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European Heart Journal 1993 14(9):1253-1257;
Copyright © 1993 by the European Society of Cardiology.
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© 1993 The Europen Society of Cardiology

Experimental evidence for beta adrenergic blocking properties of propafenone and for their potential clinical relevance

G. MALFATTO*, P. PESSANO*, A. ZAZA{dagger} and P. J. SCHWARTZ*,{ddagger},

*Clinica Medica Generale e Terapia Medica Italy
{dagger}Dipartimento di Fisiologia e Biochimica Generali, Universita'di Milano Italy
{ddagger}Dipartimento di Medicina, Universita'di Pavia Italy

Received 23 April 1993; .

Correspondence Prof Peter J Schwartz, Clinica Medica Generale e Terapia Medica, Universita' di Milano, via Francesco Sforza, 35—20122 Milano, Italy

Abstract

The magnitude and biological relevance in vivo of the beta-blocking properties, observed in vitro, of propafenone remains controversial. We studied the effects of propafenone on the heart rate response to graded stimulation of the right stellate ganglion in 13 anaesthetized, vagotomized cats. The decentralized ganglion was stimulated (3 ms, 10 to 15 V) for periods of 45s at frequencies from 1 to 14 Hz. The effects of sympathetic stimulation on heart rate were evaluated by the relationship between stimulation frequency and changes in heart rate from control. The relationship was significantly displaced downward and to the right by propafenone (4mg.kg–1, n = 7), indicating a blunted response to sympathetic stimulation. This effect was lost at the highest frequencies. The frequency range at which propafenone was effective is the same as that elicited in cardiac sympathetic nerves by acute myocardial ischaemia. With propranolol (0.5mg.kg–1 n = 4), the effects on the heart rate response were similar but of greater magnitude. Another sodium channel blocker (flecainide, 4 mg.kg–1 n = 2) was administered, and no changes were observed in the heart rate response. Thus, propafenone has significant beta-blocking effects, which would be of clinical relevance during the reflex sympathetic activation consequent to myocardial ischaemia.

Key Words: Propafenone • antiarrhythmic drugs • beta-adrenergic blockade


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