title: Lymphatic system as a path underlying the spread of lung and gut injury after intestinal ischemia/reperfusion in rats.
abstract: We investigated in rats the influence of the lymphatic system and of tumor necrosis factor (TNF) on the lung inflammation resulting from intestinal ischemia/reperfusion (I/R) performed by 45-min occlusion of the superior mesenteric artery followed by 2 h of reperfusion. A group of rats had the thoracic lymph duct ligated before I/R. In lungs, intestinal I/R evoked a significant neutrophil recruitment, and enhanced microvascular permeability, in addition to generation of TNF in serum. In the gut, there was lowered lactate dehydrogenase (LDH) activity and increased microvascular permeability. Upon lymph duct ligation, I/R rats had a significant reduction of pulmonary neutrophil recruitment and plasma extravasation, in addition to high amounts of TNF in the lymph, contrasting with undetectable levels in the serum. In addition, LDH gut levels in these animals were close to basal values; there was also some (yet significant) reduction of microvascular permeability, suggesting that the ligation of the lymphatic duct exerted some degree of protection against the intestinal injury caused by I/R. In I/R rats, the treatment with pentoxifylline (PTX) reduced TNF in serum and blunted other lung alterations. The gut alterations caused by intestinal I/R were largely blocked by PTX. On the other hand, in I/R rats with lymph duct ligation, PTX exacerbated the reduction of pulmonary neutrophil recruitment, but did not affect pulmonary and intestinal microvascular permeabilities. Similarly, intestinal LDH activity and serum TNF levels were unaffected. Overall, our data show that the pulmonary and gut injuries induced by intestinal I/R are partially dependent on TNF, which is conceivably generated in the injured gut tissue due to intestinal I/R and carried by the lymphatic system. Thus, the mesenteric lymphatic drainage seems to play a role as a path modulator of the pulmonary and intestinal dysfunctions that follow a gut trauma.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brasil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cavriani
authors.forename: Helori Vanni
authors.initials: HV
authors.lastname: Domingos
authors.forename: Alexandre Learth
authors.initials: AL
authors.lastname: Soares
authors.forename: Aryene Goes
authors.initials: AG
authors.lastname: Trezena
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ligeiro-Oliveira
authors.forename: Ricardo Martins
authors.initials: RM
authors.lastname: Oliveira-Filho
authors.forename: Lia Siguemi
authors.initials: LS
authors.lastname: Sudo-Hayashi
authors.forename: Wothan
authors.initials: W
authors.lastname: Tavares de Lima
mesh_terms: D000818:Animals; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008196:Lymph / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism / Q000473:pathology*; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008833:Microcirculation; D009504:Neutrophils / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D010431:Pentoxifylline