Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle.

Abstract

Extracellular and intracellular longitudinal resistances (ro and ri), transmembrane potentials, and conduction velocity were determined in arterially blood-perfused rabbit papillary muscles. Cable analysis was made possible by placing the muscle in a H2O-saturated gaseous environment, which acted as an electrical insulator. Ischemia was produced by exchanging the O2 in the atmosphere by N2 (94% N2-6% CO2) in addition to arresting coronary flow. The first 10-15 minutes of ischemia were characterized by an increase in ro, while ri remained constant. The early part of the increase in ro coincided with the drop in perfusion pressure and was probably due to the diminution of intravascular volume. Rapid electrical uncoupling, reflected by an increase in ri (threefold within 5 minutes), occurred thereafter. The dissociation between the early increase in ro and the delayed increase in ri produced an initial increase in the ratio ro:ri, which subsequently decreased. The decrease in conduction velocity was less than observed in intact hearts with ischemia. This difference is explained by the relatively small changes in resting membrane potential and action potential amplitude in the preparation used. Our results suggest that in the early, reversible phase of ischemia, the increase in ro contributes to a small but significant extent to the slowing of conduction. After 15-20 minutes, the rapid cellular uncoupling, which was most likely coincident with breakdown of cellular homeostasis, may contribute to the occurrence of arrhythmias during this phase of ischemia. Moreover, the early change in the ratio ro:ri will influence the amplitude of the extracellular electrograms following coronary occlusion (TQ-segment and ST-segment shifts).

Ischemic, genetic and pharmacological origins of cardiac arrhythmias: The contribution of the Quebec Heart Institute

“…Action potential amplitude and APD were decreased during LPC superfusion, but we showed that cell excitability was preserved when cell coupling was reduced sufficiently to block action potential transfer. Taking into account the time lag of LPC action, our results are consistent with the delay of ischemiainduced increase in internal resistance in papillary muscle reported by Kléber et al (68). Thus, in addition to changes in pH o and long-chain acylcarnitines, which also have been shown to reduce junctional conductance (77,78), LPC can be a major cause for electrical uncoupling and cardiac arrhythmias early in ischemia.…”

“…They showed that internal longitudinal resistance (the sum of the cytoplasmic and junctional resistances over a length of a cardiac fiber) increases 1.4 times after 10 min of hypoxia. It was Kléber et al (68) who showed a rapid increase in internal resistance after 15 min to 20 min of ischemia, which may have contributed to the occurrence of arrhythmias observed at this duration of ischemia. Dekker et al (69) have more recently shown that the onset of cellular uncoupling that occurs during ischemia is always preceded by an increase in intracellular calcium.…”

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

“…Tissue resistance R can be considered as arising from intracellular (G i ) and extracellular (G e ) conductances connected in series. 8 Because G e is believed to not change during phase 1B, 10 then (1) where and are intracellular conductances of normal and ischemic tissue, respectively, with assumed equal to as per Kléber et al 18 In Eq. 1, R normal and R ischemic are overall tissue resistance values in NZ and CIZ, respectively, for the 4 stages of ischemia shown in Figure 2.…”

“…The latter becomes inexcitable predominantly due to the increase in extracellular potassium concentration. 8 In addition, increased intracellular calcium concentration and dephosphorylation of gap junction proteins 9 during phase 1B result in gap junctional uncoupling, and thus in an increase in tissue resistance in the ischemic region. 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).…”

Involvement of nitric oxide and reactive oxygen species in the early and delayed antiarrhythmic effects of preconditioning

“…The slowing conduction causes re-entry upset in the refractory tissue 18 . The electrical uncoupling contributes to the conduction slowing and blocking in the initial phase of ischemia through the myocytes gap junctions 19 .…”