Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1☆,☆☆,★,★★
Section snippets
Animal protocols
All care and procedures were reviewed and approved by the Oregon Health Sciences University Animal Care and Use Committee. Surgery was performed in 11 fetal sheep at 119 to 124 days' gestation as previously described.2, 16 General anesthesia was induced with a diazepam-ketamine mixture, the ewe was intubated, and anesthesia was maintained with 1.5% halothane and 50% nitrous oxide–50% oxygen. Polyvinyl catheters (1.19 mm inner diameter) were placed in the fetal descending aorta and inferior vena
Generation and characterization of chronic anemia in fetal sheep
Chronic anemia was induced in fetal lambs by daily isovolemic hemorrhage over 6.2 ± 0.3 days (range 5 to 8 days). Two groups of tissue were studied, with one set analyzed for RNA and protein expression and the other set analyzed by capillary morphometry. The gestational age, hematocrit, or hemodynamic data did not differ between these two sets and therefore the anemic fetuses are presented as one group (Table I).
Empty Cell Start Final Statistical
Comment
The major finding of this study was that in ovine fetuses with chronic anemia ventricular concentrations of HIF-1α protein increased significantly, as did VEGF mRNA and protein. In concert, capillary density in the left ventricle was maintained and was actually greater in the right ventricle as the heart-to-body weight ratio increased. Studies in chronically anemic fetal sheep have demonstrated significant cardiac adaptations including an approximately 30% increase in heart-to-body weight ratio
Acknowledgements
We thank N. Ferrara (Genentech) for the polyclonal antibody raised against recombinant human VEGF.
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From the Department of Obstetrics and Gynecology and the Congenital Heart Center, Oregon Health Sciences University,a and the Center for Medical Genetics, Departments of Pediatrics and Medicine, Johns Hopkins University School of Medicine.b
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Supported by grants from the American Heart Association (G.L.S.), National Institutes of Health grants No. R01-HL55338 (G.L.S.) and R01-HL45043 (L.D.), and Multidisciplinary Training Program in Lung Diseases T32-HL07534 (A.Y.Y.). G.L.S. is an Established Investigator of the American Heart Association.
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Reprint requests: Lowell Davis, MD, Department of Obstetrics and Gynecology, OB Research, L458, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098.
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