Influence of Reserpine and βTM 10 on Digitalis-Induced Ventricular Arrhythmia

Abstract

After catecholamine depletion by reserpine, the capacity of the digitalis materials to induce ventricular arrhythmia is diminished. In papillary muscles from cats pretreated with reserpine, the incidence of ouabain-induced extra beats is reduced. The dose of ac. stroph. necessary to induce ventricular arrhythmia in combination with vagal stimulation is increased by reserpine pretreatment. Threshold doses comparable to those in cats not pretreated with reserpine produced arrhythmia after the catecholamine stores were repleted with norepinephrine or isoproterenol. In dogs with A-V block, βTM 10, an agent which prevents the release of catecholamines, markedly reduces the response of the ventricular pacemaker to ac. stroph. Since the arrhythmias induced by large doses of ac. stroph. are not affected by reserpine pretreatment, it is concluded that while catecholamine release is the primary mechanism involved in the arrhythmia produced by small doses, another mechanism also plays a role in this action after larger doses. Only in the dose of 10 mg/kg did it appear that catecholamine depletion did not account entirely for the action of reserpine. The ac. stroph. threshold dose was not increased to the same degree as with the smaller doses of reserpine, and the incidence of ventricular fibrillation induced by the large dose of ac. stroph was reduced. Hypotension produced by reserpine and βTM 10 did not seem to be an important factor in depression of the responsiveness of the ventricular pacemaker to ac. stroph. While the incidence of ouabain-induced extra beats was reduced by reserpine pretreatment, the action of ouabain to increase the tension developed by isolated papillary muscles was not affected.

Effect of Reserpine and Pronethalol on the Therapeutic and Toxic Actions of Digitalis in the Dog Heart‐lung Preparation

“…But here again one could also argue that reserpine may leave some cardiac catechol amine stores too small to be measured. Our results are not in harmony with those of Takagi, Zanuttini, Khalil & Bellet (1965) who studied the influence of reserpine on the toxic action of digoxin on intact dogs and of Roberts, Ito, Reilly & Cairoli (1963) who used cat papillary muscle and intact cats and dogs.…”

Effects of the myocardial‐selective α1‐adrenoceptor antagonist UK‐52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs

“…The pacemaker site is usually located in a left bundle branch or the Purkinje fibre network (Damato et al, 1971). It has been suggested that the arrhythmia may be due in part to catecholamine release (Roberts et al, 1963), but although early studies with pronethalol had demonstrated antiarrhythmic efficacy in the ouabain model (Vaughan Williams & Sekiya, 1963), subsequent work by Lucchesi (1965) indicated that this antiarrhythmic effect was not related to pronethalol's #-blocking properties. Pronethalol in conjunction with the class 1 antiarrhythmic agents has significant membrane-stabilizing properties and it is this action that accounts for its antiarrhythmic activity in the ouabain model (Somani & Lum, 1965).…”

Effect of Quinidine and Pronethalol on Acetylstrophanthidin-Induced Ventricular Arrhythmia in Cats Treated with Reserpine

“…In animals not treated with reserpine, the control dose of acetylstrophanthidin required to produce arrhythmia closely agrees with the dose previously reported from this laboratory. 1 In that study, Although the control thresholds in the quinidine series were determined against a background of critical S-A nodal rate in one case and higher rates in the other (see Methods), the average threshold doses were not significantly different. (Table 1; P>0.1).…”

“…1 ' 2 Roberts et al 1 demonstrated that ventricular arrhythmias produced by small doses of acetylstrophanthidin could be prevented by treatment with reserpine, whereas those produced by large doses were not affected. Erlij and Mendez 2 reported that reserpine as well as sympathectomy and adrenalectomy caused an increase in the dose of digitoxin necessary to produce death.…”