The effects of small doses of oligopeptide elastase inhibitors on elastase-induced emphysema in hamsters: a dose-response study.

Abstract

Our previous studies have indicated that the synthetic elastase inhibitor N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanyl chloromethylketone (AAPACK) administered intraperitoneally in divided doses totaling 19 mg, prior to and after a single intratracheal injection of elastase, substantially inhibited the development of experimental emphysema. The present studies evaluated the effects of 1.1, 4.1 and 8.0 mg AAPACK administered in divided doses 10 min prior to and 10, 30, and 50 min after a single intratracheal dose of elastase. The development of emphysema was essentially eliminated by 4.1 and 8.0 mg of AAPACK and markedly diminished with 1.1 mg AAPACK. The AAPACK was excreted rapidly in the urine at 30 to 60 min after its administration. Elastase inhibitory capacity (EIC) in urine was elevated to 14 times that in serum at the corresponding collection times. The plasma elastase inhibitory capacity was only slightly increased after administration of AAPACK and was not a sensitive indicator of elastase inhibition in the plasma.