心肺复苏中肾上腺素对大鼠心肌损伤的研究
|
摘要
目的:本研究探讨心肺复苏中在自主循环恢复(ROSC)前肾上腺素对大鼠心肌的损伤情况,以及心肌损伤与β1-肾上腺素能受体(β1-AR)的关系及可能机制。方法:SD雄性大鼠50只,随机分为4组:空白对照组(A组、10只)、复苏对照组(B组、10只)、标准剂量肾上腺素组(C组、15只)、大剂量肾上腺素组(D组、15只)。采用大鼠心肺复苏模型,麻醉大鼠、气管切开置管、动静脉插管,除了正常对照组不诱发心脏骤停外,其余组均在呼气末夹闭气管插管,中断通气,致大鼠心跳骤停。大鼠心跳骤停5min后松开夹闭的气管,连接呼吸机辅助呼吸,同时进行快速胸外心脏按压,经尾静脉注射肾上腺素。标准剂量组、大剂量组在2.5±0.5min出现自主心律、脉搏波、平均动脉压(MAP)≥60mmHg,停止复苏观察15秒后剖胸取心脏留标本。复苏对照组不注射肾上腺素,在心外按压2.5min后直接剖胸取心脏留标本。检测各组心肌组织,用硫代巴比妥酸比色法检测大鼠心肌组织丙二醛(MDA)浓度;用黄嘌呤氧化法检测大鼠心肌组织超氧化物歧化酶(SOD)活力;用定磷法检测心肌组织Na+K+-ATP酶的活力;应用双抗体夹心酶标免疫分析法测定大鼠心肌组织匀浆并计算环磷腺苷(cAMP)浓度;记录心外按压时平均动脉压;电镜观察心肌细胞超微结构变化。结果:1)检测心肌组织MDA发现,未用肾上腺素的复苏对照组比标准剂量组、大剂量组心肌MDA浓度低(P<0.01),标准剂量组心肌MDA浓度比大剂量组低(P<0.05);2)检测心肌组织Na+K+-ATP酶和SOD活力发现,复苏对照组比标准剂量组、大剂量组心肌Na+K+-ATP酶和SOD活力高(P<0.01),标准剂量组心肌ATP酶和SOD活力比大剂量组高(P<0.01);3)复苏对照组心肌cAMP含量比标准剂量组、大剂量组低(P<0.01),标准剂量组与大剂量组心肌cAMP含量无统计学差异(P>0.05);4)心外按压时标准剂量组平均动脉压比大剂量组低(P<0.01)。大剂量组心肌纤维变细,各带线结构显示不清,部分肌丝溶解,线粒体水肿、空泡化,线粒体峭排列紊乱,细胞浆内糖原颗粒减少等,而在标准剂量组亦发现上述超微结构变化,但是比大剂量组损伤程度轻。结论:在心肺复苏中,比较对照组,大剂量和标准剂量肾上腺素组在自主循环恢复前就已经加重了心肌组织的损伤,大剂量组心肌损伤更为明显;在自主循环恢复前加重心肌损伤可能不是心肌β1-AR激活引起,其可能的损伤机制需要进一步的实验研究。
Objective: After cardiopulmonary resuscitation, cardiac insufficiency is important reason that death rate of patient is high at acute stage. To investigate epirenamine’s myocardial damage condition before ROSC’rat, during CPR. To investigate relationehip and possible mechanism between myocardial damage andβ1-AR. Methods: Fifty SD male were randomly divided into groups 4: blank group (A, n=10); resuscitation control group (B, n=10); standard-dose epinephrine group (C, n=15); high-dose epinephrine group (D, n=15) .To apply rat CPR’model, to anesthetize experimental rat, incision of trachea and to put arterial and venous cannual. except blank group, the rest group will occlude trachea cannula at end expiration, to result rat’s cardiac arrest. After 5 min of rat’s cardiac arrest, trachea cannula would be unclamped to connect breathing machine and assist respiration, meanwhile we would carry out closed cardiac massage and inject epinephrine through caudal vein. Groups C and D will stop CPR and observe for 15 second to remain heart’s sample after appearing independent cardiac rhythm. Pulse wave arterial blood pressure (MAP)≥60mmhg, group B don’t inject epinephrine and directly remain heart’s sample after 30 secend of closed cardiac massage. This sample would be detected for vigor of ATPase, SOD and concentration of MDA, cAMP, then to take statistical analysis. Heart’s sample would be observed ultramicrostructure of cardic muscle cell through electron microscope. Results: Concetration of cardiac muscle’MDA in groups A?B is lower than groups C, D (P<0.01). Concetration of cardiac muscle’MDA in group C is lower than groups D (P<0.05).Vigors of cardiac muscle’ATPase, SOD in groups A, B is higher than groups C, D (P<0.01), and group C is higher than group D (P<0.01). There was no significant difference in cardiac muscle’cAMP concentration between group C and group D (P>0.05). Transmission electron microscopy showed the myocardial cell damage performance in rats after CPR. Nuclear deformation, marginated chromatin, the nuclear membrane rupture, pyknosis, mitochondrial swelling, ridge fracture or even disappear.There was significant difference between group C and group D in observing ultramicrostructure of cardiac muscle cell. Conclusion: During CPR, high-dose epinep- hrine has increased myocardial damage before ROSC compare with standard-dose epinephrine, but high-dose epinephrine has increased myocardial damage which might be not effect ofβ1-AR’increased excitability.
Objective: After cardiopulmonary resuscitation, cardiac insufficiency is important reason that death rate of patient is high at acute stage. To investigate epirenamine’s myocardial damage condition before ROSC’rat, during CPR. To investigate relationehip and possible mechanism between myocardial damage andβ1-AR. Methods: Fifty SD male were randomly divided into groups 4: blank group (A, n=10); resuscitation control group (B, n=10); standard-dose epinephrine group (C, n=15); high-dose epinephrine group (D, n=15) .To apply rat CPR’model, to anesthetize experimental rat, incision of trachea and to put arterial and venous cannual. except blank group, the rest group will occlude trachea cannula at end expiration, to result rat’s cardiac arrest. After 5 min of rat’s cardiac arrest, trachea cannula would be unclamped to connect breathing machine and assist respiration, meanwhile we would carry out closed cardiac massage and inject epinephrine through caudal vein. Groups C and D will stop CPR and observe for 15 second to remain heart’s sample after appearing independent cardiac rhythm. Pulse wave arterial blood pressure (MAP)≥60mmhg, group B don’t inject epinephrine and directly remain heart’s sample after 30 secend of closed cardiac massage. This sample would be detected for vigor of ATPase, SOD and concentration of MDA, cAMP, then to take statistical analysis. Heart’s sample would be observed ultramicrostructure of cardic muscle cell through electron microscope. Results: Concetration of cardiac muscle’MDA in groups A?B is lower than groups C, D (P<0.01). Concetration of cardiac muscle’MDA in group C is lower than groups D (P<0.05).Vigors of cardiac muscle’ATPase, SOD in groups A, B is higher than groups C, D (P<0.01), and group C is higher than group D (P<0.01). There was no significant difference in cardiac muscle’cAMP concentration between group C and group D (P>0.05). Transmission electron microscopy showed the myocardial cell damage performance in rats after CPR. Nuclear deformation, marginated chromatin, the nuclear membrane rupture, pyknosis, mitochondrial swelling, ridge fracture or even disappear.There was significant difference between group C and group D in observing ultramicrostructure of cardiac muscle cell. Conclusion: During CPR, high-dose epinep- hrine has increased myocardial damage before ROSC compare with standard-dose epinephrine, but high-dose epinephrine has increased myocardial damage which might be not effect ofβ1-AR’increased excitability.
引文
[1]张维,沈洪.肾上腺素和血管加压素在心肺复苏中的评价[J].中华急诊医学杂志, 2003, 12 (7) : 499-500.
[2] One MEH, Chan YH, Anantharaman V, et al. Cardiac arrest and resuscitation epidemiology in gingapore (CARE I study) [J]. Prehosp Emerg Care, 2003, 7 (4) : 427-433.
[3] Rudner R, Jalowiecki P, Karpel E, et al. Survial after out-of-hospital cardiac arrests in katowice (Poland) : outcome report according to the“Utstelnstyle”[J] Resuscitation, 2004, 61 (3) : 315-325.
[4] Eckstein M, Stratto SJ, Chan LS. Cardiac Arrest Resuscitation Evaluation in Los Angeles: CARE-LA [J]. Ann Emerg Med, 2005, 45 (5) : 504-509.
[5] Nad Karni VM, Larkin GL, Peberdy MA, et al. First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults [J]. JAMA, 2006, 295 (1) : 50-57.
[6] Lindner K, Ahnefeld F, Bowdler I. Comparison of differrent doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model [J]. Am J Emerg Med, 1991, 9: 27-31.
[7] Gallaham M. Epinephrine doses in cardiac arrest: is it time to outgrow the orthodoxy of ACLS[J]. Am Emerg Meg, 1989, 18: 101-1012.
[8] Stiell IG, Herbert PC, Weitzman BN, et al. High-dose epinephrine in adult cardic arrest[J]. N Engl J Med, 1992, 327: 1045-1050.
[9] Ohshige K, Shimazaki S, Hirasawa H, et al. Evaluation of out-of-hospital cardiaopulmonary resuscitation with resuscitative drug: a prospective comparative study in Japan [J]. Resuscitation, 2005, 66 (1) : 53-61.
[10]Babbs CF, Berg RA, Kette F et al. Use of pressors in the treatment of cardiac arrest [J]. Ann Emerg Med, 2001, 37 (4sappl) : S152-162.
[11]邢绣荣,秦俭,李春盛等.复苏早期应用氨茶碱对心肌超微结构的影响[J]中华急诊医学杂志2005年5月第14卷第5期: 368-372.
[12]Ditchey RV, Lindenfeld J. Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs. Circulation, 1998: 78 (2) ?: 382-389.
[13]Rivers EP, Wortsman J, Rady M Y, et al. The effete of the total cumulative epinephrineand dose administered during human CPR on hemodynarnic oxygen transport and utilization variables in the Postresuscitation period[J]. Chest, 1994, 106: 1499-1507.
[14]高瑞,奚万山,陈伟宏等.大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响[J].中国危重病急救医学, 1998, 1011: 649-651.
[15]Cheryl R, Chih-chang, et al. Short-Actingβ-Adrenergic Antahonist Esmolol Given at eperfusion Improves Survial After Prolonged Ventricular Fobrllation[J]. Circulation, 2004, 109: 2469-2474.
[16]Loeckinger A, Kleinsasser A, Wenzel V, et al. Pulmonary gas exchange after cardiopulmonary resuscitation with either vasopressin or epinephrine [J]. Crit Care Med, 2002, 30 (9) : 2059-2062.
[17]Tang W, Weil MH, et al. Eprnephrine increases the severity of postresuscitation myocardial dysfunction [J]. Circulation. 1995, 92: 3089-3093.
[18]Vandycke C, Martens P, et al. High dose versus standard dose epinephrine in cardiac arrest: ameta-analysis[J]. Resuscitation 2000, 45: 161-167.
[19]涂昌弟.院内心肺复苏成败影响因素的回顾性分析[J].现代预防医学杂志, 2005, 32 (3) : 258-259.
[20]Dltchey RV, Perez RA, Slinker BK. Beta-adrenergic blockade reduces myocardial injury during experiment cardiopulmonary resuscitation [J]. Am Coll Cardiol, 1994, 24 (3) : 804-812.
[21]Huang L, Wei MH, Cammarata G, et al. Nonselective bete-blocking agent improves the outcome of cardiopulmonary resuscitation in a rat model [J]. Crit Care Med, 2004, 32 (9suppl) : 378-380.
[22]BrownCG, WermaHA, DartsEA. He effeet of graded doses of epinePhine of regional myceantial blood flaw during cardiopulmonary resuseitation circulation. JAMA. 1997. 75: 491.
[23]Manningge E, Batson DN. Aorticarhvers ascenralvenouse epinephrine during CPR. Ann Emerg Med, 1993, 22: 703-704.
[24]张全贵,刘光耀,杨志焕等.电击室颤时注射大剂量肾上腺素对犬血流动力学的作用[J].中华创伤杂志, 1995, 11 (5) : 320-322.
[25]郑昌军,丁永莉,樊明满等.大剂量肾上腺素治疗心跳骤停的临床观察[J].实用全科医学, 2005, 3 (6) : 518-519.
[26]侯洪,不同剂量肾上腺素对心肺复苏的影响[J].重庆医学, 2005, 4 (8) : 1263-1264.
[27]Pardis NA, MartinGB, RnsenhergJ. The effect of standard and high doseepinephrineon coronary pcfusion pressure during prolongedcardiopulmonary resuseition. JAMA, 1991, 256: 1139.
[28]张全贵.静注大剂量肾上腺素抢救心脏骤停的初步研究[J].全军第二届急救医学学术交流会论文汇编, 1991, 81-83.
[29]邓普诊.关于CPCR术成败的几个问题的探讨[J]第六届急救医学学术会议论文汇编, 1996, 328-330.
[30]陈寿权,李章平,王珊珊等.窒息法致大鼠心脏骤停模型复苏的影响因素[J].中华急诊医学杂志, 2005, 14 (10) : 814-817.
[31]陈尔真,蒋健·复苏实验研究Utstein模式[J]·中国急救医学, 1999, 19 (2) : 70-73.
[32]Chen MH, Liu TW, Xie L, et al. A simpler cardiac arrest model in rats [J] . Am J Emergmed, 2007, 25 (6) : 623-630.
[33]吴景录.不同剂量肾上腺素对心肺复苏的效应[J].临床和实验医学杂志, 2007, 6 (9) : 131-132
[34]AHA. 2005 American Heart Association Guideline for CPR and ECC. Circulation, 2005, 133 (4) : 1-84.
[35]The American Heart Association in collaboration with the International Liaison Committee on Resuscitation Guidelines 2005 for Cardiopulmonary Resuscitation and Emergency Cardiovascular care [J]. Circulation. 2005, 112: W-1-IV-200.
[36]李宗盛,樊寻梅,聚焦2005年ECC及CPR治疗推荐国际会议[J].中华急诊医学杂志, 2005, 14: 871-873.
[37]Gedeborg R, Silander HC. Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation. Crit Care Med, 2000, 28: 1423-1430.
[38]Berg RA, otto CW, Kem KB, et al. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: A Prospective, randomized study. Crit Care Med, 1994, 22: 282-290.
[39]Berg RA, otto CW, Kem KB, et al. A randomized, blinded trial of high-dose epinephrine verse standard-dose epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med, 1996, : 1695-1700.
[40]Cammarata G, Weil MH, Sun S, et al. Betal-adrenergic bloekade during cardiopulmonary resuscitation improves survival [J]. Crit Care Med, 2004, 32: S440-453.
[41]王道庄.心肺复苏的发展争论与展望[M].人民卫生出版社2007年8月第1版, 168-169.
[42]Bristow MR. Down-regulation ofβ-adrenergic receptor and recepror mRNA in heart cell chronically exposed to norepinephrine. Clin Res, 1991; 39: 256-258.
[43]Hadcock JR, Malbon CC. Regulation of receptor expression by agonists: transcriptional and post– transcriptional controls. Trends Neurosci, 1991; 14: 242-247.
[44]RichardMS, CarolBP, AmyCetal. Down-regulation and dese suscistation of the Beta-adrenergic receptor system of human lymphoeyte safter eardiae surgery. AnesthAnalg, 1993, 77: 653-661.
[45]DiteheyRV, SlinkeyBK. Phenyl ephrineplus propren old improves the balance between myocardial oxygen supply demand during experiment CPR. Am Heart J. 1994, 127: 324-330.
[46]Fries M, Tang W, Chang YT, et al. Microvascular blood flow during cardiopulmonary resuscitation is predictive of outcome [J]. Resuscitation, 2006, 71 (2) : 248-253.
[47]Pellis T, Weil MH, Tang W, et al. Evidence favoring the use of an alpha2-selective vasopressor agent for cardiopulmonary resuscitation [J]. Circulation, 2003, 108 (21) : 2716-2721.
[48]Fries M, Weil MH, Chang YT, et al. Microcirculation during cardiac arrest and resuscitation [J]. Crit Care Med, 2006, 34 (12 Suppl) : S454-457.
[49]Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation [J]. Crit Care Med, 2007, 35 (9) : 765-769.
[50]Cerchiari EL, Safar P, Klein E, et al. Cardiovascular function and neurological outcome after cardiac arrest in dog. The cardiovascular Postresuscitation syndrome. Resuscitation, 1993, 25 (1) : 9-33.
[51]DeBehnke D J, Angelos M G, Leasure JE. Use of cardiopulmonary by pass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from postcountershock electromechanical dissociation. Ann Emerg Med, 1992, 21: 1051-1057.
[52]David NT, John BD, Robert AS, et al. epinephrine contrain dieated during CPR. Cireulation, 1997, 96: 2709-2714.
[1] Emergency Cardiac Care Committee and Subcolnmlttees. Ameriean Heastasoeiation. Guidelines for cardioPuImonaly resuseitation and emergency cardiac care. Part3. Adult advanced cardiac life support. JAMA, 1992, 268: 2199-2241.
[2] Strader CD, Fong TM, Tota MR, et al. Strueture and function of G Protein-couPled receptors. Ann Rev biochem, 1994, 63: 101-32.
[3]董尔丹,徐琪,韩启德.β-肾上腺素受体的研究现状.中国科学基金, 2000, 14 (6) : 321-327.
[4]刘俊杰,赵俊.现代麻醉学.第2版.北京:人民卫生出版社, 1998: 808-809
[5] Stiell IG, Hebert PC, Wells GA, et al. Vasopressinv- ersus epinephrinefor inhospital cardiac arrest: a randomize controlled trial. Lancet, 2001, 358: 105-109.
[6]. Ya Kaitis RW, Otto CW, Blitt CD. Relative importance of al-pha and beta adrenergic receptors during resuscitation[J]Crit Care Med, 1979, 7: 293-296.
[7] Lindner K, Ahnefeld F, Bowdler I. Comparison of differrent doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model [J]. Am J Emerg Med, 1991, 9: 27-31.
[8] Gallaham M. Epinephrine doses in cardiac arrest: is it time to outgrow the orthodoxy of ACLS [J]. Am Emerg Meg, 1989, 18: 101-102.
[9] Stiell IG, Herbert PC, Weitzman BN, et al. High-dose epinephrine in adult cardic arrest [J]. N Engl J Med, 1992, 327: 1045-1050.
[10]Brown CG, Werma HA, Darts EA. He effeet of graded doses of epinephine of Regional myoeantial blood flaw during cardiopulmonary resuseitation circulation. JAMA. 1987, 475: 491.
[11]Pardis NA, Martin GB, Rnsenherg J. The effect of standard and high dose epinephrine on coronary pcfusion pressure during prolonged cardiopulmonary resuseition. JAMA, 1991, 256: 1139.
[12]张全贵.静注大剂量肾上腺素抢救心脏骤停的初步研究[J].全军第二届急救医学学术交流会论文汇编, 1991, 81-83.
[13]邓普诊.关于CPCR术成败的几个问题的探讨[J]第六届急救医学学术会议论文汇编, 1996, 328-330.
[14]Standarda and guidelinesrcp. R and ECC. JAMA, 1986, 255-260.
[15]高瑞,奚万山,陈伟宏等.大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响.中国危重病急救医学, 1998, 10 (11) : 648-651.
[16]Lindner KH, Ahnefeld FW, Bowdler IM, Prengel AW. Influence of epinephrine on systemic myocardial and cerebral acid-base statusduring cardiopulmonary resuscitation [J]. Anesthesiology, 1991, 74 (2) : 333-339.
[17]Cheryl R, Chih-chang, et al. Short-Acting-Adrenergic Antahonist Esmolol Given at eperfusion Improves Survial After Prolonged Ventricular Fobrllation[J]. Circulation, 2004, 109: 2469-2474.
[18]David NT, John BD, Robert AS, et al. Epinephrine contrain dieated during CPR. Cireulation, 1997, 96: 2709-2714.
[19]Tang W, Weil MH, et al. Eprnephrine increases the severity of postresuscitation myocardial dysfunction[J]. Circulation. 1995, 92: 3089-3093.
[20]Vandycke C, Martens P, et al. High dose versus standard dose epinephrine in cardiacarrest: ameta-analysis [J]. Resuscitation 2000, 45: 161-167.
[21]涂昌弟.院内心肺复苏成败影响因素的回顾性分析[J].现代预防医学杂志, 2005, 32 (3) : 258-259.
[22]邢绣荣,秦俭,李春盛等.复苏早期应用氨茶碱对心肌超微结构的影响[J]中华急诊医学杂志2005年5月第14卷第5期: 368-372.
[23]Dltchey RV, Perez RA, Slinker BK. Beta-adrenergic block adereduces myocardial injury during experiment cardiopulmonary resuscitation[J]. Am Coll Cardiol, 1994, 24 (3) : 804-812.
[24]Cammarata G, Weil MH, Sun S, et al. Betal-adrenergic bloekade during cardiopulmonary resuscitation improves survival [J]. Crit Care Med, 2004, 32: S440-453.
[25]王道庄心肺复苏的发展争论与展望[M].人民卫生出版社2007年8月第1版, 168-169.
[26]Richard MS, Carol BP, Amy Cetal. Down-regulation and dese suscistation of the Beta-adrenergic receptor system of human lymphoeyte safter eardiae surgery. AnesthAnalg, 1993, 77: 653-661.
[27]DiteheyRV, SlinkeyBK, Phenyl. ephrineplus propren old improves the balance between myocardial oxygen supply demand during experiment CPR. AmHeartJ. 1994, 127: 324-330.
[28]PrengelAW, LinderKH, ThomasA, etal. Regulation of Beta-adrenergic receptor senmononu clear leukoeytes in Patient swith acute is ehemicheart disease. Crie Care Med, 1997, 25: 646- 651.
[29]Rivers EP, Wortsman J, Rady MY, et al. The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest, 1994, 106: 1499-1507.
[30]张全贵,刘光耀,杨志焕等.电击室颤时注射大剂量肾上腺素对犬血流动力学的作用[J].中华创伤杂志, 1995, 11 (5) : 320-322.
[31]Berg RA, Otto CW, Kern KB, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pe-diatric asphyxial cardiac axrest. Crit Care Med, 1996, 24: 1695-1700.
[32]Achleiter U, Wenzel V, Strohmenger HU, et al. The effect of repeated doses of vasopressin or epinephrine on ventricular fibrillation in a proeine model of prolonged cardiopulmonary resuscitation. Anesth Analg, 2000, 90: 1065-1075.
[33]Berkowitz ID, Gervais H, Sehleien CL, et al. Epinephrine dosage effects on cerebral and myoeardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology, 1991, 75: 1041-1050.
[34]DeBehnke DJ, Angelos MG, Leasure JE. Use of cardiopulmonary bypass, High-dose epinephine, and standard-dose epinephrine in resuscitation from post-counter shockel ectromechanical dissociation. Ann Emerg Med, 1992, 21: 1051-1057.
[35]Manningge E, Batson DN. Aorticarhvers ascenral venouse epinephrine during CPR. Ann Emerg Med, 1993, 22: 703-704.
[2] One MEH, Chan YH, Anantharaman V, et al. Cardiac arrest and resuscitation epidemiology in gingapore (CARE I study) [J]. Prehosp Emerg Care, 2003, 7 (4) : 427-433.
[3] Rudner R, Jalowiecki P, Karpel E, et al. Survial after out-of-hospital cardiac arrests in katowice (Poland) : outcome report according to the“Utstelnstyle”[J] Resuscitation, 2004, 61 (3) : 315-325.
[4] Eckstein M, Stratto SJ, Chan LS. Cardiac Arrest Resuscitation Evaluation in Los Angeles: CARE-LA [J]. Ann Emerg Med, 2005, 45 (5) : 504-509.
[5] Nad Karni VM, Larkin GL, Peberdy MA, et al. First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults [J]. JAMA, 2006, 295 (1) : 50-57.
[6] Lindner K, Ahnefeld F, Bowdler I. Comparison of differrent doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model [J]. Am J Emerg Med, 1991, 9: 27-31.
[7] Gallaham M. Epinephrine doses in cardiac arrest: is it time to outgrow the orthodoxy of ACLS[J]. Am Emerg Meg, 1989, 18: 101-1012.
[8] Stiell IG, Herbert PC, Weitzman BN, et al. High-dose epinephrine in adult cardic arrest[J]. N Engl J Med, 1992, 327: 1045-1050.
[9] Ohshige K, Shimazaki S, Hirasawa H, et al. Evaluation of out-of-hospital cardiaopulmonary resuscitation with resuscitative drug: a prospective comparative study in Japan [J]. Resuscitation, 2005, 66 (1) : 53-61.
[10]Babbs CF, Berg RA, Kette F et al. Use of pressors in the treatment of cardiac arrest [J]. Ann Emerg Med, 2001, 37 (4sappl) : S152-162.
[11]邢绣荣,秦俭,李春盛等.复苏早期应用氨茶碱对心肌超微结构的影响[J]中华急诊医学杂志2005年5月第14卷第5期: 368-372.
[12]Ditchey RV, Lindenfeld J. Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs. Circulation, 1998: 78 (2) ?: 382-389.
[13]Rivers EP, Wortsman J, Rady M Y, et al. The effete of the total cumulative epinephrineand dose administered during human CPR on hemodynarnic oxygen transport and utilization variables in the Postresuscitation period[J]. Chest, 1994, 106: 1499-1507.
[14]高瑞,奚万山,陈伟宏等.大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响[J].中国危重病急救医学, 1998, 1011: 649-651.
[15]Cheryl R, Chih-chang, et al. Short-Actingβ-Adrenergic Antahonist Esmolol Given at eperfusion Improves Survial After Prolonged Ventricular Fobrllation[J]. Circulation, 2004, 109: 2469-2474.
[16]Loeckinger A, Kleinsasser A, Wenzel V, et al. Pulmonary gas exchange after cardiopulmonary resuscitation with either vasopressin or epinephrine [J]. Crit Care Med, 2002, 30 (9) : 2059-2062.
[17]Tang W, Weil MH, et al. Eprnephrine increases the severity of postresuscitation myocardial dysfunction [J]. Circulation. 1995, 92: 3089-3093.
[18]Vandycke C, Martens P, et al. High dose versus standard dose epinephrine in cardiac arrest: ameta-analysis[J]. Resuscitation 2000, 45: 161-167.
[19]涂昌弟.院内心肺复苏成败影响因素的回顾性分析[J].现代预防医学杂志, 2005, 32 (3) : 258-259.
[20]Dltchey RV, Perez RA, Slinker BK. Beta-adrenergic blockade reduces myocardial injury during experiment cardiopulmonary resuscitation [J]. Am Coll Cardiol, 1994, 24 (3) : 804-812.
[21]Huang L, Wei MH, Cammarata G, et al. Nonselective bete-blocking agent improves the outcome of cardiopulmonary resuscitation in a rat model [J]. Crit Care Med, 2004, 32 (9suppl) : 378-380.
[22]BrownCG, WermaHA, DartsEA. He effeet of graded doses of epinePhine of regional myceantial blood flaw during cardiopulmonary resuseitation circulation. JAMA. 1997. 75: 491.
[23]Manningge E, Batson DN. Aorticarhvers ascenralvenouse epinephrine during CPR. Ann Emerg Med, 1993, 22: 703-704.
[24]张全贵,刘光耀,杨志焕等.电击室颤时注射大剂量肾上腺素对犬血流动力学的作用[J].中华创伤杂志, 1995, 11 (5) : 320-322.
[25]郑昌军,丁永莉,樊明满等.大剂量肾上腺素治疗心跳骤停的临床观察[J].实用全科医学, 2005, 3 (6) : 518-519.
[26]侯洪,不同剂量肾上腺素对心肺复苏的影响[J].重庆医学, 2005, 4 (8) : 1263-1264.
[27]Pardis NA, MartinGB, RnsenhergJ. The effect of standard and high doseepinephrineon coronary pcfusion pressure during prolongedcardiopulmonary resuseition. JAMA, 1991, 256: 1139.
[28]张全贵.静注大剂量肾上腺素抢救心脏骤停的初步研究[J].全军第二届急救医学学术交流会论文汇编, 1991, 81-83.
[29]邓普诊.关于CPCR术成败的几个问题的探讨[J]第六届急救医学学术会议论文汇编, 1996, 328-330.
[30]陈寿权,李章平,王珊珊等.窒息法致大鼠心脏骤停模型复苏的影响因素[J].中华急诊医学杂志, 2005, 14 (10) : 814-817.
[31]陈尔真,蒋健·复苏实验研究Utstein模式[J]·中国急救医学, 1999, 19 (2) : 70-73.
[32]Chen MH, Liu TW, Xie L, et al. A simpler cardiac arrest model in rats [J] . Am J Emergmed, 2007, 25 (6) : 623-630.
[33]吴景录.不同剂量肾上腺素对心肺复苏的效应[J].临床和实验医学杂志, 2007, 6 (9) : 131-132
[34]AHA. 2005 American Heart Association Guideline for CPR and ECC. Circulation, 2005, 133 (4) : 1-84.
[35]The American Heart Association in collaboration with the International Liaison Committee on Resuscitation Guidelines 2005 for Cardiopulmonary Resuscitation and Emergency Cardiovascular care [J]. Circulation. 2005, 112: W-1-IV-200.
[36]李宗盛,樊寻梅,聚焦2005年ECC及CPR治疗推荐国际会议[J].中华急诊医学杂志, 2005, 14: 871-873.
[37]Gedeborg R, Silander HC. Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation. Crit Care Med, 2000, 28: 1423-1430.
[38]Berg RA, otto CW, Kem KB, et al. High-dose epinephrine results in greater early mortality after resuscitation from prolonged cardiac arrest in pigs: A Prospective, randomized study. Crit Care Med, 1994, 22: 282-290.
[39]Berg RA, otto CW, Kem KB, et al. A randomized, blinded trial of high-dose epinephrine verse standard-dose epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med, 1996, : 1695-1700.
[40]Cammarata G, Weil MH, Sun S, et al. Betal-adrenergic bloekade during cardiopulmonary resuscitation improves survival [J]. Crit Care Med, 2004, 32: S440-453.
[41]王道庄.心肺复苏的发展争论与展望[M].人民卫生出版社2007年8月第1版, 168-169.
[42]Bristow MR. Down-regulation ofβ-adrenergic receptor and recepror mRNA in heart cell chronically exposed to norepinephrine. Clin Res, 1991; 39: 256-258.
[43]Hadcock JR, Malbon CC. Regulation of receptor expression by agonists: transcriptional and post– transcriptional controls. Trends Neurosci, 1991; 14: 242-247.
[44]RichardMS, CarolBP, AmyCetal. Down-regulation and dese suscistation of the Beta-adrenergic receptor system of human lymphoeyte safter eardiae surgery. AnesthAnalg, 1993, 77: 653-661.
[45]DiteheyRV, SlinkeyBK. Phenyl ephrineplus propren old improves the balance between myocardial oxygen supply demand during experiment CPR. Am Heart J. 1994, 127: 324-330.
[46]Fries M, Tang W, Chang YT, et al. Microvascular blood flow during cardiopulmonary resuscitation is predictive of outcome [J]. Resuscitation, 2006, 71 (2) : 248-253.
[47]Pellis T, Weil MH, Tang W, et al. Evidence favoring the use of an alpha2-selective vasopressor agent for cardiopulmonary resuscitation [J]. Circulation, 2003, 108 (21) : 2716-2721.
[48]Fries M, Weil MH, Chang YT, et al. Microcirculation during cardiac arrest and resuscitation [J]. Crit Care Med, 2006, 34 (12 Suppl) : S454-457.
[49]Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation [J]. Crit Care Med, 2007, 35 (9) : 765-769.
[50]Cerchiari EL, Safar P, Klein E, et al. Cardiovascular function and neurological outcome after cardiac arrest in dog. The cardiovascular Postresuscitation syndrome. Resuscitation, 1993, 25 (1) : 9-33.
[51]DeBehnke D J, Angelos M G, Leasure JE. Use of cardiopulmonary by pass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from postcountershock electromechanical dissociation. Ann Emerg Med, 1992, 21: 1051-1057.
[52]David NT, John BD, Robert AS, et al. epinephrine contrain dieated during CPR. Cireulation, 1997, 96: 2709-2714.
[1] Emergency Cardiac Care Committee and Subcolnmlttees. Ameriean Heastasoeiation. Guidelines for cardioPuImonaly resuseitation and emergency cardiac care. Part3. Adult advanced cardiac life support. JAMA, 1992, 268: 2199-2241.
[2] Strader CD, Fong TM, Tota MR, et al. Strueture and function of G Protein-couPled receptors. Ann Rev biochem, 1994, 63: 101-32.
[3]董尔丹,徐琪,韩启德.β-肾上腺素受体的研究现状.中国科学基金, 2000, 14 (6) : 321-327.
[4]刘俊杰,赵俊.现代麻醉学.第2版.北京:人民卫生出版社, 1998: 808-809
[5] Stiell IG, Hebert PC, Wells GA, et al. Vasopressinv- ersus epinephrinefor inhospital cardiac arrest: a randomize controlled trial. Lancet, 2001, 358: 105-109.
[6]. Ya Kaitis RW, Otto CW, Blitt CD. Relative importance of al-pha and beta adrenergic receptors during resuscitation[J]Crit Care Med, 1979, 7: 293-296.
[7] Lindner K, Ahnefeld F, Bowdler I. Comparison of differrent doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model [J]. Am J Emerg Med, 1991, 9: 27-31.
[8] Gallaham M. Epinephrine doses in cardiac arrest: is it time to outgrow the orthodoxy of ACLS [J]. Am Emerg Meg, 1989, 18: 101-102.
