ELECTROPHYSIOLOGICAL ASPECTS OF CARDIAC A CTION OF A NEW ANTIARRHYTHMIC DRUG NIBENTAN (EXPERIMENTAL-STUDY)

Nibentan [N-(4-nitrobenzoil)-N-N-diethyl-1-5 pentadiamin hydrochlorid] (C22H29N3O3 . HCl) in experiments on in situ dog hearts in the dose o f 0.25 mg/kg i.v. increased atrial and ventricular refractory periods by 36+/-4.5% and 26.5+/-2.3%, respectively, without significant change s of S - A, A - H, H - V intervals on His bundle electrogram, No chang es were also noted in systolic or diastolic arterial or left ventricul ar pressures. Nibentan (0.25 mg/kg i.v.) prevented ventricular fibrill ation after acute coronary artery occlusion in 6 of 9 experiments. On isolated Purkinje fibers from dog hearts nibentan dose-dependently pro longed (10(-8) - 10(-6)M) action potential duration at 90% and 50% lev els of repolarization and at pacing cycle lengths of 1000 and 400 ms. An increase in action potential duration (maximally by 35% initial val ue) was not followed by changes in magnitude of resting potential and of the maximum upstroke velocity of the action potential. Racemic nibe ntan increased duration of Purkunje fibers action potentials to a grea ter extent than each of its (+) or (-) enantiomers. On isolated guinea pig papillary muscles nibentan (1 mc) prolonged action potential at t he level of 90% repolarization by 19+/-4.8% and relaxation phase by 22 .6+/-4.0%. Nibentan produced no significant effect on papillary muscle contraction force. Action potentials and ionic currents were studied in isolated frog atrial trabeculae under conditions of a double saccha rose gap. It was shown that 0.1, 1.0 and 5.0 mcM of nibentan increased action potential duration at the level of 80% repolarization by 21%, 35% and 45%, respectively. In interval of potentials between -25 mV an d -35 mV, a decrease of total outflow current by 44% was noted at conc entration of nibentan 5 mcM. The data obtained allowed one to cassify nibentan as an antiarrhythmic drug of the amido-darone group.