Affiliation:
1. From the Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (M.W., E.R., S.R., T.V.); and Klinik für Anästhesiologie, Universitätsklinikum Regensburg, Regensburg, Germany (Y.A.Z., M.G., B.M.G.).
Abstract
Abstract
Background:
Cardiovascular resuscitation upon intoxication with lipophilic ion channel–blocking agents has proven most difficult. Recently, favorable results have been reported when lipid rescue therapy is performed, i.e., the infusion of a triglyceride-rich lipid emulsion during resuscitation. However, the mechanism of action is poorly understood.
Methods:
The authors investigate the effects of a clinically used lipid emulsion (Lipovenös® MCT 20%; Fresenius Kabi AG, Bad Homburg, Germany) on the block of the fast Na+ current (INa) induced by the lipophilic local anesthetic bupivacaine in adult rat left ventricular myocytes by using the whole cell patch clamp technique.
Results:
Bupivacaine at 10 µm decreased INa by 54% (−19.3 ± 1.9 pApF−1vs. −42.3 ± 4.3 pApF−1; n = 17; P < 0.001; VPip = −40 mV, 1 Hz). Addition of 10% lipid emulsion in the presence of bupivacaine produced a 37% increase in INa (−26.4 ± 2.8 pApF−1; n = 17; P < 0.001 vs. bupivacaine alone). To test whether these results could be explained by a reduction in the free bupivacaine concentration by the lipid (lipid-sink effect), the authors removed the lipid phase from the bupivacaine–lipid mixture by ultracentrifugation. Also, the resulting water phase led to an increase in INa (+19%; n = 17; P < 0.001 vs. bupivacaine), demonstrating that part of the bupivacaine had been removed during ultracentrifugation. The substantially less lipophilic mepivacaine (40 µm) reduced INa by 27% (n = 24; P < 0.001). The mepivacaine–lipid mixture caused a significant increase in INa (+17%; n = 24; P < 0.001). For mepivacaine, only a small lipid-sink effect could be demonstrated (+8%; n = 23; P < 0.01), reflecting its poor lipid solubility.
Conclusion:
The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Anesthesiology and Pain Medicine
Cited by
31 articles.
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