Protection of single-chain urokinase-type plasminogen activator (scu-PA) in aprotinin treated cardiac surgical patients undergoing cardiopulmonary bypass.
Intraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity during and after cardiopulmonary bypass (CPB). Here we report on the effects of aprotinin on urokinase-type plasminogen activator, especially on the protection of the zymogen single-chain urokinase-type plasminogen activator (scu-PA). scu-PA occurs cell associated as well as free in the circulation (concentration 50 pM, half-life 5 min), and is potentially activated by kallikrein and plasmin, both potent targets for aprotinin. The generated active two-chain u-PA (tcu-PA) is a powerful activator of fibrinolysis. Sixteen male patients undergoing myocardial revascularization were randomly assigned to aprotinin treatment (A) or control group (C). Plasma concentration of total u-PA antigen and of the specific forms scu-PA(zymogen) and tcu-PA(active enzyme) were measured at different stages intraoperatively and two hours postoperatively. After an initial drop due to haemodilution at the onset of CPB, the concentrations of circulating u-PA forms restored intraoperatively in A, but remained subnormal in C until the end of the observation period. The concentration of total u-PA antigen of shed mediastinal blood was both in A and C two-fold higher than in the circulation, but the antigen was preserved as the zymogen scu-PA in A and largely converted to an inactive, non activatable form in C. Intra- and postoperative blood losses were less than half the amount in A as compared to C.(ABSTRACT TRUNCATED AT 250 WORDS)
D007611:Aprotinin / Q000494:pharmacology / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001798:Blood Proteins / Q000032:analysis; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D011292:Premedication; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D001798:Blood Proteins; D004792:Enzyme Precursors; D005338:Fibrin Fibrinogen Degradation Products; D007611:Aprotinin; D014568:Urokinase-Type Plasminogen Activator