The Ib Phase of Ventricular Arrhythmias in Ischemic In Situ Porcine Heart Is Related to Changes in Cell-to-Cell Electrical Coupling

Abstract

Background This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias. Methods and Results Regional ischemia was induced by 60 minutes of mid–left anterior descending coronary artery ligation in open-chest swine (n=10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (R t ). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K + ([K + ] e ) and pH (pH e ) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling ( R 2 =.885). Cell-to-cell electrical uncoupling superimposed on changes of [K + ] e and pH e contributed to the failure of impulse propagation between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum TQ-segment depression was −10 mV at 19 minutes, after which TQ-segment depression slowly recovered. The onset of the TQ-segment recovery was correlated to the second rise in R t ( R 2 =.886). Conclusions In the regionally ischemic in situ porcine heart, loss of cell-to-cell electrical interaction is related to the occurrence of VF and changes in the amplitude of the injury current. Cellular electrical uncoupling contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K + ] e and low pH e . These data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction.