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 HCI (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 < 0.05). Acid aspiration was associated with increased protein concentration in bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900-mu-g/ml in the aspirated and nonaspirated lungs, respectively, which were higher than control values of 420 and 400-mu-g/ml (P < 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 < 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-mu-g/ml) as well as the increased lung W/D (4.6 and 4.0; all P < 0.05). Treatment of other rats at 90 min (n = 18) with the elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloro-methylketone (0.4-mg/kg bolus, 0.4 mg.kg-1.h-1) protected only the nonaspirated lung segments from injury. Finally, because scavengers of reactive oxygen species inhibited thromboxane synthesis, another group was treated at 90 min with the thromboxane synthase inhibitor OKY-046 (2 mg . kg-1 . h-1). There was a modest and significant decrease in BAL fluid protein and W/D of the aspirated and nonaspirated segments compared with untreated acid-aspirated animals, but this benefit was substantially less than treatment with superoxide dismutase-catalase (P < 0.05). The data indicate generalized lung PMN sequestration after localized acid aspiration. Reactive oxygen species and elastase, which are presumably released by these cells, decrease the vascular barrier function.