The prevention of elastase-induced emphysema in hamsters by the intratracheal administration of a synthetic elastase inhibitor bound to albumin microspheres.
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.
D000418:Albumins; D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D006224:Cricetinae; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008647:Mesocricetus; D008863:Microspheres; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine
D000418:Albumins; D000590:Amino Acid Chloromethyl Ketones; C031135:succinyl-alanyl-alanyl-prolyl-valine chloromethyl ketone; D010196:Pancreatic Elastase