The antihistamine drugs (Hi-blockers) dimebone and especially phencarol exhibit antiarrhythmic activity under conditions of neurogenic ventricular fibrillation. The antiarrhythmic activity of phencarol is associated with pronounced vagolytic effect, while that of dimebone is due to both vagolytic and moderate cardiotropic effect. Key Words: phenearol; dimebone; neurogenic ventricular fibrillation; vagolytic effect; cardiotropic effectThe Hi-histamine receptor blockers phencarol (quinuclidyl-3-diphenylcarbinol hydrochloride) and dimebone [3,6 -dimethyl -9-(2-methylpyridyl-5)-ethyl-1,2, 3,4-tetrahydro-3,-carboline dihydrochloride) [2,4] exhibit antiarrhythmic activity in modeled cardiac arrhythmias (CA). For instance, phencarol stops and prevents arrhythmias induced by calcium chloride, adrenalin, and strophanthin without affecting the ECG parameters, heart rate and producing no cardiodepressive effect. The antiarrhythmic activity of phencarol is attributed to its effect not only on Hi-histamine receptors, but also on the cardiomyocyte membrane permeability for calcium ions [9]. Dimebone exerts an antiarrhythmic effect in CA induced not only by chemical agents (adrenalin, strophanthin, calcium and barium chloride), but also by damage to the sinus node (atrial arrhythmia) or by myocardial infarction (ventricular arrhythmias), in some CA being superior or close by its activity and therapeutic range to quinidine, etmozin, bonnecor, and isoptin. The mechanism of this effect includes a primary effect of dimebone on slow calcium channels as well as prolongation of the effective refrac- MATERIALS AND METHODSThe study was performed on 16 cats weighing 2.5-4.5 kg narcotized with Chloralose and Nembutal (75 and 15 mg/kg, respectively) and artificially ventilated; body temperature was controlled automatically (37~ The right vagus nerve was cut at the level of the thyroid cartilage and its peripheral end was pinned on bipolar needle electrodes (the distance between the poles was 2.5 mm) and embedded into medical wax-vaseline oil mixture. Bipolar platinum probes were inserted into the right ventricle through the right femoral and jugular veins and used for recording the intra-atrial ECG (using an intervalograph assembled in our laboratory [7]) and electrical stimulation. The atrium was stimulated (5 msec, 1.5-4.0 threshold voltage) either in a periodic mode or with singe pulses synchronized with the P wave of the ECG using an ESU-2 electrostimulator. The vagus nerve was stimulated in either periodic (2

Antiarrhythmic activities of KLN-93 (crystaUographically homogeneous paraaminobenzoic acid ester derivative), dicaine, and lidocaine in cats with neurogenic atrial fibrillation rank in the order in which these agents are named and depend on their vagolytic but not cardiotropic effect whose intensity decreases in the following series: dicaine>lidocaine> KLN-93. Key Words: neurogenic atrial fibrillation; local anesthetics; antiarrhythmic effect; vagolytic effect; cardiotropic effectLocal anesthetics lidocaine, trimecaine, richlocaine, etc., exert antiarrhythmic effect which is determined by molecular structure of these drugs [1,4]. This prompts thorough studies of antiarrhythmic activities of not only known local anesthetics, but also of new compounds with such effects, one of which is crystallographically homogeneous derivative of paraaminobenzoic acid ester (laboratory name prepared at the Bioeffect Institute.An important aspect of the problem is selection of the optimal model of cardiac arrhythmia; we consider neurogenic atrial fibrillation (NAF) easily induced in healthy animals as such a model [5,9,10]. It is maximally similar to natural cardiac rhythm disorders which usually develop in subjects with satisfactory somatic and hemodynamic status. We compared the antiarrhythmic effects of KLN-93, dicaine, and lidocaine in neurogenously induced atrial arthythmia. MATERIALS AND METHODSExperiments were carried out on 36 cats weighing 2.5-4.5 kg narcotized intraperitoneally with Chloralose and Nembutal in doses of 75 and 15 mg/kg, Department of Pharmacology, Department of Normal Physiology, Kuban State Medical Academy, Krasnod~r; Bioeffect Institute, Ministry of Science and Technological Strategy, Moscow respectively, under conditions of forced ventilation at body temperature 37~ In all animals the right vagus nerve was cut on the neck; the peripheral end of the nerve was stimulated by an ESU-2 electric stimulator (2 msec, 40 Hz, 6 thresholds) or with a single flash of pulses (2 msec, 40 Hz, 6 thresholds, 3 pulses) synchronously with the P wave [5,6]. Bipolar platinum probes were inserted through the right jugular and femoral veins. One probe served as a lead for intra-atrial ECG through cardiosynchronizing block of an original design [8], the other served for stimulation of the atrium (5 msec, 1.5'4.0 threshold) with an ESU-2 stimulator [7]. The ECG was recorded by an N3031-4 automated recorder, the processes were visually assessed using an IM-789 oscillograph.The duration of the P-P (To) and P-Q intervals, time of sinoatrial conduction of excitation [5,11,12], excitation thresholds for the vagus nerve and atrium, the effective refractory period of the atrium, and synchronizing (within the cycle) and tonic components of the chronotropic effect during stimulation of the vagus nerve with a single flash of pulses were assessed [5,6]. Manifestation of the intracycle component was assessed from the prolongation of the cardiocycle, during which test flash of pulses was delivered, and tonic effect was estimated from the m...

In experiments on anesthetized cats, aconitine produced direct arrhythmogenic and cardiotoxic effects on the myocardium combined with indirect cardiotropic effects mediated via activation of extracardial nerves. Aconitine demonstrated pronounced cholinolytic properties and blocked vagal arrhythmogenic effect.

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