DIURNAL VARIATION OF COMPONENTS OF THE FIBRINOLYTIC SYSTEM
To elucidate the causes of the well known diurnal variations of the fibrinolytic activity we have studied severed parameters of the fibrinolytic system in 8 healthy male volunteers during a period of 24 h. Blood sanples were taken at 8, 10 and 12 a.m., 4 and 8 p.m. and at 8 a.m. next morning. Hie following parameters were analyzed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates (FPA), antigen concentrations of tissue-type plasminogen activator (t-PA) by ELISA and of urokinase (u-PA) and plasminogen activator inhibitor-1 (PAI-1) by RIA, the overall PA-inhibitor activity by the indirect chranogenic substrate assay (Verheijen et al; 1984) and the electrophoretic-zymogra-phic analysis of the euglobulins fraction.Global fibrinolytic activity increased from 1.0 ±0.3 U/ml at 8 a.m. to 2.5 ±1.1 U/ml at 8 p.m. (p <0.002) as measured by ECLT (U=300/lysis time in minutes) and from 2.3 ±0.4 IU/ml to 4.7 ±1.1 IU/ml (p <0.001) as determined by FPA. In contrast, t-PA antigen decreased from 5.1 ±0.8 ng/ml at 8 a.m. to 2.9 ±1.5 ng/ml at 8 p.m. (p<0.01) and u-PA antigen from 8.1 ±1.2 ng/ml to 7.1 ±0.7 ng/ml (p<0.05). Most pronounced was the decrease of PAI-1 antigen from 23.5 ± 7.6 ng/ml in the morning to 8.8 ±2.6 ng/ml at 8 p.m. (p <0.001), while PAI activity decreased from 8.8 ±3.6 U/ml to 5.5 ±1.8 U/ml at 4 p.m. (p <0.002). During the entire study period the electro-phoretic-zymographic analysis did not reveal any free t-PA; the latter was present throughout in the form of the 110 kD t-PA/PAI-1 ccnplex. During the day the intensity of the 110 kD band decreased progressively.These findings confirm the physiological diurnal fluctuation of the fibrinolytic activity. All components of the fibrinolytic system are involved in this fluctuation and participate in the modulation of fibrinolytic activity.Our study demonstrates that the diurnal increase of fibrinolytic activity is due principally to a marked decline of the PAI-1 concentration during the day and not to an increase of PA antigen levels.