THE EFFECT OF LIDOCAINE ON DE-NOVO PHOSPHOLIPID BIOSYNTHESIS IN THE ISOLATED HAMSTER HEART

Lidocaine is used clinically as an antiarrhythmic agent, but its effec t on cardiac phospholipid metabolism has not been defined. In this stu dy, hamster hearts were perfused with [1,3-H-3]glycerol in the presenc e of 0.5 mg/mL lidocaine. The incorporation of radioactivities into ly sophosphatidic acid, phosphatidic acid, phosphatidylethanolamine, cyti dine diphosphate diacylglycerol, phosphatidylinositol, phosphatidylser ine, diacylglycerol and triacylglycerol were enhanced by lidocaine tre atment, whereas the labelling of phosphatidylcholine was reduced. Anal yses of enzyme activities in the heart after perfusion with lidocaine revealed that the activities of phosphatidate phosphatase and acyl-coe nzyme A (CoA):1,2-diacylglycerol acyltransferase were enhanced. The pr esence of lidocaine in the assay did not directly stimulate these enzy mes. However, the activity of acyl-CoA:glycerol-3-phosphate acyltransf erase was stimulated by lidocaine whereas the activity of cytidine dip hosphocholine:1,2-diacylglycerol cholinephosphotransferase was inhibit ed by lidocaine. We conclude that lidocaine affects the regulation of phospholipid biosynthesis in the heart by both direct and indirect mod ulation of phospholipid biosynthetic enzymes.