Progression of infarct-mediated arrhythmogenesis in a rodent model of heart failure
Autor: | Talal Moukabary, Ikeotunye Royal Chinyere, Steven Goldman, Elizabeth Juneman, Mathew D. Hutchinson, Jordan J. Lancaster |
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Rok vydání: | 2021 |
Předmět: |
Male
medicine.medical_specialty Time Factors Refractory Period Electrophysiological Physiology Myocardial Infarction Ischemia Action Potentials 030204 cardiovascular system & hematology Ventricular tachycardia Ventricular Function Left Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Heart Rate Physiology (medical) Internal medicine Ventricular Pressure medicine Animals cardiovascular diseases 030212 general & internal medicine Heart Failure Ischemic cardiomyopathy Monomorphic Ventricular Tachycardia business.industry Incidence (epidemiology) Stroke Volume Rodent model medicine.disease Disease Models Animal Heart failure Disease Progression Tachycardia Ventricular cardiovascular system Cardiology Cardiology and Cardiovascular Medicine business Research Article |
Zdroj: | Am J Physiol Heart Circ Physiol |
ISSN: | 1522-1539 0363-6135 |
DOI: | 10.1152/ajpheart.00639.2020 |
Popis: | Heart failure (HF) post-myocardial infarction (MI) presents with increased vulnerability to monomorphic ventricular tachycardia (mmVT). To appropriately evaluate new therapies for infarct-mediated reentrant arrhythmia in the preclinical setting, chronologic characterization of the preclinical animal model pathophysiology is critical. This study aimed to evaluate the rigor and reproducibility of mmVT incidence in a rodent model of HF. We hypothesize a progressive increase in the incidence of mmVT as the duration of HF increases. Adult male Sprague-Dawley rats underwent permanent left coronary artery ligation or SHAM surgery and were maintained for either 6 or 10 wk. At end point, SHAM and HF rats underwent echocardiographic and invasive hemodynamic evaluation. Finally, rats underwent electrophysiologic (EP) assessment to assess susceptibility to mmVT and define ventricular effective refractory period (ERP). In 6-wk HF rats (n = 20), left ventricular (LV) ejection fraction (EF) decreased (P < 0.05) and LV end-diastolic pressure (EDP) increased (P < 0.05) compared with SHAM (n = 10). Ten-week HF (n = 12) revealed maintenance of LVEF and LVEDP (P > 0.05), (P > 0.05). Electrophysiology studies revealed an increase in incidence of mmVT between SHAM and 6-wk HF (P = 0.0016) and ERP prolongation (P = 0.0186). The incidence of mmVT and ventricular ERP did not differ between 6- and 10-wk HF (P = 1.0000), (P = 0.9831). Findings from this rodent model of HF suggest that once the ischemia-mediated infarct stabilizes, proarrhythmic deterioration ceases. Within the 6- and 10-wk period post-MI, no echocardiographic, invasive hemodynamic, or electrophysiologic changes were observed, suggesting stable HF. This is the necessary context for the evaluation of experimental therapies in rodent HF. NEW & NOTEWORTHY Rodent model of ischemic cardiomyopathy exhibits a plateau of inducible monomorphic ventricular tachycardia incidence between 6 and 10 wk postinfarction. |
Databáze: | OpenAIRE |
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