Contribution of endogenous bradykinin to fibrinolysis, inflammation, and blood product transfusion following cardiac surgery: a randomized clinical trial.
Bradykinin increases during cardiopulmonary bypass (CPB) and stimulates the release of nitric oxide, inflammatory cytokines, and tissue-type plasminogen activator (t-PA), acting through its B2 receptor. This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis, inflammation, and subsequent transfusion requirements. Patients (N = 115) were prospectively randomized to placebo, ε-aminocaproic acid (EACA), or HOE 140, a bradykinin B2 receptor antagonist. Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA, but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding. Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss, these treatments did not reduce the proportion of patients transfused. These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB, but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment.
Department of Cardiac Surgery, Vanderbilt University Medical School, Nashville, Tennessee, USA.
J M
JM
Balaguer
C
C
Yu
J G
JG
Byrne
S K
SK
Ball
M R
MR
Petracek
N J
NJ
Brown
M
M
Pretorius
D015119:Aminocaproic Acid / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001803:Blood Transfusion / Q000706:statistics & numerical data*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D019106:Postoperative Hemorrhage / Q000188:drug therapy
D000933:Antifibrinolytic Agents; D065168:Bradykinin Receptor Antagonists; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; C065679:icatibant; D001920:Bradykinin; D015119:Aminocaproic Acid