title: Characterizing preclinical models of ischemic heart failure: differences between LAD and LCx infarctions.
abstract: Large animal studies are an important step toward clinical translation of novel therapeutic approaches. We aimed to establish an ischemic heart failure (HF) model with a larger myocardial infarction (MI) relative to previous studies, and characterize the functional and structural features of this model. An MI was induced by occluding the proximal left anterior descending artery (LAD; n = 15) or the proximal left circumflex artery (LCx; n = 6) in Yorkshire pigs. Three pigs with sham procedures were also included. All pigs underwent hemodynamic and echocardiographic assessments before MI, at 1 mo, and 3 mo after MI. Analyses of left ventricular (LV) myocardial mechanics by means of strains and torsion were performed using speckle-tracking echocardiography and compared between the groups. The proximal LAD MI approach induced larger infarct sizes (14.2 ± 3.2% vs. 10.6 ± 1.9%, P = 0.03), depressed systolic function (LV ejection fraction; 39.8 ± 7.5% vs. 54.1 ± 4.6%, P < 0.001), and more LV remodeling (end-systolic volume index; 82 ± 25 ml/m(2) vs. 51 ± 18 ml/m(2), P = 0.02, LAD vs. LCx, respectively) compared with the LCx MI approach without compromising the survival rate. At the papillary muscle level, echocardiographic strain analysis revealed no differences in radial and circumferential strain between LAD and LCx MIs. However, in contrast with the LCx MI, the LAD MI resulted in significantly decreased longitudinal strain. The proximal LAD MI model induces more LV remodeling and depressed LV function relative to the LCx MI model. Location of MI significantly impacts the severity of HF, thus careful consideration is required when choosing an MI model for preclinical HF studies.
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and kiyotake.ishikawa@mssm.edu.
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Jaume
authors.initials: J
authors.lastname: Aguero
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tilemann
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Dennis
authors.initials: D
authors.lastname: Ladage
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Nadjib
authors.initials: N
authors.lastname: Hammoudi
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawase
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Santos-Gallego
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fish
authors.affiliation: Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; and.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000818:Animals; D017023:Coronary Angiography; D054059:Coronary Occlusion / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D004195:Disease Models, Animal; D018618:Echocardiography, Doppler, Color; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D006439:Hemodynamics; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D012720:Severity of Illness Index; D013314:Stress, Mechanical; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
keywords: anterior; posterior; remodeling; sphericity; torsion