title: The comparative effects of lipid, epinephrine, and their combination in the reversal of bupivacaine-induced asystole in the isolated rat heart.
abstract: BACKGROUND
  It remains unclear whether lipid combined with epinephrine is superior or inferior to either drug alone in treating bupivacaine cardiotoxicity. We compared the effects of lipid, epinephrine, and the combination of the two in reversing bupivacaine-induced asystole in the isolated rat heart model. We also measured the effects of lipid, epinephrine, and the combination of the two on bupivacaine content in cardiac tissue.
  
  
  METHODS
  Hearts from male Sprague-Dawley rats were excised and retrograde-perfused in a nonrecirculating Langendorff preparation. Bupivacaine 100 μmol/L was perfused until 3 minutes after asystole. Two percent lipid and 30 μmol/L bupivacaine mixture was then perfused in the lipid group; 0.15 μg/mL epinephrine and 30 μmol/L bupivacaine mixture in the epinephrine group; 2% lipid combined with 0.15 μg/mL epinephrine and 30 μmol/L bupivacaine in the combination group; and 30 μmol/L bupivacaine alone in the control group. Recovery of heartbeat was defined as unassisted regular rhythm with a rate-pressure product (RPP) >10% of baseline for >1 minute. We compared the time from the end of 100 μmol/L bupivacaine infusion to recovery of heartbeat (T(recovery)) for each group. The variables of cardiac function were recorded for 40 minutes after recovery of heartbeat. The cardiac apex of each heart was taken for measurement of the bupivacaine content by liquid chromatography-tandem mass spectrometry at the end of the experiment.
  
  
  RESULTS
  Time to recovery (T(recovery)) in the lipid and combination groups was significantly shorter than that in the epinephrine and control groups (P < 0.001), and T(recovery) in the epinephrine group was shorter than that in the control group (P < 0.05). The rank order of the mean RPP during the 40 minutes after recovery of heartbeat from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). The rank order of the highest RPP value during recovery (RPP(maximum)) and the ratio of RPP(maximum) to baseline value (RPP(maximum)/RPP(baseline)) from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). There was no significant difference between the lipid and epinephrine groups for RPP, RPP(maximum), and RPP(maximum)/RPP(baseline). Cardiac tissue bupivacaine content in the epinephrine and control groups was higher than that in the lipid and combination groups (P < 0.001).
  
  
  CONCLUSIONS
  Lipid combined with epinephrine resulted in better recovery of cardiac function than either drug alone in reversal of bupivacaine-induced asystole in the isolated rat heart model.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Wenzhou Medical College, 2 Fuxue Road, Wenzhou City, Zhejiang Province, 325000, China.
authors.forename: Le
authors.initials: L
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Quanguang
authors.initials: Q
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Shi
authors.forename: Fangyan
authors.initials: F
authors.lastname: Wang
authors.forename: Robert H
authors.initials: RH
authors.lastname: Small
authors.forename: Xuzhong
authors.initials: X
authors.lastname: Xu
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000493:pharmacokinetics / Q000633:toxicity*; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use*; D006323:Heart Arrest / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D002045:Bupivacaine; D004837:Epinephrine