title: Mechanical function, glycolysis, and ultrastructure of perfused working mouse hearts following thoracic aortic constriction.
abstract: BACKGROUND
  Glycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described.
  
  
  METHODS
  The main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure-volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of (3)H-glucose to (3)H(2)O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs.
  
  
  RESULTS
  Results revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks.
  
  
  CONCLUSIONS
  The results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Dunn
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Manfredi
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Cosmas
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Vetter
authors.forename: Joshua N
authors.initials: JN
authors.lastname: King
authors.forename: Robert L
authors.initials: RL
authors.lastname: Rodgers
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery*; D001706:Biopsy; D002302:Cardiac Output; D003971:Diastole; D004195:Disease Models, Animal; D005355:Fibrosis; D006019:Glycolysis; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010477:Perfusion; D013599:Systole; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling