The use of hypertonic saline (HTS)
resuscitation in major
trauma patients is still controversial. The objective of this study is to determine if inhibition of
inducible nitric oxide synthase (iNOS) to stabilize the endothelial permeability and to retain HTS in the vascular space will reverse its exacerbating effect on
burn-induced lung damage. In Experiment 1, specific pathogen-free (SPF) rats underwent 35% total body surface area (TBSA)
burn and were resuscitated with 7.5 mL/kg HTS (7.5% NaCl), 7.5 mL/kg saline, or 50 mL/kg saline (nearly equal
sodium load as HTS) via femoral veins for 15 min immediately after the
burn. In Experiment 2,
S-methylisothiourea (SMT) (7.5 mg/kg, i.p.) was given immediately after the
burn to rats from the different groups of Experiment 1. At 8 h after the
burn, the permeability and
myeloperoxidase (MPO) activity of lung tissues were determined, and plasma samples were assayed for
peroxynitrite levels.
Burn significantly induced lung MPO activity, lung permeability, and blood
dihydrorhodamine 123 (DHR 123) oxidation in rats. HTS administration after
burn significantly increased the blood DHR 123 oxidation level, lung MPO activity, lung permeability, and inflammatory cell infiltration in comparison with those of
burn plus 7.5 mg/kg saline and
burn plus 50 mL/kg saline rats. In contrast,
burn plus SMT rats with HTS injection showed significant 54%, 11%, and 35% decreases in blood DHR 123 oxidation level, lung MPO activity, and lung permeability, respectively, in comparison with
burn plus SMT plus 7.5 mg/kg saline rats. In conclusion, restoration of extracellular fluid in early
burn shock with HTS supplementation significantly exacerbates
burn-induced lung neutrophil deposition, lung hyperpermeability, and blood
peroxynitrite production. Inhibition of iNOS before HTS supplementation reverses the deteriorating effects of HTS on thermal injury-induced lung damage to beneficial ones. Using HTS in thermal injury
resuscitation without the inhibition of iNOS is dangerous.