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Quantitative assessment of hemoglobin-induced endothelial barrier dysfunction.
Randal O Dull1, Bracken J DeWitt, Ramani Dinavahi
1Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA. Randal.Dull@hsc.utah.edu
Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 27, 2004
Summary
Hemoglobin-based O2 carriers (HBOCs) increase microvascular permeability. This study quantifies how different HBOCs affect endothelial cell permeability and their own diffusion, revealing insights into potential clinical risks.
Area of Science:
- Biomedical Engineering
- Vascular Biology
- Biochemistry
Background:
- Hemoglobin-based oxygen carriers (HBOCs) are developed as blood substitutes.
- A key challenge is their propensity to increase microvascular permeability and vascular resistance.
Purpose of the Study:
- To quantitatively assess HBOC-induced changes in endothelial cell permeability.
- To evaluate the impact of HBOC size on their own permeability and diffusion.
Main Methods:
- Utilized bovine lung microvascular endothelial cell monolayers.
- Measured transendothelial electrical resistance, albumin permeability, and Hb permeability (PDH).
- Tested human Hb-A, Hb-Polytaur (500 kDa), and Hb-(Polytaur)n (1,000,000 Da).
Main Results:
- All tested Hb molecules rapidly decreased transendothelial electrical resistance to 30% of baseline.
- Diffusive albumin permeability increased approximately ninefold upon Hb exposure.
- Hb molecules increased their own permeability (Hb-induced Hb permeability), with changes related to Hb size.
Conclusions:
- Polymerized HBOCs significantly alter endothelial barrier function.
- Increased HBOC permeability and potential for extravasation are critical considerations for clinical use.
- Findings provide quantitative data on HBOC diffusion and its implications for safety.