INFLUENCE OF 1-DESAMINO-8-D-VASOPRESSIN ON ENDOGENOUS FIBRINOLYSIS, HEMODYNAMICS AND LIVER BLOOD-FLOW IN HEALTHY-SUBJECTS

1. Endogenous fibrinolytic capacity increases after administration of 1-desamino-8-D-vasopressin. This increase is commonly attributed to an increase in release of tissue-type plasminogen activator from the end othelium. However, the possibility that 1-desamino-8-D-vasopressin inf luences liver blood flow, which is a major determinant of tissue-type plasminogen activator clearance, cannot be ruled out. 2. The influence of 1-desamino-8-D-vasopressin on haemodynamics, liver blood flow and fibrinolytic parameters was investigated in a randomized double-blind cross-over study in nine healthy male subjects (age 20-26 years). 3. 1 -Desamino-8-D-vasopressin exerted significant haemodynamic effects: me an arterial pressure decreased maximally 12 (95% confidence interval 8 -15) mmHg and heart rate increased maximally 21 (95% confidence interv al 15-27) beats/min.4. Endogenous fibrinolytic parameters increased af ter administration of 1-desamino-8-D-vasopressin. Both tissue-type pla sminogen activator antigen and tissue-type plasminogen activator activ ity were elevated and showed the maximal response shortly after drug a dministration was completed. 5. 1-Desamino-8-D-vasopressin increased p ortal venous blood flow as measured with echo-Doppler. The maximal inc rease in mean blood flow of 55 (95% confidence interval 19-92)% was ob served at the end of the 1-desamino-8-D-vasopressin infusion and coinc ided with the maximal changes in systemic haemodynamics and fibrinolyt ic parameters. The increase in portal blood flow was not reflected in significant changes in Indocyanine Green clearance. It appears that th e Indocyanine Green method is relatively insensitive to increases in l iver blood flow. 6. The observed increase in fibrinolytic activity due to tissue-type plasminogen activator activity after 1-desamino-8-D-va sopressin administration may be due to an increased release of tissue- type plasminogen activator from the endothelium and is not caused by c hanges in clearance.