Oxygen free radical injury and its relation to bacterial and endotoxin translocation after delayed fluid resuscitation: clinical and experimental study.
OBJECTIVE
To examine whether there is generation of oxygen free radicals (OFR) and lipid peroxidation of cell membrane after volume replacement for burn shock, and to study the relationship between OFR injury and enterogenous endotoxemia.


METHODS
Forty-seven burn patients were involved in this study. Among them, 18 had delayed fluid resuscitation (DR) and the others had early fluid resuscitation (ER) within 6 hours postburn. Sixty-six gnotobiotic rats were used in a collaborating experiment as burn models. They were divided into 4 groups: sham injury (n = 6), early resuscitation (n = 24), late resuscitation (n = 24) and vitamins E and C treatment group (n = 12). All the rats, except those in the sham injury group, were inflicted with 40% total body surface area (TBSA) third-degree burns. OFR was determined in the blood of patients with electron spin resonance (ESR). S/W ratio and tau c values of patients' erythrocytes were measured with ESR spectrometer. Blood superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities, malondialdehyde contents and plasma endotoxin levels were assayed. Rats were sacrificed at the 12th, 24th, 48th and 72nd hour after injury. Plasma endotoxin levels, mucosal SOD, GSHPx and malondialdehyde (MDA), as well as diamine oxidase activity of ileum were determined. Cultures of mesenteric lymph nodes (MLN), liver, spleen, heart, lung, kidney and blood were done.


RESULTS
A significant increase in blood OFR contents and plasma MDA, and a significant decline in blood SOD and GSHPx were found after resuscitation in DR group as compared with those in ER group. Both strong to weak spectra component (S/W) ratio and tau c value were higher in DR group in contrast with those in ER group. Higher elevation in plasma endotoxin level in DR group was seen. In DR group, plasma MDA content was correlated with S/W ratio, tau c value and plasma endotoxin level. In rats, the level of mucosal MDA, plasma endotoxin and incidence of bacterial translocation (BT) were significantly higher. Mucosal SOD, GSHPx and diamine oxidase (DAO) activity were significantly lower in DR group as compared with those in ER group. In DR group, mucosal MDA content was negatively correlated with mucosal DAO activity, while the latter was negatively correlated with BT. After treatment with vitamins E and C, mucosal MDA content decreased, plasma endotoxin and BT significantly declined and mucosal DAO heightened.


CONCLUSIONS
Tissue reperfusion might induce the production of OFR, resulting in lipid peroxidation injury, especially to intestinal mucosa, and resulting in disruption of mucosal barrier function followed by endotoxemia and BT.
Yang
H
H
Burn Center, Postgraduate Medical College, Hospital, Beijing, China.
Sheng
Z
Z
Guo
Z
Z
Shi
Z
Z
Lu
J
J
Chai
J
J
Sun
C
C
D000293:Adolescent; D000328:Adult; D000818:Animals; D018988:Bacterial Translocation; D002056:Burns / Q000378:metabolism* / Q000628:therapy; D019446:Endotoxemia / Q000209:etiology*; D005260:Female; D005440:Fluid Therapy; D005609:Free Radicals / Q000097:blood; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D005609:Free Radicals; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D010100:Oxygen