Cardiac electrophysiology and the susceptibility to sustained ventricular tachycardia in intact, conscious mice

Abstract

Cardiac electrophysiological dysfunction is a major cause of death in humans. Accordingly, electrophysiological testing is routinely performed in intact, conscious, humans to evaluate arrhythmias and disorders of cardiac conduction. However, to date, in vivo electrophysiological studies in mice are limited to anesthetized open-chest or closed-chest preparations. However, cardiac electrophysiology in anesthetized mice or mice with surgical trauma may not adequately represent what occurs in conscious mice. Accordingly, an intact, conscious murine model of cardiac electrophysiology has the potential to be of major importance for advancing the concepts and methods that drive cardiovascular therapies. Therefore, we describe, for the first time, the use of an intact, conscious, murine model of cardiac electrophysiology. The conscious mouse model permits measurements of atrioventricular interval, sinus cycle length, sinus node recovery time (SNRT), SNRT corrected for spontaneous sinus cycle, Wenckebach cycle length, the ventricular effective refractory period (VERP) and the electrical stimulation threshold to induce sustained ventricular tachyarrhythmias in an intact, complex model free of the confounding influences of anesthetics and surgical trauma. This is an important consideration because anesthesia and surgical trauma markedly reduced cardiac output and heart rate as well as altered cardiac electrophysiology parameters. Most importantly, anesthesia and surgical trauma significantly increased the VERP and virtually eliminated the ability to induce sustained ventricular tachyarrhythmias. Accordingly, the methodology allows for the accurate documentation of cardiac electrophysiology in complex, conscious mice and may be adopted for advancing the concepts and ideas that drive cardiovascular research.