Extracellular discontinuities in cardiac muscle - Evidence for capillary effects on the action potential foot
Extracellular discontinuities in cardiac muscle - Evidence for capillary effects on the action potential foot
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DOI：
10.1161/01.res.83.11.1144
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发表时间：
1998-11-30
影响因子：
20.1
通讯作者：
Barr, RC
中科院分区：
文献类型：
--
作者：
Spach, MS;Heidlage, JF;Barr, RC
了解动作电位上升行程形状的变化，以识别结构负荷效应，已变得至关重要。该目标的一个组成部分是在各向异性心肌中在不同方向上传播期间心脏动作电位的足（V-m足）的时间过程的详细实验分析。为此，我们进行了相平面分析跨膜动作电位在各向异性传播成人工作心肌。结果表明，在纵向传播过程中，有一个简单的指数，导致偏离的V-m脚的初始放缓，必然的变化发生在许多网站在横向传播。我们假设，在实验数据中观察到的V-m足的影响是由微观结构，特别是毛细血管。该假设预测，在存在高密度毛细管的情况下，V-m足的相平面轨迹将偏离线性，并且在不存在毛细管的情况下将发生线性轨迹。Fast和Kleber（Circ Res.1993;73：914-925）在新生心肌细胞单层中的结果与我们在新生心室肌中的结果进行比较，前者缺乏毛细血管，后者富含毛细血管，结果显示V-m足与预测的有显著差异。由于这种比较提供了毛细血管假说的实验支持，我们探讨了潜在的生物物理机制，由于间质电场效应，使用“2域”模型的肌细胞和毛细血管间隔间隙。模型结果表明，传播的间质电场在非活性毛细血管中诱导向内的电容电流，这导致对活性膜（源）的反馈效应，从而减缓其动作电位的初始上升。结果显示了与细胞外结构负荷相关的意想不到的机制，其可能在选定的传导障碍中发挥作用，例如在由正常心肌包围的再灌注缺血区域中。
It has become of fundamental importance to understand variations in the shape of the upstroke of the action potential in order to identify structural loading effects. One component of this goal is a detailed experimental analysis of the time course of the foot of the cardiac action potential (V-m foot) during propagation in different directions in anisotropic cardiac muscle. To this end, we performed phase-plane analysis of transmembrane action potentials during anisotropic propagation in adult working myocardium. The results showed that during longitudinal propagation there was initial slowing of V-m foot that resulted in deviations from a simple exponential; corollary changes occurred at numerous sites during transverse propagation. We hypothesized that the effect on V-m foot observed in the experimental data was created by the microscopic structure, especially the capillaries. This hypothesis predicts that the phase-plane trajectory of V-m foot will deviate from linearity in the presence of a high density of capillaries, and that a linear trajectory will occur in the absence of capillaries. Comparison of the results of Fast and Kleber (Circ Res. 1993;73:914-925) in a monolayer of neonatal cardiac myocytes, which is devoid of capillaries, and our results in newborn ventricular muscle, which is rich in capillaries, showed drastic differences in V-m foot as predicted. Because this comparison provided experimental support for the capillary hypothesis, we explored the underlying biophysical mechanisms due to interstitial electrical field effects, using a "2-domain" model of myocytes and capillaries separated by interstitial space. The model results show that a propagating interstitial electrical field induces an inward capacitive current in the inactive capillaries that causes a feedback effect on the active membrane (source) that slows the initial rise of its action potential. The results show unexpected mechanisms related to extracellular structural loading that may play a role in selected conduction disturbances, such as in a reperfused ischemic region surrounded by normal myocardium.