Local anesthetic actions on thromboxane-induced platelet aggregation.
Some local anesthetics (LA), in concentrations present in blood during IV or epidural infusion, inhibit thrombus formation in the postoperative period. Studies on thromboxane A2 (TXA2) signaling in a recombinant model suggest that interference with TXA2-induced platelet aggregation may explain, in part, the antithrombotic actions of epidural analgesia and IV LA infusion. In this study we investigated the effects of clinically used LAs (lidocaine, ropivacaine, and bupivacaine) on TXA2-induced early platelet aggregation (1-5 s) by using quenched-flow and optical aggregometry. Our findings demonstrate that the LAs tested seem to have only a limited ability to inhibit TXA2-induced platelet aggregation assessed at early times (1-5 s). Therefore, the clinical effects of LAs on thrombi formation are unlikely to be explained by this manner alone. At large LA concentrations, moderate effects were obtained. Prolonged incubation with LA did not significantly increase effectiveness, and the lack of an effect could not be explained by generation of secondary mediators. The results were independent of the anesthetic studied. Local anesthetic effects on TXA2-induced early platelet aggregation (1-5 s) are unlikely to play a major role in the clinically observed antithrombotic effects of local anesthetics.


CONCLUSIONS
Local anesthetic effects on thromboxane A2-induced early platelet aggregation (1-5 s) are unlikely to play a major role in the clinically observed antithrombotic effects of local anesthetics. Thus, other potential targets need to be explored.
Lo
B
B
University of Virginia Health System, Department of Anesthesiology, Charlottesville, Virginia, USA.
Hönemann
C W
CW
Kohrs
R
R
Hollmann
M W
MW
Polanowska-Grabowska
R K
RK
Gear
A R
AR
Durieux
M E
ME
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D000077212:Ropivacaine; D013928:Thromboxane A2 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology
D000577:Amides; D000779:Anesthetics, Local; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine