Myocardial Growth Response to Fetal Intralipid Infusion in Sheep

Cardiomyocyte proliferative maturation and metabolic maturation occur in the same perinatal period. Intrauterine conditions influence developmental trajectories of both processes; however, their interconnectedness is unknown. Circulating fetal lipid levels are typically low, but the heart may be prematurely exposed to elevated lipids. We experimentally increased fetal lipid levels to determine the impact on cardiomyocyte proliferative maturation. Fetal sheep were surgically instrumented with catheters. After recovery, Intralipid 20 or Lactated Ringer's Solution were infused according to a clinical g/kg schedule for 8 days until 133 ± 1 days of gestation. A left ventricular biopsy was fixed, and remaining cardiomyocytes were enzymatically dissociated. Myocardial composition was measured from Masson's Trichrome-stained sections. Cardiomyocyte length, width, nucleation, and Ki-67+ were studied in dispersed cells. Myocardial composition, cardiomyocyte dimensions, and Ki-67+ were not found to be different between groups. Cardiomyocytes of the Intralipid-treated fetuses were 14% more terminally differentiated than controls (p = 0.025). Early developmental exposure to circulating lipid accelerates fetal cardiomyocyte terminal differentiation and may contribute to fewer cardiomyocytes for life.