乌司他丁对改善猪心肺复苏后炎症反应和心肺组织损伤的作用

目的 评价乌司他丁(UTI)对猪心肺复苏(CPR)后炎症反应和心肺组织损伤的保护作用.方法 雌性家猪20只,通过程控刺激法复制心室纤颤(室颤)动物模型,室颤8 min后开始CPR,自主循环恢复(ROSC)的家猪按随机数字表法分为两组,UTI组复苏后即刻给予UTI 100 kU溶于生理盐水5 ml,缓慢注射,3h1次,直到复苏后24 h;对照组复苏后应用生理盐水5 ml作为对照.分别于室颤前基础状态及ROSC后即刻、3、12、24 h抽取家猪静脉血,采用酶联免疫吸附试验(ELISA)测定肿瘤坏死因子-α(TNF-α)、白细胞介素-1 β (IL-1 β)、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的水平.ROSC后24h处死家猪,留取心、肺组织进行病理及超微结构观察.结果 20只家猪经过8 min室颤后复苏成功15只.UTI组8只和对照组7只存活24 h.复苏后两组炎症因子均逐渐回升,两组间室颤前和ROSC后即刻TNF-α、IL-1 β、ICAM-1和VCAM-1比较差异无统计学意义;UTI组3h起TNF-α (ng/L)、IL-1 β (ng/L)水平明显低于对照组(TNF-α:28.79±9.49比44.01±17.01,IL-1β:153.50±67.47比252.09±80.41,均P＜0.05),12h起ICAM-1(μg/L)、VCAM-1(μg/L)水平明显低于对照组(ICAM-1:11.05±5.11比17.09±5.69,VCAM-1:11.17±4.75比16.62±4.63,均P＜ 0.05).ROSC后24 h时UTI组心、肺组织损伤程度明显轻于对照组.结论 复苏后应用UTI可以明显减轻炎症反应和心肺组织损伤程度.     

心肌内谷氨酸浓度变化在 CPR 后心功能障碍中的意义北大核心CSCD

目的：通过微渗透技术观察心肺复苏（ CPR）后心肌内谷氨酸浓度的变化和心功能障碍的关系。方法在6只成年新西兰兔大脑皮层和心肌内置入微量渗析管,然后建立室颤心脏骤停模型。室颤6 min,ROSC后采集渗析液检测谷氨酸浓度,超声评价左心室收缩功能,电镜观察大脑皮层和心肌细胞损伤情况。结果诱发室颤前大脑皮质内的谷氨酸浓度为（76．07±8．50）μmmol／L,ROSC后30 min迅速升高至（107．70±7．17）μmmol／L,2 h达到顶峰（139．62±15．64）μmmol／L,随后下降,3 h下降至（68．86±3．78）μmmol／L。 ROSC后30 min心肌内谷氨酸浓度为（87．26±14．14）μmmol／L,较室颤前（40．33±5．39）μmmol／L明显升高（P＜0．001）,持续1 h左右逐渐下降,ROSC后90 min左右降至（47．82±6．72）μmmol／L。 ROSC后60 min FS值为（39．00±1．79）％、EF为（47．00±3．90）％,低于基础值（44．83±3．25）％和（53．17±4．58）％（ P＝0．001和0．008）。 ROSC后4 h兔大脑皮层细胞线粒体明显肿胀,线粒体脊模糊甚至消失,部分空白化,核周围有凋亡小体形成,心肌细胞内未见凋亡小体形成。结论兔室颤6 min,ROSC后心肌内高浓度的谷氨酸可能和心功能障碍有关。     

早期经食道快速诱导低温对猪心肺复苏后肠黏膜损伤的影响北大核心CSCD

目的探讨复苏后早期经食道快速诱导低温对猪心肺复苏后肠黏膜损伤的影响。方法国产健康雄性白猪27头,体质量（36±2）kg。采用随机数字表法分为3组（每组n=9）：常温组（NT组）、体表降温组（SC组）与食道降温组（EC组）。采用电刺激法诱发室颤8min,心肺复苏5min,制备心肺复苏猪模型。自主循环恢复（ROSC）后5min时,EC组与SC组外接冰毯仪,分别经食道降温导管与体表冰毯进行降温,目标温度33℃,持续至ROSC后24h,再以1℃m复温5h。NT组全程维持正常体温（38．0±0．5℃）。ROSC后30h内动态监测核心体温,并于ROSC后3、6、12、24与30h时,应用酶联免疫吸附试验法（ELISA）检测血清肠型脂肪酸结合蛋白（IFABP）的含量与二胺氧化酶（DAO）的活性。ROSC后30h时处死猪,取小肠组织,应用ELISA法检测肿瘤坏死因子-α（TNF-α）与白细胞介素-6（IL-6）的含量,原位末端标记法检测细胞凋亡,免疫组织化学法检测半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的蛋白表达水平。结果EC组降温速率和达标时长均显著优于SC组（2．8℃／h vs．1．5℃／h,102min vs．185min,均P〈0．05）。与NT组相比,EC组在ROSC后3h、SC组在ROSC后6h的IFABP含量与DAO活性均降低（均P〈0．05）。与SC组相比,EC组在ROSC后6hIFABP含量和在ROSC后12hDAO活性均下降[IFABP（pg／ml）：6h为（710±32）vs．（777±52）,12h为（870±49）vs．（960±64）,24h为（1022±65）vs．（1143±63）,30h为（882±71）vs．（1006±45）;DAO（U／ml）：12h为（39．9±1．9）vs．（43．4±3．2）,24h为（30．6±2．4）vs．（34．0±3．1）,30h为（26．1±2．7）vs．（29．4±2．2）,均P〈0．05]。与NT组相比,EC组与SC组TNF-α、IL-6含量减少,且凋亡指数、caspase．3蛋白表达均降低（均P〈0．05）。与SC组相比,EC组炎症反应与细胞凋亡进一步减轻[TNF—α（pg／mL）：（721±94）vs．（922±125）;IL-6（pg／mL）：（454±69）vs．（697±132）;细胞凋亡指数（％）：（6．2±2．6）vs．（12．8±3．0）;caspase-3（IOD）：（8．9±1．6）vs．（15．9±1．9）,均P〈0．05]。结论经食道可以快速诱导低温,其效果优于传统的体表降温并产生更好的ROSC后肠保护效应,其机制可能与抑制炎症反应、细胞凋亡等有关。     

弥散加权成像观察去甲肾上腺素诱导的高血压灌注对心搏骤停猪脑功能的影响

目的 观察高血压灌注心搏骤停猪自主循环恢复(ROSC)后脑功能的变化.方法 采用电刺激建立猪心室纤颤(室颤)模型,室颤4 min后给予标准心肺复苏(CPR),将ROSC猪按随机数字表法分为两组,每组5只.高血压灌注组立即给予去甲肾上腺素(NE)使平均动脉压(MAP)维持在室颤前血压的130％;正常灌注组给予NE维持MAP为室颤前水平;两组均监测4h观察血流动力学变化;于室颤前及ROSC后1h、3h用弥散加权成像(DWI)技术扫描大脑顶叶皮质,观察脑功能成像的动态变化;于复苏后24 h制备脑组织切片,观察顶叶的病理学变化.结果 与正常灌注组比较,高血压灌注组于ROSC后不同时间点心率(HR,次/min)、MAP(mm Hg,1 mm Hg=0.133 kPa)、心排血量(CO,L/min)、冠状动脉灌注压(CPP,mm Hg)均出现升高趋势(ROSC 30 min HR:167±8比140±15,ROSC 1 h MAP:131 ±9比108±10,ROSC 1 h CO:4.9±0.1比3.4±0.5,ROSC 2 h CPP:118±12比88±1,P＜0.05或P＜0.01).两组复苏前后DWI未见明显异常;复苏后大脑皮质表观弥散系数(ADC)均呈下降趋势,正常灌注组下降趋势较高血压灌注组明显.光镜下观察高血压灌注对脑的保护作用优于正常灌注组.结论 高血压灌注可引起心搏骤停猪复苏后血流动力学的改变,增加脑血流量,对脑具有保护作用,有利于促进神经功能的恢复.     

经右心室电刺激致颤建立家兔心脏骤停模型

目的：建立一种简单、有效、稳定的家兔电刺激致颤心脏骤停（ CA）后脑复苏模型。方法选用20只新西兰雄性家兔,采用体表胸壁及心内膜下交流电诱发室颤的方法制作CA模型,CA 4 min后开始心肺复苏（CPR）。记录手术操作时间（TOP）、自主循环恢复时间（TROSC）、恢复率,除颤、肾上腺素次数,24 h、72 h存活率以及进行72 h大脑皮质凋亡细胞检测。另取10只兔为对照组,只进行致颤前手术操作。结果①20只家兔全部诱发CA成功,室颤发生率为100％。自主循环恢复率为80％;24 h、72 h存活率为50％、30％;除颤和肾上腺素次数为1．20±0.89、1．60±0．75;TOP和TROSC分别为（79±25）min、（268±33）s。②血浆神经元特异性烯醇化酶（NSE）水平显著升高,ROSC 72 h略有回降,但仍高于造模前（P＜0．05）。③与对照组比较,ROSC后72 h大脑皮质区出现了较多神经细胞的凋亡（P＜0．05）。④神经功能评分（NDS）在复苏后3 h时最低,以后渐趋好转。结论该模型操作简单、结果稳定、复苏成功率高,是一个较为理想的心肺脑复苏研究模型。     

七氟醚对心脏骤停大鼠心肌保护作用的研究

目的 观察吸入性麻醉药七氟醚对心肺复苏后大鼠心肌保护的作用.方法 窒息法建立心脏骤停模型.36只雄性wistar大鼠随机(随机数字法)分为假手术组、七氟醚组、对照组,假手术组仅予麻醉及气管插管,七氟醚组在心肺复苏时即予以1最小肺泡有效浓度(minimum alveolar concentration,MAC)七氟醚吸入,对照组进行常规心肺复苏.每组半数大鼠在自主循环恢复(ROSC)后4h及24 h行心脏超声测定心功能.每组剩余大鼠ROSC后4h取材、提取线粒体,分光光度计法评估线粒体通透性转换孔(MPTP)开放程度,Western blot法测定胞质中细胞色素C的表达.结果 ROSC后大鼠舒张期左室后壁明显增厚(LVPWd)、心输出量(CO)明显下降.ROSC后4h七氟醚组LVPWd增厚程度(mm)较对照组减轻(1.95±0.14) vs.(2.32±0.34),P＜0.05;心输出量(mL/min)高于对照组(46.94±3.61) vs.(38.77±6.63),P＜0.05;加入氯化钙诱发线粒体肿胀,七氟醚组吸光度下降程度较对照组减轻(0.048 ±0.007) vs.(0.069 ±0.011),P＜0.01.心肺复苏后细胞色素C在胞质表达明显增多,七氟醚组胞质中细胞色素C表达较对照组明显减少(1.02±0.22) vs.(1.59±0.31),P＜0.05.结论 七氟醚可以改善复苏后心功能不全,下调MPTP开放,减少细胞色素C向胞质的释放.     

心肺复苏后心功能障碍与心肌内质网Ca2＋调控蛋白表达关系的研究

目的探讨心肌内质网Ca2＋调控蛋白表达与心肺复苏（CPR）后心功能障碍的关系。方法38只SPF级雄性SD大鼠按随机数字表法分为对照组（12只）和心搏骤停组（26只）。静脉弹丸式注射氯化钾40μg/g诱导心搏骤停,8 min后进行CPR;对照组大鼠仅麻醉后置管并监测指标,不诱导心搏骤停。在复苏后进行有创血流动力学监测1 h,采用超声心动图测定心功能。分别于自主循环恢复（ROSC）后5 min和60 min时采集心肌标本,采用蛋白质免疫印迹试验（Western Blot）检测内质网Ca2＋ATP酶（SERCA2a）、磷酸化受磷蛋白（p-PLB）和兰尼定受体（RyR）水平。结果心搏骤停组ROSC率为92.3%（24/26）,平均复苏时间为（68±39）s。心搏骤停组复苏后1 h心功能明显下降,与对照组相比,射血分数、短轴缩短率（FS）、左室内压上升或下降最大速率（±dp/dt max）明显降低〔射血分数：0.548±0.060比0.809±0.043,F＝71.692,P＝0.000;FS：（34.4±4.4）%比（46.0±3.5）%,F＝55.443,P＝0.000;+dp/dt max （mmHg/s）：4718±743比7098±394,P＜0.01;-dp/dt max （mmHg/s）：-3824±612比-6187±473,P＜0.01〕。与对照组相比,心搏骤停组ROSC后5 min及60 min PLB磷酸化水平（灰度值）均显著降低（5 min：0.64±0.15比1.29±0.13,P＜0.01;60 min：0.95±0.08比1.30±0.09,P＜0.05）,而内质网SERCA2a活性（灰度值）和RyR水平（灰度值）差异均无统计学意义（SERCA2a 5 min：1.01±0.18比1.24±0.07,60 min：1.03±0.14比1.25±0.06;RyR 5 min：0.96±0.13比0.97±0.13,60 min：0.88±0.14比0.99±0.11,均P＞0.05）。结论内质网PLB磷酸化水平异常与CPR后心功能障碍密切相关。     

心肺复苏后早期注射冰盐水的有效性和安全性临床评价

目的：评价心搏骤停患者早期注射冰盐水实现亚低温治疗的可行性、安全性和有效性。方法采用单中心前瞻性随机对照的临床研究方法,以2011年3月到2013年10月北京市大兴区人民医院抢救的心搏骤停进行心肺复苏（CPR）后自主循环恢复（ROSC）的患者为研究对象,按随机数字表法将患者分为两组。ROSC后,冰盐水组患者立即快速静脉注射4℃生理盐水1000 mL来实现亚低温治疗,对照组给予常规头部冰袋降温治疗和腋温监测。所有患者在ROSC即刻和1 h后分别测量直肠温度;记录复苏后6 h胸片出现急性肺水肿、48 h内出现寒战、48 h再次发生心室纤颤（室颤）以及14 d内成功苏醒和死亡的患者例数。结果共有45例患者纳入本研究,其中冰盐水组23例,对照组22例。冰盐水组患者ROSC即刻直肠温度为（36.7±0.9）℃,1 h后降至（34.9±0.7）℃;对照组患者ROSC即刻直肠温度为（36.5±1.0）℃,1 h后升高至（37.9±0.9）℃,两组ROSC后1 h直肠温度比较差异有统计学意义（t＝2.228,P＝0.031）。冰盐水组14 d内成功苏醒患者例数明显多于对照组（13例比7例,χ2＝65.710,P＝0.021）,而出现急性肺水肿（4例比6例）、寒战（2例比0例）、再次发生室颤（4例比5例）和14 d内死亡（11例比12例）的患者例数与对照组比较差异均无统计学意义（均P＞0.05）。结论早期快速静脉注射4℃生理盐水来实现复苏后亚低温治疗脑复苏效果更佳理想,且是可行的、安全的、有效的。     

氢气吸入减轻长时程心脏骤停家猪复苏后脑损伤

目的:探究氢气对长时程心脏骤停家猪复苏后脑损伤的保护作用。方法:健康雄性家猪电诱发室颤并维持10分钟后开始心肺复苏(CPR)。动物恢复自主循环(ROSC)后随机分成两组:对照组ROSC后全程使用空气进行机械通气;氢气组ROSC后使用含2%氢气与21%氧气的混合气体进行通气,至复苏2小时(PR2h)改普通空气通气。动物复苏后持续监测心率、血压等血流动力学参数6 h,分别在PR0.5 h、2 h、4 h、6 h检测血清神经损伤标志物NSE、S100B的浓度。观察和评估动物复苏后24 h、48 h、72 h、以及96 h的神经功能缺损评分(NDS)及生存结局。结果:氢气吸入组动物复苏后血清神经损伤标志物NSE、S100B的浓度较对照组更低,动物的生存时间以及24 h、48 h、72 h、96 h NDS评分均明显好于对照组。结论:复苏后氢气吸入可以改善长时程心脏骤停家猪复苏后的脑功能和生存结局。     

插入式腹主动脉按压对心搏骤停兔心肺脑复苏的实验研究

目的：探讨插入式腹主动脉按压心肺复苏（IAAC-CPR）对心搏骤停兔心肺脑复苏的效果。方法健康新西兰大白兔10只,雌雄不拘,按随机数字表法分为传统胸外按压心肺复苏（CC-CPR）组和IAAC-CPR组,每组5只。经颈静脉快速推注冰氯化钾并夹闭气管导管制备心搏骤停模型;心搏骤停3 min后开始实施心肺复苏（CPR）,CC-CPR组为呼吸机辅助通气+胸外按压;IAAC-CPR组为呼吸机辅助通气+胸外按压+腹主动脉按压。观察CPR过程中血流动力学和脑皮质血流的变化;记录自主循环恢复（ROSC）时间,观察动物24 h生存情况、24 h神经功能评分及腹部器官情况等。结果 IAAC-CPR组复苏后30、60、90、120 s时脑血流量（CBF,PU值）及平均动脉压（MAP,mmHg,1 mmHg＝0.133 kPa）均明显高于CC-CPR组（CBF 30 s：16.1±6.0比7.8±2.2,60 s：91.6±11.8比57.3±23.2,90 s：259.9±74.9比163.6±50.3,120 s：301.5±60.5比208.4±23.8;MAP 30 s：46.4±9.4比31.4±8.7,60 s：55.8±13.8比34.0±11.5,90 s：61.2±11.5比38.2±10.1,120 s：63.6±11.8比40.2±10.2;均P＜0.05）。与CC-CPR组比较,IAAC-CPR组ROSC所需时间明显缩短（s：182.0±59.0比312.6±86.6,t＝2.787,P＝0.024）,24 h神经功能评分明显下降（分：2.4±1.7比4.6±0.6,t＝2.974,P＝0.023）;而复苏成功率（80.0%比60.0%,χ2＝0.000,P＝1.000）、24 h存活率升高（80.0%比40.0%,χ2＝0.417,P＝0.519）,但差异无统计学意义。ROSC后24 h尸解动物均未发现肝脏损伤。结论在心搏骤停兔复苏早期,IAAC-CPR较CC-CPR取得了更好的脑血流灌注,明显减轻了心搏骤停兔的神经系统功能损伤,且无腹部器官损伤。     

Dynamic evaluation of myocardial dysfunction in rats after cardiopulmonary resuscitation Zhao Shen北大核心CSCD

Objective: To observe the dynamic changes of myocardial structure and dysfunction during post-resuscitation period in order to establish a rat mode of post-resuscitation myocardial dysfunction after cardiac arrest resulted from electric stimulation-induced ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR). Methods: A total of 40 male Sprague-Dawley (SD) rats were randomly (random number) assigned into post-resuscitation (PR) 4 h, PR 12 h, PR 24 h, PR 72 h and sham groups. VF was induced by an alternating electric current delivered to the right ventricular endocardium and untreated for 8 min. Biphasic waveform defibrillation was attempted and mechanical ventilation was synchronized after 6 min of CPR. Myocardial function was assessed with serum myocardial enzyme activity, echocardiography, mitochondrial respiratory function and histopathologic findings at different intervals. Results: Thirty-two animals were successfully resuscitated with restoration of spontaneous circulation (ROSC) in 86% (32/37) rats. Compared with sham group, severe systolic and diastolic heart failure were found at 4 h after ROSC and then gradually improved without significant difference (P > 0. 05) in ejection fraction at PR 72 h after ROSC was found, whereas thickened ventricular wall and increased myocardial performance index as well as interstitial proliferation were observed at 72 h after ROSC. Conclusions: A rat model of post-resuscitation myocardial dysfunction after cardiac arrest resulted from electric stimulation-induced VF and CPR was successfully established.     

