Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia.

Apheresis Large animal model Normovolemic anemia Red blood cells Sheep

Journal

Current research in translational medicine
ISSN: 2452-3186
Titre abrégé: Curr Res Transl Med
Pays: France
ID NLM: 101681234

Informations de publication

Date de publication:
17 Aug 2024
Historique:
received: 01 05 2024
revised: 01 08 2024
accepted: 16 08 2024
medline: 16 9 2024
pubmed: 16 9 2024
entrez: 15 9 2024
Statut: aheadofprint

Résumé

The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4-6 g dL In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

Sections du résumé

BACKGROUND BACKGROUND
The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4-6 g dL
METHODS METHODS
In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used.
RESULTS RESULTS
Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL
CONCLUSIONS CONCLUSIONS
Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

Identifiants

pubmed: 39278153
pii: S2452-3186(24)00026-6
doi: 10.1016/j.retram.2024.103463
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103463

Informations de copyright

Copyright © 2024. Published by Elsevier Masson SAS.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Anna-Lena Semmler (AL)

Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Service Baden-Württemberg - Hessen, Sandhofstr. 1, 60528 Frankfurt, Germany.

Jan-Philipp Köhler (JP)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Lara Regolien (L)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Franziska Bayer (F)

Central Research Facility of the Medical Faculty of the Goethe University, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

Nikolay Polyansky (N)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Elise Gradhand (E)

Goethe-University Frankfurt, Dr. Senckenbergisches Department of Pathology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

Andreas von Knethen (A)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Kai Zacharowski (K)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Fabian Nocke (F)

Institute of Physiological Chemistry, University of Duisburg-Essen, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany.

Katja B Ferenz (KB)

Institute of Physiology, University of Duisburg-Essen, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany; CENIDE, University of Duisburg-Essen, Forsthausweg 2, 47057 Duisburg, Germany.

Joachim Schwäble (J)

Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Service Baden-Württemberg - Hessen, Sandhofstr. 1, 60528 Frankfurt, Germany.

Halvard Bonig (H)

Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Service Baden-Württemberg - Hessen, Sandhofstr. 1, 60528 Frankfurt, Germany; Goethe-University Frankfurt, Faculty of Medicine, Institute for Transfusion Medicine and Immunohematology, Sandhofstr. 1, 60528 Frankfurt, Germany.

Eva Herrmann (E)

Goethe-University Frankfurt, Department of Medicine, Institute of Biostatistics and Mathematical Modelling, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

Isabelle Hornung (I)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany.

Andrea U Steinbicker (AU)

Goethe-University Frankfurt, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Haus 13B, 60590 Frankfurt, Germany. Electronic address: andrea.steinbicker@uk-koeln.de.

Classifications MeSH