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...

The antiarrhythmic activity of befol (an isotoxic dose) is higher than (or comparable to) that of lidocaine and bonnecor in atrial and ventricular arrhythmias induced by acute ischemia, reperfusion, myocardial infarction, or ouabain treatment. In epinephrine-induced arrhythmia, befol is inferior to these drugs (except lidocaine) in activity and range of therapeutic action. Key Words: befol; lidocaine; bonnecor; arrhythmias; treatmentBefol [4-chloro-N-(3-morpholinopropyl)-benzamide hydrochloride], a Russian-manufactured antidepressant, is a reversible monoamine oxidase inhibitor selectively inhibiting serotonin deamination [3].This drug is effective against cardiac rhythm disturbances (CRD) of ischemic and nonischemic origin [10].The aim of the present study was to compare the antiarrhythmic activities (AAA) of befol, lidocaine, and bonnecor in experiments on animals with various CRD. MATERIALS AND METHODSExperiments were performed on 205 male Wistar rats (0.170-0.240 kg), 9 rabbits (2.4-3.6 kg), 107 cats (2.8-4.4 kg), and 25 dogs (7-25 kg).Acute toxicity (mean lethal dose, LDE0) of befol, lidocaine, and bonnecor was determined in experiments on rats (intravenous injections).The antiarrhythmic activities of the drugs were studied in atrial [16] [14] in rabbits and ouabaininduced arrhythmia in cats (0.05 mg/kg with successive injection of 0.01 mg/kg each 10 min until extrasystole and ventricular tachycardia appeared). Atrioventricular arrhythmia was induced by aconitine [5] in rats. Antiarrhythmic activity was evaluated by biological titration [17] in atrial arrhythmias, by the difference in CRD incidence in experimental and control animals with ventricular CRD induced by acute ischemia and reperfusion, and by the per, centage of ectopic ventricular contractions recorded 24 h after occlusion of descending branch of the left coronary artery in CRD induced by myocardial infarction. The AAAs of the drugs were compared by the isotoxic dose. In chemically-induced CRD, AAA was assessed by the mean effective dose (EDE0), mean lethal dose (LDE0), and antiarrhythmic index (LDJEDE0), which characterizes the range of therapeutic action [2]. Befol, lidocaine, and bonnecor were injected intravenously in ascending doses. The data were processed statistically by the methods described previously [2,8]. out of 5 cases bonnecor induced conduction disturbances of various intensities. Lidocaine was not tested in atrial CRD, since in therapeutic doses it is ineffective against these arrhythmias [6]. As Table 1 shows, occlusion arrhythmia did not develop in 40% of the control cats, while reperfusion arrhythmia occurred in all cases and in 67% cats it turned into ventricular fibrillation. Befol (11.7 mg/kg, 5% LDs0) did not prevent these CRD. Higher doses of befol (23.4 and 35.0 mg/kg, 10 and 15% LDs0, respectively) prevented the early occlusion and reperfusion arrhythmias in 85.7% (23.4 mg/kg) or 100% (35.0 mg/kg) of the cats; none of the animals developed ventricular fibrillation. At 1.4 mg/kg (5% LDs0) lidocaine exhibited no appr...

Dimebon, an antihistamine agent, exerts a moderate antianginal effect, improving the function of ischemic focus in the myocardium and decreasing the necrotic zone in experimental myocardial infarction. Dimebon is less active than obsidan, finoptin (except for the size of the necrotic zone), and cordaron. Key Words: dimebon; obsidan; .finoptin; cordaron; ischemia; myocardial infarction; treatmentThe Hx-receptor blocker dimebon exhibits antiarrhythmic activity in a wide dose range (0.1-10.8 mg/kg), being effective against cardiac rhythm disturbances of different origins, including those induced by experimental myocardial infarction [2].At 5 and 7.5 mg/kg dimebon increases the rate of coronary blood flow and decreases oxygen consumption by the myocardium, creating an oxygen reserve in the heart in local acute myocardial ischemia.In this study we compared the effects of dimebon with those of obsidan (propranolol), finoptin (verapamil), and cordaron (amiodarone) on the functional state of ischemic focus in the myocardium and on the size of the necrotic zone (NZ) in experimental myocardial infarction. MATERIALS AND METHODSExperiments were performed on 20 cats weighing 2.5-4.2 kg. The animals were anesthetized with Nembutal (40 mg/kg intraperitoneally), and local myo- The effects of the drugs on the size of NZ in experimental myocardial infarction were studied on 40 cats weighing 2.8-4.2 kg. The animals were anesthetized with Nembutal (40 mg/kg intraperitoneally). Myocardial infarction was produced by occlusion of the DBLCA between the upper and middle third. The size of NZ was determined as described elsewhere [3]. The drugs were injected intravenously 30 min before and 120 min after ligation of DBLCA.The results were statistically processed as described previously [ 1,7]. RESULTSDepression of the ST segment was observed after administration of dimebon in a dose of 7.5 mg/kg.The greatest decrease in EST (40.3%) was recorded

It is shown that the nonglycoside cardiotonic drug suphan exhibits antiarrhythmic and antifibfillatory activity, although less pronounced than that of lidocaine. When lidocaine was administered after suphan, the antifibrillatory effects of both preparations increased. Key Words: suphan; #docaine; arrhythmias; treatmentIt is established that the most common variant of ischemic heart disease, angina pectoris, arises from regional transitory insufficiency characterized by consecutive periods of ischemia and restoration of circulation, i.e., reperfusion. The use of intense perfusion and oxygenation of the myocardium (aortocoronary bypass, coronary angioplastics, fibrinolysis, etc.) can also cause postischemic reperfusion syndrome. This is usually accompanied by ominous cardiac rhythm disturbances, reperfusion arrhythmias, such as ventricular fibrillation (VF), acute heart failure, etc. [5].Recent investigation showed that the nonglycoside cardiotonic drug suphan (N-succine-dl-tryptophan dipotassium salt) exerts antihypoxic and antianginal effects in animals [4], and therapeutic effect in patients with ischemic heart disease complicated by congestive circulatory failure.The aim of the present study was to compare antiarrhythmic and antifibrillatory activity of suphan with that of lidocaine and to evaluate the efficiency of their combination in modeled early occlusion (EOA) and reperfusion (RPA) arrhythmia, including VF.Department of Pharmacology, Kuban Medical Academy, Krasnodar MATERIALS AND METHODSExperiments were carried out on 140 male Wistar rats (0.155-0.210 kg) and 75 cats (2.6-3.4 kg).Acute toxicity (mean lethal dose, LDs0 ) was determined by injecting the preparations intravenously to rats as described previously [6].In cats narcotized with Nembutal (40 mg/kg, intraperitoneally) and artificially ventilated, the chest was opened and occlusion (30 rain) and reperfusion (10 min) of the descendent branch of the left coronary artery at the level of lower edge of the auricula was performed [3]. The test preparations and their combinations were slowly injected intravenously in isotoxic doses (5, 10, 15, 20, and 30% of LDs0) 5-7 min prior to occlusion of the coronary artery. For evaluation of antiarrhythmic activity, the occurrences of EOA, RPA, and VF were recorded using an EKIT-04 electrocardiograph.The data were processed statistically using )~2 test [ 1 ]. RESULTSAs seen from Table 1, in the control series coronary occlusion led to EOA in 60% of cases, while RPA