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Abstract Background Over activity of the fibrinolytic system (hyperfibrinolysis) occurs in cirrhosis and has been shown to correlate with the risk of variceal hemorrhage. We have developed a model for assessing acute tissue plasminogen activator (t-PA) release in vivo in man. The aims of the study were to assess the contribution of basal and stimulated t-PA release to hyperfibrinolysis in patients with alcoholic cirrhosis. Methods Bilateral forearm blood flow and plasma fibrinolytic variables were measured in 8 patients with biopsy proven alcohol induced cirrhosis, ascites and portal hypertension, and 8 age and sex matched healthy controls during infusion of bradykinin (100–900 pmol/min; endothelium-dependent vasodilator that releases t-PA) followed by sodium nitroprusside (SNP 2–8 μg/min; a control endothelium-independent vasodilator). Results Baseline plasma t-PA antigen concentrations were higher in patients (14 ± 2 vs 9 ± 1 ng/mL; p < 0.05) whereas plasma plasminogen activator inhibitor type-1 (PAI-1) antigen concentrations were similar (59 ± 16 vs 55 ± 11 ng/mL; p = NS). This resulted in an increased t-PA activity (3 ± 1 vs 0 ± 0 IU/mL; p < 0.05) and reduced PAI-1 activity (9 ± 2 vs 21 ± 2 AU/mL; p < 0.05) indicating a relative deficiency of PAI-1 in patients with cirrhosis. Bradykinin and SNP caused dose-dependent vasodilatation ( p < 0.001 for both) that did not differ between the two groups. Bradykinin caused a similar release of t-PA antigen ( p < 0.05 for both) in both patients and controls (24 ± 17 vs 23 ± 7 ng/100 mL/min; p = ns) without affecting PAI-1 concentrations. Local t-PA activity was increased in patients following acute stimulated t-PA release (5 ± 1 vs 3 ± 1 IU/mL; p < 0.05). SNP caused no significant change in fibrinolytic parameters. Conclusion Patients with alcoholic cirrhosis have a higher basal plasma t-PA activity because of a failure to increase plasma concentrations of its inhibitor, PAI-1. Furthermore, despite releasing normal amounts of t-PA acutely, higher t-PA activity remained due to the relative deficiency of PAI-1. This suggests that the pathogenesis of hyperfibrinolysis in alcoholic cirrhosis is the result of a relative PAI-1 deficiency and enhanced basal t-PA release.