中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2011年
10期
608-612
,共5页
江慧琳%朱永城%陈晓辉%林珮仪%王华军
江慧琳%硃永城%陳曉輝%林珮儀%王華軍
강혜림%주영성%진효휘%림패의%왕화군
促红细胞生成素%心搏骤停%缺血/再灌注损伤,心肌%心功能不全%心肺复苏
促紅細胞生成素%心搏驟停%缺血/再灌註損傷,心肌%心功能不全%心肺複囌
촉홍세포생성소%심박취정%결혈/재관주손상,심기%심공능불전%심폐복소
Erythropoietin%Cardiac arrest%Myocardium ischemia/reperfusion injury%Myocar-dium%Myocardial dysfunction Cardiopulmonary resuscitation
目的 探讨促红细胞生成素(EPO)对窒息性心搏骤停大鼠心肺复苏(CPR)后心功能不全的心肌保护作用.方法 经夹闭气管8 min建立窒息性心搏骤停-CPR动物模型.按随机数字表法将24只SD大鼠分为3组,每组8只.CPR组窒息致心搏骤停后8 min予胸外按压和机械通气进行复苏；EPO组于自主循环恢复(ROSC)后3 min股静脉注射EPO 5 kU/kg;正常对照组不予任何处理.持续监测左心室收缩压(LVSP)、左心室舒张期末压(LVEDP)、左心室内压上升或下降最大速率(±dp/dt max)等血流动力学指标.于观察终点(ROSC后120 min)处死大鼠,采血测定血清心肌肌钙蛋白Ⅰ(cTnI)含量；光镜和透射电镜下观察心肌组织病理改变；原位末端缺刻标记法(TUNEL)检测心肌细胞凋亡.结果 CPR组和EPO组ROSC后30、60、90、120 min时LVSP、+dp/dt max和- dp/dt max绝对值均较基线水平明显下降.与正常对照组比较,CPR组和EPO组ROSC 30 min时LVSP(mm Hg,1 mm Hg=0.133 kPa)、+dp/dt max(mm Hg/s)、- dp/dt max绝对值(mm Hg/s)即明显下降(LVSP:119.52±12.68、134.32±15.78比165.82土7.05; +dp/dt max:4 457.14±826.22、6 019.85±1 192.19比10 325.93±773.09; - dp/dt max:-3 956.04±952.37、-4 957.22±838.60比-8 421.33±886.65,均P＜0.01),并持续至ROSC 120 min(LVSP:124.62±8.07、145.61±16.70比162.34±7.63; +dp/dt max:4 977.67±350.40、7 471.62±998.32比9 999.39±727.96;- dp/dt max:-4 145.51±729.77、-5 895.64±787.30比-8 089.75±981.52,均P＜0.01);经EPO处理后ROSC各时间点LVSP、+dp/dtmax和- dp/dtmax绝对值均较CPR组显著升高(均P＜0.05).CPR组和EPO组ROSC 120 min LVEDP(mm Hg/s)均较正常对照组明显升高(22.94±3.94、11.18±2.58比2.89±0.70,均P＜0.01),EPO组LVEDP则较CPR组明显下降(P＜0.05).光镜和电镜下观察,CPR组心肌细胞坏死、炎性细胞浸润,心肌细胞胞膜完整性丧失、线粒体肿胀,心肌细胞凋亡增加[凋亡细胞数(个):314.1±30.7比165.2±45.9,P＜0.01]；经EPO干预后心肌病理损伤减轻,心肌细胞凋亡较CPR组减少(凋亡细胞数:242.1±20.0比314.1±30.7,P＜0.05).CPR组和EPO组ROSC 120 min血清cTnI (μg/L)均较正常对照组明显升高(20.70土5.96、16.98±3.81比2.60±0.86,均P＜0.01),而CPR组和EPO组比较无差异.结论 EPO可以改善窒息性心搏骤停大鼠CPR后的心功能,减轻心肌损伤,其机制可能与减少线粒体损伤和心肌细胞凋亡有关.
目的 探討促紅細胞生成素(EPO)對窒息性心搏驟停大鼠心肺複囌(CPR)後心功能不全的心肌保護作用.方法 經夾閉氣管8 min建立窒息性心搏驟停-CPR動物模型.按隨機數字錶法將24隻SD大鼠分為3組,每組8隻.CPR組窒息緻心搏驟停後8 min予胸外按壓和機械通氣進行複囌；EPO組于自主循環恢複(ROSC)後3 min股靜脈註射EPO 5 kU/kg;正常對照組不予任何處理.持續鑑測左心室收縮壓(LVSP)、左心室舒張期末壓(LVEDP)、左心室內壓上升或下降最大速率(±dp/dt max)等血流動力學指標.于觀察終點(ROSC後120 min)處死大鼠,採血測定血清心肌肌鈣蛋白Ⅰ(cTnI)含量；光鏡和透射電鏡下觀察心肌組織病理改變；原位末耑缺刻標記法(TUNEL)檢測心肌細胞凋亡.結果 CPR組和EPO組ROSC後30、60、90、120 min時LVSP、+dp/dt max和- dp/dt max絕對值均較基線水平明顯下降.與正常對照組比較,CPR組和EPO組ROSC 30 min時LVSP(mm Hg,1 mm Hg=0.133 kPa)、+dp/dt max(mm Hg/s)、- dp/dt max絕對值(mm Hg/s)即明顯下降(LVSP:119.52±12.68、134.32±15.78比165.82土7.05; +dp/dt max:4 457.14±826.22、6 019.85±1 192.19比10 325.93±773.09; - dp/dt max:-3 956.04±952.37、-4 957.22±838.60比-8 421.33±886.65,均P＜0.01),併持續至ROSC 120 min(LVSP:124.62±8.07、145.61±16.70比162.34±7.63; +dp/dt max:4 977.67±350.40、7 471.62±998.32比9 999.39±727.96;- dp/dt max:-4 145.51±729.77、-5 895.64±787.30比-8 089.75±981.52,均P＜0.01);經EPO處理後ROSC各時間點LVSP、+dp/dtmax和- dp/dtmax絕對值均較CPR組顯著升高(均P＜0.05).CPR組和EPO組ROSC 120 min LVEDP(mm Hg/s)均較正常對照組明顯升高(22.94±3.94、11.18±2.58比2.89±0.70,均P＜0.01),EPO組LVEDP則較CPR組明顯下降(P＜0.05).光鏡和電鏡下觀察,CPR組心肌細胞壞死、炎性細胞浸潤,心肌細胞胞膜完整性喪失、線粒體腫脹,心肌細胞凋亡增加[凋亡細胞數(箇):314.1±30.7比165.2±45.9,P＜0.01]；經EPO榦預後心肌病理損傷減輕,心肌細胞凋亡較CPR組減少(凋亡細胞數:242.1±20.0比314.1±30.7,P＜0.05).CPR組和EPO組ROSC 120 min血清cTnI (μg/L)均較正常對照組明顯升高(20.70土5.96、16.98±3.81比2.60±0.86,均P＜0.01),而CPR組和EPO組比較無差異.結論 EPO可以改善窒息性心搏驟停大鼠CPR後的心功能,減輕心肌損傷,其機製可能與減少線粒體損傷和心肌細胞凋亡有關.
목적 탐토촉홍세포생성소(EPO)대질식성심박취정대서심폐복소(CPR)후심공능불전적심기보호작용.방법 경협폐기관8 min건립질식성심박취정-CPR동물모형.안수궤수자표법장24지SD대서분위3조,매조8지.CPR조질식치심박취정후8 min여흉외안압화궤계통기진행복소；EPO조우자주순배회복(ROSC)후3 min고정맥주사EPO 5 kU/kg;정상대조조불여임하처리.지속감측좌심실수축압(LVSP)、좌심실서장기말압(LVEDP)、좌심실내압상승혹하강최대속솔(±dp/dt max)등혈류동역학지표.우관찰종점(ROSC후120 min)처사대서,채혈측정혈청심기기개단백Ⅰ(cTnI)함량；광경화투사전경하관찰심기조직병리개변；원위말단결각표기법(TUNEL)검측심기세포조망.결과 CPR조화EPO조ROSC후30、60、90、120 min시LVSP、+dp/dt max화- dp/dt max절대치균교기선수평명현하강.여정상대조조비교,CPR조화EPO조ROSC 30 min시LVSP(mm Hg,1 mm Hg=0.133 kPa)、+dp/dt max(mm Hg/s)、- dp/dt max절대치(mm Hg/s)즉명현하강(LVSP:119.52±12.68、134.32±15.78비165.82토7.05; +dp/dt max:4 457.14±826.22、6 019.85±1 192.19비10 325.93±773.09; - dp/dt max:-3 956.04±952.37、-4 957.22±838.60비-8 421.33±886.65,균P＜0.01),병지속지ROSC 120 min(LVSP:124.62±8.07、145.61±16.70비162.34±7.63; +dp/dt max:4 977.67±350.40、7 471.62±998.32비9 999.39±727.96;- dp/dt max:-4 145.51±729.77、-5 895.64±787.30비-8 089.75±981.52,균P＜0.01);경EPO처리후ROSC각시간점LVSP、+dp/dtmax화- dp/dtmax절대치균교CPR조현저승고(균P＜0.05).CPR조화EPO조ROSC 120 min LVEDP(mm Hg/s)균교정상대조조명현승고(22.94±3.94、11.18±2.58비2.89±0.70,균P＜0.01),EPO조LVEDP칙교CPR조명현하강(P＜0.05).광경화전경하관찰,CPR조심기세포배사、염성세포침윤,심기세포포막완정성상실、선립체종창,심기세포조망증가[조망세포수(개):314.1±30.7비165.2±45.9,P＜0.01]；경EPO간예후심기병리손상감경,심기세포조망교CPR조감소(조망세포수:242.1±20.0비314.1±30.7,P＜0.05).CPR조화EPO조ROSC 120 min혈청cTnI (μg/L)균교정상대조조명현승고(20.70토5.96、16.98±3.81비2.60±0.86,균P＜0.01),이CPR조화EPO조비교무차이.결론 EPO가이개선질식성심박취정대서CPR후적심공능,감경심기손상,기궤제가능여감소선립체손상화심기세포조망유관.
Objective To examine the effects of EPO administration on the integrity of myocardium in a rat model of asphyxia-induced cardiac arrest/CPR.Methods 24 male Sprague-Dawley (SD) rats were randomly divided into three groups (8 each) to receive (1) cardiac arrest (induced by tracheal catheter clamping for 8 minutes)/CPR (by chest compressions and mechanical ventilation 8 minutes after cardiac arrest),(2) cardiac arrest/CPR+EPO (5 Ku/kg,I.V,3 minutes after restoration of spontaneous circulation (ROSC),and (3) no-treatment (control).The left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP),and maximal positive/negative filling pressure change versus time (士dp/dt max) in the animals were recorded 30,60,90,and 120 minutes after ROSC.Blood and heart tissue samples were collected 120 minutes after ROSC for the examination of serum troponin I (cTnl) level,myocardium pathological change (by light/electronic microscopy),and myocardium apoptosis [by terminal deoxynucleotidyl transferase mediated Dutp-biotin nick endlabeling (TUNEL) stainingl.Results The LVSP,+dp/dt max and - dp/dt max absolute value in CPR group and EPO group were significantly lower than that of baseline at 30,60,90,120 minutes after ROCS.In comparision with the control group,the LVSP (mm Hg,I mm Hg= 0.133 kPa:119.52土 12.68,134.32土 15.78 vs. 165.82士 7.05),+dp/dt max (mm Hg/sec:4 457.14士 826.22,6 019.85士 I 192.19 vs.10 325.93土 773.09),and -dp/dt max (mm Hg/sec:- 3 956.04土 952.37,- 4 957.22± 838.60 vs.- 8 421.33土 886.65) were significant lower (alIP<O.OI) in the CPR and EPO group 30 minutes after ROSC,and such tendency remained till 120 minutes after ROSC:(LVSP:124.62士 8.07,145.61士 16.70 vs. 162.34士 7.63; + dp/dt max:4 977.67土350.40,7 471.62士 998.32 vs. 9 999.39土 727.96; - dp/dt max:- 4 145.51土 729.77,-5 895.64士787.30 vs.- 8 089.75士 981.52).Compared to the CPR group,the value of LVSP,+dp/dt max and - dp/dt max at all time points were significantly higher in EPO group (all P<O.05).The LVEDP value was significantly higher (P<O.01) in both CPR and EPO group in comparison with the control (mm Hg/sec:22.94士3.94,11.18士 2.58 vs.2.89士0.70) 120 minutes after ROSC,and it was significantly lower in EPO group in comparision with CPR group (P<O.05).Light/electronic nucroscopy revealed myocardial necrosis,inflammatory cell infiltration,myocardial cell membrane integrity loss,mitochondrial swelling,and increased number of apoptotic cardiomycocyte (314.1+30.7 vs.165.2土45.9 as in control) in CPR group samples.In contrast,the cardiomycocyte morphologic damages were signi~icantly fewer in EPO group,so is the numbers of apoptotic cardiomycocyte (242.1士 20.O vs.314.1土 30.7,P< 0.05).In comparison with the control,the serum cTnl 120 minutes after ROSC was significantly higher (all P<O.01) in CPR and EPO group (Vg/L:20.70士5.96,16.98士3.81 vs.2.60士 0.86),but no such difference was found between these two groups.Conclusion EPO can attenuate the post resuscitation myocardial injury probably through its mitochondrial protective,anti-apoptotic effect.
