title: Revisiting animal models of aortic stenosis in the early gestation fetus.
abstract: BACKGROUND
  Mechanisms leading to left ventricular hypoplasia and endocardial fibroelastosis in the fetus remain unknown. Prevailing theory is that obstruction to blood flow through the left ventricle leads to elevated end-diastolic pressures, compromised myocardial perfusion, and endocardial ischemia. Fetal interventions are now being performed, based on the presumption that they would prevent such pathogenic mechanisms.
  
  
  METHODS
  Forty first-trimester fetal sheep (mean gestational age, 53 days) were studied. Severe fetal left ventricular outflow obstruction was created by banding the ascending aorta in 25 fetuses; 15 control fetuses underwent "sham" surgery with thoracotomy. Serial fetal echocardiography was used to assess left ventricular growth and fetal hemodynamics. Findings were correlated to morphologic and histopathologic changes, and intracardiac pressure measurements obtained from fetal cardiac catheterization.
  
  
  RESULTS
  Surviving banded fetuses (n = 13) had one of two phenotypes: compensatory left ventricular hypertrophy (n = 7) or noncompensatory left ventricular dilatation (n = 6) with hydrops and severe left ventricular dysfunction. All fetuses had elevated left ventricular end-diastolic pressures (mean, 21 mm Hg; range, 14 to 28 mm Hg), which correlated to the gradient across the ascending aorta (mean, 41 mm Hg; range, 28 to 73 mm Hg). In vivo echocardiography findings were incongruous with those at autopsy, and demonstrated preservation of left ventricular growth indices in all fetuses. Endocardial fibroelastosis and myocardial fibrosis were not observed in any banded fetus.
  
  
  CONCLUSIONS
  While early gestational obstruction to flow can compromise left ventricular function in the fetus, it does not retard normal growth. Similarly, an elevated left ventricular end-diastolic pressure is not sufficient to cause myocardial fibrosis or endocardial fibroelastosis in the fetus.
authors.affiliation: Division of Pediatric Cardiac Surgery and Pediatric Cardiology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. pirooz.eghtesady@cchmc.org
authors.forename: Pirooz
authors.initials: P
authors.lastname: Eghtesady
authors.forename: Erik
authors.initials: E
authors.lastname: Michelfelder
authors.forename: Mekibib
authors.initials: M
authors.lastname: Altaye
authors.forename: Edgar
authors.initials: E
authors.lastname: Ballard
authors.forename: Russel
authors.initials: R
authors.lastname: Hirsh
authors.forename: Robert H
authors.initials: RH
authors.lastname: Beekman
mesh_terms: D000818:Animals; D001011:Aorta; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000196:embryology* / Q000473:pathology; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004452:Echocardiography; D004487:Edema / Q000196:embryology / Q000209:etiology; D047108:Embryonic Development; D005318:Fetal Heart / Q000473:pathology; D005865:Gestational Age; D006321:Heart / Q000196:embryology; D006352:Heart Ventricles; D006973:Hypertension / Q000209:etiology / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000196:embryology / Q000209:etiology / Q000473:pathology; D008026:Ligation; D012756:Sheep; D016216:Ultrasonography, Prenatal; D018487:Ventricular Dysfunction, Left / Q000196:embryology / Q000209:etiology; D014694:Ventricular Outflow Obstruction / Q000196:embryology / Q000209:etiology