.
BIGGER, J.T., JR. & JAFFE, C.C. (1971). The effect of bretylium tosylate
on electrophysiological properties of ventricular muscle and Purkinje
fibres. Am. J. Cardiol., 27, 82-92.
CARLISLE, E.J.F., ALLEN, J.D., KERNOHAN, W.G., ANDERSON, J. &
ADGEY, A.A.J. (1990). Fourier analysis of ventricular fibrillation of
varied aetiology. Eur. Heart J., 11, 173-181.
CHEUNG, J.Y., BONVENTRE, J.V., MALIS, C.D. & LEAF, A. (1986).
Calcium and ischemic injury. N. Engl. J. Med., 314, 1670-1676.
CLARK, R.E., FERGUSON, T.B., WEST, P.N., SCHUCHLIEB, R.C. &
HENRY, P.D. (1977). Pharmacological preservation of the ischemic
heart. Ann. Thorac. Surg., 24, 307-314.
COLTART, D.J. & SHAND, D.G. (1970). Plasma propranolol levels in
the quantitative assessment of beta adrenergic blockade in man.
Br. Med. J., 3, 731-734.
DAHL, G. & ISENBERG, G. (1980). Decoupling of heart muscle cells:
correlation with increased cytoplasmic calcium activity and with
changes of nexus ultrastructure. J. Memb. Biol., 53, 63-75.
DAVIS, L.D. & TEMTE, J.V. (1968). Effects of propranolol on the transmembrane
potentials of ventricular muscle and Purkinje fibers of
the dog. Circ. Res., 22, 661-677.
DE MELLO, W.C. (1976). Influence of the sodium pump on intercellular
communication in heart fibres: effect of intracellular injection
of sodium ion on electrical coupling. J. Phyisol., 263, 171-197.
ELHARRAR, V., GAUM, W.E. & ZIPES, D.P. (1977). Effect of drugs on
conduction delay and incidence of ventricular arrhythmias
induced by acute coronary occlusion in dogs. Am. J. Cardiol., 39,
FIRST INTERNATIONAL STUDY OF INFARCT SURVIVAL COLLABORATIVE
GROUP (1986). Randomised trial of intravenous atenolol
among 16027 cases of suspected acute myocardial infarction: ISIS
1. Lancet, ii, 57-65.
FLEET, W.F., JOHNSON, T.A., GRAEBNER, C.A., ENGLE, C.L. &
GETTES, L.S. (1986). Effects of verapamil on ischemia-induced
changes in extracellular K+, pH and local activation in the pig.
Circulation, 73, 837-846.
GEUZE, R.H. & DEVENTE, J. (1983). Effects of duration of ventricular
fibrillation and heart massage on haemodynamic responses after
defibrillation in dogs. Cardiovasc. Res., 17, 282-289.
GILMORE, J.P. & SIEGEL, J.H. (1962). Mechanism of the myocardial
effects of bretylium. Circ. Res., 10, 347-353.
HIRATA, Y., KODAMA, I., IWAMURA, N., SHIMIZU, T., TOYAMA, J. &
YAMADA, K. (1979). Effects of verapamil on canine Purkinje fibres
534 E.J.F. CARLISLE et al.
and ventricular muscle fibres with particular reference to the alternation
of action potential duration after a sudden increase in
driving rate. Cardiovasc. Res., 13, 1-8.
KUPERSMITH, J. (1979). Electrophysiological and antiarrhythmic
effects of lidocaine in canine acute myocardial ischemia. Am. Heart
J., 97, 360-366.
LITTLE, R.A., FRAYN, K.N., RANDALL, P.E., STONER, H.B., YATES,
D.W., LAING, G.S., KUMAR, S. & BANKS, J.M. (1985). Plasma catecholamines
in patients with acute myocardial infarction and
cardiac arrest. Quart. J. Med., 54, 133-140.
MARTIN, G., COSIN, J., SUCH, M., HERNANDEZ, A. & LLAMAS, P.
(1986). Relation between power spectrum time course during ventricular
fibrillation and electromechanical dissociation. Effects of
coronary perfusion and nifedipine. Eur. Heart J., 7, 560-569.
PANTRIDGE, J.F., WEBB, S.W., ADGEY, A.A.J. & GEDDES, J.S. (1974).
The first hour after the onset of acute myocardial infarction. In
Progress in Cardiology, vol 3. ed. Yu, P.N. & Goodwin, J.F. pp.
173-188. Philadelphia: Lea and Febiger.
REIMER, K.A., LOWE, J.E. & JENNINGS, R.B. (1977). Effect of the
calcium antagonist verapamil on necrosis following temporary
coronary artery occlusion in dogs. Circulation, 55, 581-587.
REIMER, K.A., RASMUSSEN, M.M. & JENNINGS, R.B. (1973).
Reduction by propranolol of myocardial necrosis following temporary
coronary artery occlusion in dogs. Circ. Res., 33, 353-363.
ROSEN, M.R., HOFFMAN, B.F. & WIT, A.L. (1975). Electrophysiology
and pharmacology of cardiac arrhythmias. V. Cardiac antiarrhythmic
effects of lidocaine. Am. Heart J., 89, 526-536.
SANNA; G. & ARCIDIACONO, R. (1973). Chemical ventricular defibrillation
of the human heart with bretylium tosylate. Am. J. Cardiol.,
SINGH, B.N. & NADAMANEE, K. (1982). The electrophysiological classification
of antiarrhythmic drugs. In Recent Developments in Cardiovascular
Drugs. ed. Coltart, J. & Jewitt, D. pp. 73-77.
SINGH, B.N. & VAUGHAN-WILLAIMS, E.M. (1971). Effect of altering
potassium concentration on the action of lidocaine and diphenylhydantoin
on rabbit atrial and ventricular muscle. Circ. Res., 29,
SINGH, B.N. & VAUGHAN WILLIAMS, E.M. (1972). A fourth class of
antidysrhythmic action. Effect of verapamil on ouabain toxicity,
on atrial and ventricular intracellular potentials, and on other features
of cardiac function. Cardiovasc. Res., 6, 109-119.
TAGGART, P., DONALDSON, R., ABED, J. & NASHAT, F. (1984). Class
III action of beta-blocking agents. Cardiovasc. Res., 18, 683-689.
VAUGHAN WILLIAMS, E.M. (1984). A classification of antiarrhythmic
actions reassessed after a decade of new drugs. J. Clin. Pharmacol.,
WORLEY, S.J., SWAIN, J.L., COLAVITA, P.G., SMITH, W.M. & IDEKER,
R.E. (1985). Development of an endocardial-epicardial gradient of
activation rate during electrically-induced, sustained ventricular
fibrillation. Am. J. Cardiol., 55, 813-820.