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 ( 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + d P/dt (7496 ± 225 versus 5502 [Formula: see text] s), LV - dP/dt (7723 ± 208 versus 3819 [Formula: see text]), LV ejection fraction (79 ± 3 versus [Formula: see text]), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased ( 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: [Formula: see text] 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 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.
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 ( 0.05) by elevated left ventricular (LV) end-diastolic pressure (5 ± 1 versus 18 ± 2 mmHg), decreased LV + d P/dt (7496 ± 225 versus 5502 [Formula: see text] s), LV - dP/dt (7723 ± 208 versus 3819 [Formula: see text]), LV ejection fraction (79 ± 3 versus [Formula: see text]), peak developed pressure (176 ± 4 versus 145 ± 9 mmHg), and prolonged time constant of LV relaxation Tau (18 ± 1 versus 29 ± 2 ms). The EP data showed decreased ( 0.05) electrogram amplitude in border and infarct zones (Healthy zone (H): 8.7 ± 2.1 mV, Border zone (B): 5.3 ± 1.6 mV, and Infarct zone (I): 2.3 ± 1.2 mV), decreased MAP amplitude in the border zone (H: [Formula: see text] 1.0 mV, B: 9.7 ± 0.5 mV), and increased repolarization heterogeneity in the border zone (H: 8.1 ± 1.5 ms, B: 20.2 ± 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.
Authors: Ikeotunye Royal Chinyere; Talal Moukabary; Mathew D Hutchinson; Jordan J Lancaster; Elizabeth Juneman; Steven Goldman Journal: Am J Physiol Heart Circ Physiol Date: 2020-11-08 Impact factor: 4.733
Authors: Caroline Mendonca Costa; Gernot Plank; Christopher A Rinaldi; Steven A Niederer; Martin J Bishop Journal: Front Physiol Date: 2018-04-09 Impact factor: 4.566