Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.
Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.
复制标题
麻醉犬心动过缓后短暂速率增加后左心室复极和离子通道电流的变化。
DOI：
10.1111/j.1540-8167.2000.tb00028.x
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发表时间：
2000
影响因子：
2.7
通讯作者：
Zipes,DP
中科院分区：
文献类型：
--
作者：
Rubart,M;Lopshire,JC;Fineberg,NS;Zipes,DP
心率引起的心脏电重构。导论：我们之前在狗身上证明，短暂的心率增加叠加在心动过缓上，会导致心室难治性延长，这种延长在心动过缓恢复后持续数小时。在这项研究中，我们研究了与这种现象相关的膜电流的变化。方法与结果：采用全细胞膜片钳技术，分别记录AV完全阻断1周犬单只左心室中心肌细胞的跨膜电压和跨膜电流；狗要么以120次/分的速度进行1小时左心室起搏，要么不进行起搏。起搏显著提高了平均1相和峰值平台振幅，分别提高了~ 6和~ 3 mV （P < 0.02）。90%复极时动作电位持续时间从235±8 msec延长至278±8 msec （1 Hz; P = 0.02）。快速起搏诱导的跨膜离子电流变化包括：(1)4 -氨基吡啶敏感的瞬时外向K+电流在生理频率范围内的累积失活更为明显，导致快速再激活通道数量减少约30%；(2) L型Ca2+电流的峰值密度增加；在+10和+60 mV之间降低15%至35%；(3) Ca2+激活氯离子电流ICl的峰值密度增加。在+30和+50毫伏之间，衰减30%至120%。结论：ito的频率依赖性降低与ica . i的增强导致净内向电流的增加，这可能是观察到的心室复极变化的原因。净阳离子流入的增加部分被向外离子离子的增加所抵消。
Electrical Remodeling of the Heart due to Rate.Introduction:We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon.Methods and Results:The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid‐myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ∼6 and ∼3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing‐induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4‐aminopyridine‐sensitive transient outward K+current, Itoover the range of physiologic frequencies, resulting from a ∼30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L‐type Ca2+currents, Ica.I.'by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+‐activated chloride current, ICl.Ca'by 30% to 120% between +30 and +50 mV.Conclusion:Frequency‐dependent reduction in Itocombined with enhanced ICa.I.causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl.