In vivo Electrophysiological Study of Induced Ventricular Tachycardia in Intact Rat Model of Chronic Ischemic Heart Failure

Objective: The objective of this study was to define the clinical relevance of in vivo electrophysiologic (EP) studies in a rat model of chronic ischemic heart failure (CHF). Methods: Electrical activation sequences, voltage amplitudes, and monophasic action potentials (MAPs) were recorded from adult male Sprague–Dawley rats six weeks after left coronary artery ligation. Programmed electrical stimulation (PES) sequences were developed to induce sustained ventricular tachycardia (VT). The inducibility of sustained VT was defined by PES and the recorded tissue MAPs. Results: Rats in CHF were defined ( $p 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 $ \pm $ 1 versus 18 $ \pm $ 2 mmHg), decreased LV + d P /d t (7496 $ \pm $ 225 versus 5502 $ \pm\ \text{293 mmHg}/$ s), LV − d P /d t (7723 $\pm $ 208 versus 3819 $\pm \,\text{571 mmHg}$ ), LV ejection fraction (79 $\pm $ 3 versus $\text{30} \pm \text{3}\% $ ), peak developed pressure (176 $\pm $ 4 versus 145 $\pm $ 9 mmHg), and prolonged time constant of LV relaxation Tau (18 $\pm $ 1 versus 29 $\pm $ 2 ms). The EP data showed decreased ( $p 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 $\pm $ 2.1 mV, Border zone (B): 5.3 $\pm $ 1.6 mV, and Infarct zone (I): 2.3 $\pm $ 1.2 mV), decreased MAP amplitude in the border zone (H: $\text{14.0}\ \pm $ 1.0 mV, B: 9.7 $\pm $ 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 $ \pm $ 1.5 ms, B: 20.2 $\pm $ 3.1 ms). With PES we induced sustained VT (>15 consecutive PVCs) in rats with CHF (10/14) versus Sham (0/8). Conclusions: These EP studies establish a clinically relevant protocol for studying genesis of VT in CHF. Significance: The in vivo rat model of CHF combined with EP analysis could be used to determine the arrhythmogenic potential of new treatments for CHF.