药物预处理对离体心脏保存作用的实验研究
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摘要
目的:
     研究药物预处理及在改良的St.Thomas Ⅱ液中加入钾离子通道开放剂和阿片受体激动剂对离体心脏的保存效果。以及尼可地尔再灌注对减轻钙离子超载的作用。为改善供心保存寻求更有效的方法。
     方法:
     1.利用改良的Langendorff灌注装置,建立离体心脏灌注模型。
     2.在ST,Thomans Ⅱ液中加入尼可地尔作为实验组Ⅰ组的离体心脏保存液(钾离子浓度8.0mmol/L)。观察药物预处理及低温保存不同时间和再灌注30min后离体心脏的恢复情况;对照组用UW液作为离体心脏的保存液;
     3.在尼可地尔预处理和低温下保存8h的基础上,在K-H灌注液中加入尼可地尔,观察其保护效果。与尼可地尔预处理和低温保存8h组相比较。
     4.在ST,Thomans Ⅱ液中加入U50,448H作为实验组Ⅱ组的离体心脏保存液(钾离子浓度8.0mmol/L)。观察药物预处理及低温保存不同时间和再灌注30min后离体心脏的恢复情况;与尼可地尔预处理低温保存组比较。观察二者对离体心脏保存作用的差异。
     5.实验动物大白兔在麻醉前分别用尼可地尔或阿片受体激动剂U50,488H预处理。
     6.实验动物依据离体供心的保存时间不同分为4个时间点进行观察:保存4h,6h,8h,10h。尼可地尔预处理和低温保存+尼可地尔再灌注组只观察保存8h的心脏变化。
     7.记录冷灌前心功能指标。测定再灌注30min时离体心脏的左室发展压(DP)和左室压力微分(±dp/dt)、冠状动脉流量(CF)、并计算心功能恢复百分比,留取冠状动脉引流液测定心肌酶(LDH、CK)、心肌线粒体钙含量、肌浆
    
     举四军反大掌硕士研究生毕业论文
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     网ca2+一ATPase活性、心肌细胞ATP含量,心肌组织含水量,并观察心肌
     超微结构。
    结果:
    1.尼可地尔预处理低温保存组:离体心脏在经尼可地尔预处理低温保存后随
     着保存时间的延长钙离子仍有明显的超载,实验组与对照组相比心功能恢
     复率及钙离子超载程度在保存6h内的结果差异性不显著(p>0.05);在
     sh后二个时间点的钙离子超载程度结果差异性明显(p<0.01)。
    2.离体心脏在经尼可地尔预处理和低温保存后对Caz+一ATPase活性有保护作
     用;实验组和对照组CaZ十一ATPase活性在相应的时间点存在明显差异(P<
     0.01);两组线粒体钙离子含量在8h组存在明显差异(P<0.05)。
    3.尼可地尔预处理可以明显改善心肌结构的改变;Uw液对冠脉血管内皮损
     伤严重,使心脏再灌注后冠状动脉流量恢复率明显减少
    4.尼可地尔预处理和低温保存+尼可地尔再灌注可以进一步减轻钙离子的
     超载,减轻心肌结构的变化,但心功能的恢复较尼可地尔预处理和低温保
     存组降低,且有明显差异(p<0.05)。
    5.U50,4 88H预处理和低温保存离体心脏可以减轻钙离子超载;实验组不同
     保存时间点的组间比较,钙离子超载程度、Ca2+一ATPase活性、ATP含量
     等相比较存在明显的差异。但与对照组相比较,钙离子的超载程度、
     ca2+一ATPase活性在不同的保存时间点,没有明显的差异(p>0.05)。
    6.阿片受体激动剂U50488H和钾离子通道开放剂尼可地尔对离体心脏预处
     理和低温保存作用没有明显的差异性
    结论:
    1.尼可地尔预处理和低温保存离体心脏可以减少心肌细胞的钙离子超载,
     减轻缺血再灌注损伤.供心保存时间在6h内,与Uw液的保存效果相当。
     在sh组UW液的保存效果较尼可地尔预处理和低温保存差
    2.改良ST,ThomanSH(K+浓度8n’uno1/L)液可以使心脏平稳的停跳,砂自脏停
     跳所需时间较高钾的Uw液有所延长,但差异性不显著
    3.高钾的Uw液对心脏血管内皮有明显的损伤。并且使心肌组织的水肿程度
     增加。
    注.尼可地尔再灌注可以进一步减轻钙离子超载,减轻缺血再灌注损伤,但
    
    举四军反大学硕士研究生华业论文
     对心功能的恢复有一定的负面影响。尼可地尔再灌注与尼可地尔预处理
     对心脏结构保存和保护有协同作用。
    5.阿片受体激动剂U50,488H预处理和低温保存对离体心脏有一定的保护作
     用,其作用和钾离子通道开放剂尼可地尔作用效果基本相同。
Objective
    To study the action of Pretreatment to isolated rabbit hearts with the Potassium ionic channel opener Nicorandil and the opium recepter Excitation opener U50588H by improve Langendorff perfusion model. The preservation action was observed for the Nicorandil to re-perfuse the isolated rabbit hearts to relieve calcium ions overloading and to preserve time. To observed the preservation effect for isolated rabbit hearts with improved St.Thomas II solution, to explore a new operative preservation way for the isolated heart in clinical heart transplantation. Method
    1. The Langendorff perfusion assembly was used to set up perfusion model for isolated hearts.
    2. The Nicorandil was added into ST,Thomans II solution as isolated hearts' preservation solution for study group I (K+ was 8mmol/L). To observe the variation of Cardiac function restoration, cardiac muscle cell calcium ions, myocardium Adenosine triphosphate (ATP), myocardium enzyme, the water in myocardium, myocardium ultrastructure, et al. The University of Wisconsin solution (UW) as a kind of preservation solution was used for isolated hearts in control group.
    3. On the base of Nicorandil Pretreatment and Nicorandil solution to hypothermia preserve the isolated hearts for 8h, moreover added the Nicorandil into the Krebs-Hensleit solution to perfuse the isolated rabbit hearts, to observe its protection effect for isolated rabbit hearts. The control group that was Pretreatment by Nicorandil and Nicorandil solution to preserve in hypothermia the isolated hearts for 8h.
    4. The U50488H was added into ST.Thomans II solution as a kind of isolated
    
    
    
    hearts' preservation solution for study group II (K+ was 8mmol/L). To observe the variation of Cardiac function restoration, cardiac muscle cell calcium ions, myocardium ATP, myocardium enzyme, and the water in myocardium, myocardium ultrastructure, et al. To compare with the different for the isolated rabbit hearts between in this group and Nicorandil Pretreatment group.
    5. Experiment animals the big white rabbits were pretreatment by Nicorandil or U50,488H before anesthetized.
    6. According to the different preservation times for the isolated rabbit hearts, the experiment animals were divided into four time points to observe: four hours; six hours; eight hours and ten hours. About the Nicorandil re-perfusion, we only observed the isolated hearts that were preserved for eight hours group.
    7. Read-in the Cardiac function markers about the isolated hearts before them were perfuse the cardioplegia solution. To assay the left ventricular developed pressure (LVDP), left ventricular pressure differential and integral calculus (眃p/dt), coronary artery flow (CF) and to compute the percentage for Cardiac function recover; Assay the myocardium enzyme (lactate dehydrogenase, LDH; the cardiac muscle phosphokinase, CK) from the coronary artery drainage solution , the Content of calcium in myocardium mitochondrion, sarcoplasmic reticulum Ca2+-ATPase activity, ATP content in myocardium, myocardium water content and to obverse the myocardium ultrastructure.
    Result
    1. There wasn't obviously difference for the rate of the cardiac function recover between test group and control group when the preservation time less then six hours (P>0.05) ,but the rate of the cardiac function recover there was obviously difference in two groups(p<0.05); at ten hours the cardiac function recover there wasn't obviously difference (P > 0.05) .
    2. Nicorandil Pretreatment could safeguard the Ca2+-ATPase activity, meanwhile it could relieve calcium ions overloading. About the Ca2+-ATPase activity at the same time there was obviously difference between test group and control
    
    group(p<0.01); After eight hours, the mitochondrion calcium ions there were obviously difference (p<0.05).
    3. Nicorandil Pretreatment could obviously improve myocardium structural; UW solution could cause Severity injury for coronary artery endothelium, this made the recovery rate of the corona
引文
1.夏求明,臧旺福.心脏移植进展.中华器官移植杂志,1999,20(4):201-203。
    2. Keck BM, White R, Breen TJ, Daily OP,Hosenpud JD. Thoracic orang transplants in the United States: a report from the UNOS/ISHLT Scientific registry for Organ Transplants, United Network for Organ Sharing. International Society for heart and lung transplantation. Clin Transplant, 1994, 37-46.
    3.肖礼祖,罗伟.体外循环心肌保护的研究进展.心肺血管病杂志,2000,21(3):178-180.
    4. Lichtensein SV, Ashe KA, Dalati H, Cusimano RJ,Panos A,Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg, 1991,101(2):269-274.
    5. Argano V, Galinanes M, Edmondson S,Hearse DJ.Effect of cardioplegia on vascular function and the"No-Reflow"phenomenon after ischemia and reperfusion:study in the isolated blood-perfued rat heart. J Thorac Carsiovasc Surg, 1996,111 (2): 432-441.
    6. Follete DM. Advantage of blood cardioplegia over continous coronary perfusion or intermitted ischemia: Experimental and clinical study. J Thorac Cardiovasc Surg, 1978,776:604-612.
    7. Samuel VL, Abel JC, Salerno AT. Warm heart suegery and results of operation for recent myocardial infarction. Ann Thorac Surg,1991, 5(3):455-458.
    8. Christakis GT, Graver JM, Deam.ar KA, Fremes SE,Sinclair L,Chen E,Salemo TA,Goldman BS,Lichtenstein SV.A randomized study of systemic effects of warm heart surgery. Ann Thorac Surg, 1992,54(3): 449-457.
    9. Martin TD, Graver JM, Gott JP, Weintraub WS, Ramsay J,Mora CT, Guyton RA. Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefits and neurologic threat. Ann Thorac Surg, 1994, 57(2): 298-320.
    10. Cave AC, Hearse DJ. Ischemic preconditioning and contractile function: studies with normothermic hypothermic global ischemic. J Mol Cell Cardiol,1992, 24(10):1113-1119.
    11. Illes RW, Wright JK, Inners-McBride K,Yang CJ,Tristan A.Ischemic preconditioning improves preservation with crystailoid cardioplegia. Ann Thorac Surg 1994, 58(5):
    
    1481-1485.
    12.陈胜喜,殷桂林,张殿堂,鲁尔雄。缺血预处理与心麻液结合对离体大鼠心脏缺血再灌注损伤的保护。中华胸心血管外科杂志,1997,13(2):110-112。
    13. Belzer FO, Southard JH. Priciples of solid organ preservation by cold storage. Transplantation,1988,45 (4):673-676.
    14.韩涛,姚祖武,鲍家银,李梅珍。前列腺素El及硝酸甘油在离体肺保护中应用的实验研究。中华器官移植杂志,1998,19(2):89-91。
    15.邱罕凡,廖崇先,陈道中。持续低流量灌注对兔心肺联合保存的作用。中华器官移植杂志,1998,19(4):197-199。
    16. Wicomb WN, Collins GM. 24-hour rabbit heart tsorage with UW solution: effects of low-flow perfusion colloid and shelf storage. Transplantation, 1989, 48(1): 6-9.
    17. Ferrera R, Larese A, Marcsek P, Guidollet J,Verdys M,Dittmar A,Dureau G.Comparison of different techniques of hypothermic pig heart preservation.Ann Thorac Surg,1994,57(5):1233-1239.
    18. Minten J, Van-Hecke P, Vanstapel F, Flameng W. 31P-NMR study of cardiac preservation: St.Thomas' Hospital cardioplegic solution versus UW preversation solution.Transpl-Int, 1991,4(2):82-87.
    19. Tsutsumi H, Oshima K, Mohara J,Takeyoshi I,Aizaki M,Tokumine M,Matsumoto K,Morishita Y. Cardiac transplantantion following a 24h preservation using a perfusion apparatus.J Surg Res,2001,96(2):260-267.
    20. Mohaea J, Tsutusmi H, Takeyoshi I, Tokumine M,Aizaki M,Ishiawa S,Matsumoto K,Morishita Y.The optima pressure, for initial flush with UW solution in heart procurement. J Heart Lung transplant,2002,21 (3):383-390.
    21. Stringham JC, Love RB, Welter D,Canver CC,Mentzer RM Jr. Impact of University of Wisconsin solution on clinical heart transplantation.A comparison with Stanford solution for extended preservation. Criculation, 1998,98(19suppl): 157-161。
    22. Alvarez L, Torralba A, Escudero C.Structural and ultrastructural sturdy of the myocardium after 24-hour preservation in University of Wisconsin solution. Histol histopathol, 1997,12(2):375-382.
    23. Askenasy N, Navon G. Intracellular volumes and membrane permeability in rat hearts during prolonged hypothermic preservation with St Thomas and University of
    
    Wisconsin solution. J Mol Cell Cardiol, 1998,30(7): 1329-1339.
    24. Mocanu MM, Gadgil S, Yellon DM, Baxter GF. Mibefradil, a T-type and L-type calcium channel blocker, limits infarct size through a glibenclamide-sensitive mechanism Cardiovasc Drugs Ther, 1999, 13(2): 115-122.
    25. Lawton JS, Hsia PW, Damiano RJ Jr. The adenosine-triphosphate-sensitive potassium-channel opener pinacidil is effective in blood cardioplegia. Ann Thorac Surg, 1998, 66(3): 768-773.
    26. Tanaka H, Okazaki K, Shigenobu K. Cardioprotective effects of NIP-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium. J Cardiovasc Pharmacol, 1996,27(5):695-701.
    27. Grover GJ. Protective effects of ATP-sensitive potassium-channel openers in experimental myocardial ischemia. J Cardiovasc Pharmacol, 1994, 24(suppl 4):S18-27.
    28. Jayawant AM, Stephenson ER, Mattw GS,Prophet GA,LaNoue KF, Griffith JW, Damiano RJ Jr. Potassium-channel opener cardioplegia is superior to St. Thomas' solution in the intact animal. Ann Thorac Surg, 1999,68(1):67-74.
    29. Behling RW, Malone HJ. KATP-channel openers protect against increased cytosolic calcium during ischaemia and reperfusion. J Mol Cell Cardial, 1995,27(9):1809-1817.
    30. Monticello TM, Sargent CA, Mc Gill JR,Barton DS,Grover GJ. Amelioration of ischemia/reperfusion injury in isolated rats hearts by the ATP-sensitive potassium channel opener BMS-180448. Cardiovasc Res,1996,31 (1):93-101.
    31. Satoh K, Yamada H, Taira Nl. Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries. Naunyn Schmiedebergs Arch Pharmacol, 1991,343(1):76-82.
    32. Murry CE, Jenning RB, Reimer KA. Preconditioning with ischemia; delay of lethal cell injury in ischimc myocardium. Circulation, 1986, 74(5): 1124-1136.
    33. Reimer A, Jennings RB, Tatum AH. Pathologey of acute myocardidal ischemia: metabolic, functional and ultrastructural studies. Am J Cardiol,1983, 52(2):72A-81A.
    34. Goto M, Liu Y, Yang XM, Ardell JL, Cohen MV, Downey JM. Role of bradykin in protection of ischemiic preconditioning in rabbit hearts. Circ Res, 1995,77(3):611-612.
    35. Liu Y, Downey JM. Preconditioning against infarction in the rat heart does not involve a pertussis tox in sensitive G protein. Cardiovasc Res, 1993, 27(4):608-611.
    
    
    36. Noda K, Sasagui M, Idesishi M, Ikeda M, Arakawa K. Role of locally formed angiotens in Ⅱ and bradykin in the reduction of myocardial infarct size in dogs. Cardiovasc Res, 1993, 27(2):334-340.
    37. Wikstrom BG, Ronquist G, Waldenstom A. Dynamics of myocardial metabolism in the preconditioning porcine heart studied using continuous microdialysis. Eur Heart J, 1995,16(4):563-569.
    38. Deutsch E, Berger M, Kussmaul WG, Hirshfeld JW Jr, Herrmann Hc. Adaptation to ischemia during percutaneous translum inal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation, 1990, 82(8):2044-2051.
    39. Tauskela JS, Chakravarthy BR, Murray CL, Wang Y, Comas T, Hogan M. Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart. Brain Res,1999, 827(1-2): 143-151.
    40. Wylen PGL. Effect of ischemic preconditioning on interstitial purine metabolite and accumulation during myocardial ischemia. Circulation, 1994, 89(5): 2283-2287.
    41. Brew EC, Mitchell MB, Rehing TF, Gamboni-Robertson F, McIntyre,RC Jr, Harken AH,Baneriee B.Role of bradykinin in cardiac functional protection after global ischemia reperfusion in rat heart.Am J Physiol, 1995,269(4 pt 2):H1370-1378.
    42. Mitchell MB, Meng X, Ao L, Brown JM, Harken AH, Banerjee A. Preconditioning of isolated rat heart is mediated by protein kinase C. Cire Res, 1995,76(1):73-81.
    43. Parrat JR. Protection of the heart by ischemic preconditioning: mechanisms and possibilities for pharmacological exploitation. Trends Pharmacol Sic, 1994,15(1): 19-25.
    44. Schultz JE, Hsu AK, Gross GJ, Nagase H, Gross GJ.TAN-67,a delta-opioid receptor agonist reduces infarct size via cativation of Gi/o proteins and KATP channels.Am J Physiol,1998,274(3 pt 2):H909-H914.
    45. Li YJ, Xiao ZS, Peng CF, Deng HW.Calcition in gene-related peptide-induced preconditioning protects against ischemia-reoerfusion injury in isolated rat hearts.Eur J Pharmacol, 1996, 311 (2-3): 163-167.
    46. Ferdinandy P, Csont T, Csonka C, Torok M, Dux M, Nemeth J,et al.Capsaicin-sensitive local sensory innervation is involved in pacing-induced preconditioning in rat hearts:role of nitric oxide and CGRP?.Naunyn Schmiedebergs Arch Pharmacol, 1997, 356(3): 356-363.
    
