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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
LIPID RESCUE REVERSES BUPIVACAINE-INDUCED ALTERATIONS OF THE VENTRICULAR ACTION POTENTIAL
Abstract number: O8
Wagner1 *M., Zausig2 Y., Ruf1 S., Graf2 B., Volk1 T.
1FAU Erlangen-Nrnberg, Institut fr Zellulre und Molekulare Physiologie, Erlangen, Germany
2Universittsklinikum Regensburg, Klinik fr Ansthesiologie, Regensburg, Germany
Cardiovascular depression secondary to intoxications with lipophilic drugs such as tricyclic antidepressants or local anesthetics is more and more frequently treated with infusion of lipid solutions ("lipid rescue"). However, their mechanism of action is poorly understood. Here we investigate the effects of a clinically used lipid solution (Lipovenös® MCT 20%) on alterations of the action potential (AP) induced by the local anesthetics bupivacaine (lipophilic) and mepivacaine (hydrophilic) in adult rat left ventricular myocytes. Myocytes were isolated from the left ventricular free wall of female Wistar rats and investigated by whole-cell patch-clamp. APs were elicited at 1 Hz at room temperature. 10 mM bupivacaine significantly reduced the rate of rise (dV/dtmax) (103.1 ± 10.3 Vs-1 vs. 246.1 ± 13.4 Vs-1, n = 9, p < 0.001) as well as the overshoot of the AP (22.2 ± 2.8 mV vs. 39.2 ± 1.4 mV, n = 9, p < 0.001) and prolonged the AP duration (APD90 = 52.3 ± 4.9 ms vs. 41.7 ± 5.1 ms, n = 9, p < 0.001). Bupivacaine hyperpolarized the resting membrane potential by less than a millivolt. Washout was similar in Tyrodes's solution containing 10% of the lipid solution and control. In the presence of bupivacaine, the lipid was able to partially reverse the effects on dV/dtmax (126.1 ± 11.6 Vs-1, p < 0.001), overshoot (27.8 ± 2.3 mV, p < 0.001) and APD90 (44.8 ± 4.2 ms, p < 0.001). Moreover, when the lipid phase of a solution containing bupivacaine and lipid was removed by ultracentrifugation, the water phase had a similar effect as the lipid-containing solution. This is consistent with absorption of bupivacaine by the lipid, reducing its free concentration ("lipid sink"). Addition of lipid solution did not reverse the effects of the hydrophilic mepivacaine (40 mM). Taken together we demonstrate the effectiveness of lipid rescue therapy on the single cell level and provide evidence for a "lipid sink" as mechanism of action of the lipid solution.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :O8