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Journal of applied physiology (Bethesda, Md. : 1985)2005; 99(3); 915-921; doi: 10.1152/japplphysiol.00438.2005

Reticulocyte changes after experimental anemia and erythropoietin treatment of horses.

Abstract: Availability of recombinant human erythropoietin (EPO) has facilitated use to enhance red blood cell production, and therefore aerobic performance, in human and equine athletes. Recombinant human EPO promotes growth and differentiation of equine erythroid precursor cells, but in some horses repeat administration induces immune interference with endogenous EPO resulting in fatal anemia. Although blood reticulocyte parameters acquire unique changes in humans treated with EPO, with manual enumeration methods, horses were not considered to release reticulocytes from the bone marrow into circulation, even under severe erythropoietic stress. The goals of this study were to determine whether reticulocytes could be detected and characterized in horses that are anemic or have been treated with EPO using a modern hematology analyzer. Anemia was induced in six horses by removal of 30 ml of blood/kg of body wt over 24 h. After 28 days, the horses were treated twice with 55 U/kg of EPO (Eprex), and after 65 days they were treated thrice with 73 U/kg of EPO. Blood samples were analyzed with the ADVIA120 instrument every 3-5 days and bone marrow samples 7 days after anemia and EPO treatments. Analysis of blood reticulocyte parameters by ANOVA in a randomized complete block design determined that anemia and EPO induced significant (P < or = 0.05) increases in red cell distribution width and reticulocyte mean cell volume. Parameters changed only after EPO treatment were cellular hemoglobin concentration mean, mean cell volume, reticulocyte concentration, proportion of macrocytic reticulocytes, and reticulocyte cellular hemoglobin. These findings indicate that horses under erythropoietic stress and after EPO treatment release reticulocytes with unique characteristics into circulation.
Publication Date: 2005-08-17 PubMed ID: 16103516DOI: 10.1152/japplphysiol.00438.2005Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research paper studies changes in reticulocytes, immature red blood cells, in horses under conditions of induced anemia and treatment with erythropoietin (EPO). The study finds that these conditions result in significant changes in reticulocyte characteristics, contrary to prior beliefs.

Objective and Methodology

  • This paper examines how reticulocytes, immature red blood cells capable of carrying oxygen, change in horses when they’re subjected to anemia and then treated with EPO, a hormone that stimulates the production of red blood cells.
  • Anemia was induced in six horses via the removal of a large volume of blood, after which they were treated with EPO. The ability to scrutinize reticulocytes was enabled through the use of a modern hematology analyzer known as the ADVIA120 instrument.
  • Blood and bone marrow samples were taken and analyzed at various intervals across the study.

Findings and Significance

  • The results showed that anemia and EPO treatment led to significant increases in red cell distribution width and reticulocyte mean cell volume.
  • Additional parameters that only changed following EPO treatment included cellular hemoglobin concentration mean, mean cell volume, reticulocyte concentration, the proportion of larger-than-normal reticulocytes, and reticulocyte cellular hemoglobin.
  • The ANOVA statistical method was used to determine significant changes in reticulocyte parameters, following a randomized complete block design.
  • A noteworthy finding from this research is that contrary to previous understanding, horses do release reticulocytes from the bone marrow into their circulation under severe erythropoietic stress, such as after having anemia induced or being treated with EPO.
  • This study therefore provides new insights into equine biology and medicine, specifically with regard to blood cell production and medical interventions for conditions like anemia.

Cite This Article

APA
Cooper C, Sears W, Bienzle D. (2005). Reticulocyte changes after experimental anemia and erythropoietin treatment of horses. J Appl Physiol (1985), 99(3), 915-921. https://doi.org/10.1152/japplphysiol.00438.2005

Publication

ISSN: 8750-7587
NlmUniqueID: 8502536
Country: United States
Language: English
Volume: 99
Issue: 3
Pages: 915-921

Researcher Affiliations

Cooper, C
  • Dept. of Pathobiology, Univ. of Guelph, ON, Canada N1G 2W1.
Sears, W
    Bienzle, D

      MeSH Terms

      • Anemia / blood
      • Anemia / immunology
      • Anemia / veterinary
      • Animals
      • Dose-Response Relationship, Drug
      • Erythropoietin / administration & dosage
      • Hematopoiesis / drug effects
      • Hematopoiesis / immunology
      • Horse Diseases / blood
      • Horse Diseases / immunology
      • Horses
      • Recombinant Proteins
      • Reticulocyte Count / veterinary
      • Reticulocytes / drug effects
      • Reticulocytes / immunology

      Citations

      This article has been cited 3 times.
      1. Dahlgren AR, Knych HK, Arthur RM, Durbin-Johnson BP, Finno CJ. Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses.. Genes (Basel) 2021 Nov 24;12(12).
        doi: 10.3390/genes12121874pubmed: 34946824google scholar: lookup
      2. Kämpf S, Seiler E, Bujok J, Hofmann-Lehmann R, Riond B, Makhro A, Bogdanova A. Aging Markers in Equine Red Blood Cells.. Front Physiol 2019;10:893.
        doi: 10.3389/fphys.2019.00893pubmed: 31379601google scholar: lookup
      3. Correia CN, McLoughlin KE, Nalpas NC, Magee DA, Browne JA, Rue-Albrecht K, Gordon SV, MacHugh DE. RNA Sequencing (RNA-Seq) Reveals Extremely Low Levels of Reticulocyte-Derived Globin Gene Transcripts in Peripheral Blood From Horses (Equus caballus) and Cattle (Bos taurus).. Front Genet 2018;9:278.
        doi: 10.3389/fgene.2018.00278pubmed: 30154823google scholar: lookup