Abstract

Introduction: We have developed a computer user interface able to provide prescribed programmed electrical stimulation (PES) to induce sustained-ventricular tachycardia (VT) in rats with chronic heart failure (CHF). We propose this program to examine the cardiac electrophysiology (EP) properties and arrhythmogenic potential in varying disease models and as a method of evaluating drug safety in an intact animal. Methods: Using custom MATLAB software developed in our laboratory, we performed monophasic action potential (MAP) recordings and initiated protocols to induce sustained-VT through right ventricular epicardium PES outputs. Studies were performed in adult male Sprague-Dawley rats (N=22) six weeks after left coronary artery ligation under anesthesia and open chest. Results: CHF was verified by standard hemodynamic and echocardiographic parameters as is standard in our laboratory. In the CHF group, 71% (10/14) of the rats exhibited sustained-VT in response to PES versus 0% (0/8) of Sham rats. MAP recordings taken prior-to and during VT induction provided examples of localized activity for arrhythmia mechanisms such as delayed afterdepolarizations. Mechanical alternans, electrical alternans, intermittent pulse generations, and pulseless electrical activity were all observed in this model. EP data analysis showed a decreased (p<0.05) electrogram amplitude in border and infarct zones (Healthy (H): 8.7 ±2.1 mV, Border: 5.3±1.6 mV, Infarct (I): 2.3±1.2 mV), a similar trend for MAP amplitudes, and an increased (p<0.05) repolarization heterogeneity in the border zone (H: 8.1±1.5 ms, B: 20.2±3.1 ms). Conclusions: We have developed a custom computer user interface capable of performing clinically relevant in-vivo EP studies in rats with CHF. This rat model reproduces common clinical prognosis factors such as mechanical alternans, electrical alternans, and pulseless electrical activity. These EP studies demonstrate this program’s ability to test the arrhythmogenic potential of pharmaceutic agents, biologics, and implantables in an intact animal model before clinical advancement. We introduce this program to study an animal model’s EP characteristics before, during, and after treatments for CHF, and potentially other disease states.

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