title: Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium.
abstract: OBJECTIVE
  Abnormal hemodynamic loading often accompanies congenital heart disease both before and after surgical repair. Adaptive and maladaptive myocardial responses to increased load are numerous. This study examined the hypothesis that myocyte loss occurs during compensatory hypertrophic growth in the developing infant myocardium subjected to progressive pressure overload.
  
  
  METHODS
  Pressure-overload left ventricular hypertrophy was induced in 7- to 10-day-old rabbits by banding the thoracic aorta. Left ventricular function and mechanics were quantified by serial echocardiography and noninvasive left ventricular wall stress analysis. Left ventricular tissue sections were examined for fibrosis by using Masson's trichrome stain and for myocyte apoptosis by using a myocyte-specific DNA fragmentation assay and caspase-3 activation (specific fluorescent substrate).
  
  
  RESULTS
  Significant myocyte apoptosis (198 +/- 37/10(6) myocytes, P < .01 vs control) and caspase-3 activation were present in early hypertrophy when left ventricular contractility was preserved and compensatory hypertrophy had normalized wall stress. By 6 weeks, multiple indices of left ventricular contractility were reduced, and left ventricular wall stress was increased. Myocyte apoptosis was accelerated (361 +/- 56/10(6) myocytes), caspase-3 activity further increased, and the estimated total number of left ventricular myocytes was significantly reduced by 18% +/- 4%.
  
  
  CONCLUSIONS
  In experimental infant left ventricular hypertrophy, myocyte apoptosis is initiated in the face of normalized wall stress and preserved contractility. The ongoing rate of apoptosis causes a measurable decrease in myocyte number that is coincident with the onset of ventricular dysfunction. It thus appears that pressure overload, even at its earliest stages, is not well tolerated by the developing ventricle.
authors.affiliation: Department of Anesthesiology and Perioperative and Pain Medicine, Children's Hospital Boston, and Harvard Medical School, Boston, Mass 02115, USA. yh.choi@uk-koeln.de
authors.forename: Yeong-Hoon
authors.initials: YH
authors.lastname: Choi
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cowan
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Moran
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
authors.forename: Christof
authors.initials: C
authors.lastname: Stamm
authors.forename: Koh
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Friehs
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: del Nido
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D002452:Cell Count; D018450:Disease Progression; D005355:Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D011817:Rabbits; D013314:Stress, Mechanical; D014463:Ultrasonography; D017725:Ventricular Pressure
chemical_list: D053148:Caspase 3