Secretory leukoprotease inhibitor attenuates lung injury induced by continuous air embolization into sheep

James R Gossage, E. A. Perkett, J. M. Davidson, B. C. Starcher, D. Carmichael, K. L. Brigham, B. Meyrick

Research output: Contribution to journalArticle

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Abstract

Continuous air embolization (CAE) into the pulmonary arterial circulation of sheep results in functional and structural changes of chronic pulmonary hypertension. Release of elastin peptides into lung lymph during CAE and attenuation of CAE-induced pulmonary hypertension by neutrophil depletion suggest that neutrophil elastase may contribute to these changes. To investigate this notion, we treated awake sheep with a potent neutrophil elastase inhibitor, recombinant secretory leukoprotease inhibitor (SLPI) (100 mg/day by aerosol), during 12 days of CAE (CAE + SLPI; n = 7). Controls included sheep receiving CAE + vehicle (VEH) (n = 6), VEH alone (n = 3), and SLPI alone (n = 3). SLPI significantly attenuated the CAE-induced increases in lung lymph flow (day 8; 2.3 ± 0.5 vs. 5.6 ± 1.7 ml/15 min), protein clearance (day 8; 1.36 ± 0.32 vs. 3.08 ± 0.84 ml/15 min), and elastin peptide concentration (day 8; 243 ± 41 vs. 398 ± 44 ng/ml). SLPI delayed the onset of sustained pulmonary hypertension from day 8 to day 12. Both CAE groups showed similar structural changes in the pulmonary arteries. SLPI was well tolerated in control sheep and did not affect hemodynamics or structure. We conclude that serine proteases may contribute to the early initiation of chronic pulmonary hypertension but do not play a striking role in its eventual development.

Original languageEnglish (US)
Pages (from-to)1163-1172
Number of pages10
JournalJournal of Applied Physiology
Volume79
Issue number4
DOIs
StatePublished - Jan 1 1995

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Lung Injury
Sheep
Air
Pulmonary Hypertension
Elastin
Lymph
Secretory Proteinase Inhibitory Proteins
Lung
Leukocyte Elastase
Peptides
Pulmonary Circulation
Serine Proteases
Aerosols
Pulmonary Artery
Neutrophils
Hemodynamics

Keywords

  • aerosol
  • chronic pulmonary hypertension
  • elastase inhibitor
  • elastin
  • lung lymph
  • neutrophil elastase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Secretory leukoprotease inhibitor attenuates lung injury induced by continuous air embolization into sheep. / Gossage, James R; Perkett, E. A.; Davidson, J. M.; Starcher, B. C.; Carmichael, D.; Brigham, K. L.; Meyrick, B.

In: Journal of Applied Physiology, Vol. 79, No. 4, 01.01.1995, p. 1163-1172.

Research output: Contribution to journalArticle

Gossage, James R ; Perkett, E. A. ; Davidson, J. M. ; Starcher, B. C. ; Carmichael, D. ; Brigham, K. L. ; Meyrick, B. / Secretory leukoprotease inhibitor attenuates lung injury induced by continuous air embolization into sheep. In: Journal of Applied Physiology. 1995 ; Vol. 79, No. 4. pp. 1163-1172.
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