The effect of submaximal exercise on fibrinolysis

We studied the relationship between sustained submaximal exercise, increased tissue plasminogen activator (t-PA) levels and decreased hepatic clearance of t-PA. Six healthy male volunteers exercised for 35 min while receiving constant rate infusions of either saline or two different doses of recombinant t-PA for 90 min (40 min before, 35 min during and 15 min after exercise). Liver blood flow was estimated simultaneously by constant rate indocyanine green infusion. Since t-PA is cleared rapidly by the liver in direct proportion to liver blood flow, it was expected that a significant decrease in liver blood flow during sustained submaximal exercise would be associated with a proportional increase in plasma t-PA. During submaximal exercise with a saline (placebo) infusion, steady-state t-PA antigen increased from a resting baseline of 6.3 +/- 3.1 to 15.1 +/- 5.1 ng/ml; with a 20 microg/min t-PA infusion, t-PA antigen increased from 33 +/- 12 to 84 +/- 25 ng/ml during exercise; and with a 40 microg/min t-PA infusion, t-PA antigen increased from 77 +/- 38 to 166 +/- 42 ng/ml during exercise. During submaximal exercise, liver blood flow fell on average 71, 68 and 70%, respectively, during the three procedures, while calculated t-PA clearance decreased on average 59, 59 and 53%. t-PA concentration versus time curves, displayed in proportional units, were similar. The comparable relative increases in endogenous and exogenous t-PA with simultaneous proportional decreases in liver blood flow suggests that diminished hepatic t-PA clearance is the major cause of increased t-PA concentration and blood fibrinolytic activity enhancement during sustained submaximal exercise.