Hemodynamic alteration by fetal surgery accelerates myocyte proliferation in fetal guinea pig hearts.
BACKGROUND
Fetal heart development occurs by hyperplasia as myocytes lose the capacity to proliferate at birth. This potential for cell division may have application in altering fetal growth patterns in congenital cardiac malformations, but it is not known whether the proliferative activity can be modified by intrauterine surgical manipulation. The purpose of this study was to determine whether hemodynamic alteration by fetal surgery influences myocyte proliferation and myocardial development.


METHODS
Six pregnant guinea pigs of 50 to 52 days of gestation (term, 65 days) underwent hysterotomy, and the fetal ascending aorta was banded and narrowed by 50% (AoB). Cesarean section was performed near term, and the heart was assessed for myocyte proliferative activity (Ki-67 monoclonal antibody), apoptosis, and morphologic features.


RESULTS
The heart to body weight ratio (1.02% +/- 0.12% versus 0.42% +/- 0.02%, p < 0.01) and left ventricular posterior wall thickness (1.89 +/- 0.25 mm versus 1.31 +/- 0.19 mm, p < 0.01) were significantly higher in the AoB group. The percentage of Ki-67 positive cells was increased in AoB group (29.5% +/- 4.4% versus 15.3% +/- 1.3% in right ventricle, 35.8% +/- 5.1% versus 13.1% +/- 1.7% in interventricular septum, and 39.8% +/- 3.2% versus 12.0% +/- 2.0% in left ventricle (p < 0.01). The apoptotic cell to myocyte ratio was less than 1/1000 in both groups.


CONCLUSIONS
Fetal hemodynamic alteration by aortic banding accelerates myocardial cellular proliferation without affecting apoptosis, suggesting that in utero cardiac interventions have a greater influence on myocardial development compared with postnatal intervention.
Saiki
Y
Y
Division of Cardiovascular Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Konig
A
A
Waddell
J
J
Rebeyka
I M
IM
D000818:Animals; D001012:Aorta, Abdominal / Q000196:embryology* / Q000502:physiology / Q000601:surgery*; D017209:Apoptosis; D001835:Body Weight; D002455:Cell Division; D005314:Embryonic and Fetal Development; D005260:Female; D005318:Fetal Heart / Q000033:anatomy & histology / Q000502:physiology*; D005333:Fetus; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000196:embryology; D006439:Hemodynamics; D019394:Ki-67 Antigen / Q000032:analysis; D009206:Myocardium / Q000166:cytology; D009929:Organ Size; D011247:Pregnancy
D019394:Ki-67 Antigen