Secretory leukoprotease inhibitor attenuates lung injury induced by
continuous air embolization into sheep.
Gossage, James R., Elizabeth A. Perkett, Jeffrey M. Davidson, Barry C.
Starcher, David Carmichael, Kenneth L. Brigham, Barbara Meyrick.
Center for Lung Research, Division of Pulmonary and Critical Care
Medicine, Departments of Medicine, Pediatrics, and Pathology,
Vanderbilt University School of Medicine, and the Departments of
Medicine and Pathology, Veterans Administration Medical Center, 37232
Nashville, Tennessee, and the Department of Biochemistry, University
of Texas Health Center, 75710 Tyler, Texas.
APStracts 2:0207A, 1995.
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/d by
aerosol, during 12 days of CAE (CAE+SLPI, n=7). Controls included
sheep receiving CAE + vehicle (CAE+VEH, n=6), vehicle alone (VEH,
n=3) and SLPI alone (SLPI, n=3). SLPI significantly attenuated the
CAE-induced increases in lung lymph flow (day 8, 2.3+/-1.3 versus
5.6+/-4.1 ml/15 min), protein clearance (day 8, 1.36+/-0.79 versus
3.08+/-2.05 ml/15 min), and elastin peptide concentration (day 8,
243+/-101 versus 398+/-109 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.
Received 4 November 1994; accepted in final form 12 May 1995.
APS Manuscript Number A1134-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.