title: Effect of bupivacaine on sevoflurane-induced preconditioning in isolated rat hearts.
abstract: Volatile anesthetics protect the heart against ischemia-reperfusion injury. As an adjunct to general anesthesia, local and regional application of bupivacaine is often used. However, systemic plasma levels of bupivacaine might be cardiodepressant and interfere with sevoflurane-induced cardioprotection. Effects of bupivacaine on sevoflurane-induced cardioprotection were assessed in isolated Langendorff-perfused rat hearts subjected to 35 min of global ischemia followed by 60 min reperfusion. Hearts (n=40) were randomized to different groups: 1. CONTROL; 2. Bupivacaine: addition of 0.125 or 1.0 μg/ml bupivacaine to the perfusate for 40 min prior to ischemia-reperfusion; 3. Sevoflurane: preconditioning induced by three times 5-min episodes of sevoflurane (2.5 vol.%) prior to ischemia-reperfusion; 4. Bupivacaine-sevoflurane: combined application of bupivacaine and sevoflurane. After ischemia-reperfusion, cardioprotection was assessed from infarct size and recovery of ventricular function, and phosphorylation levels of glycogen synthase kinase 3β (GSK3β) and 5'AMP activated protein kinase (AMPK) were determined. Infarct size was reduced in the sevoflurane and bupivacaine-sevoflurane groups (Sevo: 23±7% and Bupi-Sevo: 23±5% vs.
  
  
  METHODS
  59±6%, P<0.05). In the bupivacaine group infarct size was reduced as well (34±3%). In the sevoflurane and bupivacaine-sevoflurane groups the recovery of left ventricular function (+dP/dt) was improved (Sevo: 59±2% and Bupi-Sevo: 59±2% vs.
  
  
  METHODS
  47±3%, P<0.05), but not in the bupivacaine group (48±3%). AMPK and GSK3β phosphorylation were increased by sevoflurane but not by bupivacaine. Sevoflurane-induced cardioprotection was not affected by bupivacaine in the non-cardiotoxic range. Bupivacaine alone also reduced infarct size. Both anesthetics activated different signaling kinases, indicating the existence of different cardioprotective intracellular signaling cascades.
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center (VUMC), Amsterdam, The Netherlands. a.bouwman@vumc.nl
authors.forename: R Arthur
authors.initials: RA
authors.lastname: Bouwman
authors.forename: M Jumoke A
authors.initials: MJ
authors.lastname: Vreden
authors.forename: Nazha
authors.initials: N
authors.lastname: Hamdani
authors.forename: Lisan E J
authors.initials: LE
authors.lastname: Wassenaar
authors.forename: Lonneke
authors.initials: L
authors.lastname: Smeding
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Loer
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Stienen
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
mesh_terms: D018685:Anesthetics, Inhalation / Q000378:metabolism / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000378:metabolism / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008738:Methyl Ethers / Q000378:metabolism / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D010766:Phosphorylation; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D008738:Methyl Ethers; D020011:Protective Agents; D000077149:Sevoflurane; D002045:Bupivacaine