The electrophysiological effects of a series of drugs with Class I antiarrhythmic activity were examined in sheep Purkinje fibres, superfused in vitro with either a normal or hypoxic, hyperkalaemic and acidotic physiological salt solution (PSS).

In normal sheep Purkinje fibres, lignocaine, disopyramide, nicainoprol and propranolol all significantly reduced action potential height and the maximum rate of depolarization of phase zero (MRD) and abbreviated the action potential, without modifying resting membrane potential (RMP).

Verapamil at the highest concentration studied, 8 μm, significantly reduced MRD with an associated slight membrane depolarization and abbreviated action potential duration measured at 50% repolarization (APD50).

Superfusion of sheep Purkinje fibres with a hypoxic, hyperkalaemic and acidotic PSS resulted in marked reductions in resting membrane potential, upstroke and duration of the action potential.

In the presence of modified PSS, lignocaine, propranolol and verapamil all reduced MRD to a greater extent than in normal PSS. The effects of nicainoprol on MRD were not affected whereas those of disopyramide were significantly attenuated.

Under simulated ischaemic conditions, lignocaine, propranolol and nicainoprol did not produce a concentration‐dependent reduction in action potential duration whereas disopyramide and verapamil, respectively, prolonged and abbreviated both APD50 and APD90.

The Na+ channel blocking actions of the different subtypes of Class I antiarrhythmic agents studied, as well as their effects on action potential duration, were modified differently by simulated ischaemia.

1991-08-01·European Heart Journal1区 · 医学

Dose-related antiarrhythmic effects of nicainoprol in patients with chronic ventricular arrhythmias — a double-blind, placebo-controlled, cross-over multicentre trial

1区 · 医学

Article

作者: Ostrowski, J. ; Reifart, N. ; Blaeser, A. ; Kaltenbach, M. ; Schneider, W. ; Kober, G.

One hundred and three patients with a history of ventricular arrhythmia were screened by baseline 24-h Holter monitoring for a minimal mean number of 30 premature ventricular beats (PVB) per hour. One hundred and one patients were subsequently enrolled in a double-blind, cross-over trial, including four 4-day periods with administration of placebo (PL) or nicainoprol (N.) in doses of 200, 400, 600 mg three times daily in randomized order. Antiarrhythmic efficacy could be evaluated in 61 patients who met all requirements of the protocol, including a complete sequence of valid Holter recordings (greater than 18 h each). Total PVBs were significantly reduced by the 400-mg dose (65%) and the 600-mg dose (71%) as compared to baseline. Two hundred mg N. and PL led to a non-significant reduction of PVBs by 41% and 24%, respectively. An individual response, assumed where there was simultaneous reduction of total PVBs greater than 75%, of ventricular pairs greater than 90% and elimination of ventricular runs, was found in 6 (10%), 10 (16%), 21 (34%), and 22 (36%) patients with PL, 200 mg N., 400 mg N. and 600 mg N., respectively. Four hundred and 600 mg N, significantly prolonged the PR interval (0.17 s and 0.18 s; median values) as compared with baseline (0.16 s), while the QRS duration was significantly increased only by the 600-mg dose (from 0.10 to 0.11 s). Heart rate, mean blood pressure, QT and JTc intervals were not significantly influenced by any dose of N.(ABSTRACT TRUNCATED AT 250 WORDS)

1991-02-01·Journal of Cardiovascular Pharmacology4区 · 医学

Effects of a New Antiarrhythmic Drug TYB-3823* on Canine Ventricular Arrhythmia Models

4区 · 医学

Article

作者: Sugiyama, Atsushi ; Hirasawa, Akira ; Matsuzaki, Takushi ; Hashimoto, Keitaro ; Haruno, Akihiro

The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, TYB-3823 [1-(2,6-dimethylphenyl)-4,4-dimethyl-aminoguanidine hydrochloride], were investigated. To determine the antiarrhythmic effects, spontaneously occurring adrenaline-, digitalis-, and two-stage coronary ligation-induced arrhythmias were used. TYB-3823 suppressed these three arrhythmia models. The antiarrhythmic plasma concentrations, IC50, of TYB-3823 for digitalis-, coronary ligation-, and adrenaline-induced arrhythmias were 7.8, 16.8, and 5.0 micrograms/ml, respectively. In the blood perfused sinoatrial (SA) node and papillary muscle (PM) preparations, TYB-3823 decreased the sinoatrial rate (SAR) and contractile force following an initial small positive inotropic effect and increased the intraventricular conduction time and coronary blood flow. These results indicate that TYB-3823 is similar to other class I antiarrhythmic agents, such as aprindine and nicainoprol, in the antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug.

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