    
    47. Zhou FW, Li YJ, Lu R, Deng HW. Protection of calctionin gene-related peptide-mediated preconditioning against cornary endothelial dysfunction induced by reperfusion in the isolated rat heart. Life Sic, 1999, 64(13): 1091-1097.
    48. Lu R, Li YJ, Deng HW.Evidence for calcitionin gene-related peptide-mediated ischemic preconditioning in the rat heart. Regul Pept,1999, 82(1-3):53-57.
    49. Noma A. ATP regulated K+ channelin cardiac muscle. Nature 1983;305:147~8.
    50.刘秀华,王士雯。受体 氨酸激酶在心肌缺血预处理延迟保护机制中的作用。心血管病进展。1999,20(4):207—209
    51. Amrani M, Corbett J, Boateng SY, Duan MJ,Yacoub MH. Kinetics of induction and protective effect of heat-shock proteins after cardioplegic arrest. Am rani M,et al.Ann thorac surg, 1996,61 (5): 1407-1412.
    52. Zhou X, Zhai X,Ashraf M. Direct evidence that initial oxidative stress triggered by preconditioning contributes to second window of protection by endogenous antioxidant enzyme in myocytes. Circulation, 1996, 93(6): 1177-1184.
    53. Pang C, Doubell AF. Mitogen-activated protein kinase (MAPK) in cardiac tissues. Mol Cell Biochen, 1996,157(1-2):49-57.
    54. Van Winkle DM, Thornton J, Downey JM. Cardioprotection from ischemic preconditioning is lost following prolonged reperfusion in the rabbit. Coronary Artery Dis, 1991, 2(12):613-618.
    55.宗普。人类心肌预适应的最新研究进展。国外医学,疾病分册,1996,287(5):284-287.
    56. Baxter GF, Marber MS,Patel VC,Yellon DM. Adenosine receptor involved in a delayed phase of myocardial protection 24 h after ischemic preconditioning.Circulation, 1994, 90(6):2993-3000.
    57. Bouchard JF, Lainontagne D. Mechanisms of protection afforded by preconditioning to endothelial function against ischemic injury.Am J Physio,1996,271(5 pt 2):HI 801-806.
    58. Liu GS, Thornton J,Van Winkle DM, Stanley AW, Olsson RA. Protection against infarction afforded by preconditioning is mediated by Al adenosine recerptor in rabbit heart. Circulation,1991,84(1):350-356.
    59. Schwars ER, Mohri M, Sack S, et al. The role of adenosine and its Al recerpor in ischmic preconditioning. Circulation, 1991,84(Sup 11): 192.
    
    
    60. Thornton JD, Liu GS, Downet JM. Preteratment with pertussis toxin blocks the protective effects of preconditioning evidence for a G protein machanism. J Mol Cell Cardiol,1993, 25(3):311-320.
    61. Toombs CF, MeCee DS, Johnston WE, Witen-Johansen J. Myocardial protective effects of adenosine: infract size reduction with ptetretment and continued recerpter stimulation during ischemia. Circulation, 1992, 86(3):986-994
    62. Cara AC, Colliscs, Doweny JM, et al. Improved functioal recorery by ischemic preconditioning is not mediated by adenosine in the gioblly ischemic indated rat heart. Cardiovasc Res, 1993, 27:663.
    63. Ihnken K, Morita K, Breckberg GD.New approaches to blood cardioplegia delivering to reducing hemodilution and cardioplegic overdose.J Card Surg 1994;9:26,
    64. Liu Y, Ytrehus K, Downey JM. Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J Mcc Carkic,1994, 26(5):661-668.
    65. Speechly-Dick ME, Mocanu MM, Yellon DM. Protein kinase C. Its role in ischemic preconditioning in the rat. Circ Res, 1994,75(3):586-590.
    66. Cohen MV, Doweney JM. Myocardial preconditioning promises to be a novel approach to the treatment of ischemic heart disease. Annu Rev Med, 1996, 47:21-29.
    67. Yoshiyama M, Kim S, Yanagishi H, Omura T, Tani T, Yanagi S,Toda I, Teragaki M,Akioka K, Takeuchi K. Cardioprotective effect of the angiotensin in type receptor antagonist TCV-116 on ischemia-reperfusion injury. Am Heart J. 1994, 128(1): 1-6.
    68. Schultz JE, Rose E,Yao Z, Gross GJ. Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol, 1995, 286(5 pt 2):H2157-2161.
    69. Lazclunaki M. Agonists and antagonists of ATP-sensitive potassium channels. Adv Nephr, 1992;21 (2): 195-205.
    70. Thuringer D, Escande D. Apparent competition between ATP and the potassium channel opener, RP49356, on ATP-sensitive K+ channels of cardiac myocytes. Mol Phamacol, 1990; 36(6): 897-902
    71. Richard V, Blauc T, Kaeffer N,et al. Myocardial and coronary endothelial protective effects of acetylcholineafter myocardial ischemia and reperfusion in rats:role of nitric oxide. Br J Phamacol, 1995,115(8):1532.
    
