HEPARIN-ENHANCED PLASMA PHOSPHOLIPASE A(2) ACTIVITY AND PROSTACYCLIN SYNTHESIS IN PATIENTS UNDERGOING CARDIAC-SURGERY

Although eicosanoid production contributes to physiological and pathop hysiological consequences of cardiopulmonary bypass (CPB), the mechani sms accounting for the enhanced eicosanoid production have not been de fined. Plasma phospholipase A(2) (PLA(2)) activity, 6-keto-prostagland in F-1 alpha (6-keto-PGF(1 alpha)), and thromboxane B-2 (TXB(2)) level s were measured at various times during cardiac surgery. Plasma PLA(2) activity increased after systemic heparinization, before CPB. This wa s highly correlated with concurrent increases in plasma 6-keto-PGF(1 a lpha). TXB(2) concentrations did not increase with heparin administrat ion but did increase significantly after initiation of CPB. High plasm a PLA(2) activity, 6-keto-PGF(1 alpha), and TXB(2) concentrations were measured throughout the CPB period. Protamine, administered to neutra lize the heparin, caused an acute reduction of both plasma PLA(2) acti vity and plasma 6-keto-PGF(1 alpha), but no change in plasma TXB(2) co ncentrations. Thus the ratio of TXB(2) to 6-keto-PGF(1 alpha) increase d significantly after protamine administration. Enhanced plasma PLA(2) activity was also measured in patients with lower doses of heparin us ed clinically for nonsurgical applications. Human plasma PLA(2) was id entified as group II PLA(2) by its sensitivity to deoxycholate and dit hiothreitol, its substrate specificity, and its elution characteristic s on heparin affinity, chromatography. Heparin addition to PMNs in vit ro resulted in dose-dependent increases in cellular PLA(2) activity an d release of PLA(2). The PLA(2) released from the PMN had characterist ics similar to those of post-heparin plasma PLA(2). In conclusion, pla sma PLA(2) activity and 6-keto-PGF(1 alpha) concentrations are markedl y enhanced with systemic heparinization. Part of the anticoagulant and vasodilating effects of heparin may be due to increased plasma prosta cyclin (PGI(2)) levels. In addition the pulmonary vasoconstriction som etimes associated with protamine infusion during cardiac surgery might be due to decreased plasma PLA(2) activity, with an associated increa sed TXB(2)/6-keto-PGF(1 alpha) ratio.