After induction of hemofiltration for the hemic prime of a cardiopulmonary bypass, the initial drop in blood pressure disappears, and postoperative edema rarely occurs. We have suspected that bradykinin, a strong vasodilator generated through the activation of factor XII, prekallikrein, and high molecular weight kininogen was removed by ultrafiltration. We examined the changes in the activities of plasma-factor XII, prekallikrein, high molecular weight kininogen and in the levels of bradykinin in the priming blood using red cell concentrates before and after hemofiltration, and evaluated the effectiveness of hemofiltration. Ten circuits were used, and ten sets of blood samples were collected from red cell concentrates, the priming blood before hemofiltration, after hemofiltration, and the filtrate. During circulation in the circuit, factor XII, prekallikrein and high molecular weight kininogen were completely consumed and a large amount of bradykinin was generated, but it was filtered well by ultrafiltration. Factor XII, prekallikrein and high molecular weight kininogen could be activated through the dilution of red cell concentrates during the priming and contact with the circuits. Because bradykinin is the most potent vasodilator, increasing microvascular permeability and relating to several other inflammatory mediators, the removal of bradykinin generated from factor XII, prekallikrein and high molecular weight kininogen is very significant in the prevention of non-specific inflammatory reactions during and after open-heart surgery.
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Cells
December 2024
Astria Pharmaceuticals, Boston, MA 02210, USA.
The plaques associated with Alzheimer's disease are formed as a result of the aggregation of Aβ peptides, which vary in length from 38 to 43 amino acids. The 1-40 peptide is the most abundant, while the 1-42 peptide appears to be the most destructive to neurons and/or glial cells in a variety of assays. We have demonstrated that aggregated Aβ, a state prior to plaque formation, will activate the plasma bradykinin-forming pathway when tested in vitro.
View Article and Find Full Text PDFOchsner J
January 2024
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Irvine, CA.
Prolongation of the activated partial thromboplastin time (aPTT) may signify an intrinsic factor deficiency or the presence of an inhibitor of coagulation, potentially placing a patient at increased risk for bleeding. However, a contact factor (ie, factor XII, prekallikrein, and high molecular weight kininogen) deficiency, which may also cause a prolonged aPTT, is not associated with clinical bleeding. A 71-year-old female had an isolated prolonged aPTT discovered during preoperative laboratory testing.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.
Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK), and high molecular weight kininogen interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.
View Article and Find Full Text PDFThromb Res
January 2025
Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Nephrology, Odense University Hospital, Odense, Denmark. Electronic address:
Background And Hypothesis: The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.
View Article and Find Full Text PDFFront Allergy
September 2024
Takeda Development Center Americas Inc., Cambridge, MA, United States.
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