THE EFFECTS OF LIDOCAINE AND HYPOXIA ON PHOSPHOLIPID BIOSYNTHESIS IN THE ISOLATED HAMSTER HEART

In this study, the effects of lidocaine and hypoxia on the biosynthesi s of phospholipids in the hamster heart were examined. Hamster hearts were perfused with [1,3-H-3]glycerol under normal and hypoxic conditio ns, and in the absence or presence of 0.5 mg/mL lidocaine. After perfu sion, the radioactivity incorporated into the various phospholipid fra ctions was determined. With the exception of phosphatidylcholine, the synthesis of phospholipids was generally stimulated by lidocaine perfu sion. In contrast, hypoxia caused a general decrease in phospholipid b iosynthesis which was partially restored by lidocaine. ATP and CTP lev els were severely reduced under hypoxic conditions, but their levels w ere not restored by lidocaine treatment. The activities of enzymes for phospholipid synthesis were determined under the various perfusion co nditions. The activity of phosphatidic acid phosphatase was elevated b y lidocaine and decreased by hypoxic treatment. The activity of CTP:ph osphatidic acid cytidylyltransferase wars increased under hypoxia, wit h or without lidocaine. Despite the reduction in phosphatidylcholine b iosynthesis, no change in the activity of cytidine diphosphocholine (C DPcholine):diacylglycerol cholinephosphotransferase was detected follo wing lidocaine or hypoxic perfusion. However, enzyme activity was inhi bited by the presence of lidocaine in the assay mixture. Our results i ndicate that the reduction in phospholipid biosynthesis under hypoxic conditions was caused mainly by diminishing high-energy nucleotide lev els. The enhancement of phospholipid biosynthesis by lidocaine appeare d to be mediated in part by modulation of enzyme activities.