This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wolf, R. B. Articles by Brace, R. A. Search for Related Content PubMed PubMed Citation Social Bookmarking                   What's this?

Antibody-Induced Anemia in Fetal Sheep: Model for Hemolytic Disease of the Fetus and Newborn

Kenneth J. Moise, Jr., MD

Department of Reproductive Medicine, Division of Perinatal Medicine, University of California, San Diego, School of Medicine, La Jolla, California; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Robert A. Brace, PhD

Department of Reproductive Medicine, Division of Perinatal Medicine, University of California, San Diego, School of Medicine, La Jolla, California; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina bobbrace{at}ucsd.edu

Objective: Our purpose was to produce a condition analogous a alloimmune hemolytic disease of the fetus and newborn by infusing antierythrocyte antibodies in fetal sheep.

Methods: Antierythrocyte antibodies were infused intravascularly into late-gestation ovine fetuses over a 10-day period. Fetal blood was sampled dialy for complete blood cell counts, blood gases, iron, erythropietin (EPO), and electrolyte concentrations. Red cell mass (RCM) and blood volume were determined every other day using indicator dilution techniques. Results were compared with eight similarly aged control animals. Statistical analysis included Student t test, three-factor analysis of variance, and least squares regression.

Results: The hematocrit in seven fetal sheep receiving antibody infusion declined significantly by 10.3 ± 1.7%, whereas it increased in control animals 2.3 ± 0.6% (P < .001). RCM was reduced by 18.9 ± 3.2% over the 10-day protocol while increasing 34.1 ± 4.2% in control animals, representing more than a 50% difference in RCM (P < .001). Fetal EPO was significantly increased with lower hematocrit and lower Po₂ (P < .001). As fetal hematocrit declined below 25%, lactate and reticulocytes also increased (P < .001). Plasma iron concentration was not significantly altered (P = .47).

Conclusions: The chronically catheterized fetal sheep is a viable model for studying immunologically induced fetal anemia as hematocrit can be tirated and the fall in RCM and hematocrit are associated with fetal hypoxia and elevated EPO as occurs in the anemic human fetus. Furthermore, there appears to be a threshold degree of anemia required to elicit responses as the fetal EPO, Po₂, and lactate appeared unresponsive until hematocrit fell below 25%.

Key Words: Hemolytic disease • Rh disease • antibody • animal model • sheep

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?