Reversal of the effect of albumin on gut barrier function in burn by the inhibition of inducible isoform of nitric oxide synthase.
OBJECTIVE
The use of albumin in the early resuscitation formula after major burn has been forbidden because of its damaging effect on the gut barrier function. We hypothesize that inhibition of the inducible isoform of nitric oxide synthase to stabilize endothelial permeability and to retain albumin in the vascular space will ameliorate the major trauma-induced gut barrier dysfunction.


METHODS
In experiment 1, specific pathogen-free rats undergoing 35% total body surface area burn or sham burn were given equal volumes (7.5 mL/kg) of isotonic sodium chloride solution or albumin from femoral veins for fluid resuscitation at 0, 4, or 8 hours after burn. In experiment 2, intraperitoneal S-methylisothiourea sulfate (7.5 mg/kg) was given immediately after burn to rats from different groups, as in experiment 1 (SMT groups). At 24 hours after burn, the intestinal mucosa was assayed for myeloperoxidase activity as an index for neutrophil sequestration, the distribution of fluorescein isothiocyanate-dextran across the lumen of small intestine was determined to evaluate the intestinal permeability, and bacterial translocation (BT) to the mesenteric lymph nodes (MLNs) and histological findings in the ileum were also examined.


RESULTS
Compared with sham burn, burn induced significant increases in intestinal mucosa myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi sloughing in rats. Albumin administration at 0 or 4 hours after burn enhanced the increases in neutrophil sequestration, permeability, and villi sloughing compared with saline injection at the same times. In contrast, injection of albumin in the burn-SMT group did not aggravate these changes in intestinal myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi edema. Burn-SMT rats with albumin injections at 4 or 8 hours after burn showed significant 35% and 52% decreases, respectively, in intestinal permeability compared with burn-SMT-saline rats. Use of albumin at 8 hours after burn in combination with S-methylisothiourea significantly attenuated BT to the MLNs and reduced villi edema.


CONCLUSIONS
Early albumin resuscitation aggravated the burn-induced gut damage. Albumin administration and inhibition of the inducible isoform of nitric oxide synthase in combination decreased burn-induced gut barrier dysfunction and reversed the damaging effect of albumin on gut barrier function and decreased BT.
Chen
Lee-Wei
LW
Department of Surgery, Kaohsiung Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
Wang
Jyh-Seng
JS
Hwang
Bonnie
B
Chen
Jin-Shyr
JS
Hsu
Ching-Mei
CM
D000418:Albumins / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D002056:Burns / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005440:Fluid Therapy / Q000379:methods; D007410:Intestinal Diseases / Q000209:etiology / Q000628:therapy; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology*; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010539:Permeability / Q000187:drug effects*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D010952:Plasma Substitutes / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D004791:Enzyme Inhibitors; D010952:Plasma Substitutes; D007550:Isothiuronium; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium