The novel hemoglobin-based oxygen carrier HRC 101 improves survival in murine sickle cell disease
| Autor: | Gord Adamson, Peter C.W. Kim, Thomas Engelhardt, Tal Shichor, Mark W. Crawford, David Bell, F. J. Lou Carmichael |
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| Rok vydání: | 2007 |
| Předmět: |
Hemolytic anemia
medicine.medical_specialty Time Factors chemistry.chemical_element Mice Transgenic Anemia Sickle Cell Kaplan-Meier Estimate Oxygen Hydroxyethyl Starch Derivatives Hemoglobins Mice Interquartile range Blood Substitutes Heart Rate Internal medicine Albumins medicine Animals Lactic Acid Hypoxia business.industry Albumin medicine.disease Survival Analysis Sickle cell anemia Disease Models Animal Anesthesiology and Pain Medicine Hemoglobinopathy Endocrinology Treatment Outcome chemistry Immunology Anesthetics Inhalation Breathing Hemoglobin Blood Gas Analysis business Halothane |
| Zdroj: | Anesthesiology. 107(2) |
| ISSN: | 0003-3022 |
| Popis: | Background Erythrocyte transfusion decreases morbidity in sickle cell disease, but is not without risk. Use of a hemoglobin-based oxygen carrier could offer the benefits of erythrocyte transfusion while reducing related complications. The authors tested the hypothesis that the novel hemoglobin-based oxygen carrier, HRC 101, would improve survival during exposure to acute hypoxia in a murine model of sickle cell disease, the transgenic mouse expressing hemoglobin SAD (alpha2beta2). Methods Wild-type (n = 30) and transgenic SAD (n = 36) mice received 0.02 ml/g HRC 101 (hemoglobin concentration, 10 g/dl) or an equal volume of 5% albumin. Thirty percent or 6% oxygen was administered to spontaneously breathing mice during halothane anesthesia (inspired concentration, 0.5%). The time to cessation of cardiac electrical activity was recorded. Survival was compared using Kaplan-Meier analysis. Results Control mice survived the 60-min study period, whether breathing 30% or 6% oxygen. In contrast, all SAD mice given albumin and 6% oxygen died, with a median survival time of 9.0 min (interquartile range, 6.9-11.6 min; P < 0.0001). HRC 101 significantly increased survival in SAD mice breathing 6% oxygen. Of 12 SAD mice given HRC 101 and 6% oxygen, 4 survived the entire study period and 8 died, with a median survival time of 48 min (19-60 min; P < 0.0001 vs. albumin). Conclusion HRC 101 significantly decreased sickle-related mortality during exposure to acute hypoxic stress in transgenic mice expressing hemoglobin SAD. HRC 101 warrants further evaluation as a therapeutic modality in sickle cell disease. |
| Databáze: | OpenAIRE |
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