Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction.
Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a considerable reocclusion rate. Thrombin activity is enhanced, and contact-system activation via plasminemia might be possible. Prospectively we examined the contact phase and the kallikrein-kinin system and additional molecular markers of hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was performed at admission and < or =10 days afterward. Eleven patients received 1.5 Mio U streptokinase (group A) and were compared with 11 AMI patients without thrombolytic therapy (group B). All patients had systemic heparinization (5,000 IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein-factor XII system was significantly activated (3 h after start of therapy): kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94 +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular-weight kininogen consumption indicating bradykinin generation was enhanced (p < 0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative state with increased fibrin degradation products (d-dimer) was found. Plasmin activation in group A was reflected by decreased plasminogen and antiplasmin levels (p < 0.01). The findings indicate that streptokinase induces activation of the contact phase-kinin system in vivo associated with a consecutive increase of thrombin and bradykinin generation. Activation of this pathway might substantially contribute to reocclusion after initially successful thrombolytic therapy and to hypotensive reactions observed after streptokinase.
Hoffmeister
H M
HM
Medizinische Klinik, Abt. III, Tübingen, Germany.
Ruf
M
M
Wendel
H P
HP
Heller
W
W
Seipel
L
L
D000208:Acute Disease; D000368:Aged; D000704:Analysis of Variance; D005174:Factor XII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D011446:Prospective Studies; D013300:Streptokinase / Q000494:pharmacology*; D013917:Thrombin / Q000187:drug effects* / Q000378:metabolism
D005174:Factor XII; D005337:Fibrin; D013300:Streptokinase; D007610:Kallikreins; D013917:Thrombin