EGLIN-C PREVENTS MONOCROTALINE-INDUCED VENTILATORY DYSFUNCTION

The present study was carried out to investigate the relationship betw een elastase and monocrotaline (MCT)induced ventilatory dysfunction in rats. TO accomplish this, we used an elastase inhibitor eglin-c to su ppress the activity of endogenous elastase. Thirty-five young Sprague- Dawley rats were randomly divided into six groups: control, MCT, eglin -c(1), eglin-c(2), eglin-c(1)+MCT, and eglin-c(2)+MCT. Rats in the con trol group received no treatment. Each MCT rat received a single subcu taneous injection of MCT (60 mg/kg) 1 wk before the functional test. E ach eglin-c(1) rat was intratracheally instilled with eglin-c (9 mg/ra t) twice in 1 wk. Each eglin-c(2) rat was intratracheally instilled wi th eglin-c (9 mg/rat) five times in I wk. Both eglin-c+MCT groups were treated with the combination of eglin-c(1) or eglin-c(2) and MCT. In the MCT group, there were significant decreases in dynamic respiratory compliance, maximal expiratory flow rate at 50% total lung capacity, and the slopes of the maximal expiratory flow-%total lung capacity cur ve and the maximal expiratory flow-static recoil pressure curve. Howev er, in the eglin-c(1)+MCT and eglin-c(2)+MCT groups, all of the above- mentioned MCT-induced changes were prevented. All ventilatory values o f the eglin-c(1) and eglin-c(2) groups were not significantly differen t from those of the control group. These results demonstrate that egli n-c treatment prevents MCT-induced ventilatory dysfunction and suggest that endogenous elastase may play an important role in MCT-induced in flammation-mediated ventilatory abnormality.