Effects of MS-551, a new class III antiarrhythmic drug, on programmed stimulation-induced ventricular arrhythmias, electrophysiology, and hemodynamics in a canine myocardial infarction model.
We examined the effects of MS-551 (1,3-dimethyl-6-[(2-[N-(2-hydroxyethyl)-3-(4- nitrophenyl)propylamino]ethylamino] 2,4(1H,3H)-pyrimidinedione hydrochloride), a new class III antiarrhythmic drug, on programmed electrical stimulation (PES)-induced ventricular arrhythmias, the effective refractory period (ERP), intraventricular conduction, and hemodynamics in a canine myocardial infarction (MI) model. MS-551 was administered intravenously (i.v.) in two consecutive doses; the first dose (low dose) was 0.5 mg/kg/min after a bolus injection of 0.3 mg/kg, and a second dose (high dose) was 0.1 mg/kg/min after a bolus injection of 0.3 mg/kg. PES induced ventricular tachycardia (VT) or ventricular fibrillation (VF) in 10 of 12 animals. MS-551 abolished or lessened the ventricular arrhythmias in 7 of 10 animals at both doses. ERP was significantly prolonged by MS-551 in both the normal and infarcted zones in a dose-dependent fashion. Ventricular conduction of a premature excitation induced by a premature stimulation with various coupling intervals was decreased only at a coupling interval approximating that of ERP. MS-551 at either low or high dose did not significantly change the heart rate (HR), mean blood pressure (MBP), cardiac output (CO), or maximum rate of increase in left ventricular pressure (LVP) significantly. MS-551 produced a suppression of the PES-induced ventricular arrhythmias through prolongation of ERP without having any significant effect on hemodynamics in a canine MI model.
Kondoh
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Fujinomiya City, Japan.
Hashimoto
H
H
Nishiyama
H
H
Umemura
K
K
Ozaki
T
T
Uematsu
T
T
Nakashima
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology*; D011744:Pyrimidinones / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant