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Red Blood Cell Antibody Induced Anemia Causes Differential Degrees of Tissue Hypoxia
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in Kidney and Brain
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Authors:
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Nikhil Mistry1,2, C David Mazer1,2,3, John G Sled4,5, Alan H Lazarus3,6, Lindsay S Cahill4, Max
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Solish3, Yu-Qing Zhou4, Nadya Romanova7, Alexander GM Hare3, Allan Doctor8, Joseph A
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Fisher2,9, Keith R Brunt10, Jeremy A Simpson7, Gregory MT Hare1,2,3,11
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Affiliation:
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Running Head:
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Cardiovascular and hypoxic responses to anemia
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Corresponding Author:
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Gregory MT Hare, Department of Anesthesia, St. Michael’s Hospital, 30 Bond Street, Toronto,
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Ontario M5B 1W8, Phone: 416-864-5259, Fax: 416-864-6014, Email:
[email protected]
1. Department of Anesthesia, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada 2. Department of Physiology, University of Toronto, Toronto, Ontario, Canada 3. Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada 4. Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada 5. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada 6. The Canadian Blood Services Centre for Innovation, Ottawa, Ontario, Canada 7. Department of Human Health and Nutritional Sciences and Cardiovascular Research Group, University of Guelph, Guelph, Ontario, Canada 8. Department of Pediatrics; Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri, USA 9. Department of Anesthesia, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada 10. Department of Pharmacology, Dalhousie University, Saint John, New Brunswick, Canada 11. St. Michael’s Hospital Center of Excellence in Patient Blood Management
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Abstract:
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Moderate anemia is associated with increased mortality and morbidity, including acute kidney
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injury (AKI), in surgical patients. A red blood cell (RBC)-specific antibody model was utilized
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to determine if moderate subacute anemia could result in tissue hypoxia as a potential
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mechanism of injury. Cardiovascular and hypoxic cellular responses were measured in
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transgenic mice capable of expressing hypoxia-inducible factor-1α (HIF-1α)-luciferase activity
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in vivo. Antibody-mediated anemia was associated with mild intravascular hemolysis (6 hours)
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and splenic RBC sequestration (day 4), resulting in a nadir hemoglobin concentration of 89±13
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g/L at day 4. At this time point, renal tissue oxygen tension (PtO2) was decreased in anemic
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mice relative to controls (13.1±4.3 vs. 20.8±3.7 mmHg; p
