Effect of ONO-5046, a specific neutrophil elastase inhibitor, on the phorbol myristate acetate-induced injury in isolated dog lung.


Journal Article

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.

Full Text

Cited Authors

  • Wang, HG; Shibamoto, T; Miyahara, T; Haniu, H; Tanaka, S; Fujimoto, K; Honda, T; Kubo, K; Koyama, S

Published Date

  • January 1999

Published In

Volume / Issue

  • 25 / 1

Start / End Page

  • 55 - 67

PubMed ID

  • 10027079

Pubmed Central ID

  • 10027079

Electronic International Standard Serial Number (EISSN)

  • 1521-0499

International Standard Serial Number (ISSN)

  • 0190-2148

Digital Object Identifier (DOI)

  • 10.1080/019021499270420


  • eng