山莨菪碱对心脏骤停大鼠及缺氧/复氧心肌细胞影响的研究
|
摘要
有研究发现,复苏中增加肾上腺素的用量,尽管可以增加心脑灌注压和血液灌流量,但同时可能对心肌和脑组织造成损害,终导致复苏成功率下降。而山莨菪碱(anisodamine,Ani)具有增加冠脉血流量、改善微循环、降低血小板聚集、抑制血栓形成、减轻心肌及脑组织的缺血/再灌注损伤等作用。心肺复苏早期应用Ani干预可能会改善组织的灌注,改善复苏后心肌及脑组织的功能,减轻肾上腺素的负作用,以期提高复苏成功率和改善预后,本研究对山莨菪碱在心肺复苏中的作用进行实验研究以探讨其对缺血心肌细胞的保护作用。
目的在建立一个标准化大鼠心脏骤停及心肺复苏模型基础上,应用盲法给药,观察山莨菪碱对心脏骤停大鼠心肌及脑组织代谢的影响,并进一步从细胞凋亡观察山莨菪碱对缺氧/复氧心肌细胞的作用。
方法实验共4部分:第一部分,成年Sprague-Dawley(SD)大鼠30只,随机分成两组,生理盐水对照组(n=15),肾上腺素组(n=15)。采用交流电生理刺激仪经食道调搏诱发心脏骤停模型,5min后开始心肺复苏,应用自行设计大鼠心脏胸外按压机进行心脏按压。观察心脏骤停类型分布,诱发成功时间,自主循环恢复率及复苏成功率,试验后尸体解剖观察食道及心脏有无灼伤,内脏有无破裂。第二部分,模型操作同第一部分,65只sD大鼠随机分为5组,生理组(n=5)、生理盐水组(n=15)、肾上腺素组(n=15)、肾上腺素联合山莨菪碱组(n=15)、山莨菪碱组(n=15),采用盲法给药,调搏前静脉注射2-[~(18)F]氟-2-脱氧-D-葡萄糖(FDG)0.6ml。复苏后30min内留取部分实验大鼠心脏及脑组织进行放射性计数,留取静脉血送检血浆心房利尿钠肽。第三部分,在第二部分基础上留取存活大鼠脑及心肌组织,检测细胞晚期凋亡及电镜观察线粒体损伤情况。第四部份,细胞培养研究:取乳鼠心室肌细胞培养传一代后分成五组,正常生理对照组、缺氧/复氧组、肾上腺素组、肾上腺素联合山莨菪碱组、山莨菪碱组,缺氧2h/复氧12h,每组至少3瓶细胞。采用流式细胞仪检测缺氧/复氧后的细胞凋亡情况,同时用TUNEL法检测晚期细胞凋亡。RT-PCR法检测心肌细胞M1-3受体亚型的表达。
结果1.所有大鼠均诱发心脏骤停成功,其中心室颤动10例(33.3%),无脉搏电活动15例(50.0%),心电静止5例(16.7%),诱发时间60～150s;自主循环恢复率对照组为6.7%,肾上腺素组为46.6%;复苏成功率对照组为0,肾上腺素组为33.3%。食道粘膜存在轻度灼伤,心脏未见灼伤,食道及腹腔内脏未见破裂。2.肾上腺素联合山茛菪碱组复苏成功率为70%,高于其它各组,其复苏成功率分别为肾上腺素组33.3%、生理盐水组0、山莨菪碱组26.7%(P＜0.01)。肾上腺素复苏成功的心脏和脑组织放射性计数均明显低于肾上腺素联合山莨菪碱组,分别为心脏(25.71±2.83 vs 38.3±7.2,P＜0.05),脑组织(16.06±2.93 vs31.02±2.72,P＜0.05)。肾上腺素联合山莨菪碱组及单纯山茛菪碱组复苏成功大鼠血浆心房利尿钠肽水平明显低于肾上腺素组,分别为(1963.1±1096.7,483.6±205.9vs 4417.6±2235.9,P＜0.05),但均高于生理组(238.3±190.0,P＜0.05)。3.肾上腺素存活组的脑组织凋亡细胞百分数明显多于正常生理对照组及肾上腺素联合山莨菪碱组(8.85±1.2 vs 0.87±0.25,4.25±1.05,P＜0.01),肾上腺素存活组的心肌组织凋亡细胞百分数明显多于正常生理对照组及肾上腺素联合山莨菪碱组(8.15±1.60 vs 2.13±0.65,4.07±1.55,P＜0.01)。肾上腺素联合山莨菪碱组复苏成功大鼠脑及心肌线粒体损伤明显较肾上腺素组轻。4.细胞培养:缺氧2h/复氧12h,肾上腺素组早期凋亡细胞明显高于其他各组(P＜0.01),山莨菪碱组及肾上腺素联合山莨菪碱组早期凋亡细胞低于缺氧/复氧组。肾上腺素组晚期凋亡细胞明显高于山莨菪碱组(P＜0.01),略低于缺氧/复氧组及肾上腺素联合山莨菪碱组,但无统计学意义。RT-PcR检测出心肌细胞M_2受体亚型表达,组间表达相对量无统计学差异。
结论1.经食道交流电调搏可建立稳定可靠的大鼠心脏骤停模型,应用大鼠电动心脏按压机可实现标准化心肺复苏实验要求。2.复苏早期应用山莨菪碱干预可以提高复苏成功率,改善心肌及脑组织的代谢,减轻线粒体的损伤,抑制心肌及脑组织细胞凋亡,对心肺复苏大鼠有保护作用。3.山莨菪碱可减少细胞凋亡,对缺氧/复氧心肌细胞有保护作用。
According to some researches in CPR,the increase of dose of epinephrine could increase cardiac and cerebral perfusion pressure and blood perfusion flow,but it could also do damage to the myocardia and the brain tissues,resulting in the decrease success rate of CPR.anisodamine can increase the coronary blood flow,improve the microcirculation,reduce the aggregation of platelet,prevent the thrombosis,and alleviate the ischemia-reperfusion injury of the myocardia and the brain tissues,etc.In the early stage of CPR the application of anisodamine may improve tissue perfusion, improve the function of cardiac and cerebral tissues,reduce the side-effect of epinephrine,increase the CPR success rate and improve the prognosis.Therefore,the function of anisodamine in CPR was experimented and studied.
Objective To establish a standard rats' cardiac arrest and CPR model for preclinical medicine research,using blind method to deliver the medicine,observe anisodamine's effect on functions of myocardia and brain tissues of rats which suffers from cardiac arrest during CPR,and further observe anisodamine's protection effect on hypoxia/reoxygenation cardiomyocyte in terms of apoptosis.
Methods There were four parts in the experiment.In partⅠ:Thirty Sprague-Dawley(SD) rats were randomly devided 2 groups,the physiological saline control group(n=15) and epinephrine group(n=15).The cardiac arrest model of rats were induced by alternating current(AC) via pacing electrode placed in esophagus. Five minutes after onset of cardiac arrest,CPR was initiated.Cardiac compression was performed by machinery which was made by our group.The types of cardiac arrest:vntricular fibrillation(VF),pulseless electrical activity(PEA),asystole were inspected,duration of the pace,restored of self circulation(ROSC) and success resuscitation were also detected.Necropsy of the esophaguses,the hearts and the organs of the abdominal were performed after the test to see whether the esophagus or the heart were burned and whether the internal organs were broken.In partⅡ65 SD rats were randomly divided to physical group(n=5),physiological saline group(n=15), epinephrine group(n=15),anisodamine and epinephrine combination group(n=15), anisodamine(Ani) group(n=15).We injected 0.6ml FDG before the stimulation.The cardiac arrest rates modle were created and treated as partⅠ.Medicine was given in blind way.The hearts and brain of the rats were removed for radiocounting,and the plasma A-type natriuretic peptide(ANP) were checked.In partⅢ:On the base of partⅡ,apoptosis of cardiamyocytes and brain cells were identified as DNA fragmentation by TUNEL.Mitochondrion were detected by electron microscope.In partⅣwas cell culture study.The ventricular muscle cells of suckling mice were cultured,and after one generation they were divided into 5 groups,normal physiological control group, hypoxia/reoxygenation group,epinephrine group,epinephrine and anisodamine group, anisodamine group,each group hypoxia 2 hours/reoxygenation 12 hours.In each group there were at least 3 bottles of cells.By means of flow cytometry the cells' apoptosis was checked after hypoxia/reoxygenation.Meanwhile,TUNEL method was used to check the non-viable apoptotic cells and the RT-PCR method was used to check the myocardia cell M1-3 receptor subtype expression.
Results 1.All of the rats were induced into cardiac arrest,VF(n=10,33.3%), PEA(n=15,50%),asystole(n=5,16.7%).Duration of the pacing was 60s to 150s. RSOC and success resuscitation rates of the controll group and the epinephrine group were(6.7%vs 0) and(46.6%vs 33.3%) respectively.Necropsy showed that there was no gross evidence of thermal injury on the surface layer of the heart,only mild to moderate thermal injury of the esophagus and no perforation,no rupture of the belly organ.2.The recovery rate of Ani and Epi combination group was higher than that of Epi group and Ani group.The myocardium and the cerebrum radiocounting of the Api recovery group were lower than those of the Ani and Epi combination recovery group, which of the myocardium were(25.71±2.83 vs 38.3±7.2,P＜0.05) and the cerebrum were(16.06±2.93 vs 31.02±2.72,P＜0.05),respectively.The plasma ANP level of the recovery in the Ani and Epi combination group and the Ani group were lower than that of the Epi group(1963.1±1096.7,483.6±205.9 vs 4417.6±2235.9,P＜0.05),but all of these groups were higher than that of the physical group(238.3±190.0,P＜0.05).3.The apoptotic cell percentage of brain tissues of surviving rats in Epi group was much higher than that in normal physiological group and Epi and Ani combination group, which was(8.85±1.2 vs 0.87±0.25,4.25±1.05,P＜0.01).The apoptotic cell percentage of myocardia of surviving rats in Api group was much more than that in normal physiological group and Epi and Ani combination group,which was(8.15±1.60 vs 2.13±0.65,4.07±1.55,P＜0.01).The injury of brain and myocardia mitochondria of rats which experience successful CPR in Epi and Ani combination group was much milder than that in Epi group.4.The cell culture:Reoxygenation 12 hours later,the early apoptotic cells of Epi group were much higher than those of the other groups (P＜0.01).The early apoptotic cells of Api group and Epi and Ani combination group were lower than those of hypoxia/reoxygenation group.The Non-viable apoptotic cells of epinephrine group was much higher than those of Ani group(P＜0.01),and lower than those of hypoxia/reoxygenation group and Epi and Ani combination group, but there's no sense in terms of statistics.RT-PCR checks the myocardia cell M2 receptor subtype expression,which had no statistic differences among the groups.
Conclusions 1.A good cardiac arrest model of rats can induced by alternating current via pacing electrode placed in esophagus.Cardiac compression performed by machinery can give a standard CPR research in the rat.2.Anisodamine is useful in CPR,and can improve metablism ofmyocadium and cerebrum.3.Anisodamine may decrease the apoptosis in hypoxia/reoxygenation myocardium cell,so as to protect the hypoxia/reoxygenation myocardium cell.
目的在建立一个标准化大鼠心脏骤停及心肺复苏模型基础上,应用盲法给药,观察山莨菪碱对心脏骤停大鼠心肌及脑组织代谢的影响,并进一步从细胞凋亡观察山莨菪碱对缺氧/复氧心肌细胞的作用。
方法实验共4部分:第一部分,成年Sprague-Dawley(SD)大鼠30只,随机分成两组,生理盐水对照组(n=15),肾上腺素组(n=15)。采用交流电生理刺激仪经食道调搏诱发心脏骤停模型,5min后开始心肺复苏,应用自行设计大鼠心脏胸外按压机进行心脏按压。观察心脏骤停类型分布,诱发成功时间,自主循环恢复率及复苏成功率,试验后尸体解剖观察食道及心脏有无灼伤,内脏有无破裂。第二部分,模型操作同第一部分,65只sD大鼠随机分为5组,生理组(n=5)、生理盐水组(n=15)、肾上腺素组(n=15)、肾上腺素联合山莨菪碱组(n=15)、山莨菪碱组(n=15),采用盲法给药,调搏前静脉注射2-[~(18)F]氟-2-脱氧-D-葡萄糖(FDG)0.6ml。复苏后30min内留取部分实验大鼠心脏及脑组织进行放射性计数,留取静脉血送检血浆心房利尿钠肽。第三部分,在第二部分基础上留取存活大鼠脑及心肌组织,检测细胞晚期凋亡及电镜观察线粒体损伤情况。第四部份,细胞培养研究:取乳鼠心室肌细胞培养传一代后分成五组,正常生理对照组、缺氧/复氧组、肾上腺素组、肾上腺素联合山莨菪碱组、山莨菪碱组,缺氧2h/复氧12h,每组至少3瓶细胞。采用流式细胞仪检测缺氧/复氧后的细胞凋亡情况,同时用TUNEL法检测晚期细胞凋亡。RT-PCR法检测心肌细胞M1-3受体亚型的表达。
结果1.所有大鼠均诱发心脏骤停成功,其中心室颤动10例(33.3%),无脉搏电活动15例(50.0%),心电静止5例(16.7%),诱发时间60～150s;自主循环恢复率对照组为6.7%,肾上腺素组为46.6%;复苏成功率对照组为0,肾上腺素组为33.3%。食道粘膜存在轻度灼伤,心脏未见灼伤,食道及腹腔内脏未见破裂。2.肾上腺素联合山茛菪碱组复苏成功率为70%,高于其它各组,其复苏成功率分别为肾上腺素组33.3%、生理盐水组0、山莨菪碱组26.7%(P＜0.01)。肾上腺素复苏成功的心脏和脑组织放射性计数均明显低于肾上腺素联合山莨菪碱组,分别为心脏(25.71±2.83 vs 38.3±7.2,P＜0.05),脑组织(16.06±2.93 vs31.02±2.72,P＜0.05)。肾上腺素联合山莨菪碱组及单纯山茛菪碱组复苏成功大鼠血浆心房利尿钠肽水平明显低于肾上腺素组,分别为(1963.1±1096.7,483.6±205.9vs 4417.6±2235.9,P＜0.05),但均高于生理组(238.3±190.0,P＜0.05)。3.肾上腺素存活组的脑组织凋亡细胞百分数明显多于正常生理对照组及肾上腺素联合山莨菪碱组(8.85±1.2 vs 0.87±0.25,4.25±1.05,P＜0.01),肾上腺素存活组的心肌组织凋亡细胞百分数明显多于正常生理对照组及肾上腺素联合山莨菪碱组(8.15±1.60 vs 2.13±0.65,4.07±1.55,P＜0.01)。肾上腺素联合山莨菪碱组复苏成功大鼠脑及心肌线粒体损伤明显较肾上腺素组轻。4.细胞培养:缺氧2h/复氧12h,肾上腺素组早期凋亡细胞明显高于其他各组(P＜0.01),山莨菪碱组及肾上腺素联合山莨菪碱组早期凋亡细胞低于缺氧/复氧组。肾上腺素组晚期凋亡细胞明显高于山莨菪碱组(P＜0.01),略低于缺氧/复氧组及肾上腺素联合山莨菪碱组,但无统计学意义。RT-PcR检测出心肌细胞M_2受体亚型表达,组间表达相对量无统计学差异。
结论1.经食道交流电调搏可建立稳定可靠的大鼠心脏骤停模型,应用大鼠电动心脏按压机可实现标准化心肺复苏实验要求。2.复苏早期应用山莨菪碱干预可以提高复苏成功率,改善心肌及脑组织的代谢,减轻线粒体的损伤,抑制心肌及脑组织细胞凋亡,对心肺复苏大鼠有保护作用。3.山莨菪碱可减少细胞凋亡,对缺氧/复氧心肌细胞有保护作用。
According to some researches in CPR,the increase of dose of epinephrine could increase cardiac and cerebral perfusion pressure and blood perfusion flow,but it could also do damage to the myocardia and the brain tissues,resulting in the decrease success rate of CPR.anisodamine can increase the coronary blood flow,improve the microcirculation,reduce the aggregation of platelet,prevent the thrombosis,and alleviate the ischemia-reperfusion injury of the myocardia and the brain tissues,etc.In the early stage of CPR the application of anisodamine may improve tissue perfusion, improve the function of cardiac and cerebral tissues,reduce the side-effect of epinephrine,increase the CPR success rate and improve the prognosis.Therefore,the function of anisodamine in CPR was experimented and studied.
Objective To establish a standard rats' cardiac arrest and CPR model for preclinical medicine research,using blind method to deliver the medicine,observe anisodamine's effect on functions of myocardia and brain tissues of rats which suffers from cardiac arrest during CPR,and further observe anisodamine's protection effect on hypoxia/reoxygenation cardiomyocyte in terms of apoptosis.
Methods There were four parts in the experiment.In partⅠ:Thirty Sprague-Dawley(SD) rats were randomly devided 2 groups,the physiological saline control group(n=15) and epinephrine group(n=15).The cardiac arrest model of rats were induced by alternating current(AC) via pacing electrode placed in esophagus. Five minutes after onset of cardiac arrest,CPR was initiated.Cardiac compression was performed by machinery which was made by our group.The types of cardiac arrest:vntricular fibrillation(VF),pulseless electrical activity(PEA),asystole were inspected,duration of the pace,restored of self circulation(ROSC) and success resuscitation were also detected.Necropsy of the esophaguses,the hearts and the organs of the abdominal were performed after the test to see whether the esophagus or the heart were burned and whether the internal organs were broken.In partⅡ65 SD rats were randomly divided to physical group(n=5),physiological saline group(n=15), epinephrine group(n=15),anisodamine and epinephrine combination group(n=15), anisodamine(Ani) group(n=15).We injected 0.6ml FDG before the stimulation.The cardiac arrest rates modle were created and treated as partⅠ.Medicine was given in blind way.The hearts and brain of the rats were removed for radiocounting,and the plasma A-type natriuretic peptide(ANP) were checked.In partⅢ:On the base of partⅡ,apoptosis of cardiamyocytes and brain cells were identified as DNA fragmentation by TUNEL.Mitochondrion were detected by electron microscope.In partⅣwas cell culture study.The ventricular muscle cells of suckling mice were cultured,and after one generation they were divided into 5 groups,normal physiological control group, hypoxia/reoxygenation group,epinephrine group,epinephrine and anisodamine group, anisodamine group,each group hypoxia 2 hours/reoxygenation 12 hours.In each group there were at least 3 bottles of cells.By means of flow cytometry the cells' apoptosis was checked after hypoxia/reoxygenation.Meanwhile,TUNEL method was used to check the non-viable apoptotic cells and the RT-PCR method was used to check the myocardia cell M1-3 receptor subtype expression.
Results 1.All of the rats were induced into cardiac arrest,VF(n=10,33.3%), PEA(n=15,50%),asystole(n=5,16.7%).Duration of the pacing was 60s to 150s. RSOC and success resuscitation rates of the controll group and the epinephrine group were(6.7%vs 0) and(46.6%vs 33.3%) respectively.Necropsy showed that there was no gross evidence of thermal injury on the surface layer of the heart,only mild to moderate thermal injury of the esophagus and no perforation,no rupture of the belly organ.2.The recovery rate of Ani and Epi combination group was higher than that of Epi group and Ani group.The myocardium and the cerebrum radiocounting of the Api recovery group were lower than those of the Ani and Epi combination recovery group, which of the myocardium were(25.71±2.83 vs 38.3±7.2,P＜0.05) and the cerebrum were(16.06±2.93 vs 31.02±2.72,P＜0.05),respectively.The plasma ANP level of the recovery in the Ani and Epi combination group and the Ani group were lower than that of the Epi group(1963.1±1096.7,483.6±205.9 vs 4417.6±2235.9,P＜0.05),but all of these groups were higher than that of the physical group(238.3±190.0,P＜0.05).3.The apoptotic cell percentage of brain tissues of surviving rats in Epi group was much higher than that in normal physiological group and Epi and Ani combination group, which was(8.85±1.2 vs 0.87±0.25,4.25±1.05,P＜0.01).The apoptotic cell percentage of myocardia of surviving rats in Api group was much more than that in normal physiological group and Epi and Ani combination group,which was(8.15±1.60 vs 2.13±0.65,4.07±1.55,P＜0.01).The injury of brain and myocardia mitochondria of rats which experience successful CPR in Epi and Ani combination group was much milder than that in Epi group.4.The cell culture:Reoxygenation 12 hours later,the early apoptotic cells of Epi group were much higher than those of the other groups (P＜0.01).The early apoptotic cells of Api group and Epi and Ani combination group were lower than those of hypoxia/reoxygenation group.The Non-viable apoptotic cells of epinephrine group was much higher than those of Ani group(P＜0.01),and lower than those of hypoxia/reoxygenation group and Epi and Ani combination group, but there's no sense in terms of statistics.RT-PCR checks the myocardia cell M2 receptor subtype expression,which had no statistic differences among the groups.
Conclusions 1.A good cardiac arrest model of rats can induced by alternating current via pacing electrode placed in esophagus.Cardiac compression performed by machinery can give a standard CPR research in the rat.2.Anisodamine is useful in CPR,and can improve metablism ofmyocadium and cerebrum.3.Anisodamine may decrease the apoptosis in hypoxia/reoxygenation myocardium cell,so as to protect the hypoxia/reoxygenation myocardium cell.
引文
1.Brown CG,Werman HA,Davis EA,et al.The effects of graded doses of epinephrineon regional myocardial blood flow during cardiopulmonary resuscitation in swine[J].Circulation,1987,75(2):491-497.
2.Berg RA,Otto CW,Kern KB,et al.High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs:a prospective,randomized study[J].Ctit Care Med,1994,22(2):282-290.
3.卢玉平.大剂量肾上腺素用于心肺复苏的争议[J].国外医学麻醉学与复苏分册,1995,16(6):355-358.
4.刘晓亮,邢吉红,马涤辉,等.心肺复苏期间肾上腺素剂量对兔脑复苏的影响[J].中华急诊医学杂志,2003,12(10):681-683.
5.陈习进,王化忠,宋德根,等.大剂量肾上腺素用于心脏复苏(附3例报告)[J].陕西医学杂志,1994,23(6):324-326.
6.李士玉,马玉玲,李治红,等.东莨菪碱对心肺复苏后急性脑缺血-再灌流损伤的保护作用[J].中华急诊医学杂志,2003,12(1):38-39.
7.Ching LL,Williams AJ,Sitsapesan R.Evidence for Ca~(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex[J].Circ Res,2000,87:201-206.
8.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
9.Duilio C,Ambrosio G,Kuppusamy P.Neutrophils are the primary source of O_2radicals during reperfusion after prolonged myocardial ischemia[J].Am J Physiol Heart Circ Phyiol,2001,280:2649-2657.
10.黄子通,方向韶.心肺复苏动物模型的标准化问题[J.中华急诊医学杂志,2009,18(1):11-13.
11.陈蒙华,谢露,宋凤卿,等.小鼠心搏骤停动物模型的建立[J].中国急救医学,2005,25(12):897-898.
1.Boddicker KA,Yi Z,Zimmerman MB,et al.Hypothermia improve defibrillation success and resuscitation outcomes from venticular fibrillation[J].Circulation,2005,111(24):3195-3201.
2.Fisher M,B(o|¨)ttiger BW,Hossmann KA,et al.Thrombolysis using plasminogen activator and heparin reduces cerebral n flow after resuscitation from cardiac arrest:an experiment study in the cat[J].Intensive Care Med,1996,22(11):1214-1223.
3.陈蒙华,刘唐威,谢露,等.老龄大鼠心室颤动模型的建立[J].中华老年心脑血管病杂志,2006,8(3):208.
4.Mayr VD,Wenzel V,Voelckel WG,et al.Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest[J].Circulation,2001,104(14):1651-656.
5.王学斌,杨兴易,林兆奋,等.心肺复苏后大鼠肾脏损伤的实验研究[J.中国急救医学,2006,26(6):435-434.
6.Abella BS,Zhao D,Alvarado J,et al.Intra-arrest cooling improves outcomes in a murine cardiac arrest model[J].Circulation,2004,109(22):2786-2791.
7.Eisenberg MS,Horwood BT,Cummins RO,et al.Cardiac arrest and resuscitation:A tale of 29 cities[J].Ann Emerg Med,1990,19(2):179-186.
8.Wann Sr SR,Weil MH,Sun S,et al.Pharmacologic defibrilation[J].Crit Care Med,2002,30(4):S154-156.
9.Krep H,Brinker G,Schwindt W,et al.Endothelin type A-antagonist improves long-term meurological recovery after cardiac arrest in rats.Crit Care Med[J],2000,28(8):2873-2880.
10.Leonov Y,Sterz F,Safar P,et al.Moderate hypothermia after cardiac arrest of 17minutes in dogs.Effect on cerebral and cardiac outcomes[J].Stroke,1990,21(11):1600-1606.
11.Yarbrouph WM,Spinale FG.Large animal models of congestive failure:a Critical step in translating basic observation into clinical application[J].J Nucl Cardiol,2003,10(1):77-86.
12.Schmitz B,Fisscher M,Bockhorst K,et al.Resuscitation from cardiac arrest in cats:influence of epinephrine dosage on brain recovery[J].Resuscitation,1995,30:251-262.
13.Krep H,B(o|¨)ttiger BW,Bock C,et al.Time course of circulatory and metabolic recovery of cat brain after cardiac arrest assessed by perfusion and diffusion weighted imaging and MR-spectroscopy[J].Resuscitation,2003,58(5):337-348.
14.康州军,余猛进,梅冰,等.东菱克魅栓酶在心脏骤停兔心肺复苏时的治疗作用[J].中国急救医学,2005,25(2):114-115.
15.Chen MH,Liu TW,Xie L,et al.A comparison of tansossphageal cardiac arrest pacing and epinephrine for cardiopulmonary resuscitation.Am J Emerg[J],2006,24(5)545-552.
16.Bottiger BW,Krumnikl JJ,Gass P,et al.The cerebral 'no flow' phenomenon after cardiac arrest in rats-influence of low-flow reperfusion[J].Resuscitation,1997,34(1):79-87.
17.Bottiger BW,Schmitz B,Wiessner C,et al.Nueronal stress response and neuronal cell damage after cardiocirculatory arrest in rats[J].J Cereb Flow Metab,1998,18(10):1077-1087.
18.Vogel P,Putten H,Popp E,et al.Improved resuscitation.after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons[J].Anesthesiology,2003,99(1):112-121.
19.陈蒙华,谢露,宋凤卿,等.小鼠心搏骤停动物模型的建立[J].中国急救医学,2005,25(12):897-898.
20.Chen MH,Liu TW,Xie L,et al.A Simpler Cardiac Arrest Model in Rats[J].Am J Emerg Med,2007,25(1):623-630.
21.von Planta I,Weil MH,von Planta H,et al.Cardiopulmonary resuscitation in the rat[J].J Appl Physiol,1988,65(6):2641-2647.
22.Wann Sr SR,Weil MH,Sun S,et al.Pharmacologic defibrilation[J].Crit Care Med,2002,30(4):S154-156.
23.Song L,Weil MH,Tang W,et al.Cardiopulmonary resuscitation in mouse[J].J Appl Physiol,2002,93(4):1222-1226.
24.黄子通 方向韶.心肺复苏动物模型的标准化问题[J].中华急诊医学杂志,2009,18(1):11-13.
25.Idis AH,Becker LB,Ornanto JP,et al.Ustein-Style guideline for uniform reporting of laboratory CPR research[J].Circulation,1996,94(9):2324-2336.
1.Berg RA,Otto CW,Kern KB,et al.High dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs:a prospective,randomized study[J].Ctit Care Med,1994,22(2):282-290.
2.卢玉平.大剂量肾上腺素用于心肺复苏的争议[J].国外医学麻醉学与复苏分册,1995,16(6):355-358.
3.刘晓亮,邢吉红,马涤辉,等.心肺复苏期间肾上腺素剂量对兔脑复苏的影响[J].中华急诊医学杂志,2003,12(10):681-683.
4.李士玉,马玉玲,李治红,等.东莨菪碱对心肺复苏后急性脑缺血.再灌流损伤的保护作用[J.中华急诊医学杂志,2003,12(1):38-39.
5.贾立静,陈威,沈洪,等.山莨菪碱对心脏停搏大鼠复苏中微循环的影响[J].中国危重病急救医学,2008,20(12):737-739.
6.李天然,临床PET/CT诊断学(第一版)[M.北京:人民军医出版社,2007,43-99.
7.周代星,邓普珍.山莨菪碱对急性完全性脑缺血-再灌注后脑组织Ca~(2+)、SOD 活性及超微结构的影响[J.急诊医学,1998,7:32.
8.张宏图.山莨菪碱治疗重型颅脑损伤合并神经源性肺水肿疗效观察[J].中国全科医学,2006,9:836.
9.蒋崇慧,候德仁,汤彦,等.脑缺血预处理联合山莨菪碱对大鼠脑缺血-再灌注损伤的保护作用[J].中国急救医学,2002,22:26.
10.邓普珍.重视山莨菪碱的脑保护机制在临床心肺复苏中的应用[J].中华急诊医学杂志,2003,12:344.
11.汤彦,杨光田,蒋崇慧,等.山莨菪碱在大鼠急性全脑缺血再注损伤中对一氧化氮、内皮素-1及能量代谢的影响[J.中国急救医学,2000,20:4.
12.杨国栋主编.微循环障碍与莨菪碱类药物的临床应用(第二版)[M].北京:人民卫生出版社,1999,98.
13.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
14.俞长兴,肖蓬,苏志红,等.山莨菪碱类药物临床应用评价[J].中国医院用药评价与分析,2002,2:208-210.
15.许翔,鲍颖霞,李庆平.山莨菪碱对大鼠肠系膜微循环及产时宫颈水肿微循环的影响[J.中国现代医学杂志,2002,12(24):5-7.
16.占成业,邓普珍.山莨菪碱对乳鼠急性全脑缺血-再灌注损伤期间兴奋性氨基酸释放及生存状况的影响[J].中国急救医学,1999,19:3.
17.Ching LL,Williams AJ,Sitsapesan R.Evidence for Ca~(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex[J].Circ Res,2000,87:201-6.
18.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
19.Duilio C,Ambrosio G,Kuppusamy P.Neutrophils are the primary source of O_2radicals during reperfusion after prolonged myocardial ischemia[J].Am J Physiol Heart Circ Phyiol,2001,280:2649-2657.
20.蔡锡腾.实用微循环学[M.中国医药科技出版社,1990,84.
21.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
22.金芳.山莨菪碱对缺钙复钙所致内皮细胞损伤的保护作用[J].中国病理生理学杂志,1992,8:328.
23.刘书勤,臧伟进,李增利,等.电压激活的钾通道阻断剂抑制山莨菪碱松弛去甲肾上腺素预收缩的兔主动脉平滑肌[J].生理学报,2005,57:21-26.
24.Gueugniaud PY,Dubien PY,David JS,et al.Epinephrine and outcome of cardiac arrest[J].Current Opinion in Critical Care,2000,6(3):196-199.
25.Parasis NA,Wenzel V,Southall J.Pressor drugs in the treatment of cardiac arrest[J].Cardiol Clin,2002,20(1):61-78.
26.Timothy K,Kerry K,Shadi V,et al.Innovative pharmacologic approaches to cardiopulmonary resuscitation[J].Heart Disease,2001,3(1):46-541.
27.Brown CG,Martin DR,Pepe PE,et al.A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital.The Multicenter High-DoseEpinephrine Study Group[J].New Engl J Med,1992,327(15):051-5.
28.Stiell IG,Hebert PC,Weitzman BN,et al.High-dose epinephrine in adult cardiacarrest[J].New Engl J Med,1992,27(15):1045-50.
29.Meyer M,Schulz Knappe P,Kuse ER,et al.Urodilatin,use of new peptide in intensive care[J].Anaesthetist,1995,44(2):81-91.
30.Meyer M,Stief CG,Becker AJ,et al.The renal paracrine peptide system-possible urologic implications of urodilatin[J].World J Urol,1996,14(6):375-379.
31.Levin ER,Gardner DG,Samson WK.Natriuretic peptide[J].New Engl J Med,1998,339(5):321-328.
32.Melo LG,Pang SC,Ackermann V.Atrial natriuretic peptides:Regulator of chronic arterial blood pressure[J].News Physiol Sci,2000,15(1):143-149.
33.Maria AC,Laura VGB,Monica PM.Atrial natriuretic peptides modifies arterial blood pressure through nitric oride pathway in rata[J].Hypertension,2000,35:1119-1125.
34.Hoiks G,Thomson NC.High dose inhaled arterial blood pressure is a bronchodilator in asthmatic subjects[J].Eur Respir,1994,7(9):1593-1597.
35. Robichaud A,Michoad MC,Hanmet P,et al.Plasma arterial blood pressure during spontanooes bronchoconstriction in asthmatics[J].Peptides,1995,16(4):653-656.
36.Lin YX,Zhang BF,Qi HW,et al.Influences of intravenous infusion of cardionatrin on TNF-a,IL-8 and ET-1 contents in blood and bronchioalveolar lavage fluid of rabbits with acute lung injury induced by oleic acid[J].J Fourth Mil Med Univ,2001,22(15):1395-1397.
37.Gerdts EW,achtell K,Omvik P,et al.Left atrial size and risk of major cardiovascular events during antihypertensive treatment losartan intervention for,endpoint reduction in hypertension trial[J].Hypertension,2007,49(2):311-316.
38.Munagala VK,Burnett JC,Redfield MM.The natriuretic peptides in cardiovascul-ar medicine[J].Curr Probl Cardiol,2004,29(12):707-769.
1.Crow MT,Mani K,Nam YJ,et al.The mitochondrial death pathway and cardiac myocyte apoptosis[J].Circ Res,2004,95(10):957-970.
2.唐燕华,陈朋,胡大仁,等.山莨菪碱心肌保护作用的临床研究[J].中国危重病急救医学,2001,13(10):603-605.
3.Fngit MD,Rnbal BJ,Donovan KJ.Effects of intracoronary nicardipine,diltiazem and veraparmil on coronary blood flow[J].J Invasive Cardiol,2000,12:80-85.
4.扬军.山莨菪碱对缺血心肌保护作用[J].中国病理生理杂志,1992,8:330.
5.蔡锡腾.实用微循环学[M.中国医药科技出版社,1990,84.
6.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
7.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
8.Mott JI,Zhang D,Freeman JC,et al.Cardiac disease due to random mitochondrial DNA mutations is prevented by cyclosporin A[J].Biochem Biophys Res Commun,2004,319(4):1210-1215.
9.Clarke SJ,Mcstay GP,Halestrap AP,et al.Sanglifehrin A acts as a potent inhibitor of the mitochondrialpermeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A[J].J Biol Chem,2002,277(38):34793-34799.
10.Akao M,O Rourke B,Kusuoka H,et al.Differential actions of cardioprotective agents on the mitoehondrial death pathway[J].Circ Res,2003,92(2):195-202.
11.Avkiran M,Gross G,Karmazyn M,et al.Na~+/H~+exchange in ischemia,reperfusion and preconditioning[J].Cardiovasc Res,2001,50(1):162-166.
12.Lim KH,Halestrap AP,Angelini GD,et al.Propofol is cardioprotective in a clinically relevant model of norulotherulic blood cardioplegic arrest and cardiopulmonary bypass[J].Exp Biol Med,2005,230(6):413-420.
13.Maulik M,Maulik SK,Kumarir.Importance of timing of magnesium administration:a study on the isolated ischemic-repeffused rat heart[J].Magnes Res,1999,12(1):37-42.
14.Ruiz M,Pinnap,Garcia D,et al.Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition[J].J Physiol,2004,558(3):873-882.
15.Rosenfeldt F,Marascos,Lyon W,et al.Coenzyme Q1 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial[J].J Thorac Cardiovasc Surg,2005,129(1):25-32.
16.Hayakawa Y,Chandra M,Miao W,et al.Inhibition of Cardiac Myocyte Apoptosis Improves Cardiac Function and Abolishes Mortality in the Peripartum Cardiomyopathy of Transgenic Mice[J].Circulation,2003,108(24):3036-3041.
17.Fujimura H,Kambyshi JI,Mondem M,et al.Coagulation factor V leidenmutation may have a racial background[J].Throm Haem,1995,74:1381.
18.周代星,邓普珍.山莨菪碱对急性完全性脑缺血.再灌注后脑组织Ca~(2+)、SOD 活性及超微结构的影响[J].急诊医学,1998,7:32.
19.张宏图.山莨菪碱治疗重型颅脑损伤合并神经源性肺水肿疗效观察[J].中国全科医学,2006,9:836.
20.蒋崇慧,候德仁,汤彦,等.脑缺血预处理联合山莨菪碱对大鼠脑缺血-再灌注损伤的保护作用[J.中国急救医学,2002,22:26.
21.邓普珍.重视山莨菪碱的脑保护机制在临床心肺复苏中的应用[J].中华急诊医学杂志,2003,12:344.
22.汤彦,杨光田,蒋崇慧,等.山莨菪碱在大鼠急性全脑缺血再注损伤中对一氧化氮、内皮素-1及能量代谢的影响[J].中国急救医学,2000,20:4.
23.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
1.Freude B,Masters TN,Robicsek F,et al.Apoptosis is initiated by myocardial ischemia and executed during reperfusion[J].J Mol Cell Cardiol,2000,32(2):197-208.
2.Yaoita H,Ogawa K,Maehara K,et al.Apoptosis in relevant clinical situations:contribution of apoptosis in myocardial infarction[J].Cardiovasc Res,2000,45(3):630-41.
3.Kajstura J,Cheng W,R.eiss K,et al.Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats[J].Lab Invest,1996,74:86-107.
4.Musat-Marcu S,Gunter HE,Jugdutt BI,et al.Inhibition of apoptosis after ischemia reperfusion in rat myocardium by cycloheximide[J].J Mol Cell Cardiol,1999,31:1073-1082.
5.Xin L,Sanjay Kumar,Feng Gao,et al.Inhibition of p38 Mitogen-Activated Protein Kinase Decreases Cardiomyocyte Apoptosis and Improves Cardiac Function After Myocardial Ischemia and Reperfusion[J].Circulation,1999,99:1685-1691.
6.Yaoita H,Ogawa K,Maehara K,et al.Attenuation of ischemia/reperfusion injury in rats by caspase inhibitor[J].Circulation,1998,97:276-281.
7.占成业,邓普珍.山莨菪碱对乳鼠急性全脑缺血-再灌注损伤期间兴奋性氨基酸释放及生存状况的影响[J].中国急救医学,1999,19:3.
8.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
9.周喜春,牛蕴蕴,梁学颖,等.早期凋亡的流式细胞术分析[J].军医进修学院学报,2004,25(1):10-11.
10.王珊,李宁,于力,等.流式细胞术检测细胞凋亡比较研究[J.标记免疫分析与临床,2005,12(3):8-10.
11.Gueugniaud PY,Dubien PY,David JS,et al.Epinephrine and outcome of cardiac arrest[J].Current Opinion in Critical Care,2000,6(3):196-199.
12.Parasis NA,Wenzel V,Southall J.Pressor drugs in the treatment of cardiac arrest[J].Cardiol Clin,2002,20(1):61-78.
13.俞长兴,肖蓬,苏志红,等.山莨菪碱类药物临床应用评价[J].中国医院用药评价与分析,2002,2:208-210.
14.Timothy K,Kerry K,Shadi V,et al.Innovative pharmacologic approaches to cardiopulmonary resuscitation[J].Heart Disease,2001,3(1):46-541.
15.Brown CG,Martin DR,Pepe PE,et al.A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital.The Multicenter High-Dose Epinephrine Study Group[J].N Engl J Med,1992,327(15):1051-5.
16.Stiell IG,Hebert PC,Weitzrnan BN,et al.High-dose epinephrine in adult cardiacarrest[J].N Engl J Med,1992,327(15):1045-50.
17.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
18.蔡锡腾.实用微循环学[M].中国医药科技出版社,1990,84.
19.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
20.金芳.山莨菪碱对缺钙复钙所致内皮细胞损伤的保护作用[J].中国病理生理学杂志,1992,8:328.
21.Gavrieli Y,Sherman Y,Ben-Sasson SA.Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation[J].J Cell Biol,1992,119:493-501.
22.Wijsman JH,Jonker RR,Keijzer R,et al.A new method to detect apoptosis in paraffin sections:In situ end labeling of fragmented DNA[J].J Histochem Cytochem,1993,41:7-12.
23.Eschenhagen T,Mende U,Diederich M,et al.Chronic treatment with carbachol sensitizes the myocardium to cAMP induced arrhythmial[J].Circulation,1996,93:7632-7711.
24.Matsui S,Fu ML,Hayase M,et al.Beneficial effect of muscarinic antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic receptor[J].J Cardiovasc Pharmacol,2001,38(Suppl 1):S432-S491.
25.Ponicke K,Heinroth-Hoffmann I,Brodde OE.Demonstration of functional M3-muscarinic receptor in ventricular cardiomyocytes of adult rats[J].Br J Pharmacol,2003,138(1):156-160.
26.Krejci A,Tucek S.Quantitation of mRNAs for M(1) to M(5) subtypes of muscarinic receptors in rat heart and brain cortex[J].Mol Pharmacol,2002,61(6):1267-1272.
27.胥晓丽,藏伟进,康新勤,等.大鼠心房与心室胆碱能神经和M_2受体的分布比较[J].南方医科大学学报,2006,26(8):1096-1110.
28.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
29.扬军.山莨菪碱对缺血心肌保护作用[J].中国病理生理杂志,1992,8:330.
30.刘振国,姚秀娟,李小强,等.山莨菪碱抑制成年大鼠离体心室肌细胞钙瞬变和收缩及其机制[J].中国临床药理学与治疗学,2005,10(6):645-650.
1.Takemura G,Fujivara H.Role of apoptosis in remodeling after myocardial infarction[J].Pharmacol Ther,2004,104(1):1204-1212.
2.Zhang T,Brown JH.Role of Ca~(2+)/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure[J].Cardiovasc Res,2004,63(3):476-486.
3.Crow MT,Mani K,Nam YJ,et al.The mitochondrial death pathway and cardiac myocyte apoptosis[J].Circ Res,2004,95(10):957-970.
4.Morin D,Pires F,Plin C,et al.Role of the permeability transition pore in cytochrome C release from mitochondria during ischemia-reperfusion in rat Hver[J].Biochem Pharmacol,2004,68(10):2065-2073.
5.Nakagawa T,Shimizu S,Watanabe T,et al.Cyclophilin dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death[J].Nature,2005,434(7033):652-658.
6.Varga E,Nagy N,Lazar J,et al.Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts:the role of cytochrome C release[J].Life Sci,2004,75(20):2411-2423.
7.Czerski I,Nunez G.Apoptosome formation and caspase activation:is it different in the heart[J].J Mol Cell Cardiol,2004,37(3):643-652.
8.Gurevich RM,Regula KM,Kirshenbaum LA,et al.Serpin protein CrmA suppresses hypoxia-mediated apoptosis of ventricular myocytes[J].Circulation,2001,103(15):1984-1991.
9.Hayakawa Y,Chandra M,Miao W,et al.Inhibition of Cardiac Myocyte Apoptosis Improves Cardiac Function and Abolishes Mortality in the Peripartum Cardiomyopathy of Transgenic Mice[J].Circulation,2003,108(24):3036-3041.
10. Mott JI,Zhang D,Freeman JC,et al.Cardiac disease due to random mitochondrial DN A mutations is prevented by cyclosporin A[J].Biochem Biophys Res Commun,2004,319(4):1210-1215.
11.Guaiquil VH,Golde DW,Beckles DI,et al.A VitaminC inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts[J].Free Radlic Biol Med,2004,37(9):1419-1429.
12.Scarabelli TM,Stephanou A,Pasini E,et al.Minocycline inhibits caspase activation and reactivation,increases the ratio of XIAP to smac/DIABLO,and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO[J].J Am Coil Cardiol,2004,43(5):865-874.
13.Rajesh KG,Sasaguri S,Suzuki R,et al.Ischemic preconditioning prevents reperfusion heart injury in cardiac hypertrophy by activation ofmitochondrial K_(ATP) channels[J].Int J Cardiol,2004,96(1):41-49.
14.曾源,龙超良,李艳芳,汪海.开放线粒体K_(ATP)通道对心肌细胞氧化应激损伤的保护作用[J].中国临床药理学与治疗学,2006,11(7):806-809.
15.Oldenburg O,Cohen MV,YeHon DM,Downey JM.Mitochondrial K~+ channels:role in cardioprotection[J].Cardiovasc Res,2002,55:429-437.
16.Ardehali H,O'Rourke B.Mitochondrial K~+ channels in cell survival and death[J].J Mol Cell Cardiol,2005,39:7-16.
17.Sato T,Sasaki N,Seharaseyon J,et al.Selective pharmacological agents implicate mitoehondrial but not saycolemmal K~+ channels in ischemic cardioprotecion[J].Circulation,2000,101:2418-2423.
18.Liu Rongguo,Wang Weijian,Song Na,et al.Dilazoxide preconditioning alleviates apoptosis of hippocampal neurons induced by noxia-reoxygenaticon in vitro thro -ugh up regulation of bcl-2/Bax protein ratio[J].Acta Physiologica Sinica,2006,58(4):345.
19.黄河,肖颖彬,杨天德,等.线粒体K_(ATP)通道开放剂对培养大鼠心肌细胞缺血/再灌注损伤心肌线粒体的保护作用[J].重庆医学,2008,53(37):479-483.
20.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
21.唐燕华,陈朋,胡大仁,等.山莨菪碱心肌保护作用的临床研究[J].中国危重病急救医学,2001,13(10):603-605.
22.Fujimura H,Kambyshi JI,Mondem M,et al.Coagulation factor V leidenmutation may have a racial background[J].Throm Haem,1995,74:1381.
23.刘中民,张轶,范慧敏,等.东莨菪碱在心肌再灌注损伤中的作用[J].同济大学学报(医学版),2002,23(2):86-89.
24.Clarke SJ,Mcstay GP,Halestrap AP,et al.Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A[J].J Biol Chem,2002,277(38):34793-34799.
25.Akao M,O Rourke B,Kusuoka H,et al.Differential actions of cardioprotective agents on the mitoehondrial death pathway[J].Circ Res,2003,92(2):195-202.
26.Avkiran M,Gross G,Karmazyn M,et al.Na~+/H~+exchange in ischemia,reperfusion and preconditioning[J].Cardiovasc Res,2001,50(1):162-166.
27.Lim KH,Halestrap AP,Angelini GD,et al.Propofol is cardioprotective in a clinically relevant model of norulotherulic blood cardioplegic arrest and cardiopulmonary bypass[J].Exp Biol Med,2005,230(6):413-420.
28.Maulik M,Maulik SK,Kumarir.Importance of timing of magnesium administration:a study on the isolated ischemic-repeffused rat heart[J].Magnes Res,1999,12(1):37-42.
29.Ruiz M,Pinnap,Garcia D,et al.Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition[J].J Physiol,2004,558(3):873-882.
30.Rosenfeldt F,Marascos,Lyon W,et al.Coenzyme Q1 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial[J].J Thorac Cardiovasc Surg,2005,129(1):25-32.
31.Hausenloy D J,Maddock HL,Baxter GF,et al.Inhibiting mitochondrial permeability transition pore opening:a new paradigm for myocardial preconditioning[J].Cardiovasc Res,2002,55(3):534-543.
32.Javadov SA,Clarke S,Das M,et al.Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart[J].J Physiol,2005,549(2):513-524.
33.Vinten J,Yellon DM,Opie LH.Postconditioning:a simple,clinically applicable procedure to improve revascularization in acute myocardial infarction[J]. Circulation,2005,112(14):2085-2088.
34.Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62(1):74-85.
35.Yang XM,Proctor JB,Cui L,et al.Multiple,brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J].J Am Coll Cardiol,2004,44(5):1103-1110.
36.Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):579-588.
37.赵志青,臧益民.再灌注心脏保护的新策略:后处理和预处理的比较[J].心脏杂志,2006,18(1):1-13.
38.Guaiouil VH,Golde DW,Beckles DL,et al.Vitamin C inhibits hypoxia induced damage and apoptotic signaling pathways in cardiomyocytcs and iachemic hearts[J].Free Radlic Biol Med,2004,37(9):1419-1429.
39.Melo LG,Agrawal R,Zhang L,et al.Gene Therapy Strategy for Long-Term Myocardial Protection Using Adeno-Associated Virus-Mediated Delivery of Heme Oxygenase Gene[J].Circulation,2002,105(5):602-607.
40.Li Q,Guo Y,Xuan YT,et al.Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism[J].Circ Res,2003,92(7):741-748.
41.Yuan CQ,Li Y-N,Zhang XF.Down-regulation of apoptosis-inducing factor protein by RNA interference inhibits UVA-induced cell death[J].Biochem Biophys Res Commun,2004,317(4):1108-1113.
42.Zender L,Hutker S,Liedtke C,et al.Caspase 8 small interfering RNA prevents acute liver failure in mice[J].Proc Natl Acad Sci USA,2003,100(13):7797-7802.
2.Berg RA,Otto CW,Kern KB,et al.High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs:a prospective,randomized study[J].Ctit Care Med,1994,22(2):282-290.
3.卢玉平.大剂量肾上腺素用于心肺复苏的争议[J].国外医学麻醉学与复苏分册,1995,16(6):355-358.
4.刘晓亮,邢吉红,马涤辉,等.心肺复苏期间肾上腺素剂量对兔脑复苏的影响[J].中华急诊医学杂志,2003,12(10):681-683.
5.陈习进,王化忠,宋德根,等.大剂量肾上腺素用于心脏复苏(附3例报告)[J].陕西医学杂志,1994,23(6):324-326.
6.李士玉,马玉玲,李治红,等.东莨菪碱对心肺复苏后急性脑缺血-再灌流损伤的保护作用[J].中华急诊医学杂志,2003,12(1):38-39.
7.Ching LL,Williams AJ,Sitsapesan R.Evidence for Ca~(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex[J].Circ Res,2000,87:201-206.
8.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
9.Duilio C,Ambrosio G,Kuppusamy P.Neutrophils are the primary source of O_2radicals during reperfusion after prolonged myocardial ischemia[J].Am J Physiol Heart Circ Phyiol,2001,280:2649-2657.
10.黄子通,方向韶.心肺复苏动物模型的标准化问题[J.中华急诊医学杂志,2009,18(1):11-13.
11.陈蒙华,谢露,宋凤卿,等.小鼠心搏骤停动物模型的建立[J].中国急救医学,2005,25(12):897-898.
1.Boddicker KA,Yi Z,Zimmerman MB,et al.Hypothermia improve defibrillation success and resuscitation outcomes from venticular fibrillation[J].Circulation,2005,111(24):3195-3201.
2.Fisher M,B(o|¨)ttiger BW,Hossmann KA,et al.Thrombolysis using plasminogen activator and heparin reduces cerebral n flow after resuscitation from cardiac arrest:an experiment study in the cat[J].Intensive Care Med,1996,22(11):1214-1223.
3.陈蒙华,刘唐威,谢露,等.老龄大鼠心室颤动模型的建立[J].中华老年心脑血管病杂志,2006,8(3):208.
4.Mayr VD,Wenzel V,Voelckel WG,et al.Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest[J].Circulation,2001,104(14):1651-656.
5.王学斌,杨兴易,林兆奋,等.心肺复苏后大鼠肾脏损伤的实验研究[J.中国急救医学,2006,26(6):435-434.
6.Abella BS,Zhao D,Alvarado J,et al.Intra-arrest cooling improves outcomes in a murine cardiac arrest model[J].Circulation,2004,109(22):2786-2791.
7.Eisenberg MS,Horwood BT,Cummins RO,et al.Cardiac arrest and resuscitation:A tale of 29 cities[J].Ann Emerg Med,1990,19(2):179-186.
8.Wann Sr SR,Weil MH,Sun S,et al.Pharmacologic defibrilation[J].Crit Care Med,2002,30(4):S154-156.
9.Krep H,Brinker G,Schwindt W,et al.Endothelin type A-antagonist improves long-term meurological recovery after cardiac arrest in rats.Crit Care Med[J],2000,28(8):2873-2880.
10.Leonov Y,Sterz F,Safar P,et al.Moderate hypothermia after cardiac arrest of 17minutes in dogs.Effect on cerebral and cardiac outcomes[J].Stroke,1990,21(11):1600-1606.
11.Yarbrouph WM,Spinale FG.Large animal models of congestive failure:a Critical step in translating basic observation into clinical application[J].J Nucl Cardiol,2003,10(1):77-86.
12.Schmitz B,Fisscher M,Bockhorst K,et al.Resuscitation from cardiac arrest in cats:influence of epinephrine dosage on brain recovery[J].Resuscitation,1995,30:251-262.
13.Krep H,B(o|¨)ttiger BW,Bock C,et al.Time course of circulatory and metabolic recovery of cat brain after cardiac arrest assessed by perfusion and diffusion weighted imaging and MR-spectroscopy[J].Resuscitation,2003,58(5):337-348.
14.康州军,余猛进,梅冰,等.东菱克魅栓酶在心脏骤停兔心肺复苏时的治疗作用[J].中国急救医学,2005,25(2):114-115.
15.Chen MH,Liu TW,Xie L,et al.A comparison of tansossphageal cardiac arrest pacing and epinephrine for cardiopulmonary resuscitation.Am J Emerg[J],2006,24(5)545-552.
16.Bottiger BW,Krumnikl JJ,Gass P,et al.The cerebral 'no flow' phenomenon after cardiac arrest in rats-influence of low-flow reperfusion[J].Resuscitation,1997,34(1):79-87.
17.Bottiger BW,Schmitz B,Wiessner C,et al.Nueronal stress response and neuronal cell damage after cardiocirculatory arrest in rats[J].J Cereb Flow Metab,1998,18(10):1077-1087.
18.Vogel P,Putten H,Popp E,et al.Improved resuscitation.after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons[J].Anesthesiology,2003,99(1):112-121.
19.陈蒙华,谢露,宋凤卿,等.小鼠心搏骤停动物模型的建立[J].中国急救医学,2005,25(12):897-898.
20.Chen MH,Liu TW,Xie L,et al.A Simpler Cardiac Arrest Model in Rats[J].Am J Emerg Med,2007,25(1):623-630.
21.von Planta I,Weil MH,von Planta H,et al.Cardiopulmonary resuscitation in the rat[J].J Appl Physiol,1988,65(6):2641-2647.
22.Wann Sr SR,Weil MH,Sun S,et al.Pharmacologic defibrilation[J].Crit Care Med,2002,30(4):S154-156.
23.Song L,Weil MH,Tang W,et al.Cardiopulmonary resuscitation in mouse[J].J Appl Physiol,2002,93(4):1222-1226.
24.黄子通 方向韶.心肺复苏动物模型的标准化问题[J].中华急诊医学杂志,2009,18(1):11-13.
25.Idis AH,Becker LB,Ornanto JP,et al.Ustein-Style guideline for uniform reporting of laboratory CPR research[J].Circulation,1996,94(9):2324-2336.
1.Berg RA,Otto CW,Kern KB,et al.High dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs:a prospective,randomized study[J].Ctit Care Med,1994,22(2):282-290.
2.卢玉平.大剂量肾上腺素用于心肺复苏的争议[J].国外医学麻醉学与复苏分册,1995,16(6):355-358.
3.刘晓亮,邢吉红,马涤辉,等.心肺复苏期间肾上腺素剂量对兔脑复苏的影响[J].中华急诊医学杂志,2003,12(10):681-683.
4.李士玉,马玉玲,李治红,等.东莨菪碱对心肺复苏后急性脑缺血.再灌流损伤的保护作用[J.中华急诊医学杂志,2003,12(1):38-39.
5.贾立静,陈威,沈洪,等.山莨菪碱对心脏停搏大鼠复苏中微循环的影响[J].中国危重病急救医学,2008,20(12):737-739.
6.李天然,临床PET/CT诊断学(第一版)[M.北京:人民军医出版社,2007,43-99.
7.周代星,邓普珍.山莨菪碱对急性完全性脑缺血-再灌注后脑组织Ca~(2+)、SOD 活性及超微结构的影响[J.急诊医学,1998,7:32.
8.张宏图.山莨菪碱治疗重型颅脑损伤合并神经源性肺水肿疗效观察[J].中国全科医学,2006,9:836.
9.蒋崇慧,候德仁,汤彦,等.脑缺血预处理联合山莨菪碱对大鼠脑缺血-再灌注损伤的保护作用[J].中国急救医学,2002,22:26.
10.邓普珍.重视山莨菪碱的脑保护机制在临床心肺复苏中的应用[J].中华急诊医学杂志,2003,12:344.
11.汤彦,杨光田,蒋崇慧,等.山莨菪碱在大鼠急性全脑缺血再注损伤中对一氧化氮、内皮素-1及能量代谢的影响[J.中国急救医学,2000,20:4.
12.杨国栋主编.微循环障碍与莨菪碱类药物的临床应用(第二版)[M].北京:人民卫生出版社,1999,98.
13.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
14.俞长兴,肖蓬,苏志红,等.山莨菪碱类药物临床应用评价[J].中国医院用药评价与分析,2002,2:208-210.
15.许翔,鲍颖霞,李庆平.山莨菪碱对大鼠肠系膜微循环及产时宫颈水肿微循环的影响[J.中国现代医学杂志,2002,12(24):5-7.
16.占成业,邓普珍.山莨菪碱对乳鼠急性全脑缺血-再灌注损伤期间兴奋性氨基酸释放及生存状况的影响[J].中国急救医学,1999,19:3.
17.Ching LL,Williams AJ,Sitsapesan R.Evidence for Ca~(2+) activation and inactivation sites on the luminal side of the cardiac ryanodine receptor complex[J].Circ Res,2000,87:201-6.
18.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
19.Duilio C,Ambrosio G,Kuppusamy P.Neutrophils are the primary source of O_2radicals during reperfusion after prolonged myocardial ischemia[J].Am J Physiol Heart Circ Phyiol,2001,280:2649-2657.
20.蔡锡腾.实用微循环学[M.中国医药科技出版社,1990,84.
21.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
22.金芳.山莨菪碱对缺钙复钙所致内皮细胞损伤的保护作用[J].中国病理生理学杂志,1992,8:328.
23.刘书勤,臧伟进,李增利,等.电压激活的钾通道阻断剂抑制山莨菪碱松弛去甲肾上腺素预收缩的兔主动脉平滑肌[J].生理学报,2005,57:21-26.
24.Gueugniaud PY,Dubien PY,David JS,et al.Epinephrine and outcome of cardiac arrest[J].Current Opinion in Critical Care,2000,6(3):196-199.
25.Parasis NA,Wenzel V,Southall J.Pressor drugs in the treatment of cardiac arrest[J].Cardiol Clin,2002,20(1):61-78.
26.Timothy K,Kerry K,Shadi V,et al.Innovative pharmacologic approaches to cardiopulmonary resuscitation[J].Heart Disease,2001,3(1):46-541.
27.Brown CG,Martin DR,Pepe PE,et al.A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital.The Multicenter High-DoseEpinephrine Study Group[J].New Engl J Med,1992,327(15):051-5.
28.Stiell IG,Hebert PC,Weitzman BN,et al.High-dose epinephrine in adult cardiacarrest[J].New Engl J Med,1992,27(15):1045-50.
29.Meyer M,Schulz Knappe P,Kuse ER,et al.Urodilatin,use of new peptide in intensive care[J].Anaesthetist,1995,44(2):81-91.
30.Meyer M,Stief CG,Becker AJ,et al.The renal paracrine peptide system-possible urologic implications of urodilatin[J].World J Urol,1996,14(6):375-379.
31.Levin ER,Gardner DG,Samson WK.Natriuretic peptide[J].New Engl J Med,1998,339(5):321-328.
32.Melo LG,Pang SC,Ackermann V.Atrial natriuretic peptides:Regulator of chronic arterial blood pressure[J].News Physiol Sci,2000,15(1):143-149.
33.Maria AC,Laura VGB,Monica PM.Atrial natriuretic peptides modifies arterial blood pressure through nitric oride pathway in rata[J].Hypertension,2000,35:1119-1125.
34.Hoiks G,Thomson NC.High dose inhaled arterial blood pressure is a bronchodilator in asthmatic subjects[J].Eur Respir,1994,7(9):1593-1597.
35. Robichaud A,Michoad MC,Hanmet P,et al.Plasma arterial blood pressure during spontanooes bronchoconstriction in asthmatics[J].Peptides,1995,16(4):653-656.
36.Lin YX,Zhang BF,Qi HW,et al.Influences of intravenous infusion of cardionatrin on TNF-a,IL-8 and ET-1 contents in blood and bronchioalveolar lavage fluid of rabbits with acute lung injury induced by oleic acid[J].J Fourth Mil Med Univ,2001,22(15):1395-1397.
37.Gerdts EW,achtell K,Omvik P,et al.Left atrial size and risk of major cardiovascular events during antihypertensive treatment losartan intervention for,endpoint reduction in hypertension trial[J].Hypertension,2007,49(2):311-316.
38.Munagala VK,Burnett JC,Redfield MM.The natriuretic peptides in cardiovascul-ar medicine[J].Curr Probl Cardiol,2004,29(12):707-769.
1.Crow MT,Mani K,Nam YJ,et al.The mitochondrial death pathway and cardiac myocyte apoptosis[J].Circ Res,2004,95(10):957-970.
2.唐燕华,陈朋,胡大仁,等.山莨菪碱心肌保护作用的临床研究[J].中国危重病急救医学,2001,13(10):603-605.
3.Fngit MD,Rnbal BJ,Donovan KJ.Effects of intracoronary nicardipine,diltiazem and veraparmil on coronary blood flow[J].J Invasive Cardiol,2000,12:80-85.
4.扬军.山莨菪碱对缺血心肌保护作用[J].中国病理生理杂志,1992,8:330.
5.蔡锡腾.实用微循环学[M.中国医药科技出版社,1990,84.
6.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
7.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
8.Mott JI,Zhang D,Freeman JC,et al.Cardiac disease due to random mitochondrial DNA mutations is prevented by cyclosporin A[J].Biochem Biophys Res Commun,2004,319(4):1210-1215.
9.Clarke SJ,Mcstay GP,Halestrap AP,et al.Sanglifehrin A acts as a potent inhibitor of the mitochondrialpermeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A[J].J Biol Chem,2002,277(38):34793-34799.
10.Akao M,O Rourke B,Kusuoka H,et al.Differential actions of cardioprotective agents on the mitoehondrial death pathway[J].Circ Res,2003,92(2):195-202.
11.Avkiran M,Gross G,Karmazyn M,et al.Na~+/H~+exchange in ischemia,reperfusion and preconditioning[J].Cardiovasc Res,2001,50(1):162-166.
12.Lim KH,Halestrap AP,Angelini GD,et al.Propofol is cardioprotective in a clinically relevant model of norulotherulic blood cardioplegic arrest and cardiopulmonary bypass[J].Exp Biol Med,2005,230(6):413-420.
13.Maulik M,Maulik SK,Kumarir.Importance of timing of magnesium administration:a study on the isolated ischemic-repeffused rat heart[J].Magnes Res,1999,12(1):37-42.
14.Ruiz M,Pinnap,Garcia D,et al.Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition[J].J Physiol,2004,558(3):873-882.
15.Rosenfeldt F,Marascos,Lyon W,et al.Coenzyme Q1 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial[J].J Thorac Cardiovasc Surg,2005,129(1):25-32.
16.Hayakawa Y,Chandra M,Miao W,et al.Inhibition of Cardiac Myocyte Apoptosis Improves Cardiac Function and Abolishes Mortality in the Peripartum Cardiomyopathy of Transgenic Mice[J].Circulation,2003,108(24):3036-3041.
17.Fujimura H,Kambyshi JI,Mondem M,et al.Coagulation factor V leidenmutation may have a racial background[J].Throm Haem,1995,74:1381.
18.周代星,邓普珍.山莨菪碱对急性完全性脑缺血.再灌注后脑组织Ca~(2+)、SOD 活性及超微结构的影响[J].急诊医学,1998,7:32.
19.张宏图.山莨菪碱治疗重型颅脑损伤合并神经源性肺水肿疗效观察[J].中国全科医学,2006,9:836.
20.蒋崇慧,候德仁,汤彦,等.脑缺血预处理联合山莨菪碱对大鼠脑缺血-再灌注损伤的保护作用[J.中国急救医学,2002,22:26.
21.邓普珍.重视山莨菪碱的脑保护机制在临床心肺复苏中的应用[J].中华急诊医学杂志,2003,12:344.
22.汤彦,杨光田,蒋崇慧,等.山莨菪碱在大鼠急性全脑缺血再注损伤中对一氧化氮、内皮素-1及能量代谢的影响[J].中国急救医学,2000,20:4.
23.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
1.Freude B,Masters TN,Robicsek F,et al.Apoptosis is initiated by myocardial ischemia and executed during reperfusion[J].J Mol Cell Cardiol,2000,32(2):197-208.
2.Yaoita H,Ogawa K,Maehara K,et al.Apoptosis in relevant clinical situations:contribution of apoptosis in myocardial infarction[J].Cardiovasc Res,2000,45(3):630-41.
3.Kajstura J,Cheng W,R.eiss K,et al.Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats[J].Lab Invest,1996,74:86-107.
4.Musat-Marcu S,Gunter HE,Jugdutt BI,et al.Inhibition of apoptosis after ischemia reperfusion in rat myocardium by cycloheximide[J].J Mol Cell Cardiol,1999,31:1073-1082.
5.Xin L,Sanjay Kumar,Feng Gao,et al.Inhibition of p38 Mitogen-Activated Protein Kinase Decreases Cardiomyocyte Apoptosis and Improves Cardiac Function After Myocardial Ischemia and Reperfusion[J].Circulation,1999,99:1685-1691.
6.Yaoita H,Ogawa K,Maehara K,et al.Attenuation of ischemia/reperfusion injury in rats by caspase inhibitor[J].Circulation,1998,97:276-281.
7.占成业,邓普珍.山莨菪碱对乳鼠急性全脑缺血-再灌注损伤期间兴奋性氨基酸释放及生存状况的影响[J].中国急救医学,1999,19:3.
8.谷新顺,王荣英,马宁,等.山莨菪碱对小型猪缺血再灌注心肌的保护作用[J].中国急救医学,2006,26:197-199.
9.周喜春,牛蕴蕴,梁学颖,等.早期凋亡的流式细胞术分析[J].军医进修学院学报,2004,25(1):10-11.
10.王珊,李宁,于力,等.流式细胞术检测细胞凋亡比较研究[J.标记免疫分析与临床,2005,12(3):8-10.
11.Gueugniaud PY,Dubien PY,David JS,et al.Epinephrine and outcome of cardiac arrest[J].Current Opinion in Critical Care,2000,6(3):196-199.
12.Parasis NA,Wenzel V,Southall J.Pressor drugs in the treatment of cardiac arrest[J].Cardiol Clin,2002,20(1):61-78.
13.俞长兴,肖蓬,苏志红,等.山莨菪碱类药物临床应用评价[J].中国医院用药评价与分析,2002,2:208-210.
14.Timothy K,Kerry K,Shadi V,et al.Innovative pharmacologic approaches to cardiopulmonary resuscitation[J].Heart Disease,2001,3(1):46-541.
15.Brown CG,Martin DR,Pepe PE,et al.A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital.The Multicenter High-Dose Epinephrine Study Group[J].N Engl J Med,1992,327(15):1051-5.
16.Stiell IG,Hebert PC,Weitzrnan BN,et al.High-dose epinephrine in adult cardiacarrest[J].N Engl J Med,1992,327(15):1045-50.
17.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
18.蔡锡腾.实用微循环学[M].中国医药科技出版社,1990,84.
19.于玉蓉.山莨菪碱对缺血/再灌注心肌损伤的保护作用及细胞内钙的关系[J].中国心血管学药理通讯,1991,9:135.
20.金芳.山莨菪碱对缺钙复钙所致内皮细胞损伤的保护作用[J].中国病理生理学杂志,1992,8:328.
21.Gavrieli Y,Sherman Y,Ben-Sasson SA.Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation[J].J Cell Biol,1992,119:493-501.
22.Wijsman JH,Jonker RR,Keijzer R,et al.A new method to detect apoptosis in paraffin sections:In situ end labeling of fragmented DNA[J].J Histochem Cytochem,1993,41:7-12.
23.Eschenhagen T,Mende U,Diederich M,et al.Chronic treatment with carbachol sensitizes the myocardium to cAMP induced arrhythmial[J].Circulation,1996,93:7632-7711.
24.Matsui S,Fu ML,Hayase M,et al.Beneficial effect of muscarinic antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic receptor[J].J Cardiovasc Pharmacol,2001,38(Suppl 1):S432-S491.
25.Ponicke K,Heinroth-Hoffmann I,Brodde OE.Demonstration of functional M3-muscarinic receptor in ventricular cardiomyocytes of adult rats[J].Br J Pharmacol,2003,138(1):156-160.
26.Krejci A,Tucek S.Quantitation of mRNAs for M(1) to M(5) subtypes of muscarinic receptors in rat heart and brain cortex[J].Mol Pharmacol,2002,61(6):1267-1272.
27.胥晓丽,藏伟进,康新勤,等.大鼠心房与心室胆碱能神经和M_2受体的分布比较[J].南方医科大学学报,2006,26(8):1096-1110.
28.修瑞娟.微循环-微妙的生命泉源[J].微循环杂志,1997,7:1-3.
29.扬军.山莨菪碱对缺血心肌保护作用[J].中国病理生理杂志,1992,8:330.
30.刘振国,姚秀娟,李小强,等.山莨菪碱抑制成年大鼠离体心室肌细胞钙瞬变和收缩及其机制[J].中国临床药理学与治疗学,2005,10(6):645-650.
1.Takemura G,Fujivara H.Role of apoptosis in remodeling after myocardial infarction[J].Pharmacol Ther,2004,104(1):1204-1212.
2.Zhang T,Brown JH.Role of Ca~(2+)/calmodulin-dependent protein kinase II in cardiac hypertrophy and heart failure[J].Cardiovasc Res,2004,63(3):476-486.
3.Crow MT,Mani K,Nam YJ,et al.The mitochondrial death pathway and cardiac myocyte apoptosis[J].Circ Res,2004,95(10):957-970.
4.Morin D,Pires F,Plin C,et al.Role of the permeability transition pore in cytochrome C release from mitochondria during ischemia-reperfusion in rat Hver[J].Biochem Pharmacol,2004,68(10):2065-2073.
5.Nakagawa T,Shimizu S,Watanabe T,et al.Cyclophilin dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death[J].Nature,2005,434(7033):652-658.
6.Varga E,Nagy N,Lazar J,et al.Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts:the role of cytochrome C release[J].Life Sci,2004,75(20):2411-2423.
7.Czerski I,Nunez G.Apoptosome formation and caspase activation:is it different in the heart[J].J Mol Cell Cardiol,2004,37(3):643-652.
8.Gurevich RM,Regula KM,Kirshenbaum LA,et al.Serpin protein CrmA suppresses hypoxia-mediated apoptosis of ventricular myocytes[J].Circulation,2001,103(15):1984-1991.
9.Hayakawa Y,Chandra M,Miao W,et al.Inhibition of Cardiac Myocyte Apoptosis Improves Cardiac Function and Abolishes Mortality in the Peripartum Cardiomyopathy of Transgenic Mice[J].Circulation,2003,108(24):3036-3041.
10. Mott JI,Zhang D,Freeman JC,et al.Cardiac disease due to random mitochondrial DN A mutations is prevented by cyclosporin A[J].Biochem Biophys Res Commun,2004,319(4):1210-1215.
11.Guaiquil VH,Golde DW,Beckles DI,et al.A VitaminC inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts[J].Free Radlic Biol Med,2004,37(9):1419-1429.
12.Scarabelli TM,Stephanou A,Pasini E,et al.Minocycline inhibits caspase activation and reactivation,increases the ratio of XIAP to smac/DIABLO,and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO[J].J Am Coil Cardiol,2004,43(5):865-874.
13.Rajesh KG,Sasaguri S,Suzuki R,et al.Ischemic preconditioning prevents reperfusion heart injury in cardiac hypertrophy by activation ofmitochondrial K_(ATP) channels[J].Int J Cardiol,2004,96(1):41-49.
14.曾源,龙超良,李艳芳,汪海.开放线粒体K_(ATP)通道对心肌细胞氧化应激损伤的保护作用[J].中国临床药理学与治疗学,2006,11(7):806-809.
15.Oldenburg O,Cohen MV,YeHon DM,Downey JM.Mitochondrial K~+ channels:role in cardioprotection[J].Cardiovasc Res,2002,55:429-437.
16.Ardehali H,O'Rourke B.Mitochondrial K~+ channels in cell survival and death[J].J Mol Cell Cardiol,2005,39:7-16.
17.Sato T,Sasaki N,Seharaseyon J,et al.Selective pharmacological agents implicate mitoehondrial but not saycolemmal K~+ channels in ischemic cardioprotecion[J].Circulation,2000,101:2418-2423.
18.Liu Rongguo,Wang Weijian,Song Na,et al.Dilazoxide preconditioning alleviates apoptosis of hippocampal neurons induced by noxia-reoxygenaticon in vitro thro -ugh up regulation of bcl-2/Bax protein ratio[J].Acta Physiologica Sinica,2006,58(4):345.
19.黄河,肖颖彬,杨天德,等.线粒体K_(ATP)通道开放剂对培养大鼠心肌细胞缺血/再灌注损伤心肌线粒体的保护作用[J].重庆医学,2008,53(37):479-483.
20.周代星,占成业,邓普珍,等.全脑缺血再灌注后脑线粒体功能变化及山莨菪碱的保护作[J].中国急救医学,2003,23(5):300-301.
21.唐燕华,陈朋,胡大仁,等.山莨菪碱心肌保护作用的临床研究[J].中国危重病急救医学,2001,13(10):603-605.
22.Fujimura H,Kambyshi JI,Mondem M,et al.Coagulation factor V leidenmutation may have a racial background[J].Throm Haem,1995,74:1381.
23.刘中民,张轶,范慧敏,等.东莨菪碱在心肌再灌注损伤中的作用[J].同济大学学报(医学版),2002,23(2):86-89.
24.Clarke SJ,Mcstay GP,Halestrap AP,et al.Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A[J].J Biol Chem,2002,277(38):34793-34799.
25.Akao M,O Rourke B,Kusuoka H,et al.Differential actions of cardioprotective agents on the mitoehondrial death pathway[J].Circ Res,2003,92(2):195-202.
26.Avkiran M,Gross G,Karmazyn M,et al.Na~+/H~+exchange in ischemia,reperfusion and preconditioning[J].Cardiovasc Res,2001,50(1):162-166.
27.Lim KH,Halestrap AP,Angelini GD,et al.Propofol is cardioprotective in a clinically relevant model of norulotherulic blood cardioplegic arrest and cardiopulmonary bypass[J].Exp Biol Med,2005,230(6):413-420.
28.Maulik M,Maulik SK,Kumarir.Importance of timing of magnesium administration:a study on the isolated ischemic-repeffused rat heart[J].Magnes Res,1999,12(1):37-42.
29.Ruiz M,Pinnap,Garcia D,et al.Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition[J].J Physiol,2004,558(3):873-882.
30.Rosenfeldt F,Marascos,Lyon W,et al.Coenzyme Q1 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial[J].J Thorac Cardiovasc Surg,2005,129(1):25-32.
31.Hausenloy D J,Maddock HL,Baxter GF,et al.Inhibiting mitochondrial permeability transition pore opening:a new paradigm for myocardial preconditioning[J].Cardiovasc Res,2002,55(3):534-543.
32.Javadov SA,Clarke S,Das M,et al.Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart[J].J Physiol,2005,549(2):513-524.
33.Vinten J,Yellon DM,Opie LH.Postconditioning:a simple,clinically applicable procedure to improve revascularization in acute myocardial infarction[J]. Circulation,2005,112(14):2085-2088.
34.Kin H,Zhao ZQ,Sun HY,et al.Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion[J].Cardiovasc Res,2004,62(1):74-85.
35.Yang XM,Proctor JB,Cui L,et al.Multiple,brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways[J].J Am Coll Cardiol,2004,44(5):1103-1110.
36.Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):579-588.
37.赵志青,臧益民.再灌注心脏保护的新策略:后处理和预处理的比较[J].心脏杂志,2006,18(1):1-13.
38.Guaiouil VH,Golde DW,Beckles DL,et al.Vitamin C inhibits hypoxia induced damage and apoptotic signaling pathways in cardiomyocytcs and iachemic hearts[J].Free Radlic Biol Med,2004,37(9):1419-1429.
39.Melo LG,Agrawal R,Zhang L,et al.Gene Therapy Strategy for Long-Term Myocardial Protection Using Adeno-Associated Virus-Mediated Delivery of Heme Oxygenase Gene[J].Circulation,2002,105(5):602-607.
40.Li Q,Guo Y,Xuan YT,et al.Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism[J].Circ Res,2003,92(7):741-748.
41.Yuan CQ,Li Y-N,Zhang XF.Down-regulation of apoptosis-inducing factor protein by RNA interference inhibits UVA-induced cell death[J].Biochem Biophys Res Commun,2004,317(4):1108-1113.
42.Zender L,Hutker S,Liedtke C,et al.Caspase 8 small interfering RNA prevents acute liver failure in mice[J].Proc Natl Acad Sci USA,2003,100(13):7797-7802.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |