Treatment of cardiac arrhythmias with phentolamine

1 We studied the antiarrhythmic and electrophysiological effects of UK 52,046-27 (10-8M and 5 x 10-M), a highly selective a,-adrenoceptor antagonist, during global ischaemia (flow reduced to 10% of control for 30 min) and reperfusion, in isolated, buffer-perfused hearts of guinea-pigs. 2 The compound had few electrophysiological effects during normal perfusion, although action potential amplitude and V,,WX were reduced with 10 8 M (by 9% and 22%) and refractory period was increased with 5 x 10-8 M (by 13%) compared to control hearts. 3 Perfusion with 5 x 10-8M UK 52,046-27 reduced the incidence of ventricular tachycardia during ischaemia from 67% to 25%, and during reperfusion reduced the incidence of ventricular tachycardia (from 83% to 17%) and ventricular fibrillation (from 67% to 8%). 4 The compound prolonged significantly action potential duration and refractory period during ischaemia and reperfusion. V,,x was reduced to a greater extent during reperfusion in the treated hearts, while greater increases in QRS width and stimulation threshold occurred during ischaemia in the treated group.5 These results confirm that blockade of the a,-adrenoceptor subpopulation during myocardial ischaemia and reperfusion decreases the incidence of arrhythmias and alters cellular electrophysiology during ischaemia and reperfusion.

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“…Although some early anecdotal reports suggest that a-adrenoceptor blockade may be antiarrhythmic in man (Gould et al, 1969) …”

Section: Discussionmentioning

confidence: 99%

Electrophysiological and Antiarrhythmic Effects of UK 52046-27 during Ischaemia and Reperfusion in the Guinea Pig Heart

Flores

Sheridan

1988

Clinical Science

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“…There have been conflicting reports concerning the effect ofa-adrenoceptor blocking agents on the arrhythmogenic effects of cardiac glycosides in different experimental animals. Both protection (Ettinger et al, 1969;Gould et al, 1969;Rothans & Powell, 1975) or no effect (Erlig & Mendez, 1964;Melville et al, 1970;Mukherjee et al, 1972) were reported. (Lechat & Schmitt, 1982).…”

Section: Introductionmentioning

confidence: 99%

Effects of α‐adrenoceptor agonists and antagonists on ouabain‐induced arrhythmias and cardiac arrest in guinea‐pig

Thomas

Tripathi

1986

British J Pharmacology

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1 Effects of a-adrenoceptor agonists and antagonists with different affinity for ak-and ot2-receptors on ouabain-induced arrhythmias in guinea-pigs were studied. 2 Early arrhythmias, ventricular fibrillation and cardiac arrest were induced in anaesthetized guineapigs by the slow intravenous infusion of ouabain. 3 Phenylephrine and yohimbine potentiated the cardiotoxicity of ouabain significantly whereas prazosin and clonidine showed significant antiarrhythmic effects and delayed the cardiac arrest. 4 It is concluded that selective ax-receptor stimulation and a2-receptor blockade increases the cardiotoxic effects of ouabain and selective 2-receptor stimulation and a,-receptor blockade inhibits ouabain-induced arrhythmias and cardiac arrest in guinea-pigs.

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“…Its possible mechanisms would be related to a blocking action on beta-adrenoceptors, an inhibition of postganglionic cardiac sympathetic neural discharges, and a direct depression of cardiac excitability in a manner similar to quindine (Lucchesi 1965;Somani and Lum 1965). On the other hand, many authors observed that alpha-adrenoceptor blocking agents also have anti-arrhythmic properties in man and laboratory animals (Leimdorfer 1952; Morris et al 1952; Gould et al 1969). However, its possible mechanism is not clear enough.…”

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confidence: 99%

Effects of thymoxamine on ouabain-induced arrhythmias in dogs.

Oguro

Hashimoto

Nakashima

1982

Tohoku J. Exp. Med.

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The effect of thymoxamine, a pure alpha-adrenoceptor blocking agent, on ouabain-induced arrhythmias was investigated in dogs to clarify whether thymoxamine has an arrhythmogenic or an anti-arrhythmic action. Thymoxamine, 1 mg/kg i.v., inhibited the manifestation of ventricular arrhythmias (VA) and the pressor effect produced by ouabain infusion (1,ug/kg/min i.v.) as 5 mg/ kg i.v. of phentolamine did. Low doses of these drugs did not affect the VA. Simultaneous infusion of phenylephrine (5 yg/kg/min i.v.) with ouabain enhanced the manifestation of VA accompanying pressor effects, which were inhibited by thymoxamine (1 mg/kg) in a parallel manner. Infusion of isoprenaline (0.2 µg/ kg/min i.v.) with ouabain enhanced the manifestation of VA, but the enhancement was to a lesser extent than with phenylephrine. Thymoxamine, 1 mg/kg, did not affect the VA. The infusion of CaC12 (20 mg/kg/min i.v.) with ouabain enhanced the manifestation of VA, which was not inhibited by thymoxamine. These results show the possibility that the protective effect of thymoxamine on the manifestation of VA may be mainly associated with inhibitions of pressor effects mediated through vascular alpha-adrenoceptors. alpha blocker; thymoxamine; phentolamine; ouabain-induced arrhythmias It has been generally recognized that many of beta-adrenoceptor blocking agents have anti-arrhythmic actions. Its possible mechanisms would be related to a blocking action on beta-adrenoceptors, an inhibition of postganglionic cardiac sympathetic neural discharges, and a direct depression of cardiac excitability in a manner similar to quindine (Lucchesi 1965;Somani and Lum 1965). On the other hand, many authors observed that alpha-adrenoceptor blocking agents also have anti-arrhythmic properties in man and laboratory animals (Leimdorfer 1952;Morris et al. 1952;Gould et al. 1969). However, its possible mechanism is not clear enough. In the present experiments, the effects of phentolamine and thymoxamine on ouabain-induced arrhythmias were examined and a possible involvement of alpha-adrenoceptors in the heart or peripheral vascular beds in manifestation of ventricular arrhythmias (VA) was discussed.

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Treatment of cardiac arrhythmias with phentolamine

Cited by 28 publications

References 3 publications

Electrophysiological and Antiarrhythmic Effects of UK 52046-27 during Ischaemia and Reperfusion in the Guinea Pig Heart

Electrophysiological and Antiarrhythmic Effects of UK 52046-27 during Ischaemia and Reperfusion in the Guinea Pig Heart

Effects of α‐adrenoceptor agonists and antagonists on ouabain‐induced arrhythmias and cardiac arrest in guinea‐pig

Effects of thymoxamine on ouabain-induced arrhythmias in dogs.

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