title: Development of a preclinical model of ischemic cardiomyopathy in swine.
abstract: A number of promising therapies for ischemic cardiomyopathy are emerging, and the role of translational research in testing the efficacy and safety of these agents in relevant clinical models has become important. The goal of this study was to develop a chronic model of ischemic cardiomyopathy in a large animal model. In this study, 40 consecutive pigs were initially enrolled. To induce progressive stenosis, a plastic occluder with a fixed diameter of 1.0 mm fitted with an 18-gauge copper wire was placed around the proximal left anterior descending (LAD) coronary artery. Coronary angiography, hemodynamic measurements, and echocardiography were performed at 2 wk and 1, 2, and 3 mo. Overall mortality was 26% at 3 mo, and up to 80% of the pigs showed total occlusion of LAD at 1 mo. A significant depression of peak LV pressure rate of rise (+dP/dt(max)) was observed in the animals showing total artery occlusion throughout the study. Left ventricular ejection fraction was also impaired, and the left ventricular volumes tended to be larger in the pigs with occlusion. Approximately 10% of scar tissue was found in the LAD occluded pigs, whereas the coronary flow pattern in the rest of the area took the pattern of hibernating myocardium. At the same time, histological and protein analysis established the presence of fibrosis and ongoing apoptosis in the ischemic area. In this model, the timing and incidence of total occlusion and low mortality offer significant advantages over other ischemic cardiomyopathy models in conducting preclinical studies.
authors.affiliation: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Dennis
authors.initials: D
authors.lastname: Ladage
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takewa
authors.forename: Elisa
authors.initials: E
authors.lastname: Yaniz
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Chen
authors.forename: Lisa
authors.initials: L
authors.lastname: Tilemann
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakata
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawase
mesh_terms: D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003097:Collateral Circulation; D017023:Coronary Angiography; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000150:complications / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005355:Fibrosis; D006439:Hemodynamics; D008026:Ligation; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging; D017682:Myocardial Stunning / Q000209:etiology; D009206:Myocardium / Q000473:pathology; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure