Rate-dependent effects of sematilide on ventricular monophasic action potential duration and delayed rectifier K+ current in rabbits.
Rate-dependent effects of sematilide on ventricular monophasic action potential duration and delayed rectifier K+ current in rabbits.
复制标题
司马利特对兔心室单相动作电位持续时间和延迟整流 K 电流的速率依赖性影响。
DOI：
10.1097/00005344-199611000-00003
复制
发表时间：
1996
影响因子：
3
通讯作者：
B. Williams
中科院分区：
文献类型：
--
作者：
G. Beatch;D. Davis;S. Laganière;B. Williams
本研究旨在观察司马利特对家兔心室肌细胞动作电位时程（APD）的作用，并探讨延迟整流（IK）对动作电位时程（APD）频率依赖性的影响。在体内研究中，使用新西兰白色家兔，通过接触性单相动作电位（MAP）、心室有效不应期（VERP）和ECG获得司马利特对APD影响的剂量/反应曲线。司马利特或安慰剂以静脉推注给药，随后以以下累积方式输注45分钟：输注1（1 mg/kg推注+ 8 μ g/kg/min）;输注2（2 mg/kg + 20 μ g/kg/min）;和输注3（7 mg/kg + 68 μ g/kg/min）。在200- 400-ms周期长度（CL）之间的心脏起搏期间，在每个输注水平下，测量VERP和75%复极化时的APD（APD 75）。采用高效液相色谱法（HPLC）分析血清司马利特水平。在离体研究中，采用膜片钳技术观察了司马利特对离体兔心室肌细胞延迟整流的影响。在体内输注司马替利特导致在输注1、2和3期间分别稳定的血清水平为1.3 +/- 0.5、3.7 +/- 1.4和13.4 +/- 1.8微克/ml。最大效应发生在输注2时，因此在400 ms CL时，司马利特加宽了给药前APD 75（145 +/- 5 ms）增加27 +/- 4%（与安慰剂相比p < 0.001），在200 ms CL时，司马利特延长给药前APD 75（115 +/- 10 ms）仅降低18 +/- 4%（p < 0.001 vs.安慰剂; p < 0.05 vs. 400-ms CL）。在VERP中观察到类似的效果。在快速起搏的适应和恢复过程中，司马利特增强了APD的频率依赖性，并在给定的CL下产生了相同程度的APD延长。兔心室肌细胞似乎至少有两种类型的延迟整流。司马利特选择性阻断IKr，重复刺激不能缓解阻滞。总之，司马利特的APD增宽效应与既往起搏史无关。由于快速重复刺激，司马利特对可能导致APD缩短的背景过程影响不大。
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, respectively. Maximal effects occurred at infusion 2, such that at 400 ms CL, sematilide widened predrug APD75 (145 +/- 5 ms) by 27 +/- 4% (p < 0.001 vs. placebo), and at 200-ms CL, sematilide prolonged predrug APD75 (115 +/- 10 ms) by only 18 +/- 4% (p < 0.001 vs. placebo; p < 0.05 vs. 400-ms CL). Similar effects were observed in VERP. Sematilide enhanced rate dependence of APD and produced the same degree of APD prolongation at a given CL, during accommodation to and recovery from rapid pacing. Rabbit ventricular myocytes appeared to have at least two types of delayed rectifier. Sematilide selectively blocked IKr, and block was not relieved by repetitive stimulation. In conclusion, the APD-widening effect of sematilide was independent of previous pacing history. Sematilide had little influence on background processes likely responsible for shortening APD because of rapid repetitive stimulation.
N-乙酰基普鲁卡因酰胺的体内和体外抗心律失常和致心律失常作用。
DOI：
--
发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Dangman,KH;Hoffman,BF
通讯作者：
Hoffman,BF