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- Falk, Kristina, 1972, et al.
(författare)
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Antifibrinolytic proCPU is present in the peritoneal cavity during surgery.
- 2003
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 63:4, s. 287-96
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Tidskriftsartikel (refereegranskat)abstract
- The fibrinolytic capacity of the peritoneum plays a pivotal role in peritoneal wound healing. During surgery the balance between fibrin deposition and degradation is tilted towards deposition, leading to the formation of adhesions. In blood, carboxypeptidase U (CPU) stabilizes clots by retarding fibrinolysis. The purpose of this study was to investigate whether the more stable zymogen, proCPU, is also present in the peritoneal cavity and, if so, to examine its origin. Levels of proCPU were measured in plasma and serosal peritoneal fluid collected during surgery. Peritoneal biopsies were stained for proCPU. Two-dimensional gel electrophoresis was performed to study the protein composition of the serosal fluid compared to plasma and Western blotting to identify differences in glycosylation of proCPU, indicating possible different cellular origin. Cultured human mesothelial cells were examined for proCPU production under normal conditions and conditions mimicking surgery. We found comparable and correlating levels of proCPU in serosal fluid and plasma. ProCPU was also found where fibrin covered the injured peritoneal surface. A protein composition very similar in serosal fluid and plasma was shown by two-dimensional gel electrophoresis, and the proCPU pattern did not indicate a different origin. No proCPU production was found in cultured mesothelial cells. This is the first study to report on the presence of proCPU in the peritoneal cavity, which seems to be the result of plasma oozing out during the inflammatory reaction to the surgical trauma. This is likely to be important for the balance between fibrin deposition and degradation and thereby in the formation of postoperative adhesions.
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| 2. |
- Falk, Kristina, 1972
(författare)
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Strategies for postoperative adhesion control
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Abdominal surgery almost inevitably leads to adhesion formation, which often results in substantial morbidity. The formation of postsurgical adhesions seems to be determined by the balance of fibrin deposition and degradation in an early phase of peritoneal tissue repair. Several different agents and methods have been investigated in the attempt to control postoperative adhesion formation. Although some agents have had a noticeable effect, an optimal solution to the problem still remains to be found.Material and methods: The aim of the present work was to investigate different strategies for adhesion control, by investigating the adhesion prevention effects of bioadhesive polymers and a phospholipid surfactant in an experimental adhesion model in mouse (I). Potential synergistic effects from combinations of polymers were also investigated (II). The effect of stimulating the intraperitoneal fibrinolytic capacity was examined by using an antibody fragment blocking the activity of the main fibrinolytic inhibitor (plasminogen activator inhibitor type 1, PAI-1), in the mouse model (III). The presence of the antifibrinolytic procarboxypeptidase U (proCPU) in the peritoneal cavity of patients undergoing abdominal surgery was studied and its origin investigated (VI). Results: Two cellulose-derived polymers (LM-200 and HM-EHEC) demonstrated an adhesion reducing effect. The phospholipid (sphingomyelin) had no convincing effect. When combining one of the cellulose-derivatives with an oppositely charged bioadhesive polymer (sodium polyacrylate), the adhesion reducing effect was significantly improved. Stimulation of the fibrinolytic system by inhibiting PAI-1 resulted in a significant adhesion reducing effect. There were significant amounts of proCPU present in the abdominal cavity during surgery. The intra-abdominal levels corresponded to plasma concentrations. There was no evidence that proCPU was produced by cultured mesothelial cells either under normal conditions or when stimulated by proinflammatory mediators or a simulated surgical environment.Conclusions: This work has demonstrated the successful reduction of postoperative adhesion formation in an experimental model, using bioadhesive polymers. Stimulation of the fibrinolytic system by inhibition of PAI-1 can reduce adhesion formation in this experimental model. Significant amounts of the antifibrinolytic proCPU are present in the peritoneal cavity in patients undergoing abdominal surgery. ProCPU seems to be a part of the inflammatory exudate originating from plasma and is likely to be of importance for the balance between fibrin deposition and degradation in the abdominal cavity, and thereby for the formation of adhesions.
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