兔室颤心搏骤停模型的建立

目的 建立一种简单、方便、有效的兔心肺腩复苏(CPcR)模型.方法 采用体表交流电诱发室颤的方法制作兔心跳骤停(CA)模型,依据CA时间的长短,27只新西兰大白兔随机分为CA 8min、CA 5min和CA 3min组,每组9只,随后进行胸外心肺复苏术(CPR).自主循环恢复(ROSC)后4 h检测血肌钙蛋白I水平,72 h后处死动物,取海马组织尼氏染色和TUNEL法凋亡细胞检测,计算每40×倍视野下海马CAI区尼氏染色阳性细胞数和凋亡细胞数.另取2只兔作为对照组,只进行外科操作小进行敛颤和CPR.各组数据依据正态检验结果用单因素方差分析(one-way ANOVA)或秩和检验(Mann-Whitney rank),多重比较用ISD-t检验,ROSC率的比较用行X列连表χ2检验,两样本均数的比较用t检验,P＜0.05表示差异具有统计学意义.结果 CA 8 min,CA 5 min和CA 3 min组各有4,5,7只动物ROSC,各组间ROSC率差异无统计学意义.ROSC后各组动物的存活时间分别为(1.67±2.55)h,(37.78±30.27)h,(12.0±14.97)h,CA 3 min组和其他两组之间差异具有统计学意义(P＜0.05).ROSC后4 h三组之间血浆肌钙蛋白水平分别为(0.71±0.07)ne/mL,(0.55±0.08)ng/mL,(0.45±0.06)ng/mL,CA 3 min组和其他两组之间差异具有统计学意义(P＜0.05).与对照组相比,ROSC后72 h海马CA1区出现了神经元细胞的缺失和凋亡,CA 3 min组和对照组尼氏染色阳性细胞数分别为(34.33±6.19),(55.75±5.91)(P＜0.01),对照组中海马Cal区未见有凋亡细胞.结论 兔CA 3 min后进行CPR有较长的存活时间,ROSC后72 h海马CA1区可见神经元细胞缺失和凋亡,因此该模型可能是一个比较理想的CPCR研究模型.     

窒息法和室颤法致猪心脏骤停后肺损伤的研究

目的 通过窒息和室颤的心脏骤停动物模型,对心肺复苏后肺损伤进行对照研究.方法 将近交系五指山小型猪随机(随机数字法)分为窒息组(AS)和室颤组(VF),每组各24只,分别采用阻塞气管插管和程控电刺激诱导方法制模,制模成功后给予标准的心肺复苏至ROSC,分别测量基础状态、ROSC即刻、15 min、30 min、1h、2h、4h和6h的氧合指数(OI)、呼吸指数(RI)、氧输送(DO2)、血乳酸,并监测同一时刻动物的肺顺应性(Cdyn)、气道阻力(Raw)、血管外肺水指数(EVLWI)和肺血管通透性指数(PVPI);于基础状态时和ROSC 4 h时进行肺核素灌注扫描和PET-CT扫描;ROSC后6h将动物处死后取肺组织进行病理及电镜检查,检测组织中Na+-K+-ATP酶、Ca2-ATP酶、SOD、MDA、Bcl-2、Bax及Caspase3蛋白水平及凋亡指数(AI％)等.结果 窒息组的ROSC率和6h生存率均显著低于室颤组(P＜0.01);在肺组织有关酶学及蛋白(Na+-K+-ATPase、Ca2-ATPase、SOD、MDA、AI％、Bax、Bcl-2和Caspase3)检测方面,窒息组重于室颤组,且凋亡现象更严重(P＜0.01);在呼吸力学各个时间点相关指标(OI、RI、DO2、血乳酸、Cdyn、Raw、EVLWI、PVPI)的监测中,窒息组的各项指标的变化较室颤组更明显,在6h后仍未能恢复至基础状态.窒息组和室颤组在肺灌注核素扫描上,无明显的充盈缺损;而在PET-CT扫描上则可见较明显的充盈缺损区.结论 心脏骤停后肺损伤的发生与导致心脏骤停的病因密切相关,窒息明显重于室颤,而心外按压不是导致此类肺损伤的主要原因.     

心肺复苏的质量对复苏后炎症反应的影响

目的 评价临床上常见的不标准心肺复苏(N-CPR)和2005年国际CPR指南推荐的标准心肺复苏(S-CPR)对心脏停搏(CA)猪复苏后炎症反应的影响.方法 18头猪被随机均分成两组,经麻醉、插管、机械通气后,应用程控刺激方法制备心室纤颤(VF)模型.S-CPR组应用2005年指南推荐的CPR方式;N-CPR组模拟临床上经常出现的低质量CPR方式.VF 4 min后开始进行CPR,CPR 9 min后进行电除颤及高级生命支持,自主循环恢复(ROSC)后进行各项指标观察.24 h仍存活的猪经处死后取脑、心、肝、肾组织,应用免疫组化法检测核转录因子-kB(NF-kB)的表达.实验期间连续监测CPR后3、6和9 min的血流动力学变化,并抽取基础状态、CPR 9 rain、ROSC 4 h的静脉血,测定血清肿瘤坏死因子-a(TNF-α)、白细胞介素-1β(IL-1β)的浓度.结果 与N-CPR组比较,S-CPR组ROSC率(22.2%比88.9%)及24 h存活率(22.2%比88.9%)明显提高(P均＜0.05);CPR后3、6和9 min心排血量(CO)和平均动脉压(MAP)也均显著升高(P均＜0.01);并且CPR后9 min和ROSC 4 h血清促炎症因子TNF-α、IL-1β]水平和各组织NF-kB表达程度均降低.结论 高质量的CPR后不仅能提高CA猪的生存率,也明显改善CPR后的炎症反应.     

窒息法与室颤法心肺复苏动物模型的比较研究

目的 对比窒息法与室颤法心搏骤停动物模型在心肺复苏过程中生理指标的变化特点及其在顶测自主循环恢复(restoration of spontaneous circulation,ROSC)率、24 h生存率中的作用.方法 60只SD大鼠随机(随机数字法)制作窒息法与室颤法心肺复苏大鼠动物(n=30)模型,持续监测呼气末二氧化碳(PETCO2)、主动脉压、左室压、肢体Ⅱ导联心电图,对比分析这两种模型中以上监测指标在复苏前、按压10 s、按压1 min、按压3 min、ROSC 1 h、ROSC 2 h的变化及其与ROSC率及24 h存活率的关系.结果 PETCO2、主动脉压、左室压及心电图在两种复苏动物模型各有其变化规律.室颤组ROSC大鼠在复苏前、按压1 min与按压3 min时的PETCO2高于Non-ROSC大鼠(P＜0.05),24 h存活大鼠在ROSC 1 h与ROSC 2 h的PETCO2高于24 h死亡大鼠(P＜0.05).而窒息组ROSC及24 h存活大鼠在各时间点的PETCO2与Non-ROSC及24 h死亡大鼠比较差异无统计学意义.室颤组在ROSC 1 h,ROSC2h的dp/dt40与-dp/dt40均低于窒息组(P＜0.05).结论 窒息法与室颤法复苏动物模型各有特点,PETCO2在室颤法心搏骤停模型有助于预判ROSC及24 h生存率.研究者应根据自身的实验目的 以及模拟的不同临床状况对所需的动物模型作出选择.

Abstract：

Objective To compare the changes of physiological parameters after cardiac arrest caused by asphyxia with that of cardiac arrest induced by ventricular fibrillation in rats and assess the values of the parameters on predicting ROSC and 24 h survival rate. Method Two groups of Sprague-Dwaley rats, which randomly (ramdom number) included 30 animals in each group, were investigated. Cardiac arrest were induced by asphyxia (AS group) or ventricular fibrillation(VF group). PETCO2, aortic pressure, left ventricular pressure and ECG of limb lead Ⅱ were recorded continuously, dP/dt4o was calculated with the windaq software. The parameters were compared between the two groups at baseline, precordial compression(PC) 10 s, PC 1 min, PC 3 min, ROSC 1 h and ROSC 2 h. The relations were explored between the parameters and ROSC/24 h survival rate. Results PETCO2,aortic pressure, left ventricular pressure and ECG have distinctive changes in the two groups. In group VF, PETCO2 of ROSC rats at BL, PC 1 min and PC 3 min were higher than those of Non-ROSC rats (P ＜ 0.05); PETCO2of 24 h survival rats at ROSC 1 h and ROSC 2 h were higher than those of 24 h death rats (P ＜ 0.05), which were not observed in the group AS. dP/dt40 and - dP/dt40 at ROSC 1 h and ROSC 2 h in group VF were higher than those in group AS (P ＜ 0.05). Conclusions Physiological parameters after cardiac arrest caused by asphyxia or that of cardiac arrest induced by ventricular fibrillation in rats have unique features respectively. PETCO2 in cardiac arrest caused by ventricular fibrillation may predict ROSC and 24 h survival rate. Researchers have to select the appropriate cardiac arrest model according their research purposes and clinical requirments.     

A comparison of electrically induced cardiac arrest with cardiac arrest produced by coronary occlusion

OBJECTIVE: The present study was undertaken to compare an animal model of electrically induced VF with ischemically induced VF. In a preponderance of models of cardiac arrest and resuscitation in intact animals, ventricular fibrillation (VF) is induced by an alternating current delivered directly to the epicardium or endocardium. Yet, the applicability of such animal models has been challenged for it is not an electrical current alone but rather a current generated in the ischemic myocardium that triggers VF. Accordingly, a potentially more clinically relevant model was investigated in which spontaneous VF followed acute myocardial ischemia. METHODS: Twenty anesthetized pigs were randomized to either electrical fibrillation or myocardial ischemia following transient occlusion of the left anterior descending (LAD) coronary artery. RESULTS: VF was untreated for 7 min in both models after which mechanical ventilation and precordial compression were begun. Defibrillation was attempted after 5 min of CPR in both groups. VF appeared within 5.7+/-2.0 min of LAD occlusion. CONCLUSIONS: A significant increase in the number of post-resuscitation premature ventricular beats and recurrent VF followed ROSC and a significantly greater number of shocks was required for restoration of spontaneous circulation (ROSC) after LAD occlusion. Nevertheless, early post-resuscitation myocardial dysfunction, neurological recovery and 72 h survival were indistinguishable between the two models.     

心肺复苏后组织因子和组织因子途径抑制物的动态变化和临床意义

目的 观察院内心肺复苏后不同时间点组织因子(TF)和组织因子途径抑制物(TFPI)水平的动态变化特点并探讨其临床意义.方法 选择2005年9月至2007年9月温州医学院附属第一医院急诊科收治的年龄>16岁明确心搏停止时间的心肺复苏患者24例,依据是否达到自主循环恢复标准随机分为ROSC和末ROSC两组,分别记录小同患者心搏停止的病因和临床特点,并用ELISA方法 检测心肺复苏(CPR)后30 min,60 min,6 h,24 h,48 h血清TF和TFPI抗原浓度,10例来自健康体检的健康自愿者为对照组.计量数据用均数±标准差((-x)±s)来表示,两组计量数据的比较采用独立样本t检验,三组及以上计量数据比较采用单因素方差分析法,计数数据的比较采用旧格表精确x2榆验,以P<0.05为差异具有统计学意义.结果 与对照组比较,ROSC组患者在CPR 30 min血TF水平显著升高(P<0.01),在CPR 6 h达高峰,在CPR48 h时已下降;与对照组及ROSC组同时点比较,末ROSC组血TF水平更是显著升高(P<0.01).与对照组比较,在CPR后30 min,ROSC和未ROSC两组血清TFPI水平差异无统计学意义(P>0.05),60 min后ROSC组血清TFPI水平逐渐升高并有显著差别(P<0.01或<0.05).与对照组比较,未ROSC组和ROSC组患者在CPR 30 min时的TF/TFPI水平均显著性升高(P<0.01),且前者显著高于后者(P<0.01),在ROSC组IF/TFPI值在CPR后6 h有显著升高(P<0.01),在48 h下降.结论 血清TF和TFPI水平在院内心肺复苏的患者中明显升高,CPR后半小时的TF和TF/TFPI的水平可用于判断预后.     

亚低温对兔心肺复苏后凝血及脑微循环的影响

目的 探讨亚低温治疗对兔心肺复苏后凝血异常及脑微循环血流变化的干预作用.方法 本实验在中山大学卫生部辅助循环重点实验室进行.24只成年新西兰大白兔随机(随机数字法)分为常温(normothermic,NT)治疗组和亚低温治疗(therapeutic hypothermia,TH)组,每组12只,采用交流电致颤的方式建立心肺复苏(CPR)模型,自主循环恢复后(ROSC)NT组动物置于室温下观察12 h,TH组动物采用体表降温的方法诱导亚低温,达到目标温度后维持12 h.所有动物CPR前及ROSC后4,8,12 h分别测定PT,APTT,INR,D-D,血小板计数(BPC);测定抗凝血酶Ⅲ活性(AT-Ⅲ)和血浆蛋白C活性(PC);用PERIMED Multichannel Laser Doppler系统监测大脑皮层微循环血流.各组数据依据正态检验结果用单因素方差分析或秩和检验,多重比较用LSD-t检验,两样本均数的比较用成组t检验,相关性采用Pearson相关性分析,以P＜0.05为差异具有统计学意义.结果 NT组动物ROSC后PT,APTT,INR逐渐缩短的趋势,ROSC后12 h APTT明显短于基础值(P=0.025),而AT-Ⅲ和PC活性显著下降.和NT组相比,TH组PT,APTT,INR值显著增大,差异具有统计学意义;但AT-Ⅲ,PC活性、D-D浓度,两组差异无统计学意义.CPR前、ROSC后4,8和12 h NT组大脑皮层血流分别(401.60±11.76),(258.86±34.58),(317.59±23.36)和(371.98±5.79)mL/min,TH组为398.18±12.91.336.19±19.27,347.76±13.80和383.78±3.29 mL/min.ROSC后各时间点TH组大脑皮层血流量明显高于NT组(4 h:t=-6.025,df=16,P=0.000;8 h:t=-2.942,df=12,P=0.012;12 h:t=-3.959,df=8,P=0.004).Pearson相关分析显示ROSC后大脑皮层血流和APTT正相关(4 h:R=0.503,P=0.033;8 h:R=0.565,P=0.035;12 h:R=0.774,P=0.009),与其他凝血指标无关.结论 ROSC后亚低温治疗使凝血功能下降的同时伴随脑微循环血流的增加,CPR后亚低温治疗对ROSC后凝血失衡的影响可能是其发挥脑保护作用的机制之一.

Abstract：

Objective To study the effects of mild hypothermia (MH) on blood coagulation and cerebral microcirculation in rabbits after cardiopulmonary resuscitation (CPR). Method A total of 24 New Zealand rabbits were randomly (random number) divided equally into normothermic group (NT) and MH group. CPR model was established by ventricular fibrillation induced by using alternating current. The rabbits of NT group were observed for 12 h in room temperature after restoration of spontaneous circulation (ROSC). The mild hypothermia was induced in the rabbits of group MH by surface cooling after ROSC, and maintained for 12 h after the aimed low temperature reached. The PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio of prothrombin), D-dimmer (DD) , blood platelet count (BPC) , anti-thrombin Ⅲ activity (AT-Ⅲ) and protein C activity (PC) were measured before CPR and 4 h, 8 h and 12 h after ROSC, and at the same time the cerebral microcirculation was measured by using PERIMED Multichannel Laser Doppler system. One-way ANOVA or Mann-Whitney rank was used to determine the statistical significance between two groups. LSD-t test was used for multiple comparisons,t test for comparisons of means between two independent samples, and Pearson correlation test for correlation analysis. Results The PT, APTT and INR showed a trend of gradually shortening during the course. The APTT in 12 h after ROSC was significantly shorter than that before CPR (23.32 ±5.19 vs. 29.53 ±5.10,P = 0.025), and the activity of AT- Ⅲ and PC were decreased significantly. Compared with the group NT,the PT, APTT and INR in group MH were increased significantly, while there were no differences in the activity of AT- Ⅲ, PC and D-D between two groups. The rates of cerebral microcirculation in group NT before CPR and 4 h, 8 h and 12 h after ROSC were 401.60 ± 11.76 mL/min, 258.86 ± 34. 58 mL/min,317.59 ± 23.36 mL/min and 371.98 ± 5.79 mL/min, respectively, and those in group MT were 398.18 ±12.91 mL/min, 336.19 ± 19.27 mL/min, 347.76 ± 13.80 mL/min and 383.78 ± 3.29 mL/min, respectively. There were significant differences between two groups at each interval after ROSC (4 h: t = - 6.025,df=16, P=0.000;8 h: t= -2.942, df=12, P=0.012;12 h: t= -3.959, df=8, P=0.004). The Pearson correlation test showed that the rate of cerebral microcirculation was positive correlated with APTT after ROSC (4 h:R =0.503,P=0.033;8 h:R=0. 565,P=0. 035;12 h:R=0. 774,P=0. 009), and was not correlated with the other blood coagulants. Conclusions The mild hypothermia led to the inhibition of blood coagulation and improved the cerebral microcirculation concomitantly, which may be one of the mechanism of cerebral protection.     

Intra-arrest cooling with delayed reperfusion yields higher survival than earlier normothermic resuscitation in a mouse model of cardiac arrest

BACKGROUND: Therapeutic hypothermia (TH) represents an important method to attenuate post-resuscitation injury after cardiac arrest. Laboratory investigations have suggested that induction of hypothermia before return of spontaneous circulation (ROSC) may confer the greatest benefit. We hypothesized that a short delay in resuscitation to induce hypothermia before ROSC, even at the expense of more prolonged ischemia, may yield both physiological and survival advantages. METHODS: Cardiac arrest was induced in C57BL/6 mice using intravenous potassium chloride; resuscitation was attempted with CPR and fluid administration. Animals were randomized into three groups (n=15 each): a normothermic control group, in which 8 min of arrest at 37 degrees C was followed by resuscitation; an early intra-arrest hypothermia group, in which 6.5 min of 37 degrees C arrest were followed by 90s of cooling, with resuscitation attempted at 30 degrees C (8 min total ischemia); and a delayed intra-arrest hypothermia group, with 90s cooling begun after 8 min of 37 degrees C ischemia, so that animals underwent resuscitation at 9.5 min. RESULTS: Animals treated with TH demonstrated improved hemodynamic variables and survival compared to normothermic controls. This was the case even when comparing the delayed intra-arrest hypothermia group with prolonged ischemia time against normothermic controls with shorter ischemia time (7-day survival, 4/15 vs. 0/15, p<0.001). CONCLUSIONS: Short resuscitation delays to allow establishment of hypothermia before ROSC appear beneficial to both cardiac function and survival. This finding supports the concept that post-resuscitation injury processes begin immediately after ROSC, and that intra-arrest cooling may serve as a useful therapeutic approach to improve survival.