Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure
Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure
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DOI：
10.1161/circulationaha.110.989707
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发表时间：
2011-05-03
期刊：
影响因子：
37.8
通讯作者：
Efimov, Igor R.
中科院分区：
文献类型：
--
作者：
Lou, Qing;Fedorov, Vadim V.;Efimov, Igor R.
背景-兴奋-收缩（EC）偶联在终末期心力衰竭中发生改变。然而，这种重构的空间异质性尚未在衰竭的人类心脏的组织水平上建立。这篇文章的目的是研究功能重塑的兴奋-收缩耦合和钙处理失败和nonfailing人类hearts.Methods和结果，我们同时光学映射动作电位和钙瞬变冠状动脉灌注左心室楔制备nonfailing（n = 6）和失败（n = 5）人类心脏。我们的主要发现如下。首先，在心动过缓（40 bpm）期间，与非衰竭心脏相比，衰竭心脏内膜下的钙瞬变时间减去动作电位时间更长。其次，在快速起搏频率（100 bpm）下，衰竭心脏的钙瞬变持续时间的跨壁梯度显著小于非衰竭心脏。第三，衰竭心脏中的钙瞬变在心肌中部呈平坦平台期，并在3颗衰竭心脏的心内膜下表现出2成分缓慢上升。第四，两组内内膜下的钙瞬时舒张比心外膜下慢。在非衰竭和衰竭心脏中，肌浆网Ca 2 +-ATP酶2a的蛋白表达在内膜下低于心外膜下。肌浆网Ca 2 +-ATP酶2a蛋白表达在subendorrhage缺血性心肌病的心脏与nonischemic cardiomyosis. Conclusions相比，第一次，我们提出了直接的实验证据的跨壁异质性的兴奋-收缩耦合和钙处理在人类心脏。终末期心力衰竭与兴奋-收缩偶联和钙处理的异质性重构有关。（循环。2011;123：1881-1890.）
Background-Excitation-contraction (EC) coupling is altered in end-stage heart failure. However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective of this article was to study functional remodeling of excitation-contraction coupling and calcium handling in failing and nonfailing human hearts.Methods and Results-We simultaneously optically mapped action potentials and calcium transients in coronary perfused left ventricular wedge preparations from nonfailing (n = 6) and failing (n = 5) human hearts. Our major findings are the following. First, calcium transient duration minus action potential duration was longer at subendocardium in failing compared with nonfailing hearts during bradycardia (40 bpm). Second, the transmural gradient of calcium transient duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 bpm). Third, calcium transient in failing hearts had a flattened plateau at the midmyocardium and exhibited a 2-component slow rise at the subendocardium in 3 failing hearts. Fourth, calcium transient relaxation was slower at the subendocardium than at the subepicardium in both groups. Protein expression of sarcoplasmic reticulum Ca2+-ATPase 2a was lower at the subendocardium than the subepicardium in both nonfailing and failing hearts. Sarcoplasmic reticulum Ca2+-ATPase 2a protein expression at subendocardium was lower in hearts with ischemic cardiomyopathy compared with those with nonischemic cardiomyopathy.Conclusions-For the first time, we present direct experimental evidence of transmural heterogeneity of excitation-contraction coupling and calcium handling in human hearts. End-stage heart failure is associated with the heterogeneous remodeling of excitation-contraction coupling and calcium handling. (Circulation. 2011;123:1881-1890.)