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Platelet-activating factor (PAF) is believed to have a central role in the pathogenesis of ischemia-reperfision injury. The purpose of this study was to investigate the relationships among production of PAF, thromboxane B2 (TαB2), and cardiopulmonary sequelae in patients undergoing coronary artery bypass graft surgery (CABGS). Venous blood from nine patients (eight men, one woman) undergoing scheduled CABGS, was sampled from central venous catheters before anesthetic induction, pre-cardiopulmonary bypass (CPB), 10 and 30 minutes post-CPB, 10 and 30 minutes post-aortic declamping, and 120 minutes and 24 hours after the conclusion of CPB. Plasma levels of PAF and TαB2 were determined by radioimmunoassay kits (Amersham Canada Ltd.). PAF and TαB2 were significantly different between high-risk patients (group I; Canadian Cardiovascular Society class 3-4; n = 4) and low-risk patients (group II; Canadian Cardiovascular Society class 2; n = 5): group I PAF = 960 pg/mL, group II PAF = 159 pg/mL (P = 0.0029); group I TαB2 = 320 pg/mL, group II TαB2 = 229 pg/mL (P = 0.0262). Group I PAF was significantly greater than group II PAF: before CPB = 825 pg/mL (group I), 138 pg/mL (group II); during initiation of CPB = 1600-2015 pg/mL (group I), 158-200 pg/mL (group II) (P = 0.0143). Correlations between duration of CPB and peak PAF (r = 0.7049, P = 0.0339), peak PAF level, and time to extubation (r = 0.8863, P = 0.0079) were significant. PAF levels were different in patients requiring postoperative epinephrine (2124 ± 700 pg/mL) or dopamine (667 ± 266 pg/mL) (P = 0.0042). The production of PAF is determined by preoperative patient characteristics and duration of CPB. Increased levels of PAF in patients with unstable angina, left main coronary artery disease, or recent myocardial infarction are associated with the need for increased inotropy and prolonged ventilatory support following CABGS. The degree of PAF production during CPB may be a factor in postoperative instability in high-risk patients.