Hydrogen peroxide derived from intestine through the mesenteric lymph induces lung edema after surgical stress.
Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H2O2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H2O2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-alpha levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H2O2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-alpha production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H2O2 production in the small intestine. The H2O2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.
Nakamura
Masakatsu
M
Department of Surgery, Akita University School of Medicine, Hondo Akita City, Japan.
Motoyama
Satoru
S
Saito
Satoshi
S
Minamiya
Yoshihiro
Y
Saito
Reijiro
R
Ogawa
Jun-ichi
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000473:pathology; D008196:Lymph / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications; D011654:Pulmonary Edema / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013997:Time Factors; D014969:Xanthine Oxidase / Q000378:metabolism
D005452:Fluoresceins; D017382:Reactive Oxygen Species; C037631:2',7'-dichlorofluorescein; D006861:Hydrogen Peroxide; D009195:Peroxidase; D014969:Xanthine Oxidase