Transfusion effects on cardiomyocyte growth and proliferation in fetal sheep after chronic anemia

Chronic fetal anemia results in significant cardiac remodeling. The capacity to reverse these effects is unknown. We examined the effects of transfusion on cardiomyocyte adaptations after chronic anemia in fetal sheep subjected to daily hemorrhage beginning at 109-d GA (term ∼145 d). After 10 d of anemia, one group was killed for comparison with age-matched controls. A separate group of anemic fetuses was transfused with red blood cells at 119-d GA for comparison with controls at 129-d GA. Anemia significantly increased the heart-to-body weight ratio, an effect partially ameliorated after transfusion. Cardiomyocyte dimensions were similar among all groups, suggesting an absence of hypertrophy. The percentages of mono- and binucleated cardiomyocytes were similar between groups at 119-d GA, although the percentage of binucleated cells was significantly less in transfused fetuses compared with controls at 129-d GA. Protein levels of mitogen-activated protein kinases and protein kinase B were similar between controls and their respective intervention groups, except for a significant increase in phosphorylated c-Jun N-terminal kinase 1/2 in transfused fetuses. Thus, cardiomyocyte proliferation but not hypertrophy contributes to cardiac enlargement during fetal anemia. Transfusion results in slowing but not cessation of cardiac growth after anemia.