title: Neutrophil elastase and oxygen radicals: synergism in lung injury after hindlimb ischemia.
abstract: Hindlimb ischemia and reperfusion lead to lung injury dependent on activated polymorphonuclear neutrophils (PMN) adherence. This study tests whether elastase and oxygen radicals participate in PMN-induced injury once they have become sequestered in lungs. Anesthetized rats treated with saline (n = 9) or the specific elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloromethylketone (MAAPV, n = 6) underwent 4 h of bilateral hindlimb tourniquet ischemia followed by 4 h of reperfusion. At this time, in saline-treated rats, PMN were sequestered in lungs as assayed by myeloperoxidase activity [(MPO) 51 +/- 5 U/g tissue], higher than MPO in saline-treated sham rats (n = 9; 18 +/- 3 U/g MPO; P less than 0.01); bronchoalveolar lavage (BAL) fluid leukotriene (LT) B4 levels increased to 594 +/- 46 relative to 200 +/- 38 pg/ml in shams (P less than 0.01); increased permeability was documented by BAL fluid protein content of 599 +/- 91 compared with 214 +/- 35 micrograms/ml in sham animals (P less than 0.01); and edema was shown by increase in lung wet-to-dry weight ratio of 4.77 +/- 0.14 relative to 4.00 +/- 0.09 in sham rats (P less than 0.01). In MAAPV-treated animals, lung neutrophil sequestration (62 +/- 9 U/g MPO) and rise of LTB4 in BAL fluid (780 +/- 244 pg/ml) were not affected, but both BAL fluid protein (335 +/- 32 micrograms/ml) and lung wet-to-dry weight ratio (4.21 +/- 0.17) were reduced (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: C R
authors.initials: CR
authors.lastname: Welbourn
authors.forename: G
authors.initials: G
authors.lastname: Goldman
authors.forename: I S
authors.initials: IS
authors.lastname: Paterson
authors.forename: C R
authors.initials: CR
authors.lastname: Valeri
authors.forename: D
authors.initials: D
authors.lastname: Shepro
authors.forename: H B
authors.initials: HB
authors.lastname: Hechtman
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology; D016166:Free Radical Scavengers; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism / Q000502:physiology*; D010196:Pancreatic Elastase / Q000378:metabolism / Q000502:physiology*; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D016166:Free Radical Scavengers; D015289:Leukotrienes; D010196:Pancreatic Elastase; D010100:Oxygen