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Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep.
J Appl Physiol (1985). 1994 Sep; 77(3):1333-40.JA

Abstract

The purpose of the present study was to assess the role of polymorphonuclear leukocyte (neutrophil) elastase in endotoxin-induced acute lung injury in sheep with lung lymph fistula. We studied the effects of ONO-5046, a specific inhibitor of neutrophil elastase, on the lung dysfunction induced by the intravenous infusion of 1 microgram/kg of Escherichia coli endotoxin. Endotoxin alone produced a biphasic response as previously reported. Early (0.5-1 h) after endotoxin, pulmonary arterial pressure increased from 19.5 +/- 0.9 cmH2O at baseline to a peak of 46.8 +/- 2.4 cmH2O (P < 0.05). Pulmonary vascular resistance increased from 3.03 +/- 0.17 cmH2O.l-1.min at baseline to a peak of 9.77 +/- 0.70 cmH2O.l-1.min (P < 0.05). Circulating neutrophils decreased from 7,355 +/- 434/mm3 at baseline to a nadir of 1,762 +/- 32/mm3 (P < 0.05). Thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations in plasma and lung lymph were significantly increased. Late (3-5 h) after endotoxin, pulmonary arterial pressure and pulmonary vascular resistance returned to baseline levels, but lung lymph flow remained increased from 4.2 +/- 0.3 ml/0.5 h at baseline to 7.3 +/- 0.7 ml/0.5 h (P < 0.05), with a slight increase in lung lymph-to-plasma protein concentration ratio, suggesting increased pulmonary vascular permeability. The histopathological features of the lungs during the early period in sheep treated with endotoxin alone revealed a large increase in neutrophils per 100 alveoli and changes of pulmonary edema such as thickening of the interstitium of the lung and alveolar flooding.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7836137

Citation

Kubo, K, et al. "Effects of ONO-5046, a Specific Neutrophil Elastase Inhibitor, On Endotoxin-induced Lung Injury in Sheep." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 77, no. 3, 1994, pp. 1333-40.
Kubo K, Kobayashi T, Hayano T, et al. Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep. J Appl Physiol (1985). 1994;77(3):1333-40.
Kubo, K., Kobayashi, T., Hayano, T., Koizumi, T., Honda, T., Sekiguchi, M., & Sakai, A. (1994). Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep. Journal of Applied Physiology (Bethesda, Md. : 1985), 77(3), 1333-40.
Kubo K, et al. Effects of ONO-5046, a Specific Neutrophil Elastase Inhibitor, On Endotoxin-induced Lung Injury in Sheep. J Appl Physiol (1985). 1994;77(3):1333-40. PubMed PMID: 7836137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of ONO-5046, a specific neutrophil elastase inhibitor, on endotoxin-induced lung injury in sheep. AU - Kubo,K, AU - Kobayashi,T, AU - Hayano,T, AU - Koizumi,T, AU - Honda,T, AU - Sekiguchi,M, AU - Sakai,A, PY - 1994/9/1/pubmed PY - 1994/9/1/medline PY - 1994/9/1/entrez SP - 1333 EP - 40 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 77 IS - 3 N2 - The purpose of the present study was to assess the role of polymorphonuclear leukocyte (neutrophil) elastase in endotoxin-induced acute lung injury in sheep with lung lymph fistula. We studied the effects of ONO-5046, a specific inhibitor of neutrophil elastase, on the lung dysfunction induced by the intravenous infusion of 1 microgram/kg of Escherichia coli endotoxin. Endotoxin alone produced a biphasic response as previously reported. Early (0.5-1 h) after endotoxin, pulmonary arterial pressure increased from 19.5 +/- 0.9 cmH2O at baseline to a peak of 46.8 +/- 2.4 cmH2O (P < 0.05). Pulmonary vascular resistance increased from 3.03 +/- 0.17 cmH2O.l-1.min at baseline to a peak of 9.77 +/- 0.70 cmH2O.l-1.min (P < 0.05). Circulating neutrophils decreased from 7,355 +/- 434/mm3 at baseline to a nadir of 1,762 +/- 32/mm3 (P < 0.05). Thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations in plasma and lung lymph were significantly increased. Late (3-5 h) after endotoxin, pulmonary arterial pressure and pulmonary vascular resistance returned to baseline levels, but lung lymph flow remained increased from 4.2 +/- 0.3 ml/0.5 h at baseline to 7.3 +/- 0.7 ml/0.5 h (P < 0.05), with a slight increase in lung lymph-to-plasma protein concentration ratio, suggesting increased pulmonary vascular permeability. The histopathological features of the lungs during the early period in sheep treated with endotoxin alone revealed a large increase in neutrophils per 100 alveoli and changes of pulmonary edema such as thickening of the interstitium of the lung and alveolar flooding.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 8750-7587 UR - https://www.unboundmedicine.com/medline/citation/7836137/Effects_of_ONO_5046_a_specific_neutrophil_elastase_inhibitor_on_endotoxin_induced_lung_injury_in_sheep_ L2 - https://journals.physiology.org/doi/10.1152/jappl.1994.77.3.1333?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -