Affiliation:
1. From the Departments of Pediatrics and Cell Biology, Duke University Medical Center, Durham, NC.
Abstract
Abstract
The object of this study is to present evidence that the myocardial architecture creates inhomogeneities of electrical load at the cellular level that cause cardiac propagation to be stochastic in nature; ie, the excitatory events during propagation are constantly changing and disorderly in the sense of varying intracellular events and delays between cells. At a macroscopic level, however, these stochastic events become averaged and appear consistent with a continuous medium. We examined this concept in a two-dimensional (2D) model of myocardial architecture by exploring whether experimentally observed V̇
max
variability reflected different patterns of intracellular excitation events and junctional delays. The patterns of V̇
max
variability at randomly chosen intracellular sites were similar experimentally and in the 2D model. The 2D cellular model produced marked variability in gap junction delays; however, on the average, different gap junctions were used for cell-to-cell charge flow during conduction in different directions. During longitudinal propagation (LP), the velocity increased from the proximal to the distal end of each myocyte, and V̇
max
was lowest proximally, increased to a maximum at the distal fourth of the cell, and decreased distally. Transverse propagation (TP) produced rapid intracellular conduction with variable intracellular excitation sequences. TP V̇
max
was greater than LP V̇
max
in most subcellular regions, but near the ends of some myocytes, a reversed “TP>LP V̇
max
” relation occurred. Total charge carried by the sodium current varied inversely with V̇
max
, demonstrating feedback effects of cellular loading on the subcellular sodium current and the kinetics of the sodium channels. The results suggest that the stochastic nature of normal propagation at a microscopic level provides a considerable protective effect against arrhythmias by reestablishing the general trend of wave-front movement after small variations in excitation events occur.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
176 articles.
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