張 杰,劉亞華,代 正,周滿紅,尹雪蓮,張 維,沈 洪
·論著·
山莨菪堿對(duì)心搏驟停豬心肺復(fù)蘇后肺損傷的保護(hù)作用及其作用機(jī)制研究
張 杰,劉亞華,代 正,周滿紅,尹雪蓮,張 維,沈 洪
目的 探究山莨菪堿對(duì)心搏驟停豬心肺復(fù)蘇(CPR)后肺損傷的保護(hù)作用及其作用機(jī)制。方法 選擇健康雄性家豬23頭,按照隨機(jī)數(shù)字表法分為假手術(shù)組(A組,n=5)、腎上腺素組(B組,n=9)和山莨菪堿+腎上腺素組(C組,n=9)。采用交流電致顫法建立心搏驟停模型。A組家豬只切開(kāi)左頸外靜脈,不進(jìn)行致顫及CPR;B組和C組家豬制備心搏驟停模型后立即進(jìn)行CPR,同時(shí)B組家豬注射腎上腺素,C組家豬注射腎上腺素+山莨菪堿。ROSC成功家豬和A組家豬在基礎(chǔ)時(shí)點(diǎn)、心搏驟停 8 min、自主循環(huán)恢復(fù)(ROSC)即刻、ROSC 30 min和ROSC 24 h留取血液標(biāo)本,檢測(cè)血漿腫瘤壞死因子α(TNF-α)和白介素6(IL-6)水平;ROSC 24 h處死所有家豬,留取肺組織標(biāo)本,檢測(cè)超氧化物歧化酶(SOD)、丙二醛(MDA)、髓過(guò)氧化物酶(MPO)、TNF-α及IL-6含量,肺含水量及濕/干重比(W/D);光鏡下觀察肺組織形態(tài)學(xué)變化。結(jié)果 (1)B組和C組家豬均成功致顫,心電圖均表現(xiàn)為心室纖顫。B組ROSC成功7頭,C組ROSC成功5頭。(2)基礎(chǔ)時(shí)點(diǎn)3組家豬血漿TNF-α水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);心搏驟停8 min、ROSC即刻、ROSC 30 min及ROSC 24 h B組和C組家豬血漿TNF-α水平低于A組,ROSC即刻、ROSC 30 min及ROSC 24 h C組家豬血漿TNF-α水平低于B組(P<0.05)?;A(chǔ)時(shí)點(diǎn)、心搏驟停8 min及ROSC即刻3組家豬血漿IL-6水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);ROSC 30 min及ROSC 24 h B組和C組家豬血漿IL-6水平高于A組,ROSC 24 h C組家豬血漿IL-6水平低于B組(P<0.05)。(3)B組和C組家豬肺組織SOD含量低于A組,肺組織MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量高于A組(P<0.05)。C組家豬肺組織SOD含量高于B組,肺組織MDA含量、MPO含量、W/D、肺含水量及TNF-α含量低于B組(P<0.05)。(4)光鏡下顯示,B組家豬肺泡壁毛細(xì)血管擴(kuò)張,肺泡滲出增多,炎性細(xì)胞浸潤(rùn);而C組家豬上述表現(xiàn)明顯減輕。結(jié)論 山莨菪堿可能通過(guò)抑制TNF-α、IL-6過(guò)度釋放,減輕脂質(zhì)過(guò)氧化等來(lái)減輕心搏驟停豬CPR后肺損傷,進(jìn)而發(fā)揮保護(hù)作用。
心搏驟停;心肺復(fù)蘇術(shù);山莨菪堿;缺血再灌注損傷;肺保護(hù);豬
張杰,劉亞華,代正,等.山莨菪堿對(duì)心搏驟停豬心肺復(fù)蘇后肺損傷的保護(hù)作用及其作用機(jī)制研究[J].實(shí)用心腦肺血管病雜志,2015,23(10):40-44.[www.syxnf.net]
Zhang J,Liu YH,Dai Z,et al.Protective effect and its mechanism of anisodamine on lung injury after CPR in pigs with sudden cardiac arrest[J].Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease,2015,23(10):40-44.
近年來(lái),疾病預(yù)防領(lǐng)域雖取得一些進(jìn)展,但心搏驟停(sudden cardiac arrest)在世界很多地區(qū)死亡原因中仍位居首位[1]。大量動(dòng)物實(shí)驗(yàn)和臨床研究發(fā)現(xiàn),心肺復(fù)蘇(cardiopulmonary resuscitation,CPR)后存在不同程度肺損傷,CPR后大量炎性遞質(zhì)被激活、多種細(xì)胞因子共同參與肺炎性損傷過(guò)程[2];另外,心搏驟停、CPR后肺臟仍存在缺血再灌注損傷,且心、腦、胃腸等其他遠(yuǎn)隔臟器發(fā)生缺血再灌注損傷亦會(huì)對(duì)肺臟產(chǎn)生影響。山莨菪堿又名654-2,是我國(guó)從茄科植物唐古特莨菪中分離出來(lái)的生物堿,臨床研究顯示,其對(duì)創(chuàng)傷[3]、膿毒血癥、缺血再灌注[4-6]等多種機(jī)制引起的肺損傷均有良好的保護(hù)作用。本實(shí)驗(yàn)通過(guò)建立心搏驟停豬模型,觀察山莨菪堿對(duì)心搏驟停豬CPR后肺損傷的保護(hù)作用,并探討其可能的作用機(jī)制。
1.1 實(shí)驗(yàn)動(dòng)物及分組 雄性家豬23頭,月齡3~4個(gè)月,體質(zhì)量24~27 kg,由中國(guó)人民解放軍總醫(yī)院動(dòng)物實(shí)驗(yàn)室提供。按照隨機(jī)數(shù)字表法將23頭家豬分為假手術(shù)組(A組,n=5)、腎上腺素組(B組,n=9)和山莨菪堿+腎上腺素組(C組,n=9)。
1.2 主要試劑和儀器 腫瘤壞死因子α(TNF-α)和白介素6(IL-6)試劑盒(武漢基因美生物提供),髓過(guò)氧化物酶(MPO)試劑盒(上海碧云天生物技術(shù)研究所提供),超氧化物歧化酶(SOD)試劑盒(K335-100,美國(guó)BioVision公司),起搏電極(心諾普北京醫(yī)療技術(shù)有限公司),Heart Start XL除顫儀(PHILIPS),氣管插管導(dǎo)管(管徑6.0,英國(guó)泰美科公司)。電熱恒溫培育箱(PH4000AB型,天津泰斯特儀器有限公司),電動(dòng)勻漿器(Ultra Turrax?T10basic,德國(guó)IKA公司)。
1.3 動(dòng)物模型制備 切開(kāi)家豬左頸外靜脈并插入起搏電極至右心室,應(yīng)用右心室交流電致顫法建立心搏驟停模型[7]。成功誘發(fā)心搏驟停標(biāo)準(zhǔn):平均動(dòng)脈壓<10 mm Hg(1 mm Hg=0.133 kPa),伴正常動(dòng)脈搏動(dòng)波消失,心電圖示心室纖顫。
1.4 實(shí)驗(yàn)方法及結(jié)果判定標(biāo)準(zhǔn) A組家豬只切開(kāi)左頸外靜脈,不進(jìn)行致顫及CPR。B組和C組家豬誘發(fā)心搏驟停成功9 min后立即進(jìn)行CPR,同時(shí)經(jīng)氣管導(dǎo)管接呼吸機(jī)輔助通氣,呼吸機(jī)模式為容量控制模式,設(shè)定潮氣量15 ml/kg、呼吸頻率16次/min、氧吸入濃度100%、胸外心臟按壓頻率>100次/min、按壓幅度為豬胸廓前后徑1/4。在行CPR同時(shí)B組家豬經(jīng)左頸內(nèi)靜脈導(dǎo)管彈丸式注射腎上腺素(0.045 mg/kg)[8],C組家豬經(jīng)左頸內(nèi)靜脈導(dǎo)管彈丸式注射腎上腺素(0.045 mg/kg)+山莨菪堿(0.4 mg/kg)[9],持續(xù)胸外按壓2 min后電除顫1次(雙相,150 J)[7]。若CPR未成功,繼續(xù)胸外按壓,按照固定頻率推注復(fù)蘇藥物(1次/3 min)及電除顫(1次/2 min)。CPR 30 min后仍未出現(xiàn)自主循環(huán)恢復(fù)(resumption of spontaneous circulation,ROSC),停止CPR。ROSC標(biāo)準(zhǔn):停止心臟按壓后,出現(xiàn)竇性、房性或交界性心律伴平均動(dòng)脈壓>60 mm Hg或脈壓>20 mm Hg,且持續(xù)時(shí)間超過(guò)10 min[7]。恢復(fù)自主循環(huán)2 h后撤機(jī)。
1.5 標(biāo)本采集及檢測(cè)
1.5.1 TNF-α和IL-6 ROSC成功家豬及A組家豬在基礎(chǔ)時(shí)點(diǎn)、心搏驟停8 min、ROSC即刻、ROSC 30 min和ROSC 24 h留取靜脈血3 ml,采用EDTA抗凝管收集血液,搖勻,4 °C 1 000×g離心10 min,然后移取血漿至另一新的1 ml離心管(血漿檢測(cè)樣本),采用酶聯(lián)免疫吸附試驗(yàn)(ELISA)測(cè)定血漿TNF-α和IL-6水平或肺組織TNF-α和IL-6含量。
1.5.2 肺組織 ROSC成功家豬及A組家豬均在ROSC 24 h后處死,在左肺下葉相同部位取約5 g肺組織,稱取濕重后,置于60 ℃電熱恒溫培養(yǎng)箱內(nèi)干燥72 h,再稱取干重,計(jì)算肺組織濕/干重比(wet/dry weight ratio,W/D) 和肺含水量,肺含水量=(肺濕重-肺干重) / 肺干重×100%。取左肺上葉相同部位肺組織標(biāo)本以冰生理鹽水沖洗,采用電動(dòng)勻漿器,13 000×g離心10 min,去掉沉淀,留取上清夜備用。采用黃嘌呤氧化酶法檢測(cè)肺組織SOD含量,采用硫代巴比妥酸法檢測(cè)丙二醛(MDA)含量,采用依賴H2O2反應(yīng)產(chǎn)物比色法檢測(cè)MPO含量。
1.5.3 肺組織形態(tài)學(xué)觀察 每組家豬在處死時(shí)立即在左肺上葉相同部位取10 cm3肺組織放入10%甲醛溶液中固定。石蠟切片,二甲苯10 min,100%乙醇1 min,95%乙醇1 min,85%乙醇1 min,75%乙醇1 min脫蠟。蒸餾水沖洗5 min,然后采用蘇木素染色3 min,自來(lái)水沖洗3 min,1%鹽酸乙醇分化30 s,水洗藍(lán)化5 min,75%乙醇1 min,1%伊紅乙醇1 min,95%乙醇1 min,100%乙醇1 min,二甲苯石炭酸1 min,二甲苯(Ⅰ)1 min,二甲苯(Ⅱ)1 min,中性樹(shù)脂封片。光鏡下觀察肺組織結(jié)構(gòu)破壞、肺間質(zhì)水腫情況及炎性細(xì)胞浸潤(rùn)程度。
2.1 實(shí)驗(yàn)結(jié)果 B組和C組家豬均成功致顫,心電圖均表現(xiàn)為心室纖顫。B組ROSC成功7頭,C組ROSC成功5頭。CPR失敗6頭,其中2頭可能是肋骨骨折導(dǎo)致肺臟刺傷,其余4頭失敗原因不確定。ROSC成功后家豬均存活24 h,24 h后開(kāi)胸,肺臟表面結(jié)構(gòu)完整,無(wú)肋骨骨折導(dǎo)致肺臟刺傷情況。
2.2 3組家豬不同時(shí)間點(diǎn)血漿TNF-α和IL-6水平比較 基礎(chǔ)時(shí)點(diǎn)3組家豬血漿TNF-α水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。心搏驟停8 min、ROSC即刻、ROSC 30 min及ROSC 24 h 3組家豬血漿TNF-α水平比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);其中B組和C組家豬血漿TNF-α水平低于A組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。ROSC即刻、ROSC 30 min及ROSC 24 h C組家豬血漿TNF-α水平低于B組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表1)?;A(chǔ)時(shí)點(diǎn)、心搏驟停8 min及ROSC即刻3組家豬血漿IL-6水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。ROSC 30 min及ROSC 24 h 3組家豬血漿IL-6水平比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);其中B組和C組家豬血漿IL-6水平高于A組,差異有統(tǒng)計(jì)學(xué)意義(P>0.05)。ROSC 24 h C組家豬血漿IL-6水平低于B組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表2)。
Table 1 Comparison of plasma TNF-α level among the three groups at different time points
組別頭數(shù)基礎(chǔ)時(shí)點(diǎn)心搏驟停8minROSC即刻ROSC30minROSC24hA組54.31±0.104.30±0.094.37±0.044.25±0.054.32±0.06B組54.27±0.104.47±0.07a5.92±0.05a7.89±0.31a27.39±1.44aC組74.26±0.094.46±0.06a5.61±0.22ab6.93±0.09ab22.84±0.84abF值0.348.11145.51341.38277.24P值0.710.010.000.000.00
注:與A組比較,aP<0.05;與B組比較,bP<0.05;A組為假手術(shù)組,B組為腎上腺素組,C組為山莨菪堿+腎上腺素組;ROCS=自主循環(huán)恢復(fù)
Table 2 Comparison of plasma IL-6 level among the three groups at different time points
組別頭數(shù)基礎(chǔ)時(shí)點(diǎn)心搏驟停8minROSC即刻ROSC30minROSC24hA組53.85±0.903.84±0.073.86±0.083.85±0.063.86±0.09B組53.83±0.093.92±0.063.96±0.084.86±0.26a27.39±1.44aC組73.81±0.063.84±0.073.88±0.084.59±0.41a23.33±1.75abF值0.252.022.6014.35424.70P值0.780.160.100.000.00
注:與A組比較,aP<0.05;與B組比較,bP<0.05
2.3 3組家豬肺組織SOD含量、MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量比較 3組家豬肺組織SOD含量、MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量比較,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。其中B組和C組家豬肺組織SOD含量低于A組,肺組織MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量高于A組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。C組家豬肺組織SOD含量高于B組,肺組織MDA含量、MPO含量、W/D、肺含水量及TNF-α含量低于B組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見(jiàn)表3)。
2.4 3組家豬肺組織形態(tài)學(xué) A組家豬肺泡結(jié)構(gòu)完整,肺泡壁及間質(zhì)內(nèi)無(wú)炎性細(xì)胞浸潤(rùn)(見(jiàn)圖1);B組家豬肺泡壁毛細(xì)血管擴(kuò)張,肺泡腔水腫、滲出及大量粒細(xì)胞浸潤(rùn)(見(jiàn)圖2);C組與B組比較,肺組織充血、肺間質(zhì)水腫減輕,肺泡內(nèi)滲出明顯減少(見(jiàn)圖3)。
圖1 A組家豬肺組織形態(tài)學(xué)表現(xiàn)(HE染色,×40)
3.1 山莨菪堿對(duì)CPR后炎性因子的影響 CPR后體內(nèi)免疫細(xì)胞會(huì)釋放大量炎性因子,且各種炎性因子可產(chǎn)生化學(xué)反應(yīng),互相激活、趨化而產(chǎn)生瀑布樣鏈鎖反應(yīng)。TNF-α作為始動(dòng)因子[10],通過(guò)趨化、激活中性粒細(xì)胞(PMN)向肺部聚集而產(chǎn)生呼吸爆發(fā),且還可以促使機(jī)體釋放大量氧自由基,誘導(dǎo)其他炎性遞質(zhì)(如IL-6)大量分泌等,進(jìn)而引起肺內(nèi)皮細(xì)胞受損、血管通透性增加、通氣/血流比例失調(diào)、動(dòng)脈血氧分壓下降[11-12]。有臨床研究表明,山莨菪堿能通過(guò)抑制轉(zhuǎn)錄因子κB(NF-κB)
圖2 B組家豬肺組織形態(tài)學(xué)(HE染色,×40)
圖3 C組家豬肺組織形態(tài)學(xué)(HE染色,×40)
表3 3組家豬肺組織SOD含量、MDA含量、MPO含量、W/D、肺含水量及TNF-α和IL-6含量比較
注:與A組比較,aP<0.05;與B組比較,bP<0.05;SOD=超氧化物歧化酶,MDA=丙二醛,MPO=髓過(guò)氧化物酶,W/D=濕/干重比
活化,下調(diào)TNF-α基因的轉(zhuǎn)錄及蛋白質(zhì)合成,從源頭阻遏炎性因子的瀑布樣鏈鎖反應(yīng)[13]。湯彥等[14]通過(guò)制備油酸所致急性肺損傷家兔模型,證實(shí)山莨菪堿能有效降低家兔急性肺損傷時(shí)血漿TNF-α、IL-8水平,改善肺組織病理改變。張寰波[15]的研究結(jié)果發(fā)現(xiàn),山莨菪堿能抑制TNF-α、IL-6 等促炎性細(xì)胞因子的過(guò)量產(chǎn)生或釋放及調(diào)節(jié)抗炎細(xì)胞因子——IL-10的表達(dá),減輕肺水腫、改善氧合指標(biāo),從而保護(hù)急性肺損傷患者的肺功能。MPO是PMN胞質(zhì)中的一種特異性酶,與來(lái)自NADPH的H2O2一起構(gòu)成PMN的顆粒系統(tǒng)。本研究結(jié)果顯示,光鏡下C組家豬肺內(nèi)炎癥相對(duì)減輕、肺泡滲出液及炎性細(xì)胞浸潤(rùn)較B組減輕,且CPR后肺組織TNF-α和IL-6含量均高于A組,提示兩種炎性遞質(zhì)可能均參與介導(dǎo)CPR后肺損傷的炎性病理變化。與B組比較,C組大鼠ROSC后各時(shí)間點(diǎn)血漿TNF-α水平均下降,同時(shí)ROSC 24 h肺組織TNF-α含量、MPO含量及W/D亦降低,提示山莨菪堿可能通過(guò)抑制TNF-α、IL-6的過(guò)度分泌而降低肺毛細(xì)血管通透性、減輕肺水腫,從而減輕CPR后肺損傷。
3.2 山莨菪堿對(duì)氧化應(yīng)激反應(yīng)的干預(yù) 離體及在體缺血再灌注動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),肺泡上皮及肺血管內(nèi)皮細(xì)胞因氧自由基代謝失衡而出現(xiàn)肺毛細(xì)血管痙攣及肺泡上皮細(xì)胞變性壞死,毛細(xì)血管滲漏,進(jìn)而引發(fā)肺水腫[16]。SOD和MDA是常用的評(píng)價(jià)氧化應(yīng)激損傷的重要指標(biāo)。當(dāng)機(jī)體SOD含量降低,氧自由基清除能力出現(xiàn)下降,細(xì)胞多不飽和脂肪酸形成脂質(zhì)過(guò)氧化反應(yīng),而MDA作為代表性脂質(zhì)過(guò)氧化代謝產(chǎn)物能進(jìn)一步破壞細(xì)胞膜的完整性、損害細(xì)胞超微結(jié)構(gòu)。以往研究發(fā)現(xiàn),山莨菪堿作為抗氧化劑可以保護(hù)肺泡巨噬細(xì)胞免受內(nèi)毒素的直接氧化損傷[17],從而維持抗氧化能力平衡。劉樹(shù)元等[18]研究顯示,心搏驟停患者行CPR早期應(yīng)用山莨菪堿可提高24 h存活率,復(fù)蘇早期即能明顯減輕體內(nèi)氧化應(yīng)激反應(yīng)。本研究結(jié)果顯示,C組家豬肺組織SOD含量高于B組,MDA含量低于B組,提示山莨菪堿能通過(guò)提高SOD含量、抑制氧自由基產(chǎn)生,從而減輕肺再灌注后脂質(zhì)過(guò)氧化損傷。
綜上所述,CPR后多種因素參與肺損傷過(guò)程。山莨菪堿可能通過(guò)抑制TNF-α、IL-6過(guò)度釋放,減輕脂質(zhì)過(guò)氧化等來(lái)減輕心搏驟停豬CPR后肺損傷,進(jìn)而發(fā)揮保護(hù)作用。
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(本文編輯:謝武英)
Protective Effect and Its Mechanism of Anisodamine on Lung Injury after CPR in Pigs with Sudden Cardiac Arrest
ZHANGJie,LIUYa-hua,DAIZheng,etal.DepartmentofEmergency,GeneralHospitaloftheChinesePeople′sLiberationArmy,Beijing100853,China
Objective To investigate the protective effect and its mechanism of anisodamine on lung injury after CPR in pigs with sudden cardiac arrest.Methods A total of 23 healthy male pigs were divided into A group(n=5),B group(n=9)and C group(n=9)according to random number table.Alternating current-induced ventricular fibrillation method was used to prepare the animal models of sudden cardiac arrest.Pigs of A group only received incision of left external carotid vein,did not received alternating current-induced ventricular fibrillation or CPR;pigs of B group and C group received immediate CPR after preparation of sudden cardiac arrest models,and pigs of B group received extra injection of epinephrine,while pigs of C group received extra injection of epinephrine and anisodamine.Blood specimens of successful ROSC pigs and A group were collected to detect the plasma levels of TNF-α and IL-6 at basis point,after 8 minutes of sudden cardiac arrest,at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC.After 24 hours of ROSC,all of the pigs were killed and lung tissue samples were collected to detect the SOD,MDA,MPO,TNF-α and IL-6 contents,water content and wet/dry weight ratio(W/D).Light microscope was used to observe the morphological features of lung tissue.Results (1)Pigs of B group and C group were all successfully induced ventricular fibrillation affirmed by electrocardiogram.Of B group,7 pigs got successful ROSC;of C group,5 pigs got successful ROSC.(2)No statistically significant differences of plasma TNF-α level was found among the three groups at basis point(P>0.05);plasma TNF-α level of B group,C group was statistically significantly lower than that of A group after 8 minutes of sudden cardiac arrest,at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC,respectively,and plasma TNF-α level of C group was statistically significantly lower than that of B group at once of ROSC,after 30 minutes of ROSC and after 24 hours of ROSC,respectively(P<0.05).No statistically significant differences of plasma IL-6 level was found among the three groups at basis point,after 8 minutes of sudden cardiac arrest or at once of ROSC(P>0.05);plasma IL-6 level of B group,C group was statistically significantly higher than that of A group after 30 minutes of ROSC and after 24 hours of ROSC,respectively,and plasma IL-6 level of C group was statistically significantly lower than that of B group after 24 hours of ROSC(P<0.05).(3)SOD content of lung tissue of B group,C group was statistically significant lower than that of A group,respectively,while MDA,MPO,TNF-α,IL-6 contents,water content and W/D of B group and C group were statistically significantly higher than those of A group(P<0.05);SOD content of lung tissue of C group was statistically significant higher than that of B group,while MDA,MPO,TNF-α water content and W/D of C group were statistically significantly lower than those of B group(P<0.05).Light microscope found alveolar walls capillaries expanded,alveoli exudation elevated and infiltration of inflammatory cells of B group,while above features of C group were relatively relieved.Conclusion Anisodamine can relieve lung injury after CPR in pigs with sudden cardiac arrest through inhibiting the excessive release of TNF-α and IL-6,alleviating of lipid peroxidation,and eventually play a role of protective effect.
Cardiac arrest;Cardiopulmonary resuscitation;Anisodamine;Ischemia-reperfusion injury;Lung protection;Swine
衛(wèi)生行業(yè)基金科研專項(xiàng)(201002011)
100853北京市,中國(guó)人民解放軍總醫(yī)院急診科(張杰,沈洪);武警總醫(yī)院急救醫(yī)學(xué)中心(劉亞華);四川省人民醫(yī)院急診科(代正);遵義醫(yī)學(xué)院附屬醫(yī)院(周滿紅);北京同仁醫(yī)院(尹雪蓮);解放軍總后司令部管理保障局第一門診部(張維)
沈洪,100853北京市,中國(guó)人民解放軍總醫(yī)院急診科;E-mail:shenhong@em120.com
R 541.78
A
10.3969/j.issn.1008-5971.2015.10.010
2015-08-16;
2015-10-14)