Rate-dependent effects of sematilide on ventricular monophasic action potential duration and delayed rectifier K+ current in rabbits

Journal of Cardiovascular Pharmacology
G N BeatchB A Williams

Abstract

Our objective was to define the actions of sematilide in rabbits and to assess the contribution of the delayed rectifier (IK) to rate dependence of action potential duration (APD) in rabbit ventricular myocardium. In studies in vivo, New Zealand White rabbits were used to obtain dose/response curves of the effects of sematilide on APD from contact monophasic action potentials (MAP), ventricular effective refractory period (VERP), and ECG. Sematilide or placebo was administered as an i.v. bolus followed by a 45-min infusion in the following cumulative manner: infusion 1 (1 mg/kg bolus + 8 micrograms/kg/min); infusion 2 (2 mg/kg + 20 micrograms/kg/min); and infusion 3 (7 mg/kg + 68 micrograms/kg/min). At each infusion level, VERP and APD at 75% repolarization (APD75) were measured during cardiac pacing between 200- and 400-ms cycle length (CL). Serum sematilide levels were analyzed by high-performance liquid chromatography (HPLC). In studies in vitro, sematilide's effects on the delayed rectifier were assessed in isolated rabbit ventricular myocytes by using patch-clamp techniques. Sematilide infusion in vivo resulted in stable serum levels of 1.3 +/- 0.5, 3.7 +/- 1.4, and 13.4 +/- 1.8 micrograms/ml during infusions 1, 2, and 3, ...Continue Reading

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Citations

Apr 16, 1998·Medical & Biological Engineering & Computing·D R DickensonG N Beatch
Oct 24, 1998·Progress in Biophysics and Molecular Biology·E Carmeliet, K Mubagwa
Jan 22, 2005·European Journal of Pharmacology·Akira TakaharaKeitaro Hashimoto
Dec 20, 2002·Journal of Cardiovascular Pharmacology and Therapeutics·Paul DorianDavid Newman
Apr 8, 1998·The American Journal of Physiology·J F Spear, E N Moore

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