    
    72. Maulik N, Engelman DT, Watanabe M, Engelman RM, Maulik G, Cordis GA, Das DK. Nitric oxide signaling in ischemic heart. Cardiovasc Res, 1995, 30(4):593-601.
    73. Piacentini L, Wainwright CL,Parratt JR.The antiarrhythmic effect of ischemic preconditioning in isolated rat heart involves a pertussis tox in sensitive mechanism. Cardiovasc Res, 1993,27(4):674-680.
    74. Tsuchida A, Liu Y, Liu GS, Cohen MV, Doweny JM. Alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein Kinase C. Cire Res, 1994, 75(3):576-585
    75. Banerjee A, Locke-Winter C, Rogers KB, itchell MB, Brew EC, Caiena CB, Bensord DD, Harken AH. Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha 1-adrenergic mechanism. Circ Res, 1993,73(4):656-670.
    76. Laskey WK. Beneficial impact of preconditioning during PTCA on creatine kinase release. Circulation, 1999, 99(16):2085-2089.
    77. Szmagaia P, Morawski W, Krejca M, Gburek T, Bochenek A.evaluation of perrioperative myocardial tissue damage in ischemically preconditioning human heart during aorto-coronary bypass surgery. J Cardiovasc Surg(Torino)), 1998,39(6):791-795.
    78. Jenkins DP, Pugsley WB,Alkhulaifi AM,Kemp M,Hooper J,Yellon DM.Ischemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery.Heart, 1997,77(4):314-318.
    79. Kalliner G, Owall A,Franco-Cereceda A.Myocardial outflow CGRP in relation to metabolic stress during coronary artery bypass grafting without cardiopulmonary bypass. J Thorac Surg, 1999,117(3):447-453.
    80. Jefayri MK, Grace PA, Mathie RT. Attention of reperfusion injury by renal ischaemic preconditioning: the role of nitric oxide.BJU Int,2000; 85(9): 1007-1013.
    81.郭杰,姜洪池,王淑杰,徐学武,杨大平,鲁开化.金属硫蛋白参与皮瓣缺血预处理的延迟保护作用。中国美容医学,2002,11(1):4—7.
    82. Wu D, Pardridge WM. Neuroprotection with noninvasive delivery to the brain. Proc Natl Acad Sic USA, 1999, 96(1):254-259.
    83. Carini R, Cesaris MG, Splendore R, Vay D,Domenicotti C, Nitti MP, Paola D,Pronzato MA, Albano E. Signal pathway involved in the development of hypoxic preconditioning in rat hepatocytes. Hepatology, 2001, 33(1): 131-139.
    
    
    84.金祝秋。药物行预适应的心肌保护作用.国外医学生理、病理科学与临床分册,1997,17(2):106—109.
    85. Hori M and Kitaze M. Adenosine, the heart and coronary circulation. Hypertension, 1991, 18(5):565-574.
    86. Brew EC, Mitchell MB, Rechring TF, Gamboni-Bobertson F, McIntyre RC Jr, Harken AH, Banerjee A. Role of bradykinin in cardiac function pretection after global ischemia reperfusion in rat heart.Am J Phsiol, 1995,269(4pt 2):H1370-1178.
    87. Elliott GT. Monophosphoryl lipid A induces delayed preconditioning against cardiac ischmia reperfusion injury. J Mol Cell Cardiol,1998, 30(1):3-17.
    88. Speechly Dick ME, Mocann MM, Yellow DM. Proteir kinase C Its role in ischemic preconditioning in the rat. Cir Res,1994,75(3):586-591..
    89. Marc F, Janier, Jean-Lous J, et al. Ischemic preconditioning stimulates anaeroblic glycolysis in the isolated rabbit hearts. Am J Physiol, 1994, 267;H1 353.
    90. Yang XM, Sato H, Downey JM, Cohen MV. Protection of ischemic preconditioning is dependent upon a critical timing sequence of protein kinase C activation. J Mol Cell Cardiol, 1997, 29(3):991-999.
    91. Parrat JR. Protection of the heart by ischemic precondition: mechanisms and possibilies for pharimacological exploitation. T rends Pharmacol Sci, 1994,15(1): 19-25.
    92. Baxter GF, Marber MS, patel VC, Yellon DM. Adenosine receptor involved in a delayed phase of myocardial protection 24h after ischemic preconditioning [J].J Circulation, 1994,90(6):2993-3000.
    93. Takano H, Manchikalapudi S, Tang XL,Qiu Y, Rizvi A, Jadoon AK, Zhang Q, Bolli R. Natric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation, 1998, 98(5):441-449.
    94. Chien S, Oeltgen PR, Diana JN, Salley RK, Su TP. Extension of tissue survival time in multiorgan block preparation with a delat opioid DAALE[J]. J Thorac Cardiovasc Surg, 1994,107(3):964-967.
    95. Tai KK, Jin WQ, Chan TK, Wang TM. Characterization of [3H]-U69593 binding sites in the rat heart by receptor binding studies. J Mol Cell Cardio.. 1991;23(1):1297-1302.
    96. Reuven Z, Dov G, Heskel E, et al. Expression of opioid receptors during heart ontogeny in normotensive and hypertensive rats. Circ, 1996; 93:1020-1025.
    
