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Related Experiment Videos

Toxicity of polymerized hemoglobin solutions.

M Feola1, J Simoni, P C Canizaro

  • 1Department of Surgery, School of Medicine, Texas Tech University Health Sciences Center, Lubbock 79430.

Surgery, Gynecology & Obstetrics
|March 1, 1988
PubMed
Summary

Impurities in bovine polymerized hemoglobin solutions caused significant toxicity and mortality in rabbits. Removing these impurities resulted in a safer hemoglobin-based oxygen carrier with minimal adverse effects.

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Area of Science:

  • Biomedical Engineering
  • Toxicology
  • Hematology

Background:

  • Hemoglobin-based oxygen carriers (HBOCs) are potential blood substitutes.
  • The safety and efficacy of polymerized hemoglobin solutions require thorough investigation.
  • Identifying sources of toxicity in HBOCs is crucial for clinical application.

Purpose of the Study:

  • To evaluate the toxicity of different bovine polymerized hemoglobin solutions (BPHS) in rabbits.
  • To determine the impact of specific impurities on the safety profile of BPHS.
  • To assess the potential of purified BPHS as a blood substitute.

Main Methods:

  • Four BPHS formulations were administered to rabbits, replacing one-third of blood volume.
  • Solutions varied in purity, with impurities including stromal lipids, endotoxins, and high molecular weight polymers.

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  • Mortality, morbidity (hemodynamic, respiratory, renal, hepatic, hematologic), and histopathologic changes were assessed.

    • Main Results:

    • Impure BPHS formulations (BPHS-1, BPHS-2, BPHS-3) led to 33% mortality and severe morbidity, including disseminated intravascular coagulation (DIC) and complement activation.
    • Histopathology revealed ischemic and inflammatory lesions in multiple organs.
    • The purified BPHS-4 caused no mortality and minimal morbidity (elevated liver enzymes, reduced creatinine clearance), with only ischemic changes observed.

    Conclusions:

    • Toxicity of polymerized hemoglobin solutions is primarily attributable to impurities.
    • Purified hemoglobin-based oxygen carriers demonstrate improved safety profiles.
    • Further research into the mild toxicity of pure hemoglobin, potentially due to vasoconstrictive effects, is warranted.