The Effects With Lipid Emulsion On Bupivacaine Infusion Induced Cardiac Toxicity In Rats

Objective: To observe the effects of pretreatment with lipid emulsion on bupivacaine infusion induced cardiac coxicity in rats and to explore its mechanism.Methods: 40 SD male rats and weighting about 290-350g, were randomly divided into three groups, control group (group A) (n=8), bupivacaine treatment group (group B), lipid emulsion pretreatment group (group C), B and C group are further divided into two sub-groups groups based on the death group and the material group (n = 8). The rats were anesthetized with 2% pentobarbital sodium (50mg/kg) that was injected by intraper- itoneal. Two-lead ECG being monitored by inserting three acupuncture needles into the both upper limbs and left lower limb subcutaneouly. The trachea was incised and the femoral vein was isolated to pump liquid. The carotid artery was isolated and connected to the pressure transducer to measure blood pressure which was then connected to the computer with BL-420 bio-function experimental system.Group A, 0.9% normal saline (3ml/kg/min) was pumped in intrvenous injection continuously heart was quickly removed after 6 minutes.Group B1, 0.9% normal saline (3ml/kg/min) was pumped in intrave- nous injection 5 minutes continuously, then 0.5% bupivacaine 2ml/kg/min was not pumped in intravenous injection continuously until cardiac arrest.Group B2, 0.9% normal saline (3 ml/kg/min) was pumped in intrave- nous injection 5 minutes continuously, then 0.5% bupivacaine 2ml/kg/min was pumped in intravenous injection 1 minutes continuously then the heart was quickly removed.Group C1, 20% fat emulsion (3 ml/kg/min) was pumped in intrave- nous injection 5 minutes continuously, then 0.5% bupivacaine 2ml/kg/min was not pumped in intravenous injection continuously until cardiac arrest.Group C2, 20% fat emulsion (3 ml/kg/min) was pumped in intravenous injection 5 minutes continuously, then 0.5% bupiva- caine 2ml/kg/min was pumped in intravenous injection 1 minutes continuously then the heart was quickly removed.Animal's blood pressure(SBP/DBP)was recorded before the drugs were given,and the heart rate were recored at the same time. By tracing normal ECG and the wave of BP, the time when arrhythmia was appeared in these animals was recored, being the same as 50%HRand the time when thecardiac arrest in the death group. The electric wave has been observed after disappearing of it for 1 minute.The accumulated dose of corresponding bupivacaine was calculated at every point. The rats in the death group are quiekly done to die by cutting head. ATPase and pathological chage would be measured with the refrigerant heart from the died rats. Results:1. elementary value of haemodynamicsThere was no statistic difference on elementary value of haemodynamics(HR,SBP,NBP)between five groups. The difference was no significant difference (p> 0.05).2. The different time points and dose corresponding to the time in the death groupThe time points, arrhythmia (T1), 50% HR (T2) and cardiac arrest (T3) about group C1 is appeared later than the group B1 (p <0.05). The accumulated dose of corresponding bupivacaine in group C1 is larger than in group B1 (p <0.05), the difference has statistical significance.3. The change of activity of myocardial ATPase The comparison between each groups'activity of ATPase: group A > group C2 > group B2, the differences were significant (p <0.05).4. Changes of pathology Pathological changes are as follows: the majority of myocardial cells in control group are no abnormal; a few of the myocardial cells in group C2 are aparenced vacuolar degeneration and mild cellular edema; In group B2, the myocardial cells aparenced extensive vacuolar degeneration with hemorrhage. Meanwile, myocardial cells have fusioned, boundaries of membrane unclearand the nucleus disappears, showing the limitations of focal necrosis.5. The comparison of cardiac myocytes apoptosis in rat In the three groups, the protein level of Bcl-2 expression in group A increased, Bax protein level expression decreased and cardiac myocytes apoptosis also decreased.Compared with group A, Bcl-2 expression in group B2 significant decreased, Bax expression significant increased and cardiac myocytes apoptosis also increased. Compared with group B2, Bcl-2 expression in group C2 increased, Bax expression decreased so that to reduce myocardial apoptosis.Conclusion: The mechanisms of the lipid emulsion reduce the cardiac toxicity of bupivacaine may be due to increase activity in myocardial ATPase activity and restrict myocardial apoptosis.