Different increases of t-PA and u-PA during exercise in agreement with their plasma half lives: abstract

It has been reported that exercise induced increase of tissue type plasminogen activator (t-PA) is mediated through its decreased hepatic clearance. Besides t-PA, some other plasminogen activators might also contribute to the overall enhancement of blood fibrinolytic activity during exercise. In previous studies the comparable and concurrent increases of both t-PA and urokinase lype plasminogen activator (u-PA) during exercise were reported. In the present study six young, healthy volunteers were exposed to a constant submaximal treadmill exercise of 30 min. t-PA antigen increased by 140% (p<0.005) during exercise. Total u-PA antigen (determined by ELISA) and plasmin activatable proUK (both single chain u-PA (scu-PA) and active, two chain u-PA (tcu-PA)) (measured by BIA) increased by 46 and 38%, respectively (p<0.01). In vivo tcu-PA activity was below the detection limit in all samples. Significant decreases of PAI-1 activity (by 43%; p<0.005), a-2-AP activity (by 10%; 1/<0.05), p'.asminogcn activity (by 6.5%; p<0.005) and fibrinogen concentration (by 7.5%; p<0.05), were obtained. The increase of t-PA during physical activity was parallel with a profound reduction in liver blood flow, estimated noninvasively by indocyanine green infusion. An evident steady slate concentration was established during the last minutes of exercise. t-PA clearance was calculated to decrease by 61.5% and t-PA half life to prolong by 2.6-fold during exercise. The smaller increase of u-PA during the same exercise may be attributed to its much longer resting half life (approximately 9 min, as reported for recombinant scu-PA). It could be calculated that it would take three times longer exercise (90 min) in order to obtain the new steady state and an increase comparable to that of t-PA. Therefore, the observed increase of u-PA is compatible with the mechanism of decreased hepatic clearance shown to hold true for t-PA.