Publication Date:
2013-11-15
Description:
Acute organ failure is a major clinical concern in sickle cell disease (SCD). However, the mechanism responsible for this potentially lethal complication is poorly understood. We tested the hypothesis that extracellular hemin liberates an intracellular danger molecule that promotes acute organ failure in SCD. Transgenic homozygous SCD (SS), sickle-trait (AS) and normal human hemoglobin (Hb) AA mice were infused with purified hemin (35 µmoles/kg), which raised total plasma hemin by ∼0.45 mM (equivalent to 0.72 g/dl Hb) within 5 min in all three groups of mice. In agreement with our previous results, SS but not AA and AS mice (n= 6 for each genotype) developed cardiopulmonary depression at 30 min evident by reductions in oxygen saturation (99.88±0.23% to 92.1±1.3%, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine