title: Chronic heart failure induced by coronary artery ligation in Lewis inbred rats.
abstract: Rat models of heart failure (HF) secondary to myocardial infarction (MI) are useful in studying the progression of cardiac dysfunction and in testing therapeutic approaches. Sprague-Dawley rats are frequently used; however, this model is hampered by high mortality and a marked variability in infarct size and cardiac dysfunction, necessitating large numbers of rats and prolonged follow-up when studying the progression of dysfunction. In the present work, we developed a model of HF utilizing Lewis inbred rats. Ligation of the left anterior descending coronary artery in Lewis rats produced more uniform and larger infarcts (40 +/- 1.7 vs. 28 +/- 2.3%; P < 0.001) and lower mortality (16 vs. 36%; P < 0.001) than in Sprague-Dawley rats. Using this rat model, we further studied the course of left ventricular (LV) dysfunction and enlargement from 1 wk to 6 mo after MI with cineventriculography. LV end-systolic volume and end-diastolic volume were determined with the area-length method. LV ejection fraction ranged between 0.57 and 0.62 in control rats; after MI, it decreased significantly to 0.48 +/- 0.04 at 1 wk, 0.36 +/- 0.02 at 2 wk, 0.48 +/- 0.02 at 1 mo, 0.35 +/- 0.03 at 2 mo, 0.30 +/- 0.02 at 3 mo, 0.31 +/- 0.02 at 4 mo, and 0.24 +/- 0.02 at 6 mo (P < 0.001, MI vs. sham). LV end-diastolic volume in control rats ranged between 0.32 and 0.42 ml; it increased to 0.48 +/- 0.04 ml at 1 wk, 0.46 +/- 0.02 ml at 2 wk, and 0.46 +/- 0.03 ml at 1 mo. It markedly increased to 0.79 +/- 0.03, 0.79 +/- 0.06, 0.78 +/- 0.03, and 0.80 +/- 0.05 ml at 2, 3, 4, and 6 mo, respectively, after MI (P < 0.001 vs. sham). LV end-diastolic pressure was significantly elevated at all time points. Thus coronary ligation in Lewis inbred rats produces uniformly large infarcts with low mortality, progressive LV dysfunction, and increased LV chamber size. This model may be useful in studying chronic HF secondary to MI.
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Liu
authors.forename: X P
authors.initials: XP
authors.lastname: Yang
authors.forename: O
authors.initials: O
authors.lastname: Nass
authors.forename: H N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: E
authors.initials: E
authors.lastname: Peterson
authors.forename: O A
authors.initials: OA
authors.lastname: Carretero
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology* / Q000503:physiopathology; D002908:Chronic Disease; D003331:Coronary Vessels; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D008026:Ligation; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains