Reactive oxygen species and elastase mediate lung permeability after acid aspiration.
Acid aspiration leads to increased neutrophil (PMN) oxidative metabolism, an event associated with lung leukosequestration and permeability increase. Neutropenia protected the vascular barrier function against acid injury. This study tests whether active oxygen species and elastase (which are presumably released by adherent PMNs) affect the microvascular barrier. Anesthetized rats underwent tracheostomy and insertion of a cannula into a lung segment. This was followed by localized instillation of 0.1 N HCl (n = 18) or saline (n = 18). Sequestration of PMNs in acid-aspirated and nonaspirated segments was 77 and 46 PMNs/high-power field (HPF), respectively, which was higher than control values of 11 and 8 PMNs/10 HPF in saline-aspirated and nonaspirated regions (P less than 0.05). Acid aspiration was associated with increased protein concentration in bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900 micrograms/ml in the aspirated and nonaspirated lungs, respectively, which were higher than control values of 420 and 400 micrograms/ml (P less than 0.05). Acid aspiration also led to increased lung wet-to-dry weight ratios (W/D) of 6.6 and 5.4, which were higher than control values of 3.4 and 3.3 (P less than 0.05). Intravenous treatment of rats (n = 18) 90 min after aspiration with scavengers of reactive oxygen species, superoxide dismutase (1,500 U/kg), and catalase (5,000 U/kg), both conjugated to polyethylene glycol, did not reduce PMN sequestration but attenuated acid aspiration-induced increase in protein accumulation in BAL fluid in the aspirated and nonaspirated segments (990 and 610 micrograms/ml) as well as the increased lung W/D (4.6 and 4.0; all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Goldman
G
G
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Welbourn
R
R
Kobzik
L
L
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D002374:Catalase / Q000008:administration & dosage / Q000494:pharmacology; D005070:Evans Blue; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010539:Permeability; D011015:Pneumonia, Aspiration / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D008689:Methacrylates; D017382:Reactive Oxygen Species; D005070:Evans Blue; D013929:Thromboxane B2; D002374:Catalase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; D013930:Thromboxane-A Synthase; C034364:ozagrel; D006851:Hydrochloric Acid