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罗哌卡因胸段硬膜外阻滞对急性心肌缺血/再灌注损伤的保护作用

时间:2010-08-24 11:36:18  来源:  作者:

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Myocardial protective effects of thoracic epidural anesthesia with ropivacaine during acute myocardial ischemia reperfusion

 

李刚  许永广  刘慧贞  王萍

LI GangXU YongguangLIU Huizhenet al1 Department of AnesthesiologyShandong Provincial HospitalJinan 250021

 

Abstract

  ObjectiveTo evaluate the myocardial protective effects of thoracic epidural anesthesiaTEAwith 0.5% ropivacaine during acute myocardial ischemiareperfusion.

  MethodsEighteen healthy hybrid dogs were randomly divided into three groupsropivacaine groupgroup Ⅰ),bupivacaine groupgroup aand normal saline groupgroup b. Anesthesia was induced and maintained with intravenous anesthesia and ventilation was mechanically controlled1 Epidural catheter was placed at T627 and 0.5% ropivacaine0.5% bupivacaine or normal saline 12ml was administered epidurally. 15min after epidural administration of local anesthetics or normal salinethe anterior descending branch of left coronary artery was temporarilly occluded for 45min. Blood samples were taken from right atrium and assayed for cardiac troponin TcTnTbefore epidural administration and 6h after reperfusion. Myocardial tissues of left ventricular infarction area were examined by electron microscopy.

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  ResultsPlasma cTnT levels were comparableP<0.05ng/Lin the three groups before epidural administration but increased significantly in 4 dogs of each group 6h after reperfusion. The difference between group and group b was significantP<0.05. Electron microscope examination of the infarct myocardium showed that myocardial fibers were regularly arranged with normal mitochondria in group Ⅰ;the intercellular spaces were enlarged with unclear nuclar membrane and near normal mitochondria in groupathe myocardial fibers were irregularly arranged with a number of vacuoles and no normal sarcomere structure was seen in the cytoplasm in group b.

  ConclusionsTEA with 0.5% ropivacaine can afford effective protection against acute myocardial ischemiareperfusion injury and the effect is better than TEA with bupivacaine at the same concentration.

  Key WordsAnesthesiaepiduralMyocardial reperfusion injuryTroponin TRopivacaine

 

  临床上胸段硬膜外阻滞TEA)治疗心肌缺血在国内外已有尝试,但对预防和治疗急性心肌缺血/再灌注损伤尚未见系统的报道。本研究旨在探讨罗哌卡因行TEA治疗对急性心肌缺血/再灌注损伤的保护作用。

 

材料与方法

  健康杂种家犬18只,雌雄不拘,体重1419kg,随机分为三组,每组6只。实验组Ⅰ组罗哌卡因组),对照组a组布比卡因组,Ⅱb组生理盐水组)。所有动物术前药为吗啡5mg和阿托品0.2mg/kg肌注,2%硫喷妥钠810mg/kg静脉诱导后气管插管控制呼吸,硫喷妥钠2mg/kg、芬太尼50μg/kg及潘库溴铵0.08mg/kg维持静脉麻醉。股动脉穿刺置管持续监测动脉压,针形电极刺入皮下监测心电图和心率。行胸段硬膜外穿刺X光造影证实为T67),头向置管4cm备用。左侧第四肋间进胸暴露心脏,打开并固定心包,经上腔静脉或右心耳穿刺置管至右心房备采血。于左冠状动脉前降支根部处逢线,套一细Rumel套管备阻断用。根据分组硬膜外分别给予0.5%罗哌卡因阿斯特拉制药有限公司提供,瑞典)、0.5%布比卡因或生理盐水12ml。给药后15min收紧Rumel阻断前降支,45min后开放。分别在给药前和开放后6h采右心房血,采用Cardiac Reader台式分析仪Boehringer Mannheim公司生产,德国)半定量测定血浆心肌肌钙蛋白TcTnT)浓度。并取左心室梗塞区及非梗塞区心肌组织采用H2800型透射电镜日立公司生产,日本)观察心肌组织超微结构的改变。

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结 果

  各组动物一般资料无统计学差异。Ⅰ组及Ⅱa组在硬膜外给药后动脉压及心率均有所下降,但与Ⅱb组相比其差异无统计学意义。三组动物在阻断及开放冠状动脉前后心电图的变化相似。

  给药前各组血浆cTnT浓度均<0.05ng/L。开放后6hcTnT浓度<0.05ng/L:三组中各有2只;0.050.1ng/L:Ⅰ组4只,Ⅱa2只,Ⅱb0只;>0.1ng/L:Ⅰ组0只,Ⅱa2只,Ⅱb4只,Ⅰ组与Ⅱb组比较有显著性差异P<0.05)。

  开放后6h的梗塞区心肌组织的电镜学观察,Ⅰ组心肌肌纤维排列完整、规律,线粒体未见异常1),Ⅱa组肌纤维间隙增宽,核膜模糊,线粒体基本正常2),Ⅱb组肌纤维排列极度紊乱,正常肌节结构消失,区域内出现大量空泡区3)。

 

讨 论

  TEA心肌保护的作用机制有:⑴降低心率及心脏前后负荷,减少心脏做功,降低氧耗;⑵扩张病变冠脉,重新分配冠脉血流,增加缺血区/非缺血区、心内膜/心外膜血流比,增加缺血区氧供;⑶抑制缺血及手术所致的应激反应,减少神经内分泌反应,从而减少应激所致的心肌耗能增加;⑷减少因疼痛等所致的心脏做功增多[13]。罗哌卡因是一种纯左旋式同分异构体长效酰胺类局麻药,与布比卡因比具有对心血管系统和中枢神经系统毒性低,在低浓度时对感觉神经和运动神经阻滞分离等特点[4]。本研究心肌组织的电镜检查结果显示,Ⅰ组及Ⅱa组心肌细胞的损伤程度低于Ⅱb组,且Ⅰ组心肌细胞损伤程度最轻。说明TEA对急性心肌缺血/再灌注损伤具有保护作用,同时说明0.5%罗哌卡因的效果优于相同浓度的布比卡因,这可能与罗哌卡因对心肌钠离子通道阻滞较弱、对线粒体能量代谢干扰较小、对细胞内cAMP生成抑制较轻等因素有关[5]

  心肌肌钙蛋白cTn)是存在于心肌肌原纤维中细肌丝上的收缩调节蛋白,当心肌细胞受损时,cTn可从细胞释放至血液循环中。cTnT是在心肌细胞损伤时较早出现在血液中的亚单位之一,具有心肌特异性,不受创伤等因素的影响,是对心肌细胞损伤诊断具有特异性和敏感性的标志物之一[67]。本研究采用德国Boehringer Mannheim公司生产的快速阅读试剂条的测试方法,具有方便、快速、读数准确等特点。Ⅰ组cTnT浓度的升高明显低于Ⅱb组,而Ⅱa组与Ⅰ组、Ⅱb组相比,统计学处理无显著性差异,可能因样本较小所致。该结果与电镜观察的组织学改变基本吻合,说明cTnT的快速监测法在心肌缺血/再灌注损伤的研究中具有较高的参考价值,也证明了罗哌卡因胸段硬膜外阻滞对心肌缺血/再灌注损伤的保护作用,为今后在临床实践工作中的应用提供了依据。

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  本实验结果证实,0.5%罗哌卡因胸段硬膜外阻滞,对犬急性心肌缺血/再灌注损伤具有明显的保护作用,其效果优于相同浓度的布比卡因,这还有待于在临床研究中进一步验证。

 

参考文献

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2. Blomberg SEmanuelsson HKvist Het al1 Effect of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease.Anesthesiology199073840847.

3. Klassen GBramwell RSBromage PRet al1 Effect of acute sympathectomy by epidural anesthesia on the canine coronary circulation1 Anesthesiology198052815.

4. 王晓持. 罗比卡因. 国外医学麻醉学与复苏分册,1999201012.

5. 吕安祺. 罗哌卡因与布比卡因心脏毒性研究进展. 国外医学麻醉学与复苏分册,199920232234.

6. Katus HASchoeppenthau MTanzeem Aet al. Noninvasive assessment of perioperative myocardial cell damage by circulating cardiac troponin T1Br Heart J199165259264.

7. 张野,王钧. 肌钙蛋白T与围手术期心肌损伤. 国外医学麻醉学与复苏分册,199718324326.

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