[The antiarrhythmic action of the synthetic acetylcholine analog EDIHYP in calcium chloride- and strophanthin-induced heart rhythm disorders]. / Antiaritmicheskoe deistvie sinteticheskogo analoga atsetilkholina EDIGIP pri khloridkal'tsievykh i strofantinovykh narusheniiakh serdechnogo ritma.

The experiments on Wistar rats and chinchilla rabbits showed that EDIHYP (5 mg/kg intravenously) completely prevented cardiac fibrillation and mortality in rats with calcium-chloride-induced arrhythmias, (CaCl2-200 mg/kg intravenously). Administration of atropine (0.1 mg/kg, if administered subcutaneously, 30 minutes before the acute experiment) exerts no influence on the drug's antiarrhythmic activity but eliminates its cholinergic component--salivation and lacrimation. When administered in the same dose EDIHYP to a great extent prevents oubaine (strophanthin)-induced arrhythmias in rabbits but fails to influence aconitine-induced arrhythmias. This suggests that EDIHYP's ability of direct or indirect blockade of slow Ca-channels underlies the mechanism of its antiarrhythmic action.

[Bioelectrical mechanism of the anti-arrhythmia effect of a synthetic acetylcholine analog EDIHYP]. / Bioélektricheskii mekhanizm antiaritmicheskogo deistviia sinteticheskogo analoga atsetilkholina EDIGIP.

The synthetic acetylcholine analogue ethyl-3-(2,2-dimethyl-2-ethyl-hydrazinium) propionic iodide (EDIHYP) exerts a powerful antiarrhythmic action in cardiac ischemic, reperfusion, and adrenergic lesions, as well as in infarction and postinfarction cardiosclerosis, as evidenced by animal experiments. The study was undertaken to examine the electrophysiological mechanism of EDIHYP s action on isolated rat heart cardiomyocytes. It was shown that the agent substantially reduced the resting potential, as well as action potential amplitude and duration in total ischemia and resultant reperfusion. The antiarrhythmic changes provided a multiple decrease in the duration of ventricular tachycardia and cardiac fibrillation in reperfusion. Thus, the fact that EDIHYP has a direct action on the bioelectrical activity of cardiomyocytes may play an important role in its antiarrhythmic effect in the whole body.

Site-specific modulation of carcinogen-induced gastrointestinal tract nuclear anomalies in B6C3F1 mice by chloroform.

Chloroform (CHCl3) is an established rodent carcinogen and a prevalent contaminant of chlorine-disinfected drinking water. Thus in the United States CHCl3, along with other trihalomethanes, is regulated not to exceed 100 ppb in potable water. Recently, several studies have shown that CHCl3 also has anti-cancer properties as it inhibits tumor growth in mouse liver and in the gastrointestinal tract of the rat. In this paper we show that CHCl3 also inhibits the propensity for three gastrointestinal tract carcinogens, benzo(a)pyrene (BAP), 1,2-dimethylhydrazine (DMH) and methylnitrosourea (MNU), to induce nuclear anomalies in the proximal colon of the B6C3F1 mouse. For example, in mice pre-adapted to 1800 ppm CHCl3 for 30 days prior to the carcinogen administration the level of nuclear anomalies induced in the proximal colon by BAP was reduced by four-fold (0.9 +/- 0.7 v. 3.6 +/- 1.0 anomalies/10 crypts; p less than 0.001) and two-fold for MNU (2.4 +/- 1.0 v. 4.6 +/- 1.6; p less than 0.001) and DMH (0.9 +/- 0.9 v. 1.7 +/- 0.8; p = 0.03). In the duodenum CHCl3 was effective at inhibiting unclear anomalies only for MNU (45.3 +/- 4.6 v. 30.4 +/- 3.5; p = 0.02). The inhibitory effect of CHCl3 does not extend to nuclear anomalies of the forestomach. The anti-cancer properties of CHCl3 are discussed in light of its cancer causing potential and possible application to human risk assessment.

[Correction of disorders of electric stability of the heart and arrhythmia by using a synthetic analog of acetylcholine]. / Ustranenie narushenii élektricheskoi stabil'nosti serdtsa i aritmii s pomoshch'iu sinteticheskogo analoga atsetilkholina.

It was shown in experiments on Wistar male rats that ethyl, 3/2, ethyl, 2/2, dimethylhydrazine propionate iodate (EDIHYP), a synthetic acetylcholine analogue, eliminates in situ the fall of the ventricular fibrillation threshold and the extrasystole observed on the background of vagal bradycardia in experimental myocardial infarction and postinfarction cardiosclerosis. The elimination of disturbed heart electric stability was not accompanied by cholinergic, negative chronotropic effect of the drug. In isolated heart, high concentrations of EDIHYP (10(-4) M) had negative chronotropic effect but lacked antiarrhythmic effect in local ischemia and reperfusion. The bradycardia induced by EDIHYP was absent and the antiarrhythmic effect was strikingly pronounced on the background of muscarinic receptors blockade with atropine. Thus EDIHYP realizes its antiarrhythmic effect not via muscarinic receptors but by some other way which requires studying by methods of molecular pharmacology.