Inhibition of nitric oxide synthase reverses the effect of albumin on lung damage in burn.
BACKGROUND
Early colloid resuscitation in major burn patients has been stopped because of its deteriorating effect on thermal injury-induced vascular hyperpermeability. We hypothesized that inhibition of inducible nitric oxide synthase (iNOS) to stabilize endothelial permeability and to retain colloid solution in the vascular space will reverse its effect on lung damage.


METHODS
In experiment 1, specific pathogen free rats underwent 35% total-body surface area burn or sham burn and were given equal volumes (7.5 mL/kg) of normal saline or albumin from femoral veins for fluid resuscitation immediately after burn. In experiment 2, S-methylisothiourea (SMT, 7.5 mg/kg, IP) was given immediately after burn to rats from different groups, as in experiment 1. At 8 hours after burn, blood was assayed for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation, and lung tissues were harvested for myeloperoxidase (MPO) determination and histologic studies. Pulmonary microvascular dysfunction was quantified by measuring the extravasations of Evans blue dye.


RESULTS
Blood peroxynitrite level and iNOS expression, MPO activity, permeability, and inflammatory cell infiltration of lungs were significantly induced after thermal injury. Albumin resuscitation after burn without iNOS inhibition enhanced thermal injury-induced lung damage with 10%, 14%, and 5% increases in blood DHR oxidation level, lung MPO activity, and lung permeability, respectively, compared with saline injection. In contrast, burn + SMT rats with albumin injection showed significant, 23%, 37%, and 20%, decreases, respectively, in blood DHR 123 oxidation level, lung MPO activity, and lung permeability compared with burn + SMT + saline rats.


CONCLUSIONS
Thermal injury induced lung damage. Restoration of extracellular fluid in early burn shock with albumin markedly augmented the lung neutrophil deposition, lung permeability increase, and blood peroxynitrite level. Inhibition of iNOS before albumin supplementation reversed its damaging effects on thermal injury-induced lung dysfunction to beneficial ones.
Chen
Lee-Wei
LW
Department of Surgery, Kaohsiung Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
Hwang
Yuh-Chwen
YC
Wang
Jyh-Seng
JS
Chen
Jin-Shyr
JS
Hsu
Ching-Mei
CM
D000418:Albumins / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000201:enzymology*; D008168:Lung / Q000201:enzymology; D055370:Lung Injury; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology
D000418:Albumins; D012235:Rhodamines; D012462:Saline Solution, Hypertonic; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat