The Mechanism Of The Intralipid Treatment Of The Rat’s Cardiac Toxicity By Bupivacaine

Bupivacaine is a long-acting amide local anesthetic, with the feature of long duration of action and good effect of anesthesia,so it is widely used in clinical anesthesia such as epidural anesthesia, spinal anesthesia, brachial plexus block and so on.But bupivacaine also have certain side effects, mainly in the central nervous system toxicity and cardiotoxicity, and the most obvious performance of the side effects is cardiac toxicity, The cardiac toxicity of bupivacaine mainly including negative inotropic and negative conduction, such as PR interval and QRS prolongation, bradycardia, Premature ventricular beats and ventricular tachycardia or ventricular fibrillation or even cardiac arrest. The event of cardiac arrest resuscitation is very difficult. Research has shown that the bupivacaine-induced cardiac arrest can be treated by using fat emulsion but the mechanism is still not clear, the mechanism of the treatment of bupivacaine-induced heart arrests by intralipid mainly concentrated in the lipid pool hypothesis, mitochondrial energy metabolism hypothesis, ion channel hypothesis and so on. In this study, through establishing the animal model of cardiac arrest by bupivacaine, and recovery by intralipid, by measuring the concentration of bupivacaine in myocardial tissue, and determination of the activity of key enzymes in the mitochondrial energy metabolism in the myocardial tissue to reveal the possible mechanism of fat emulsion treatment of cardiac arrest by to bupivacaine and provide relevant theoretical basis for clinical studies.ObjectiveBy a bupivacaine-induced cardiac arrest and intralipid for the treatment of animal models to observe the effect of fat emulsion treatment of bupivacaine cardiac arrest, combined with laboratory tests to investigate the bupivacaine caused thethe mechanism of cardiac arrest to stop the treatment, to provide relevant theoretical basis for clinical studies.Methods and Material1 Subjects24 healthy adult SD rats (body weight 280 to 320g) of either sex, provided by the Experimental Animal Center of Henan Province.2 Methods24 SD rats were randomly divided into two groups, (n=12), A group, bupivacaine induced cardiac arrest, B group, bupivacaine induced cardiac arrest, and using intralipid to recovery. Anaesthetize rats by 20% hydrochloride ketamine 100mg/kg intraperitoneal injection, the animals supine on animal experiments test-bed, routine disinfect the surgical site, underwent tracheostomy, endotracheal intubation, carotid artery puncture, mechanical ventilation, femoral vein puncture, then two groups animals injected 10mg/kg0.5% hydrochloride bupivacaine induced cardiac arrest.Group After cardiac arrest, the rats in A group intravenous inject 15ml/kg of normal saline and epinephrine 10μg/kg,repeat per minute, a total of three times, then inject 10μg/kg epinephrine every 5min. Parallel manual cardiopulmonary resuscitation (CPR), the rats in B group intravenous inject 15ml/kg of LE and epinephrine 10μg/kg,repeat per minute, a total of three times, then inject 10μg/kg epinephrine every 5min. Parallel manual cardiopulmonary resuscitation (CPR), Continuous monitoring the rat ECG, HR, BP and other basic life testify during the experiment. Determinating the myocardial tissue and plasma concentration of bupivacaine hydrochloride by high performance liquid chromatography, this detection method is a liquid-liquid extractionFrance, which extract is a mixture of hexane and tert-ether, the mixture of methanol and triethylamine salt buffer pH value adjusted to 3.0, the mixture as the mobile phase.Column by Dima C 18 column, the column temperature was 30℃, detection wavelength was 215nm, flow rate 1.0ml/min; chromatography injection volume is 25μ1.2ml of 50% methanol as the solvent and 0.5mg heart tissue homogenates,30 seconds to take 200ul of the homogenate and 100μl 4% NaOH solution mixed with vortex, the vortex good mixture 3ml extract, aftervortex 3min, the vortex good mixture at 3000r/min centrifuge 10min, take the organic phase 2ml in the centrifuge tube containing the organic phase centrifuge tube placed at 35℃water bath with nitrogen organic phase blowingdry, dry residue obtained by adding 100μl mobile phase vortex 30 seconds, and 12000 r/min speed high-speed centrifugation 10min, take 75μl centrifugal good upper liquid by adding 250μl tube-shaped bottle, the HPLC system every time automatically extractThe 25μl detection.Carnitine-the activity of carnitine acyl transferase (CACT) and the the ELISA detection method for the determination of myocardial tissueResults1 The animals’ basic life such as BP, HR, WET, and etc is no significant difference in two groups(P>0.05),2 Compared with the rats in group A,the plasma bupivacaine levels of the rats in group B is significantly higher,and the bupivacaine levels in myocardial is significantly decreased(P<0.05),3 Compared with the rats in group A,the rats CACT enzyme activity of Myocardial tissue in group B is significantly decreased(P<0.05).ConclusionsA lot of bupivacaine quickly into the blood can cause serious cardiac toxicity, arrhythmia and cardiac arrest intralipid can treat the bupivacaine’s cardiac toxicity by lipid pool and the reversal the inhibition on mitochondrial CACT.