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  • Title: Effect of ONO-5046, a specific neutrophil elastase inhibitor, on the phorbol myristate acetate-induced injury in isolated dog lung.
    Author: Wang HG, Shibamoto T, Miyahara T, Haniu H, Tanaka S, Fujimoto K, Honda T, Kubo K, Koyama S.
    Journal: Exp Lung Res; 1999; 25(1):55-67. PubMed ID: 10027079.
    Abstract:
    Phorbol myristate acetate (PMA) activates neutrophils and causes acute lung injury. We determined the effect of ONO-5046, a specific neutrophil elastase inhibitor, on the increase in microvascular permeability induced by PMA in isolated dog lung perfused with autologous blood at a constant perfusion flow. The vascular permeability was assessed by the capillary filtration coefficient (Kf, c) and the solvent-drag reflection coefficient (sigma f). PMA (13.3 micrograms) increased vascular permeability, as evidenced by an increase in Kf, c from 0.18 +/- 0.02 to 0.92 +/- 0.14 mL/min/cmH2O/100 g and a decrease in sigma f to 0.35 +/- 0.01 as compared to control values of 0.69 +/- 0.06. The PMA-induced changes in Kf, c and sigma f were dose-dependently attenuated by pretreatment with ONO-5046 (2-20 mg). We conclude that ONO-5046 can effectively attenuate the PMA-induced injury in the isolated blood-perfused dog lungs.
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