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Articles in PresS, published online ahead of print May 30, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00221.2002
Submitted on March 13, 2002
Accepted on May 23, 2002
1 Physiology, University of Arizona, 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.
Two "blood substitutes", a diaspirin cross-linked human hemoglobin (DBBF-Hb) and a bovine polymerized hemoglobin (PolyHbBv), advanced to clinical trials, are used in this study. Previously we have shown that injection of DBBF-Hb into the rat circulation produces venular leakage and intestinal epithelial disruption. The purpose of this study was to determine whether PolyHbBv, currently approved for veterinary use in the U.S.A., shows similar effects. In anesthetized Sprague-Dawley rats, the mesenteric microvasculature was perfused with DBBF-Hb (n=6), PolyHbBv (n=5), cyanomet Hb (CNmet-DBBF-Hb) or Hepes buffered saline with 0.5% bovine serum albumin (HBS-BSA) (controls, n=7) for 10 min., followed by FITC-albumin for 3 min., and then fixed for microscopy. For DBBF-Hb, the mean leak number/µm venule length (2.41 ± 0.33 (SEM) x 10-3) was significantly greater than for PolyHbBv (0.53 ± 0.14 x 10-3), CNmet-DBBF-Hb (0.36 ± 0.14 x 10-3) and HBS-BSA (0.12 ± 0.08 x 10-3) (p<0.01). Corresponding quantities for leak area were 0.10 ± 0.03 µm2 /µm, 0.010 ± 0.003, 0.005 ± 0.003, and 0.02 ± 0.02. In rats injected with DBBF-Hb (n=8), intestinal epithelial integrity was significantly compromised compared to those injected with PolyHbBv (n=5) or saline (n=6). These results indicate that intravascular PolyHbBv produces significantly less disruption of the intestinal exchange barrier than does DBBF-Hb, probably because the heme is not so easily oxidized.
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