Inhibitory Effect of Lidocaine on Cultured Porcine Aortic Endothelial Cell-dependent Antiaggregation of Platelets

Abstract

Background Vascular spasm is a well-known complication during vascular surgery. Topical lidocaine is frequently used to prevent this spasm. However, the effects of lidocaine on the endothelium-dependent antiaggregation are not clear. Methods The aggregation of platelet-rich plasma (PRP) obtained from healthy volunteers was measured by the turbidimetric technique at 37 degrees C. (1) Cultured porcine aortic endothelial cells were preincubated with lidocaine (3.7 microM to 37 mM), NG-methyl-L-arginine (300 microM), or indomethacin (10 microM) for 30 min. The preincubation medium was exchanged with a medium containing +/- 1 microM bradykinin for 1-min stimulation of endothelial cells. One hundred microliters of the supernatant was then added to PRP (750 micro1) just after stimulation of PRP with collagen (4 micrograms/ml). (2) Authentic nitric oxide (NO) or prostacyclin (PGI2) was applied to collagen-stimulated PRP with or without lidocaine (100 micrograms/ml). Results (1) The supernatant from endothelial cells without bradykinin stimulation showed "basal" antiaggregation (13.8 +/- 3.2%; n = 6). Bradykinin enhanced the antiaggregation (100 +/- 0%; n = 6). NG-methyl-L-arginine or indomethacin (antagonists of NO or PGI2) inhibited the bradykinin-evoked antiaggregation (10.3 +/- 2.1% and 13.6 +/- 3.7%, respectively; n = 6). Simultaneous preincubation of both agents completely blocked the effect (-4.2 +/- 2.8%; n = 6). Lidocaine failed to influence basal antiaggregation, but it inhibited bradykinin-stimulated antiaggregation in a concentration-dependent manner (concentration causing 50% inhibition = 108 +/- 41 microM; n = 6). (2) In contrast, lidocaine did not shift the 50% effective concentration of NO (control, 1.3 +/- 0.1 microM vs. lidocaine, 1.6 +/- 0.1 microM) or PGI2 (control, 405 +/- 54 nM vs. lidocaine, 257 +/- 41 nM) for antiaggregation. Conclusions Our results suggest that lidocaine has an inhibitory effect on antiaggregation derived from endothelial cells, caused by the inhibition of NO and PGI2 released from endothelial cells.