Abstract 86: Mapping and Inducing Ventricular Tachycardia in Cardiomyopathic Animal Models

Abstract

Introduction: In the United States, one in three deaths is attributed to cardiovascular disease (CVD). With CVD, sudden cardiac death is a common cause of mortality, specifically by way of ventricular tachycardia (VT) and ventricular fibrillation. We propose the application of our custom software to evaluate the electrophysiologic (EP) properties of animal models of ischemic and non-ischemic dilated cardiomyopathies. Methods: Adult male Sprague-Dawley rats with left coronary artery ligation and adult male and female transgenic Fragile X cardiomyopathic mice were sedated with Inactin and Isoflurane, respectively, and underwent hemodynamic measurements and/or EP testing. Using a PowerLab system and LabChart software, three-lead electrocardiograms were recorded. Using a pressure catheter, hemodynamic parameters were calculated. Using a concentric microelectrode (World Precision Inc.), a clinical EP catheter (Bard Inc.), and custom MATLAB software, local epicardial monophasic action potentials (MAP) and local epicardial voltages were recorded. Using custom MATLAB software for programmed electrical stimulation (PES), VT was induced epicardially with a clinically-accepted drivetrain. Animals underwent eight equidistant ‘S1’ stimulations followed by a premature ‘S2’ stimulation. The S2 stimulation was decreased by 5 milliseconds until loss of capture, indicating the effective refractory period. Sustained ventricular tachycardia (sVT) has been defined as more than fifteen consecutive premature ventricular contractions. Results: The chronic heart failure (CHF) rats had documented hemodynamic heart failure with elevated LV EDPs, and decreased EFs. Mapping and PES was performed on the two groups of rats, namely CHF and Sham-operated. In the CHF group, 71% (27/39) of the rats exhibited sVT, while 0% (0/10) of the Sham-operated rats exhibited sVT. Mapping was also performed on the two groups of mice, namely Wild-Type and Fragile X. Conclusions: We have performed clinically-relevant EP studies in CHF rats and in Fragile X dilated cardiomyopathic mice. These EP studies demonstrate our ability to evaluate and validate the phenotypes of animal models of cardiomyopathies and demonstrate the potential to evaluate the effectiveness of new therapies.