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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Combination IK1 and IKr channel blockade: no additive lowering of the defibrillation threshold.
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Combination IK1 and IKr channel blockade: no additive lowering of the defibrillation threshold.

机译：组合IK1和IKr通道阻塞：除颤阈值无累加降低。

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摘要

Selective blockade of the inward rectifier potassium channel I(K1) by barium, or of the rapidly activating delayed rectifier potassium channel I(Kr) by D,L-sotalol, prolongs repolarization and reduces the defibrillation threshold (DFT). This study hypothesized that combination I(K1) and I(Kr) channel block would produce concentration-dependent additive effects on DFT and ventricular refractoriness. A range of barium and D,L-sotalol concentrations, alone and in combination, were examined with respect to DFT, ventricular effective refractory period (VERP), and ventricular fibrillation cycle length (VFCL) in 133 Langendorff-perfused rabbit hearts. Barium produced a concentration-dependent reduction of DFT (-49+/-4%), with concentration-dependent increases in VERP (26+/-6%) and VFCL (42+/-18%). D,L-Sotalol produced a concentration-dependent lowering of DFT (-53+/-6%) with a concentration-dependent increase in VFCL (34+/-8%) but not VERP. Low (1.6 microM), intermediate (3.1 microM), and high (12.5 microM) barium concentrations combined with varying D,L-sotalol concentrations produced equal or smaller decreases in DFT compared with corresponding doses of barium or D,L-sotalol alone. Except at the lowest concentrations of barium (1.6 and 3.1 microM) (p < 0.05), there was no significant additive interaction between barium and D,L-sotalol on VERP or VFCL. Combination I(K1) and I(Kr) channel block by barium and D,L-sotalol does not produce additive reduction of DFT.
机译：钡对内向整流钾通道I（K1）的选择性阻滞，或D，L-索他洛尔对快速活化的延迟整流钾通道I（Kr）的选择性阻滞，延长了复极化并降低了除纤颤阈值（DFT）。这项研究假设I（K1）和I（Kr）通道阻滞组合将对DFT和心室不应性产生浓度依赖性加性效应。在133个Langendorff灌注的兔心脏中，分别对DFT，心室有效不应期（VERP）和心室纤颤周期长度（VFCL）进行了一系列钡和D，L-索他洛尔浓度的检查。钡导致DFT浓度依赖性降低（-49 +/- 4％），而VERP（26 +/- 6％）和VFCL（42 +/- 18％）浓度依赖性增加。 D，L-索他洛尔产生浓度依赖性的DFT降低（-53 +/- 6％），而浓度依赖性的VFCL升高（34 +/- 8％），而不是VERP。与单独使用相应剂量的钡或D，L-索他洛尔相比，低（1.6 microM），中（3.1 microM）和高（12.5 microM）钡浓度与变化的D，L-索他洛尔浓度相结合产生的DFT降低相等或较小。除了钡的最低浓度（1.6和3.1 microM）（p <0.05）外，钡和D，L-索他洛尔之间在VERP或VFCL上没有显着的添加剂相互作用。钡和D，L-索他洛尔组合的I（K1）和I（Kr）通道阻滞不会产生DFT的累加减少。

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