title: A new model of congestive heart failure in rats.
abstract: Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.
authors.affiliation: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Chen
authors.forename: Elie R
authors.initials: ER
authors.lastname: Chemaly
authors.forename: Li Fan
authors.initials: LF
authors.lastname: Liang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: LaRocca
authors.forename: Elisa
authors.initials: E
authors.lastname: Yaniz-Galende
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000235:genetics; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D006439:Hemodynamics; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D013318:Stroke Volume; D013997:Time Factors; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: C506948:Atp2a2 protein, rat; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases