Abstract 20545: Intralipid Rescue of Bupivacaine-induced Cardiotoxicity was Abolished by Fatty Acid Oxidation Inhibitor CVT-4325
Introduction: Intralipid (ILP) has been shown to be effective in resuscitating Bupivacaine-induced cardiac arrest. Here we investigated whether inhibition of cardiac fatty acid oxidation by CVT-4325 prevented ILP-mediated rescue of Bupivacaine overdose.
Methods: Male Sprague-Dawley rats (300–350 g) were used for the study. Rats were anesthetized with an i.p. injection of mixture of ketamine (80 mg/kg) and xylazine (8 mg/kg) and then ventilated. In control (CTRL, n=3), first asystole was achieved with a single dose of Bupivacaine (10mg/kg over 20 seconds, i.v.) and then resuscitation using ILP (5ml/kg bolus, and 0.5ml/kg/min maintenance) together with cardiac massage was started immediately. In CVT group (n=12), the protocol was identical to CTRL, except that rats were pre-treated with different doses of CVT (0.5, 0.25, 0.125 and 0.0625 mg/kg bolus i.v.) for 5 min. The heart rate (HR), ejection fraction (EF) and fractional shortening (FS) were measured by echocardiography at baseline, 1, 5 and 10 min after ILP treatment. P<0.05 was considered significant. Values were mean±SE.
Results: In CTRL, the baseline HR and EF were 320±6 and 70±3%, respectively. Administration of Bupivacaine resulted in asystole and ILP resuscitation improved HR and cardiac function gradually within 10 min; HR was 73±3 beats/min at 1 min (23% recovery), increased to 180±23 beats/min at 5 min (56% recovery), and to 243±20 beats/min at 10 min (76% recovery). The left ventricular systolic function fully recovered in all rats within 5 min of ILP treatment (EF=70±3%, FS=40±3%). In CVT groups, the baseline HR and EF were similar before (HR=314±12 beats/min, EF=68±2%) and after different doses of CVT. However, pre-treatment of CVT in doses of 0.5, 0.25 and 0.125mg/kg completely abolished the ILP-induced rescue of Bupivacaine overdose, as there was no recovery of cardiac function with ILP in the CVT-pretreated groups within 10 min of ILP therapy. ILP was only able to rescue Bupivacaine-induced cardiotoxicity at lowest dose of 0.0625 mg/kg CVT as cardiac function improved gradually within 10 min (HR from 65 at 1 min to ∼170 min at 10 min; EF=∼55%, FS=∼29% at 10 min and QRS from 33 ms at 1 min to 27 ms at 10 min).
Conclusions: CVT-4325 prevents intralipid rescue of Bupivacaine-induced cardiotoxicity.
- © 2010 by American Heart Association, Inc.