The novel hemoglobin-based oxygen carrier HRC 101 improves survival in murine sickle cell disease.

Abstract

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.

• Authors: Mark W Crawford, Tal Shichor, Thomas Engelhardt, Gord Adamson, David Bell, F J Lou Carmichael, Peter C W Kim
• Journal: Anesthesiology (Anesthesiology) Vol. 107 Issue 2 Pg. 281-7 (Aug 2007) ISSN: 0003-3022 [Print] United States
• PMID: 17667573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Albumins
• Anesthetics, Inhalation
• Blood Substitutes
• HRC 101
• Hemoglobins
• Hydroxyethyl Starch Derivatives
• Lactic Acid
• Oxygen
• Halothane

Topics

• Albumins (administration & dosage)
• Anemia, Sickle Cell (drug therapy)
• Anesthetics, Inhalation (administration & dosage)
• Animals
• Blood Gas Analysis (methods)
• Blood Substitutes (therapeutic use)
• Disease Models, Animal
• Halothane (administration & dosage)
• Heart Rate (drug effects)
• Hemoglobins (therapeutic use)
• Hydroxyethyl Starch Derivatives (therapeutic use)
• Hypoxia (drug therapy, mortality)
• Kaplan-Meier Estimate
• Lactic Acid (blood)
• Mice
• Mice, Transgenic
• Oxygen (administration & dosage, blood)
• Survival Analysis
• Time Factors
• Treatment Outcome