The role of fibrinolysis in adhesion formation.
Postsurgical abdominal adhesions and their sequelae continue to present major clinical and medicoeconomic problems. A complex network of mediators and responses affecting at least five interrelated biological systems, including the fibrinolytic system, are involved in the pathogenesis of postsurgical adhesions. The fibrinolytic system degrades fibrin through the action of the enzyme plasmin, which is stored as the inactive substrate plasminogen. Fibrinolysis, by mediating fibrin degradation, appears to play a pivotal role in adhesiogenesis. Tissue-type plasminogen activator (tPA) is the chief plasminogen activator in the blood, but its activity is restricted by plasminogen activating inhibitors type 1 (PAI-1) and type 2 (PAI-2). Inadequate peritoneal fibrinolysis may result from decreased tPA, increased PAI-1 and PAI-2, or both. The causal relationship between a reduction in fibrinolytic capacity and the formation of adhesions has been demonstrated in animals. In human studies, plasminogen activator activity (PAA) was significantly reduced in peritoneal biopsies from patients with peritonitis compared with those from normal patients. During surgery, PAA declined significantly in both normal and inflamed peritoneum. tPA was responsible for about 95% of PAA. Reduced fibrinolysis in human peritoneum associated with peritonitis and abdominal surgery correlates with increased adhesion formation and may thus be an important early biochemical event leading to adhesion formation. The regulation of plasmin-mediated fibrin degradation in the peritoneal cavity is poorly understood. However, new insights in the cellular distribution of fibrinolytic components in peritoneal tissue suggest that the mesothelium appears to have a principal role in fibrin regulation in the peritoneal cavity and in the early formation of adhesions.
Holmdahl
L
L
Department of Surgery, Ostra Hospital, University of Göteborg, Sweden.
D000818:Animals; D005337:Fibrin / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D010537:Peritoneum / Q000601:surgery*; D011183:Postoperative Complications / Q000503:physiopathology*; D000267:Tissue Adhesions / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000502:physiology
D005338:Fibrin Fibrinogen Degradation Products; D005337:Fibrin; D010959:Tissue Plasminogen Activator