The prevention of elastase-induced emphysema in hamsters by the intratracheal administration of a synthetic elastase inhibitor bound to albumin microspheres

S. R. Gudapaty, I. E. Liener, J. R. Hoidal, R. V. Padmanabhan, Dennis E Niewoehner, J. Abel

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10 Scopus citations

Abstract

The peptide, succinyl-alanyl-alanyl-prolyl-valine chloromethylketone (SPCK), a synthetic inhibitor of elastase, was covalently attached to human albumin microspheres (HAM) and administered intratracheally to hamsters 15 min and 8 h prior to the instillation of porcine pancreatic elastase. Pressure-volume relationships and histologic examination of excised lungs after 4 wk showed complete protection from emphysema when SPCK-HAM was administered either 15 min or 8 h before elastase exposure. Concurrent experiments with free SPCK showed that protection was achieved only if elastase was administered within 15 min after the instillation of SPCK. Extending this period to 8 h not only led to a failure of free SPCK to prevent emphysema but actually resulted in more extensive air-space enlargement. The prolonged effectiveness conferred by the attachment of SPCK to a biodegradable carrier should reduce the frequency with which it would have to be administered for the therapeutic intervention of emphysema and should minimize any toxic side reactions.

Original languageEnglish (US)
Pages (from-to)159-163
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume132
Issue number1
StatePublished - 1985

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