[9] Stiell IG, Herbert PC, Weitzman BN, et al. High-dose epinephrine in adult cardic arrest [J]. N Engl J Med, 1992, 327: 1045-1050.
[10]Brown CG, Werma HA, Darts EA. He effeet of graded doses of epinephine of Regional myoeantial blood flaw during cardiopulmonary resuseitation circulation. JAMA. 1987, 475: 491.
[11]Pardis NA, Martin GB, Rnsenherg J. The effect of standard and high dose epinephrine on coronary pcfusion pressure during prolonged cardiopulmonary resuseition. JAMA, 1991, 256: 1139.
[12]张全贵.静注大剂量肾上腺素抢救心脏骤停的初步研究[J].全军第二届急救医学学术交流会论文汇编, 1991, 81-83.
[13]邓普诊.关于CPCR术成败的几个问题的探讨[J]第六届急救医学学术会议论文汇编, 1996, 328-330.
[14]Standarda and guidelinesrcp. R and ECC. JAMA, 1986, 255-260.
[15]高瑞,奚万山,陈伟宏等.大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响.中国危重病急救医学, 1998, 10 (11) : 648-651.
[16]Lindner KH, Ahnefeld FW, Bowdler IM, Prengel AW. Influence of epinephrine on systemic myocardial and cerebral acid-base statusduring cardiopulmonary resuscitation [J]. Anesthesiology, 1991, 74 (2) : 333-339.
[17]Cheryl R, Chih-chang, et al. Short-Acting-Adrenergic Antahonist Esmolol Given at eperfusion Improves Survial After Prolonged Ventricular Fobrllation[J]. Circulation, 2004, 109: 2469-2474.
[18]David NT, John BD, Robert AS, et al. Epinephrine contrain dieated during CPR. Cireulation, 1997, 96: 2709-2714.
[19]Tang W, Weil MH, et al. Eprnephrine increases the severity of postresuscitation myocardial dysfunction[J]. Circulation. 1995, 92: 3089-3093.
[20]Vandycke C, Martens P, et al. High dose versus standard dose epinephrine in cardiacarrest: ameta-analysis [J]. Resuscitation 2000, 45: 161-167.
[21]涂昌弟.院内心肺复苏成败影响因素的回顾性分析[J].现代预防医学杂志, 2005, 32 (3) : 258-259.
[22]邢绣荣,秦俭,李春盛等.复苏早期应用氨茶碱对心肌超微结构的影响[J]中华急诊医学杂志2005年5月第14卷第5期: 368-372.
[23]Dltchey RV, Perez RA, Slinker BK. Beta-adrenergic block adereduces myocardial injury during experiment cardiopulmonary resuscitation[J]. Am Coll Cardiol, 1994, 24 (3) : 804-812.
[24]Cammarata G, Weil MH, Sun S, et al. Betal-adrenergic bloekade during cardiopulmonary resuscitation improves survival [J]. Crit Care Med, 2004, 32: S440-453.
[25]王道庄心肺复苏的发展争论与展望[M].人民卫生出版社2007年8月第1版, 168-169.
[26]Richard MS, Carol BP, Amy Cetal. Down-regulation and dese suscistation of the Beta-adrenergic receptor system of human lymphoeyte safter eardiae surgery. AnesthAnalg, 1993, 77: 653-661.
[27]DiteheyRV, SlinkeyBK, Phenyl. ephrineplus propren old improves the balance between myocardial oxygen supply demand during experiment CPR. AmHeartJ. 1994, 127: 324-330.
[28]PrengelAW, LinderKH, ThomasA, etal. Regulation of Beta-adrenergic receptor senmononu clear leukoeytes in Patient swith acute is ehemicheart disease. Crie Care Med, 1997, 25: 646- 651.
[29]Rivers EP, Wortsman J, Rady MY, et al. The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest, 1994, 106: 1499-1507.
[30]张全贵,刘光耀,杨志焕等.电击室颤时注射大剂量肾上腺素对犬血流动力学的作用[J].中华创伤杂志, 1995, 11 (5) : 320-322.
[31]Berg RA, Otto CW, Kern KB, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pe-diatric asphyxial cardiac axrest. Crit Care Med, 1996, 24: 1695-1700.
[32]Achleiter U, Wenzel V, Strohmenger HU, et al. The effect of repeated doses of vasopressin or epinephrine on ventricular fibrillation in a proeine model of prolonged cardiopulmonary resuscitation. Anesth Analg, 2000, 90: 1065-1075.
[33]Berkowitz ID, Gervais H, Sehleien CL, et al. Epinephrine dosage effects on cerebral and myoeardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology, 1991, 75: 1041-1050.
[34]DeBehnke DJ, Angelos MG, Leasure JE. Use of cardiopulmonary bypass, High-dose epinephine, and standard-dose epinephrine in resuscitation from post-counter shockel ectromechanical dissociation. Ann Emerg Med, 1992, 21: 1051-1057.
[35]Manningge E, Batson DN. Aorticarhvers ascenral venouse epinephrine during CPR. Ann Emerg Med, 1993, 22: 703-704.