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Comparison of Bupivacaine-induced Cardiotoxicity and Intralipid Rescue in Non-Pregnant and Late Pregnant Rats
Abstract Number: GM-1
Abstract Type: Original Research
Pregnant patients routinely get neuraxial anesthesia for labor and delivery. Bupivacaine is one of the most commonly used local anesthetics in obstetric anesthesia. We have previously shown that Intralipid (ILP) rescues the heart from bupivacaine-induced cardiotoxicity in male rats. We and others have shown that ILP mediates its cardioprotective effects via glycogen synthase kinase-3b (GSK-3b) phosphorylation through inhibition of mitochondrial permeability transition pore opening. However, bupivacaine cardiotoxicity and ILP rescue have not been extensively studied in non-pregnant and pregnant rats. Here, we investigate the cardiotoxicity of bupivacaine and ILP rescue in female non-pregnant and late pregnant rats.
Late pregnant (day-20 of pregnancy, n=7) and non-pregnant female rats (200-300 g, n=4) were used. Rats were anesthetized with intraperitoneal ketamine and xylazine. Tracheostomy was performed and rats were mechanically ventilated. Temperature was maintained at 37°C. Rats received bupivacaine bolus (10 mg/kg, IV via femoral vein over ~20 seconds) to induce asystole. Resuscitation with ILP 20% (5 ml/kg bolus, and 0.5 ml/kg/min maintenance) and chest compressions were initiated. Serial B-Mode and M-Mode transthoracic echocardiography was performed using a VisualSonics Vevo 2100 system. Standard Lead II Electrocardiograms (EKG) were recorded throughout the experiment. The ejection-fraction (EF%), fractional shortening (FS%), and heart rate (HR, beats per min, bpm) were calculated at baseline and at 1, 5, and 10 minutes after ILP treatment. A group of late pregnant rats that did not undergo bupivacaine-induced cardiac arrest and ILP rescue served as sham controls (n=5). Western blot was performed on hearts to assess for GSK-3b phosphorylation.
All rats developed cardiac arrest within a few seconds after a toxic dose of bupivacaine. All of the non-pregnant rats were successfully rescued by ILP (HR recovery=259±6 at baseline vs. 220±7 bpm at 10-min post ILP and EF recovery=68±2 at baseline vs. 66±2% at 10-min post ILP). Interestingly, 6 out of 7 late pregnant rats did not recover with ILP after bupivacaine-induced cardiac arrest. The average baseline HR and EF were 341±30.44 bpm and 67±4%. One, five and ten minutes after ILP administration, the HR and EF were 0. Western immunoblots showed that the pregnant rats that were not rescued by ILP failed to have GSK-3b phosphorylation (pGSK/GSK=0.80±0.51 vs. 1.00±0.56 in late pregnant sham controls; p=0.578).
ILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats but failed to rescue cardiac arrest in pregnant rats. This failure is most likely attributed to the inability of ILP to phosphorylate GSK-3b, a known mediator of ILP’s cardioprotection. Future studies are warranted to find out the optimal rescue dosage regimen of ILP for bupivacaine-induced cardiac arrest in pregnant rats.