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Am J Physiol Heart Circ Physiol (September 26, 2002). doi:10.1152/ajpheart.00562.2002
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Articles in PresS, published online ahead of print September 26, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00562.2002
Submitted on July 8, 2002
Accepted on September 13, 2002

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, University of Arizona, College of Medicine, Tucson, AZ, USA
2 Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail: abaldwin{at}u.arizona.edu.

Modified hemoglobins are being developed as "blood substitutes" but intravascular injection of diaspirin cross-linked hemoglobin (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, half of which received 2 x 10-6 g / ml Na2 SeO3 in their drinking water for 3 weeks, 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 just 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.




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