title: Regional cardiac dysfunction and dyssynchrony in a murine model of afterload stress.
abstract: Small animal models of afterload stress have contributed much to our present understanding of the progression from hypertension to heart failure. High-sensitivity methods for phenotyping cardiac function in vivo, particular in the setting of compensated cardiac hypertrophy, may add new information regarding alterations in cardiac performance that can occur even during the earliest stages of exposure to pressure overload. We have developed an echocardiographic analytical method, based on speckle-tracking-based strain analyses, and used this tool to rapidly phenotype cardiac changes resulting from afterload stress in a small animal model. Adult mice were subjected to ascending aortic constriction, with and without subsequent reversal of the pressure gradient. In this model of compensated hypertrophic cardiac remodeling, conventional echocardiographic measurements did not detect changes in left ventricular (LV) function at the early time points examined. Strain analyses, however, revealed a decrement in basal longitudinal myofiber shortening that was induced by aortic constriction and improved following relief of the pressure gradient. Furthermore, we observed that pressure overload resulted in LV segmental dyssynchrony that was attenuated with return of the afterload to baseline levels. Herein, we describe the use of echocardiographic strain analyses for cardiac phenotyping in a mouse model of pressure overload. This method provides evidence of dyssynchrony and regional myocardial dysfunction that occurs early with compensatory hypertrophy, and improves following relief of aortic constriction. Importantly, these findings illustrate the utility of a rapid, non-invasive method for characterizing early cardiac dysfunction, not detectable by conventional echocardiography, following afterload stress.
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. mihi@tentacleriot.eu
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Unno
authors.forename: Fen-Chiung
authors.initials: FC
authors.lastname: Lin
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006332:Cardiomegaly / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003251:Constriction, Pathologic; D003971:Diastole; D004452:Echocardiography / Q000379:methods*; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000503:physiopathology
references.citation: Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H811-20
references.pmid: 19561310
references.citation: Eur J Echocardiogr. 2008 Nov;9(6):741-7
references.pmid: 18490299
references.citation: Circulation. 2006 Mar 14;113(10):e396-8
references.pmid: 16534017
references.citation: J Am Soc Echocardiogr. 2011 Mar;24(3):277-313
references.pmid: 21338865
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H496-502
references.pmid: 17384134
references.citation: Cardiovasc Ultrasound. 2012 Mar 07;10:8
references.pmid: 22397470
references.citation: Circulation. 2009 Sep 8;120(10):859-66
references.pmid: 19704101
references.citation: Eur Heart J. 2009 Mar;30(6):731-9
references.pmid: 19176536
references.citation: Physiol Genomics. 2004 Feb 13;16(3):349-60
references.pmid: 14679301
references.citation: Hypertension. 2010 Feb;55(2):241-8
references.pmid: 19996069
references.citation: J Am Soc Echocardiogr. 2009 Feb;22(2):198-205
references.pmid: 19121566
references.citation: J Am Soc Echocardiogr. 2009 Apr;22(4):337-42
references.pmid: 19269134
references.citation: Eur J Echocardiogr. 2009 Jun;10(4):527-31
references.pmid: 19174444
references.citation: Circulation. 2011 Jan 25;123(3):327-34
references.pmid: 21263005
references.citation: J Am Soc Echocardiogr. 1998 Jul;11(7):683-92
references.pmid: 9692525
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2809-16
references.pmid: 17277023
references.citation: Circ Res. 2011 Apr 15;108(8):908-16
references.pmid: 21372284
references.citation: Clin Cardiol. 2008 Dec;31(12):597-601
references.pmid: 19072883