    
    97. Jin WQ, Tai KK, Chan T, Wang TM. Further characterization of [3H] U69593 binding sites in the rat heart. J Mol Cell Candiol, 1995, 27(8): 1507-1511.
    98. Schultz J, Rose E, Yao Z, Gross GJ. Evidence for involvement of opioid receptors in ischemic preconditioning in rat heart. Am J Physiol, 1995, 268(37):H2157-H2161 .(5 pt 2)
    99. Miki T, Downey J. Opioid receptors participate in ischemic preconditioning in rabbits (Abstract). J Mol Cell Cardiol, 1996,28;A187.
    100. Miki T, Cohen M, Downey J. Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits [J].Mol Cell Biochein, 1998,186(1-2):3-12.
    101. Schultz JJ, Hsu AK, Gross GJ. Ischemic preconditioning and morphine induced cardioprotective involve the delta(δ)-opioid receptor in the intact rat heart [J]. J Mol Cell Cardiol,1997,29(5):1355-1362.
    102. Schultz JJ, Hsu AK, Gross GJ. Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart[J]. Circ Res, 1996,78(6): 1100-1104.
    103. Miyawaki H, Ashraf M. Ca2+ as a mediator of ischemic preconditioning [J]. Circ Res, 1997,80(6);790-799.
    104. Ela C, Barg J, Vogel Z, Hasin Y, El\ilam Y. Distinct components of morphine effects on cardiac myocytes are mediated by the κ and δopioid receptors. J Mol Cell Cardiol, 1997,29(2):711-720.
    105. Ventura C, Spurgeon H, Lakatta EG, Guaenieri C, Capogrossi MC. κ and δopioid receptor stimulation effects cardiac myocytes and neurons. Circ Res, 1992,70(1):66-81.
    106. Neely JR, Libermerster H, Basthersby EJ et al. Effects of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 1976;212:804.
    107. Nakanishi T, Nishioka K, Jarmakani JM. Mechanism of tissue Ca2+ gain during reoxygenation after hypoxia in rabbit myocardium. Am J Physiol 1982; 242(Heart Circ.Physiol 11):H437.
    108. Sordahl LA, Johnson C, Blailock ZK et al. The mitochondrion. In Methods in Pharmacology.New York: Appleton. 1971,P247.
    109. Lowry OH, Rosenberugh NJ,Karr AL et al. Protein measurement with Folin Phenyl
    
    regeant. J Biol Chem 1951;193:265.
    110. Zucchi JR, Ronca-Testoni S, Yu Y et al. Effects of ischemia and reperfusion on cardiac ryanocime receoptors sarcoplasmic reticulum Ca2+ channel.Circ Res 1994;74:271.
    111. Jones LR, Beseh HR. Isolation of canine sarcolemmal vesicles. In Schwartz A, Method in Pharmacology 1984, v015. Chapter Ⅰ,pp 1-11.Plenum.
    112. Hagar JM, Hale SL, Kloner RA. Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat. Circ Res, 1991,68: 61-68,
    113. Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res, 1995,77: 1030-1035.
    114. Ikonomidis JS, Tumiati LC, Weisel RD, Mickle DA, Li RK. Preconditioning human ventricular cardiomyocytes with brief periods of simulated ischaemia. Cardiovasc Res, 1994, 28: 1285-1291.
    115. Gross GJ, Auchampach JA.Blockade of ATP-sensitive potassium channels prevents myooardial preconditioning in dogs. Circ Res 1992;70(2):223.
    116. Dume MJ.Effects of cromakalim, pinacidil and nicorandil on arteries in dogs by K+ channel opening mechanism. Br J Phmacol 1990;99(1): 169
    117. Robertson DW, Steinberg ML.Potassium channel modulators: scientific applications and therapeutic promise.J Med Chem 1990;33:1529~41.
    118. Gross GJ, Fryer RM. Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and myocardial preconditioning. Circ Res, 1999,84: 973-979.
    119. Auchampach JA, Grover GJ, Gross GJ. Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate. Cardiovasc Res, 1992, 26:1054-1062
    120. Gross GJ, Fryer RM. Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and myocardial preconditioning. Circ Res, 1999,84: 973-979.
    121. Mizumura T, Nithipatikom K, Gross GJ. Bimakalim, an ATP-sensitive potassium channel opener, mimics the effects of ischemic preconditioning to reduce infarct size, adenosine release, and neutrophil function in dogs. Circulation, 1995,92: 1236-1245.
    
