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Am J Physiol Heart Circ Physiol 284: H81-H91, 2003. First published September 26, 2002; doi:10.1152/ajpheart.00562.2002
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Vol. 284, Issue 1, H81-H91, January 2003

Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesentery

Ann L. Baldwin1, Elizabeth B. Wiley1, Amber G. Summers2, and Abdu I. Alayash2

1 Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona 85724-5051; 2 Laboratory of Plasma Derivatives, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Modified Hbs are being developed as "blood substitutes," but intravascular injection of diaspirin cross-linked Hb (DBBF-Hb) can produce venular leakage. Hb toxicity may arise from reactive oxygen species, so the antioxidant sodium selenite (Na2SeO3) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which received 2 × 10-6 g/ml Na2SeO3 in their drinking water for 3 wk, the mesenteric microvasculature was perfused with 2 mg/ml DBBF-Hb (N = 8) for 10 min. Controls (N = 7) received saline. This was followed by perfusion with FITC-albumin for 3 min, fixation, and microscopic examination. In rats given DBBF-Hb, Na2SeO3 significantly reduced leak number, leak area, and mast cell degranulation. Venular leakage was also reduced in rats that only received Na2SeO3 locally during DBBF-Hb perfusion. However, Na2SeO3 did not affect animals receiving cyanomet-DBBF-Hb instead of DBBF-Hb and significantly increased leak number and mast cell degranulation in animals receiving saline. In vitro, Na2SeO3 reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na2SeO3 reduces DBBF-Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron.

blood substitutes; fluorescence microscopy; mast cells; antioxidant


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