Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling.
Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling.
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DOI：
10.1016/j.hrthm.2010.04.008
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发表时间：
2010-08
期刊：
影响因子：
5.5
通讯作者：
Trayanova NA
中科院分区：
文献类型：
--
作者：
Bayer JD;Narayan SM;Lalani GG;Trayanova NA
在心率<110次/分钟时动作电位电压交替（APV - ALT）是一种预测室性心律失常的新指标。然而，APV - ALT的频率依赖性及其在衰竭和非衰竭人心肌中的机制尚不清楚。据推测，人类心力衰竭（HF）中的APV - ALT反映了钙处理异常。
采用建模和临床方法，我们的目标是：（1）确定APV - ALT如何随起搏频率变化，以及（2）确定钙处理异常是否能解释HF中APV - ALT的频率依赖性。
使用动态起搏方案，在几种周长（CL）下对具有不同钙处理改变的人左心室楔形模型分析APV - ALT。利用建模的APV - ALT来预测采用相同起搏方案的HF（n = 3）和对照（n = 2）患者记录的左心室单相动作电位中的APV - ALT。
将肌浆网钙摄取电流降低至对照的≤25%、释放电流降低至≤11%，或将肌膜L型钙通道电流降低至≤43%，可预测APV - ALT在CL≥600ms时出现，然后在CL<400ms时幅度增加>400%。在HF患者中，APV - ALT在CL = 600ms时出现，然后在CL<350ms时幅度增加>500%。对于所有其他模型改变以及对照患者，APV - ALT仅在CL<500ms时出现。
APV - ALT在HF患者和对照患者中表现出不同的频率依赖性，在HF患者中在较慢频率时出现，并且可由钙处理异常的模型预测。未来的研究应探讨在慢频率时的APV - ALT是否能识别钙处理紊乱的患者，包括失代偿前的HF患者或有发生心律失常风险的患者。
Alternans in action potential voltage (APV-ALT) at heart rates <110 beats/min is a novel index to predict ventricular arrhythmias. However, the rate-dependency of APV-ALT and its mechanisms in failing versus non-failing human myocardium are poorly understood. It is hypothesized that APV-ALT in human heart failure (HF) reflects abnormal calcium handling. Using a modeling and clinical approach, our objectives were to: (1) determine how APV-ALT varies with pacing rate, and (2) ascertain if abnormalities in calcium handling explain the rate-dependence of APV-ALT in HF. APV-ALT was analyzed at several cycle lengths (CL) using a dynamic pacing protocol applied to a human left ventricle wedge model with various alterations in calcium handling. Modeled APV-ALT was used to predict APV-ALT in left ventricle monophasic action potentials recorded from HF (n=3) and control (n=2) patients with the same pacing protocol. Reducing the sarcoplasmic reticulum calcium uptake current ≤25%, the release current ≤11%, or the sarcolemmal L-type calcium channel current ≤43% of control predicted APV-ALT to arise at CL≥600ms, then increase in magnitude by >400% for CL<400ms. In HF patients, APV-ALT arose at CL=600ms then increased in magnitude by >500% at CL<350ms. For all other model alterations and for control patients, APV-ALT occurred only at CL<500ms. APV-ALT shows differing rate-dependence in HF versus control patients, arising at slower rates in HF and predicted by models with abnormal calcium handling. Future studies should investigate whether APV-ALT at slow rates identifies patients with deranged calcium handing, including HF patients prior to decompensation or at risk for arrhythmias.
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