In-vivo electrophysiological study in mice with chronic anterior myocardial infarction

Introduction: An increasing number of genetically altered mice with specific molecular cardiac defects are being assessed by electrophysiological studies and ECG monitoring. This approach should allow for the identification of critical genes involved in the arrhythmogenesis in myocardial infarction. Therefore it was the aim of this study to establish a standard for the in-vivo electrophysiological characteristics in the mouse model of chronic anterior myocardial infarction. Methods and Results: Using a minimized, invasive, in-vivo electrophysiological study, surface ECG parameters, sinus node function, atrial, atrio-ventricular and ventricular conduction and ventricular repolarization, and enhanced vulnerability to atrial and ventricular arrhythmia were studied in 20 wild-type C57BL/6 mice either under control or 11 weeks after large anterior myocardial infarction induced by ligation of the left anterior descending coronary artery. Telemetric ECG recording was performed in the same animals at baseline unrestrained, conscious condition to study surface ECG parameters, heart rate variability and the prevalence of supraventricular and ventricular arrhythmia. During electrophysiological study, infarcted mice showed an 81% increase of the angle of the QRS axis (p<0.001) and a prolongation of the P wave by 23% (p=0.01), the QRS complex by 39% (p=0.001), the QT interval by 23% (p<0.05), the QT(c) interval by 30% (p<0.005) and the JT(c) interval by 31% (p<0.05) in comparison to control animals. Furthermore, there was a prolongation of the atrio-ventricular interval by 28% (p<0.0005) and the atrio-ventricular functional refractory period by 26% in infarcted animals (p<0.05), and inducibility of ventricular tachycardia in 4 of 6 infarcted versus in none of control animals(0<0.01). During telemetric ECG recording, there was a marked increase in ventricular ectopic activity in infarcted mice in comparison to controls (p<0.05). Heart rate and time- and frequency-domain of heart rate variability were not significantly different in both groups (p>0.05, respectively). Conclusions: The mouse model of chronic anterior myocardial infarction is associated with significant atrial and ventricular conduction disturbances and vulnerability to ventricular arrhythmia and thus may provide a highly valuable tool to study molecular determinants of arrhythmogenesis in myocardial infarction.