Edihyp

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.

A higher vagal tone or its stimulation under certain conditions is known to increase the threshold of cardiac fibrillation and even to arrest developing arrhythmias. This effect is usually evaluated as a result of limiting the excessive adrenergic effect on the heart, which is observed in stress and ischemia. The following two facts have been first identified: 1) adaptation to moderate continuous stress may induce tonic excitation of parasympathetic regulation of the heart and enhance its resistance to ischemic and reperfusion arrhythmias; 2) this antiarrhythmic effect is completely reproducible by the recently synthesized acetylcholine analogue EDIHYP, ethyl-3/2-ethyl-2,2-dimethylhydrazinium/propionate iodate.