Bradykinin Receptor Antagonism During Cardiopulmonary Bypass
Status:
Completed
Trial end date:
2012-06-01
Target enrollment:
Participant gender:
Summary
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary
bypass (CPB). CPB is associated with significant morbidity including the transfusion of
allogenic blood products, inflammation and hemodynamic instability. In fact, approximately
20% of all blood products transfused are associated with coronary artery bypass grafting
procedures. Transfusion of allogenic blood products is associated with well-documented
morbidity and increased mortality after cardiac surgery. Enhanced fibrinolysis contributes to
increased blood product transfusion in the perioperative period. The current proposal tests
the central hypothesis that endogenous bradykinin contributes to the hemodynamic,
fibrinolytic and inflammatory response to CPB and that bradykinin receptor antagonism will
reduce hypotension, inflammation and transfusion requirements. In SPECIFIC AIM 1 we will test
the hypothesis that the fibrinolytic and inflammatory response to CPB differ during ACE
inhibition and angiotensin II type 1 receptor antagonism. In SPECIFIC AIM 2 we will test the
hypothesis that bradykinin B2 receptor antagonism attenuates the hemodynamic, fibrinolytic,
and inflammatory response to CPB. In SPECIFIC AIM 3 we will test the hypothesis that
bradykinin B2 receptor antagonism reduces the risk of allogenic blood product transfusion in
patients undergoing CPB. These studies promise to provide important information regarding the
effects of drugs that interrupt the RAS and generate new strategies to reduce morbidity in
patients undergoing CPB.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center