The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs

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http://hdl.handle.net/10138/310220

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Heinonen , J A , Schramko , A , Skrifvars , M B , Litonius , E , Backman , J T , Mervaala , E & Rosenberg , P H 2017 , ' The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs ' , Human & Experimental Toxicology , vol. 36 , no. 4 , pp. 365-375 . https://doi.org/10.1177/0960327116650010

Title: The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs
Author: Heinonen, J. A.; Schramko, A.; Skrifvars, M. B.; Litonius, E.; Backman, J. T.; Mervaala, E.; Rosenberg, P. H.
Contributor organization: Anestesiologian yksikkö
Clinicum
Department of Diagnostics and Therapeutics
HUS Perioperative, Intensive Care and Pain Medicine
Department of Clinical Pharmacology
Janne Backman / Principal Investigator
Medicum
University of Helsinki
Helsinki University Hospital Area
Eero Mervaala / Principal Investigator
Department of Pharmacology
Date: 2017-04
Language: eng
Number of pages: 11
Belongs to series: Human & Experimental Toxicology
ISSN: 0960-3271
DOI: https://doi.org/10.1177/0960327116650010
URI: http://hdl.handle.net/10138/310220
Abstract: Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid (R) (n = 7) with Ringer's acetate (n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration (p <0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid (p <0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg.min/L) than after Ringer's acetate (88.1 (7.1) mg.min/L) (p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg.min/L) was 8% lower than that of total bupivacaine (p <0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.
Subject: Bupivacaine
lipid emulsion
local anesthetic toxicity
mitochondrial respiration
PROTEIN-KINASE-C
SYSTEMIC TOXICITY
OXIDATIVE-PHOSPHORYLATION
CARDIAC MITOCHONDRIA
INDUCED ASYSTOLE
RESUSCITATION
PLASMA
INTOXICATION
RATS
ISOFLURANE
317 Pharmacy
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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