Increase of bradykinin in plasma of patients undergoing cardiopulmonary bypass: the importance of lung exclusion.

STUDY OBJECTIVES Hemodynamic complications including hypotensive episodes are frequently associated with cardiopulmonary bypass (CPB) and can be attributed to a generalized inflammatory response in which bradykinin may be a mediator. The purpose of this study was to determine the plasma levels of bradykinin-(1-9)nonapeptide in patients during CPB and the physiologic elimination of bradykinin by the lungs. DESIGN Prospective, observational study. SETTING University hospital, cardiac surgery unit. PATIENTS AND METHODS Intra-arterial BP was monitored and serial blood samples were obtained from 27 patients undergoing CPB for cardiac surgery. We measured plasma bradykinin and parameters of coagulation, fibrinolysis, complement, contact system, and the cytokine tumor necrosis factor (TNF). RESULTS Mean arterial pressure fell progressively until the end of CPB (- 18 mm Hg, p = 0.001) but returned to baseline by the end of surgery. The venous bradykinin level, normal in basal conditions (median, 1.90 fmol/mL), was increased (p = 0.001) from 15 min after the beginning of CPB (5.71 fmol/mL) to the end of the operation (7.07 fmol/mL), with a peak at the end of CPB (9.81 fmol/mL; p = 0.0001); it was normal at recovery 24 h later (2.81 fmol/mL). Bradykinin plasma levels fell 60% across the lung when the pulmonary circulation was fully restored while the patients were still receiving CPB. Activated-factor XII, thrombin-antithrombin complexes, prothrombin fragment F1 + 2, plasmin-antiplasmin complexes, C(3)a, and TNF increased significantly after the beginning of the surgical procedure, rising further during CPB, and remained elevated until the end of surgery, but they all returned to normal within 24 h. Changes in plasma bradykinin levels were not correlated with any of the other variables. CONCLUSIONS During CPB, there is a progressive increase of plasma bradykinin that is at least partially due to reduced catabolism as a consequence of shunting the lungs. The increase in bradykinin may contribute to the fall in BP.