Electrophysiological effects of SD-3212, a novel antiarrhythmic agent, on rabbit hearts in vivo and in vitro.
We examined the electrophysiological effects of SD-3212, a novel antiarrhythmic agent in rabbits in in vivo and in vitro experiments. During in vivo experiments, monophasic action potentials (MAPs) of the left ventricular endocardium were simultaneously recorded with surface ECG and arterial blood pressure (BP). Under constant atrial pacing, SD-3212 (0.1, 0.2, and 0.3 mg/kg/min) was continuously infused in rabbits for 20 min. SD-3212 > or = 0.2 mg/kg/min prolonged PQ interval, QRS duration, and MAP duration, and decreased arterial BP dose dependently. During in vitro experiments, transmembrane APs were recorded from the isolated papillary muscles by a microelectrode technique. SD-3212 (3 x 10(-6)-10(-5) M) prolonged the AP duration (APD) and decreased the maximum upstroke velocity of the AP (Vmax) in a concentration-dependent manner without affecting the amplitude of AP or resting potential. The inhibitory action of SD-3212 on Vmax was enhanced as the stimulation frequency was increased, whereas the prolongation of APD did not vary with stimulation frequency. The results suggest that SD-3212 has an inhibitory action on some outward currents as well as sodium and calcium currents.
Takahashi
N
N
Department of Laboratory Medicine, Oita Medical University, Japan.
Ito
M
M
Ishida
S
S
Fujino
T
T
Maruyama
T
T
Saikawa
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects; D011817:Rabbits; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D013844:Thiazoles; C064356:sesamodil