Document Detail


A new model of congestive heart failure in rats.
MedLine Citation:
PMID:  21685270     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jiqiu Chen; Elie R Chemaly; Li Fan Liang; Thomas J LaRocca; Elisa Yaniz-Galende; Roger J Hajjar
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-17
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-31     Completed Date:  2011-11-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H994-1003     Citation Subset:  IM    
Affiliation:
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Aorta / surgery
Atrial Natriuretic Factor / genetics
Coronary Vessels / surgery
Disease Models, Animal*
Disease Progression
Fibrosis
Gene Expression Regulation
Heart Failure / etiology*,  genetics,  physiopathology,  ultrasonography
Hemodynamics
Hypertension / etiology,  physiopathology
Hypertrophy, Left Ventricular / etiology*,  genetics,  physiopathology,  ultrasonography
Ligation
Male
Myocardial Infarction / etiology*,  genetics,  physiopathology,  ultrasonography
Myocardial Reperfusion Injury / etiology*,  genetics,  physiopathology,  ultrasonography
Myocardium / metabolism,  pathology
Natriuretic Peptide, Brain / genetics
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
Stroke Volume
Time Factors
Ventricular Dysfunction, Left / etiology*,  genetics,  pathology,  ultrasonography
Ventricular Function, Left
Ventricular Pressure
Grant Support
ID/Acronym/Agency:
P20HL-100396/HL/NHLBI NIH HHS; R01HL-07873/HL/NHLBI NIH HHS; R01HL-083156/HL/NHLBI NIH HHS; R01HL-088434/HL/NHLBI NIH HHS; R01HL-093183/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 114471-18-0/Natriuretic Peptide, Brain; 85637-73-6/Atrial Natriuretic Factor; EC 3.6.3.8/Atp2a2 protein, rat; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases
Comments/Corrections

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