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1.
Anesth Analg ; 93(5): 1240-5, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11682405

ABSTRACT

UNLABELLED: 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. IMPLICATIONS: 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.


Subject(s)
Anesthetics, Local/pharmacology , Platelet Aggregation/drug effects , Thromboxane A2/antagonists & inhibitors , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Adenosine Diphosphate/pharmacology , Amides/pharmacology , Bupivacaine/pharmacology , Humans , Lidocaine/pharmacology , Platelet Aggregation/physiology , Ropivacaine , Thromboxane A2/agonists , Thromboxane A2/physiology
2.
Reg Anesth Pain Med ; 24(4): 326-30, 1999.
Article in English | MEDLINE | ID: mdl-10445771

ABSTRACT

BACKGROUND AND OBJECTIVES: Epidural anesthesia decreases the risk of postoperative deep venous thrombosis in selected patients. Intravascular local anesthetic levels resulting from epidural anesthesia may contribute to this effect by impacting coagulation. We studied the effects of bupivacaine (1-10 micromol/L) on whole blood coagulation measured by thrombelastography (TEG) and activated clotting time (ACT). METHODS: We incubated whole blood with bupivacaine (1, 2, and 10 micromol/L) or Tyrode's solution (control) for 60 minutes and measured TEG and ACT clotting parameters. RESULTS: Bupivacaine (1 or 10 micromol/L) prolonged ACT when compared with control. The thromboxane A2 (TX) receptor antagonist SQ29548 also prolonged ACT significantly. The combination of SQ29548 and bupivacaine was equally effective as bupivacaine alone, compatible with the hypothesis that bupivacaine at these concentrations blocks TX signaling. Because SQ29548 + bupivacaine prolonged ACT more than did SQ29548 alone, bupivacaine likely inhibits processes in addition to TX signaling. This was evaluated further using TEG. After incubation with 2 microm bupivacaine, TEG reaction time and clot growth time increased significantly, and maximal amplitude decreased. CONCLUSIONS: Bupivacaine in clinically relevant concentrations influences whole blood clotting characteristics as measured by TEG and ACT. Thromboxane receptor antagonism increases ACT, confirming a role for TX in coagulation. Bupivacaine may also inhibit TX signaling, but seems to block additional factors as well. These findings might partly explain the beneficial effects of epidural anesthesia on postoperative thrombotic events.


Subject(s)
Anesthetics, Local/pharmacology , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Bupivacaine/pharmacology , Anesthesia, Epidural , Bridged Bicyclo Compounds, Heterocyclic , Fatty Acids, Unsaturated , Humans , Hydrazines/pharmacology , Receptors, Thromboxane/antagonists & inhibitors , Receptors, Thromboxane/physiology , Thrombelastography , Whole Blood Coagulation Time
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