Late ventricular arrhythmias during acute regional ischemia in the isolated blood perfused pig heart Role of electrical cellular coupling

Abstract

We show that 1B-VF can be induced within a distinct time window and coincides with a distinct range of Rt rise. Subepicardium is electrically depressed, presumably through coupling with midmyocardium, complete uncoupling causes subepicardial recovery and terminates the substrate for 1B-VF. Hence, we suggest that the substrate for 1B-VF consists of intermediate coupling of subepicardium and midmyocardium.

Reentry in survived subepicardium coupled to depolarized and inexcitable midmyocardium: Insights into arrhythmogenesis in ischemia phase 1B

“…Premature stimulation elicits a wavefront, which propagates through subepicardial tissue partially coupled to the midmyocardium (50% uncoupling), but blocks in subepicardial tissue of extended refractoriness above the region of complete uncoupling, resulting in the establishment of a figure-of-eight reentrant circuit in the subepicardium. The pattern of reentry is similar to patterns recorded subepicardially from isolated pig hearts during ventricular fibrillation episodes initiated by premature stimulation after 40 minutes of occlusion in the study by de Groot et al 2 Figure 4B presents, as a reference, the experimental activation maps of the first 2 reentrant cycles in one such episode from the this study. Clearly, in both simulations and experiments, figure-of-eight reentry is established around fixed functional lines of block.…”

“…Experimental values of overall tissue impedance, R, as reported by de Groot et al, 2 (mean ± SEM), were used as an input to the model. Figure 2 depicts the experimental data regarding the course of increase in R in CIZ, as compared to the nonischemic zone (NZ).…”

“…For each stage, we also defined a degree of uncoupling, DOU: (2) DOU was calculated as 42.4% ± 18.0% at stage 1, 81.3% ± 11% at stage 2, and 93.7% ± 12% at stage 3. Further progression of ischemia results in DOU of 100% at stage 4 (end of ischemia phase 1B).…”

“…Experiments have shown that ischemia 1B ventricular fibrillation is based on reentry around fixed lines of block, which are thought to arise from heterogeneous subepicardial electrical uncoupling in the central ischemic zone (CIZ). 2,10 We hypothesize that heterogeneous uncoupling between depressed depolarized midmyocardium and the surviving subepicardium in ischemia phase 1B results in heterogeneous refractoriness in the subepicardium and that this dispersion in effective refractory period (ERP) contributes to the substrate for reentrant arrhythmias in ischemia phase 1B. Furthermore, we investigate how vulnerability to reentrant arrhythmias is affected by the degree of heterogeneous uncoupling between subepicardial and midmyocardial layers as well as by the degree of depolarization in the inactive midmyocardial layer.…”

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

“…Gap junction channels are involved in physiological and pathological processes such as embryonic development, cell differentiation, growth [24][25][26], pathogenesis of neuropathies [27], epilepsy [28], cardiovascular diseases [29], and arrhythmias [30,31]. Numerous densely packed gap junction channels form clusters that directly connect the cytoplasmic compartment of cells [32].…”