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目的探讨脂肪乳剂对大鼠布比卡因、左布比卡因致心脏毒性的影响。方法成年健康雄性SD大鼠72只,体重220-250g,随机分为五组(n=8)。A组:生理盐水对照组,B组:布比卡因组,C组:布比卡因+脂肪乳组,D组:左布比卡因组,E组:左布比卡因+脂肪乳组。其中B、C、D、E组分为取材组和致死组两个亚组(n=8)。A组以3ml.kg-1.min-1的速率持续静脉泵入生理盐水6min。B、C、D、E组以3ml.kg-1.min-1的速率持续静脉泵注生理盐水或脂肪乳5min,以2mg.kg-1.min-1持续静脉泵局麻药1min。在取材组中,泵注1min局麻药后处死大鼠;致死组中,持续泵注局麻药直到大鼠心跳停止。记录给药前动物的基础血压(HR)、心率(BP),并记录动物出现心律失常(以QRS延长至90ms)、出现心跳停止时的时间(心电图示心脏停搏后观察1min不再出现心电波形为标准),同时计算各对应时局麻药的累积剂量。对照组及取材组断头法处死,迅速取出心脏,液氮冷冻待测ATP酶活性。结果致死组任意两组比较差异均有统计学意义(P<0.05),各组ATP酶含量比较:A组>E1>D1>C1>B1,任意两组比较差异均有统计学意义(P<0.05)。结论左旋布比卡因的毒性低于布比卡因。预先给予脂肪乳注射液可明显减轻布比卡因和左旋布比卡因对大鼠的心脏毒性,其机制可能与增加心肌ATP酶活性有关。
Objective To investigate the effects of fat emulsion on cardiotoxicity induced by bupivacaine and levobupivacaine in rats. Methods Seventy-two healthy male SD rats weighing 220-250 g were randomly divided into five groups (n = 8). Group A: saline control group, group B: bupivacaine group, group C: bupivacaine + fat emulsion group, group D: levobupivacaine group, group E: levobupivacaine + fat emulsion group. B, C, D and E were divided into two subgroups (n = 8). Group A received continuous infusion of normal saline for 6 minutes at a rate of 3 ml.kg-1.min-1. Group B, C, D and E continued to intravenous infusion of normal saline or fat emulsion at a rate of 3ml.kg-1.min-1 for 5min and continuous intravenous anesthesia for 1min at 2mg.kg-1.min-1. In the cupping group, the rats were sacrificed after 1min local anesthetic injection; in the lethal group, the local anesthetic was continuously pumped until the rat’s heartbeat stopped. The basal blood pressure (HR) and heart rate (BP) of pre-dose animals were recorded and arrhythmias were recorded in animals (prolonged by QRS to 90 ms) with time to cardiac arrest (electrocardiogram showed no cardiac arrest after 1 minute of cardiac arrest Electrical waveform as the standard), while calculating the cumulative dose of local anesthetic time. The control group and the experimental group were sacrificed by decapitation, the heart was quickly removed, and the ATPase activity was frozen in liquid nitrogen. Results There were significant differences in any two groups (P <0.05) in the lethal group. There was significant difference in ATPase between the two groups (A> E1> D1> C1> B1) 0.05). Conclusion Levobupivacaine is less toxic than bupivacaine. Pretreatment with fat emulsion injection can significantly reduce the cardiotoxicity of bupivacaine and levobupivacaine in rats, which may be related to the increase of myocardial ATPase activity.