title: The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart.
abstract: BACKGROUND
  It is unclear whether improved metabolism or a "lipid sink" effect of lipid infusion is responsible for the positive effects in local anesthetic-induced myocardial depression.
  
  
  METHODS
  We used an isolated rat heart, constant-pressure perfused, nonrecirculating Langendorff preparation and exposed hearts to 5 mug/mL l-bupivacaine and 9 microL/mL lipid emulsion. Hearts were freeze-clamped and energy was charge measured by HPLC. In a second experiment the effects of pacing hearts was evaluated. The effects of lipid addition on local anesthetic concentrations in Krebs-Henseleit buffer and human plasma were examined by using a mass spectrometer.
  
  
  RESULTS
  With spontaneously beating hearts l-bupivacaine led to a significant decrease in heart rate (to 74% +/- 7% of baseline), +dP/dt (69% +/- 7%), systolic pressure (78% +/- 6%), coronary flow (61% +/- 8%), and to an increase in PR (177% +/- 52%) and QRS intervals (166% +/- 36%). Lipid infusion exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure back to 94% +/- 11% and 102% +/- 16% of baseline in l-bupivacaine-treated hearts. Heart rate, coronary flow, PR, and QRS intervals remained unchanged after lipid intervention. Lipid infusion in paced hearts had a significant effect on +dP/dt, systolic pressure, and Mvo2. Neither l-bupivacaine nor lipids had an effect on energy charge. A lipid concentration of 500 muL/mL plasma was necessary to effect changes in the plasma concentration of local anesthetics.
  
  
  CONCLUSIONS
  Lipid application in l-bupivacaine-induced cardiac depression had a significant positive inotropic effect, which we would attribute to a direct inotropic effect. However, in an isolated heart model, indirect, local anesthetic plasma-binding effect of lipids cannot be excluded.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany. sebastian.stehr@gmx.de
authors.forename: Sebastian N
authors.initials: SN
authors.lastname: Stehr
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Ziegeler
authors.forename: Annette
authors.initials: A
authors.lastname: Pexa
authors.forename: Reinhard
authors.initials: R
authors.lastname: Oertel
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
authors.forename: Thea
authors.initials: T
authors.lastname: Koch
authors.forename: Matthias
authors.initials: M
authors.lastname: Hübler
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D023421:Models, Animal; D051381:Rats
chemical_list: D008055:Lipids; D002045:Bupivacaine