Supraventricular Myocardium in the Heart of the B6CBAF1 Mural Strain Reveals Genetically Determined Arrhythmogenic Properties due to Ectopic Automaticity and Triggered Activity

Abstract

A significant amount of studies are aimed at investigating the mechanisms of occurrence and ways to prevent supraventricular arrhythmias, in particular, atrial fibrillation. Its occurrence in most cases is associated with the electrophysiology’s features of the myocardial tissue of pulmonary veins (PVs), the most important of which is the tendency of this tissue to form ectopic automaticity. However, there is no information to date about the existence of strains of mice that are genetically predisposed to arrhythmias due to ectopic automaticity in the supraventricular myocardium. Nevertheless, rodents are becoming an increasingly frequent model object for basic electrophysiological research. In connection with the foregoing, the purpose of this work was to study the bioelectric properties of the PVs and atrial myocardium as well as to identify the electrical activity’s characteristics of the heart in F1-generation mice of interlinear hybrids of the C57Bl/6 and CBA strains (B6CBAF1). In ex vivo experiments, action potentials (APs) were recorded in tissue preparations of atrial myocardium and PV myocardium of B6CBAF1 mice and control BALB/c mice, using the standard microelectrode technique. In in vivo experiments in B6CBAF1 and BALB/c mice, standard electrocardiogram (ECG) parameters were recorded and calculated. In 80% of the experiments, the PV myocardium in B6CBAF1 mice was observed to have permanent ectopic automatic activity. In 55% of cases, spontaneous APs (SAPs) were characterized by oscillations of the membrane potential during repolarization, owing to which the duration of APs reached 1–20 s. SAPs in B6CBAF1 mice were observed not only in PVs but also in the left atrial myocardium in 80% of the experiments. In BALB/c mice, in contrast to B6CBAF1, no prolonged episodes of SAPs or AP repolarization anomalies were observed in any of the experiments either in PVs or the atrial myocardium. When registering ECG in B6CBAF1 mice, as in BALB/c, neither rhythm disturbances nor any significant deviations of the main parameters of the ECG, except for an increased heart rate, were detected. It is possible that B6CBAF1 mice are the first interlinear hybrid to be detected whose supraventricular myocardium is predisposed to arrhythmogenic automaticity due to ectopic and trigger activity.