Plasma Proteolytic Cascade Activation during Neonatal Cardiopulmonary Bypass Surgery.
Plasma Proteolytic Cascade Activation during Neonatal Cardiopulmonary Bypass Surgery.
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DOI：
10.1055/s-0038-1667198
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发表时间：
2018-09
影响因子：
6.7
通讯作者：
Mast AE
中科院分区：
文献类型：
--
作者：
Maroney SA;Peterson JA;Zwifelhofer W;Martinez ND;Yan K;Bercovitz RS;Woods RK;Mast AE
Neonates undergoing cardiopulmonary bypass (CPB) surgery to correct congenital heart defects often experience excessive bleeding. Exposure of blood to artificial materials during CPB may activate coagulation, complement and inflammatory pathways. In addition, the surgical stress placed on the haemostatic system may result in crossactivation of other plasma proteolytic cascades, which could further complicate physiological responses to the surgical procedure and post-operative recovery. Plasma protease inhibitors undergo distinct conformational changes upon interaction with proteases, and, thereby, can serve as endogenous biosensors to identify activation of the different proteolytic cascades. We tested the hypothesis that changes in the concentration and conformation of protease inhibitors regulating plasma proteolytic cascades during neonatal CPB are associated with post-operative bleeding. Plasma samples from 44 neonates were obtained at four time points across the surgical procedure. Anti-thrombin, antitrypsin, anti-chymotrypsin, antiplasmin, C1-inhibitor and tissue factor pathway inhibitor (TFPI) concentrations and conformationswereevaluatedbyenzyme-linkedimmunosorbentassay,transverseureagradient gel electrophoresis and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The most striking changes were observed following heparin administration and were associated with the appearance of inactive forms of anti-thrombin and an increase in the plasma concentration of TFPI. Changes in anti-thrombin and TFPI remained evident throughout surgery and into the post-operative period but were not different between patients with or without post-operative bleeding. The concentration of antitrypsin decreased across surgery, but there was no significant accumulation of inactive conformations of any inhibitor besides anti-thrombin, indicating that widespread cross-activation of other plasma proteolytic cascades by coagulation proteases did not occur.
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影响因子：
20.3
作者：
Ge, Xiaomei;Yamaguchi, Yasuto;Morser, John
通讯作者：
Morser, John
影响因子：
20.3
作者：
Mast, AE;Stadanlick, JE;Dietzen, DJ
通讯作者：
Dietzen, DJ
DOI：
10.1073/pnas.83.10.3161
发表时间：
1986-05-01
影响因子：
11.1
作者：
DAVIS, AE;WHITEHEAD, AS;ROSEN, FS
通讯作者：
ROSEN, FS
影响因子：
4.6
作者：
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通讯作者：
Mast, Alan E.
影响因子：
6.7
作者：
Hézard, N;Potron, G;Nguyen, P
通讯作者：
Nguyen, P