SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION

WACHTFOGEL YT, HACK CE, NUIJENS JH, KETTNER C, REILLY TM, KNABB RM, BISCHOFF R, Tschesche H, Wenzel H, KUCICH U, EDMUNDS LH, et al. (1995)
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 268(3): H1352-H1357.

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Abstract
Cardiopulmonary bypass causes hemorrhagic complications and initiates a biochemical and cellular ''whole body inflammatory response.'' This study investigates whether a variety of selective inhibitors of the contact pathway of intrinsic coagulation modulate complement and neutrophil activation during simulated extracorporeal circulation. After 60 min of recirculation in the presence of the slow tight-binding boronic acid inhibitor, Bz-Pro-Phe-boroArg-OH (10.7 mu M), complete inhibition of kallikrein-C (1) over bar-inhibitor complex formation and marked inhibition of C (1) over bar-C (1) over bar-inhibitor complex formation and the release of human neutrophil elastase were observed. Arg(15)-aprotinin (3.1 mu M), Ala(357),Arg(358) alpha(1)-antitrypsin (2.6 mu M), and soybean trypsin inhibitor (48.0 mu M) either completely or partially inhibited the generation of kallikrein C (1) over bar-inhibitor complexes but were less effective inhibitors of human neutrophil elastase release. The second-order rate constants for the inhibition of kallikrein in purified systems are consistent with the order of effectiveness of the inhibitors in blocking human neutrophil elastase release in heparinized blood. Our results suggest that low-molecular-weight selective inhibitors of kallikrein may be effective agents in the attenuation of the contact-mediated inflammatory response in cardiopulmonary bypass.
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WACHTFOGEL YT, HACK CE, NUIJENS JH, et al. SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. 1995;268(3):H1352-H1357.
WACHTFOGEL, Y. T., HACK, C. E., NUIJENS, J. H., KETTNER, C., REILLY, T. M., KNABB, R. M., BISCHOFF, R., et al. (1995). SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 268(3), H1352-H1357.
WACHTFOGEL, Y. T., HACK, C. E., NUIJENS, J. H., KETTNER, C., REILLY, T. M., KNABB, R. M., BISCHOFF, R., Tschesche, H., Wenzel, H., KUCICH, U., et al. (1995). SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 268, H1352-H1357.
WACHTFOGEL, Y.T., et al., 1995. SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 268(3), p H1352-H1357.
Y.T. WACHTFOGEL, et al., “SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION”, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, vol. 268, 1995, pp. H1352-H1357.
WACHTFOGEL, Y.T., HACK, C.E., NUIJENS, J.H., KETTNER, C., REILLY, T.M., KNABB, R.M., BISCHOFF, R., Tschesche, H., Wenzel, H., KUCICH, U., EDMUNDS, L.H., COLMAN, R.W.: SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY. 268, H1352-H1357 (1995).
WACHTFOGEL, YT, HACK, CE, NUIJENS, JH, KETTNER, C, REILLY, TM, KNABB, RM, BISCHOFF, R, Tschesche, Harald, Wenzel, Herbert, KUCICH, U, EDMUNDS, LH, and COLMAN, RW. “SELECTIVE KALLIKREIN INHIBITORS ALTER HUMAN NEUTROPHIL ELASTASE RELEASE DURING EXTRACORPOREAL-CIRCULATION”. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 268.3 (1995): H1352-H1357.
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