title: Coronary constriction impairs cardiac function and induces myocardial damage and ventricular remodeling in mice.
abstract: To establish whether coronary artery narrowing (CAN) in mice was accompanied by depressed ventricular function, tissue injury, and modifications in cardiac anatomy, the left coronary artery was constricted in FVB/N mice and the animals were killed 7 days later. CAN consisted of a 53% reduction in luminal diameter, which resulted in a twofold increase in left ventricular end-diastolic pressure. Left ventricular systolic pressure and left ventricular + and -dP/dt decreased 15, 21, and 11%, respectively. Left ventricular weight-to-body weight ratio increased 33%. This hypertrophic adaptation was characterized by a 9 and 20% increase in the longitudinal and transverse cavitary diameters, which provoked a 1.5-fold expansion in chamber volume. In contrast, wall thickness decreased 15%. These anatomic and functional changes induced a threefold elevation in diastolic stress. Foci of reparative fibrosis were found in the endomyocardium and epimyocardium, involving 2-3% of the tissue. Finally, myocyte loss in the ventricle was 15%, and myocyte hypertrophy was 38%. Impaired ventricular function, diastolic Laplace overloading, myocyte loss, and decompensated eccentric hypertrophy in mice after CAN mimic the ischemic cardiomyopathic heart in humans.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla 10595, USA.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: K P
authors.initials: KP
authors.lastname: Jana
authors.forename: G
authors.initials: G
authors.lastname: Redaelli
authors.forename: J
authors.initials: J
authors.lastname: Kajstura
authors.forename: P
authors.initials: P
authors.lastname: Anversa
mesh_terms: D000818:Animals; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology*; D003971:Diastole; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000473:pathology*; D013599:Systole; D014661:Vasoconstriction; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*; D016277:Ventricular Function, Left