Pastore Joseph M, Laurita Kenneth R, Rosenbaum David S
Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109, USA.
Heart Rhythm. 2006 Jun;3(6):711-9. doi: 10.1016/j.hrthm.2006.02.1034. Epub 2006 Mar 10.
Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells.
The purpose of this study was to investigate the hypothesis that spatial and temporal heterogeneities of restitution underlie the mechanism eliciting discordant alternans.
Steady-state pacing was used to elicit concordant cellular alternans in nine Langendorff-perfused guinea pig hearts. A single extrastimulus (S2) was applied every 51st beat following either the even or the odd beat of alternans. The cellular response to S2 was determined using optical mapping to generate action potential duration (APD) restitution curves from 256 ventricular sites for both the even and the odd beats.
Restitution kinetics were temporally heterogeneous during alternans, as restitution curves between the even and the odd beats differed significantly. Temporal heterogeneity was quantified by the average separation of restitution between the two curves, or Delta-restitution. Delta-Restitution was spatially heterogeneous and proportional to the amount of alternans at a given ventricular site. A computer simulation based on the experimental results showed the mechanism of discordant alternans was dependent on both spatial and temporal heterogeneities of restitution.
Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Delta-restitution, are proportional to the magnitude of cellular alternans. The combination of spatial and temporal heterogeneities of restitution may underlie the genesis of discordant alternans.
空间不协调的细胞交替变化形成了单向阻滞和心室颤动发生的基础。然而，导致不协调交替变化的机制仍知之甚少。先前的研究表明，电恢复特性对于单细胞中交替变化的发生至关重要。
本研究旨在探讨以下假说，即恢复特性的时空异质性是引发不协调交替变化机制的基础。
采用稳态起搏在9个Langendorff灌注的豚鼠心脏中诱发协调的细胞交替变化。在交替变化的偶数或奇数搏动后的每第51次搏动时施加单个额外刺激（S2）。使用光学标测从256个心室部位获取动作电位时程（APD）恢复曲线，以确定细胞对S2的反应，分别针对偶数和奇数搏动。
在交替变化期间，恢复动力学在时间上是异质的，因为偶数和奇数搏动之间的恢复曲线存在显著差异。时间异质性通过两条曲线之间恢复特性的平均间隔（即Δ恢复特性）来量化。Δ恢复特性在空间上是异质的，并且与给定心室部位的交替变化量成比例。基于实验结果的计算机模拟表明，不协调交替变化的机制取决于恢复特性的时空异质性。
在完整心脏的细胞交替变化过程中，恢复特性存在时间和空间上的异质性。通过Δ恢复特性量化的恢复特性时间异质性与细胞交替变化的幅度成比例。恢复特性的时空异质性组合可能是不协调交替变化发生的基础。
