Left ventricular alterations in a model of fetal left ventricular overload

Congenital aortic coarctation is well tolerated by the fetus because the fo ramen ovale and ductus arteriosus equalize intracardiac and great arteries pressures and shunts. The pathologic consequences only emerge after birth w ith closure of the foramen ovale and ductus arteriosus, There is, however, no documentation of myocardial effects in utero of the left ventricular (LV ) pressure overload induced by aortic banding. We investigated whether pren atal aortic banding could be detrimental at the structural and/or functiona l level. The goal of the present study was to investigate the cardiac effec ts of LV pressure overload in a fetal lamb model. Nine fetal lambs underwen t preductal banding of the aortic arch in utero at midgestation (CoA group) , whereas their twins underwent sham surgery. All fetuses were studied betw een 27 and 37 d after surgery for LV pressure, anatomic and histologic anom alies, and steady state sarcoendoplasmic reticulum calcium ATPase (SERCA 2a ) mRNA and protein levels and pump activity. Surgery resulted in severe aor tic coarctation in all the animals in the CoA group and was associated with a 65% increase in the LV weight to body weight ratio relative to the sham- operated group (p < 0.001). Hemodynamic and histologic studies showed an ev olutionary pattern depending on duration of the experimental coarctation wi th a shift occurring at 30 d of coarctation, The initial response of cardio myocytes to ventricular overload was hypertrophy of the myocytes, followed by myocyte hyperplasia. Compared with sham, there was an apparent decrease in the percentage of binucleated cells in the CoA group after 30 d of coarc tation, The earliest response to LV pressure overload appears to occur at t he molecular level. Indeed, sarcoendoplasmic reticulum calcium ATPase (SERC A 2a) mRNA levels fell significantly to only 28.6% of the sham group value (p = 0.023), independently of the duration of coarctation, In the fetal lam b, the pressure overload-induced hypertrophy resulting from progressive aor tic coarctation leads to hemodynamic and lesional abnormalities and slows o ntogenic maturation.