title: Timing of cardiomyocyte growth, maturation, and attrition in perinatal sheep.
abstract: Studies in altricial rodents attribute dramatic changes in perinatal cardiomyocyte growth, maturation, and attrition to stimuli associated with birth. Our purpose was to determine whether birth is a critical trigger controlling perinatal cardiomyocyte growth, maturation and attrition in a precocial large mammal, sheep (Ovis aries). Hearts from 0-61 d postnatal lambs were dissected or enzymatically dissociated. Cardiomyocytes were measured by micromorphometry, cell cycle activity assessed by immunohistochemistry, and nuclear number counted after DNA staining. Integration of this new data with published fetal data from our laboratory demonstrate that a newly appreciated >30% decrease in myocyte number occurred in the last 10 d of gestation (P < 0.0005) concomitant with an increase in cleaved poly (ADP-ribose) polymerase 1 (P < 0.05), indicative of apoptosis. Bisegmental linear regressions show that most changes in myocyte growth kinetics occur before birth (median = 15.2 d; P < 0.05). Right ventricular but not left ventricular cell number increases in the neonate, by 68% between birth and 60 d postnatal (P = 0.028). We conclude that in sheep few developmental changes in cardiomyocytes result from birth, excepting the different postnatal degrees of free wall hypertrophy between the ventricles. Furthermore, myocyte number is reduced in both ventricles immediately before term, but proliferation increases myocyte number in the neonatal right ventricle.
authors.affiliation: *Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; and Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: Sonnet S
authors.initials: SS
authors.lastname: Jonker
authors.affiliation: *Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; and Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Louey
authors.affiliation: *Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; and Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Giraud
authors.affiliation: *Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; and Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
authors.affiliation: *Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA; and Veterans Affairs Portland Health Care System, Portland, Oregon, USA.
authors.forename: J Job
authors.initials: JJ
authors.lastname: Faber
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D048429:Cell Size; D005260:Female; D005333:Fetus / Q000166:cytology; D006321:Heart / Q000254:growth & development; D016014:Linear Models; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009929:Organ Size; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors
chemical_list: D011065:Poly(ADP-ribose) Polymerases
keywords: apoptosis; cell number; fetus; neonate; proliferation