title: Cardiomyocyte enlargement, proliferation and maturation during chronic fetal anaemia in sheep.
abstract: Chronic anaemia increases the workload of the growing fetal heart, leading to cardiac enlargement. To determine which cellular process increases cardiac mass, we measured cardiomyocyte sizes, binucleation as an index of terminal differentiation, and tissue volume fractions in hearts from control and anaemic fetal sheep. Fourteen chronically catheterized fetal sheep at 129 days gestation had blood withdrawn for 9 days to cause severe anaemia; 14 control fetuses were of similar age. At postmortem examination, hearts were either enzymatically dissociated or fixed for morphometric analysis. Daily isovolumetric haemorrhage reduced fetal haematocrit from a baseline value of 35% to 15% on the final day (P < 0.001). At the study conclusion, anaemic fetuses had lower arterial pressures than control fetuses (P < 0.05). Heart weights were increased by 39% in anaemic fetuses compared with control hearts (P < 0.0001), although the groups had similar body weights; the heart weight difference was not due to increased ventricular wall water content or disproportionate non-myocyte tissue expansion. Cardiomyocytes from anaemic fetuses tended to be larger than those of control fetuses. There were no statistically significant differences between groups in the cardiomyocyte cell cycle activity. The degree of terminal differentiation was greater in the right ventricle of anaemic compared with control fetuses by 8% (P < 0.05). Anaemia substantially increased heart weight in fetal sheep. The volume proportions of connective and vascular tissue were unchanged. Cardiomyocyte mass expanded by a balanced combination of cellular enlargement, increased terminal differentiation and accelerated proliferation.
authors.affiliation: Oregon Health & Science University, 3303 SW Bond Avenue CH14T, Portland, OR 97239-4501, USA. jonkers@ohsu.edu
authors.forename: Sonnet S
authors.initials: SS
authors.lastname: Jonker
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Giraud
authors.forename: George D
authors.initials: GD
authors.lastname: Giraud
authors.forename: Natasha N
authors.initials: NN
authors.lastname: Chattergoon
authors.forename: Samantha
authors.initials: S
authors.lastname: Louey
authors.forename: Lowell E
authors.initials: LE
authors.lastname: Davis
authors.forename: J Job
authors.initials: JJ
authors.lastname: Faber
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
mesh_terms: D000740:Anemia / Q000097:blood / Q000473:pathology*; D000818:Animals; D049108:Cell Enlargement; D049109:Cell Proliferation; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000097:blood / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D012756:Sheep
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