Abstract 159: Intralipid Rescue of Bupivacaine-Induced Cardiotoxicity in Rats is Abolished by Glibenclamide, an ATP Potassium Channel Blocker
Introduction: Lipid emulsion (intralipid) is effective in resuscitating bupivacaine-induced cardiac toxicity. It has been shown that in ischemic preconditioning, ATP-sensitive K+ channels play a role as myocardial preconditioning failed to protect the heart in the presence of KATP channel antagonist glibenclamide. We investigated the role of KATP channel in lipid rescue of bupivacaine-induced cardiotoxicity.
Methods: Young male Sprague-Dawley rats (300-350 g) were anesthetized intraperitoneally with a mixture of ketamine (80 mg/kg) and xylazine (8 mg/kg), and ventilated with a ventilator. M-mode echocardiography were acquired throughout the experiment. Rats were pretreated with glibenclamide (1 mg/kg, IV) or PBS (control group). Asystole was induced 30 min later by a single injection of bupivacaine (10mg/kg over 20 seconds, intravenously) and resuscitation with Intralipid 20% (5ml/kg bolus, and 0.5ml/kg/min maintenance) along with chest compression was started immediately. HR and EF means were compared using a two way repeated measure analysis of variance (ANOVA) model. Values are mean ± SEM, n=5 rats/group, p<0.05 significant.
Results: Glibenclamide had no effect on the HR and cardiac function as there were no significant differences between the HR and EF before (HR=286±15beats/min, EF=82±2.5%) and 30 min after (HR=275±19beats/min, EF=82±2.2%) administration of glibenclamide. Administration of bupivacaine resulted in asystole in both groups and intralipid therapy improved the HR and cardiac function of rats pretreated with PBS gradually within 10 min (HR (beats/min) =86±13 at 1min (27% recovery), 216±10 at 5 min (67% recovery), and 228±14 at 10 min (71% recovery)). The left ventricular systolic function in control group fully recovered within 5 min of intralipid treatment as EF and FS were similar to their baseline values (EF=72±5%, FS=42±4%). Pre-treatment with glibenclamide, however, prevented the lipid-induced rescue of bupivacaine overdose, as there was no recovery of cardiac function within 10 min of lipid therapy.
Conclusions: Our data highlights the role of mithochondrial KATP channels in lipid rescue of bupivacaine-induced cardiotoxicity.
- © 2013 by American Heart Association, Inc.