Lipid Emulsion Restoration of Myocardial Contractions After Bupivacaine-Induced Asystole In Vitro: A Benefit of Long- and Medium-Chain Triglyceride Over Long-Chain Triglyceride

Abstract

Background: The relative efficacies of a long- and medium-chain triglyceride (LCT/MCT) emulsion and an LCT emulsion for treatment of bupivacaine (BPV)-induced cardiac toxicity are poorly defined.

Methods: After inducing asystole by BPV, varied concentrations (1%-12%) of either LCT/MCT (Lipofundin; B. Braun, Melsungen, Germany) or LCT emulsion (Intralipid; Fresenius Kabi, Upsala, Sweden) were applied to observe the recovery of stimulated contractile responses and contractile forces in either a recirculating or washout condition for 60 minutes, using guinea pig papillary muscles. The recirculation condition was used to demonstrate BPV binding by lipid emulsion. The washout condition was used to determine whether the time-dependent recovery of contraction is due to their metabolic enhancement. Oxfenicine, an inhibitor of carnitine palmitoyltransferase I in heart mitochondria, was used to evaluate the effect of each lipid emulsion on mitochondrial metabolic inhibition by BPV. To examine the effect of the lipid emulsion alone on contractility, either lipid emulsion was examined. BPV concentrations in solution and myocardial tissues were measured.

Results: In the recirculating condition, LCT/MCT emulsions (2%-12%) restored regular stimulated contractile responses in all muscles. Eight percent and 12% LCT/MCT emulsions led to complete recovery of contractile forces after 30 minutes. Meanwhile, LCT emulsions (4%-12%) did not restore regular stimulated contractile responses in some muscles (6, 3, and 2 in 9 muscles each in 4%, 8%, and 12% emulsions, respectively). Partial recovery, approximately 60%, of contractile forces was observed with 8% and 12% LCT emulsions. In the washout experiments, after asystole, LCT/MCT emulsions (1%-12%) restored contractility to baseline levels earlier and greater than LCT emulsion. Partial recovery, approximately 60%, was observed with a high concentration of LCT emulsion (12%). In the oxfenicine-pretreated group, the contractile recovery was enhanced with LCT/MCT emulsion but showed no change with LCT emulsion. Contractile depression by 40% was observed with high concentrations of LCT emulsion alone (8% and 12%), whereas no depression or enhanced contraction was observed with LCT/MCT emulsion (1%-12%) alone. Both types of lipid emulsions (2%-12%) caused concentration-related reductions of tissue BPV levels; LCT/MCT emulsions reduced tissue BPV levels slightly greater than LCT emulsion in a recirculating condition.

Conclusions: An LCT/MCT emulsion was more beneficial than an LCT emulsion in terms of local anesthetic-binding and metabolic enhancement for treating acute BPV toxicity. The metabolic benefit of MCT, combined with the local anesthetic-binding effect of LCT, in an LCT/MCT emulsion may improve contractile function better than an LCT emulsion in an isolated in vitro animal myocardium model.