Inhibition by E-4031 of the prolongation of the first returning cycle length after overdrive in anesthetized dog hearts.
Inhibition by E-4031 of the prolongation of the first returning cycle length after overdrive in anesthetized dog hearts.
复制标题
E-4031 抑制麻醉狗心脏超速后第一个返回周期长度的延长。
DOI：
10.1097/00005344-199801000-00003
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发表时间：
1998
影响因子：
3
通讯作者：
S. Chiba
中科院分区：
文献类型：
--
作者：
Y. Nagashima;Y. Furukawa;M. Hirose;Y. Hoyano;M. Lakhe;S. Chiba
窦房（SA）结起搏器活动的功能恢复的延长，即“起搏抑制”，取决于固有起搏器活动、起搏器部位和SA传导。本文观察了延迟整流钾电流（Ikr）快速型阻断剂E-4031和刺激心内副交感神经至SA结区（SAP）对麻醉开胸犬心脏去中心化后第一个返流周期长度（1st RCL）的延长作用。还测量了第二和第三RCL。我们测定了以120%、150%和200%的控制频率心房起搏1 min后的SA结恢复时间（SNRT）和校正SNRT（CSNRT），并通过恒定心房起搏方法测定了SA传导时间（SACT）。E-4031（0.1-3 μ mol/kg i.v.）剂量依赖性地增加窦性周期长度（SCL）和SNRT。然而，当起搏频率低或起搏刺激次数少时，E-4031可降低CSNRT，尽管当施加足够的起搏刺激时，药物不会引起CSNRT的显著变化。E-4031剂量依赖性地降低SACT。E-4031处理后。我们观察到心房电构型的变化，提示起搏器移位的可能性。当刺激SAP使SCL、SNRT、CSNRT和SACT延长时，E-4031选择性地抑制刺激SAP使SCL延长，但不影响CSNRT和SACT的延长。这些结果表明，SA结起搏器活动的功能恢复后，至少部分由Ikr调节，Ikr抑制衰减SCL的延长，但不是第一RCL诱导的副交感神经激活在心脏原位。
Prolongation of the functional recovery of the sinoatrial (SA) nodal pacemaker activity after overdrive, "overdrive suppression," is determined by intrinsic pacemaker activity, pacemaker site, and SA conduction. We investigated the effects of E-4031, a blocker of a rapid type of the delayed rectifier K+ current (Ikr) and stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAP) on the prolongation of the first returning cycle length (1st RCL) after overdrive in autonomically decentralized hearts of open-chest anesthetized dogs. Second and third RCLs also were measured. We determined SA node recovery time (SNRT) and corrected SNRT (CSNRT) after atrial pacing at rates of 120, 150, and 200% of the control rate for 1 min and also determined SA conduction time (SACT) by the constant-atrial-pacing method. E-4031 (0.1-3 micromol/kg i.v.) increased the sinus cycle length (SCL) and SNRT dose dependently. However, E-4031 decreased CSNRT when the pacing rate was low or the number of pacing stimuli was small, although the agent did not induce a significant change in CSNRT when sufficient pacing stimuli were applied. E-4031 decreased SACT dose dependently. After E-4031 treatment. we observed changes in atrial electrical configurations, suggesting the possibility of pacemaker shift. When SAP stimulation increased SCL, SNRT, CSNRT, and SACT, E-4031 selectively inhibited the prolongation of SCL by SAP stimulation but did not affect the prolongation of CSNRT or SACT. These results suggest that functional recovery of the SA nodal pacemaker activity after overdrive is regulated by Ikr at least in part and that Ikr inhibition attenuates prolongation of the SCL but not the 1st RCL induced by parasympathetic nerve activation in the heart in situ.