Cardiac ischemia and uncoupling: gap junctions in ischemia and infarction

Advances in Cardiology
Stefan Dhein

Abstract

Acute cardiac ischemia is often associated with ventricular arrhythmia and fibrillation. Due to the loss of ATP, the depolarization of the fibers, and the intracellular Na(+) and Ca(2+) overload with concomitant acidification as well as the accumulation of lysophosphoglyceride and arachidonic acid metabolites, propagation of action potentials will be impaired by two factors: (a) reduced sodium channel availability and (b) gap junction uncoupling. While gap junction uncoupling leads to predominant transverse uncoupling, reduced I (Na) availability results in impaired longitudinal conduction. Complete gap junction uncoupling would initiate arrhythmia, while intermediate uncoupling has been shown to enhance the safety factor (SF) of propagation, limiting the current loss to non-depolarized areas. In contrast, a reduction in I(Na) availability reduces SF, and partial gap junction uncoupling might enable effective but slow conduction which, on the other hand, could form the basis for some kind of reentrant arrhythmia, paving the way for new anti-arrhythmic approaches in gap junction coupling. In the chronic phase, remodeling processes also involve gap junctions and lead to highly heterogeneous non-uniform tissue which may serve as a...Continue Reading

Citations

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