title: Inhibition of murine cardiomyocyte respiration by amine local anesthetics.
abstract: The hydrophobic amino acyl amide-linked local anesthetics (e.g., lidocaine and bupivacaine) impose potent cardiac toxicity and direct mitochondrial dysfunction. To investigate these adverse events, an in vitro system was employed to measure their effects on O2 consumption (cellular respiration) by murine myocardium. Specimens were collected from the ventricular myocardium and immediately immersed in ice-cold Krebs-Henseleit buffer saturated with 95 % O2:5 % CO2. O2 concentration was determined as a function of time from the phosphorescence decay rates of Pd(II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. Myocardial O2 consumption was linear with time (zero-order kinetics); its rate (k, in μM O2 min(-1)), thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming the oxidation occurred in the respiratory chain. Lidocaine and bupivacaine produced immediate and sustained inhibition of cellular respiration at plasma concentrations of the drugs (low micromolar range). Bupivacaine was twice as potent as lidocaine. The inhibition was dose-dependent, saturating at concentrations ≥30 μM. At saturating doses, lidocaine produced ~20 % inhibition and bupivacaine ~40 % inhibition. Cellular ATP was also decreased in the presence of 30 μM lidocaine or bupivacaine. The studied amines inhibited myocardial cellular respiration. This effect is consistent with their known adverse events on mitochondrial function. The described approach allows accurate assessments and comparisons of the toxic effects of local anesthetics on heart tissue bioenergetics.
authors.affiliation: Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates, e.aburawi@uaeu.ac.ae.
authors.forename: Elhadi H
authors.initials: EH
authors.lastname: Aburawi
authors.forename: Abdul-Kader
authors.initials: AK
authors.lastname: Souid
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000097:blood / Q000633:toxicity*; D008012:Lidocaine / Q000097:blood / Q000633:toxicity*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D008012:Lidocaine; D002045:Bupivacaine