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 endothelium. However, the possibility that 1-desamino-8-D-vasopressin influences 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: mean arterial pressure decreased maximally 12 (95% confidence interval 8-15) mmHg and heart rate increased maximally 21 (95% confidence interval 15-27) beats/min. 4. Endogenous fibrinolytic parameters increased after administration of 1-desamino-8-D-vasopressin. Both tissue-type plasminogen activator antigen and tissue-type plasminogen activator activity were elevated and showed the maximal response shortly after drug administration was completed. 5. 1-Desamino-8-D-vasopressin increased portal venous blood flow as measured with echo-Doppler. The maximal increase in mean blood flow of 55 (95% confidence interval 19-92)% was observed at the end of the 1-desamino-8-D-vasopressin infusion and coincided with the maximal changes in systemic haemodynamics and fibrinolytic parameters. The increase in portal blood flow was not reflected in significant changes in Indocyanine Green clearance. It appears that the Indocyanine Green method is relatively insensitive to increases in liver blood flow. 6. The observed increase in fibrinolytic activity due to tissue-type plasminogen activator activity after 1-desamino-8-D-vasopressin administration may be due to an increased release of tissue-type plasminogen activator from the endothelium and is not caused by changes in clearance.