EFFECT OF THE SPECIFIC ELASTASE INHIBITOR, ALANYL ALANYL PROLYL ALANINE CHLOROMETHYLKETONE, ON ELASTASE-INDUCED EMPHYSEMA

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Abstract
The chloromethylketone derivative of the tetrapeptide, alanylalanylprolyl alanine, significantly diminishes the extent of experimental elastase-induced emphysema in hamsters. A total of 19 mg of alanylalanylprolyl alanine chloromethylketone [AAPACK] was administered i.p. in divided doses before and immediately after intratracheal instillation of a standard dose (4 units) of porcine pancreatic elastase. Morphologic evaluation and measurement of mean linear intercept, internal surface area and lung volume performed 7, 45, and 120 days after exposure to elastase indicated a marked decrease in the extent of emphysema in the group treated with AAPACK compared with the control group. Lung elastin content determined biochemically confirmed the preservation of elastin in the hamsters treated with AAPACK. At postmortem examination by light microscopy, no pathologic abnormalities were seen in the organs of hamsters treated with AAPACK. AAPACK in the doses administered had significant anti-elastase activity in vivo, markedly decreased the extent of elastase-induced emphysema and produced no adverse toxic effect during the period covered by this study protocol.