    
    122. Yao Z, Cavero I, Gross GJ. Activation of cardiac KATP channels: an endogenous protective mechanism during repetitive ischemia. Am J Physiol 1993, 264: H495-H504.
    123. Gross GJ. Effects of nicorandil on coronary circulation and myocardial ischemia.Am J Cardil 1989;63:11J
    124. Grover GJ,Dwonczyk S,Parham CS et al.The protective effects of cromakalim and pinacidil on reperfusion function and infarct size in isolated rat hearts and anesthetized dogs.Cardiovasc Drugs Ther, 1990; 15:465.
    125. Nichols C, Lederer WJ. Adenosine triphosphate-sensitive potassium channels in the cardiovascular system. Am J Physiol. 1991; 261: H1675~86.
    126. Auchampach JA, Maruyama M, Cavero T et al. Pharmacological evidence for a role of ATP-dependent potassim channels in myocardial stunning.Circulation 1992;86:311~9.
    127. Hoemcke EEM, Peterseim DS, Ducko CT, Sun X. Donor heart preservation with the potassium channel opener pinacdil;comparison with university of Wisconsin and St.Thomas' solution. J Heart Lung Transplant, 2000,19(3):286-297.
    128. Ahmet I, Sawa Y, Nishimura M,et al. Carsioprotective effect of diadenosine tetraphasphate (AP4A) preservation in hypothermic storage and its relation with mitochondiral ATP-sensitive potassium channels. Transplantation,2002, 69(1):16-20.
    129. Maskal SL, Cohen NM, Allen CA, et al. Hyperpolarizing cardioplegia with aprikalim,a potassium channel opener.Circulation 1994;909suppl 1):49
    130. Cohen NM, Wise RM, Wechsler AS et al. Elective cardiac arrest with a hyperpolarizing adenosine triphosphate-sensitive potassium channel opener. J Thorac Cardiovasc Surg 1993;106:307.
    131. Auchampach JA, Cavero I,Gross GJ.Nicorandil attenuates myocardial dysfunction assosiated with transient ischemia by opening ATP-dependent potassium channels.J Cardiovasc Pharmacol 1992;20:765~71.
    132. Sakai K, Yamagata T, Teragawa H,et al. Nicorandil-induced preconditioning as evidenced by troponin T measurements after coronary angioplasty in patients with stable angina pectoris, Jpn Heart J,2002, 43(5):443-45
    133. Koyama T, Zhu MY, Kinjo M et al. Dynamic microstructure of mitochondrial membrane from rabbit heart subjected to reperfusion after ischemia.Jpn Heart J
    
    1991;32:247.
    134. Kloner RA, Bolli R, Marban E,et al. Midical and cellular implications of stunding hibernation, and preconditioning: an NHLBI workshop. Circulation, 1998,97(18): 1848-1867.
    135. Bauza G, Lima L, Le LM,et al.12 hour preservation of rat hearts with "Fabrique d' implants et d'instrument" or University of Wisconsin oxygenated microperfused carsioplegic solution. Transplant proc, 1996, 28(5):2899-2903.
    136. Clyde S, Dsvid JH. Coronary Vascular Responsiveness to 5-hydroxytruptamine before and after infusion of hyperkalemic crystalloid cardioplegic solution in rat heart. J Thorac Cardiovasc Surg,1989, 98(5):783-787.
    137. Pankaj M, Zdenek Slavik, Magdi Yacoub. Endothelial dysfunction caused university of Wisconsin preservation in the rat heart. J cardiovasc surg, 1992,104(2): 1618-1624.
    138.钟佛添,刘处生,巫国勇。供者心脏热缺血后收缩力、三磷酸腺苷、超微结构的关系。中国胸心血管外科临床杂志,2002,7(1):28-31。
    139. Wicomb WN, Hill DJ,Avery JG, et al. Donor heart preservation limitations ofcardioplegia and warm ischemia.Transplantation, 1992,53(4):947
    140.张勇,龙村,吕国桢,等.HTK液、UW液、ST.Thmos Ⅱ液对离体鼠心低温保存的形态学观察.西北国防医学杂志,2001,22(4):356-359
    141.徐长宪,宋惠民,李守先,等.冷浸泡法保存犬心3h后原位心脏移植的实验研究.中华器官移植杂志,2000,21(6):331-333.
    142. Cohen NM, Wise RM, Wechsler AS et al. Elective cardiac arrest with a hyperpolarizing adenosine triphosphate-sensitive potassium channel opener. J Thorac Cardiovasc Surg, 1993; 106(2): 317-328
    143. Lawton JS, Hsia PW, Damiano RJ, et al. The adenosine-triphosphate-sensitive potassium-channel opener pinacidil is effective in blood cardioplegia. Ann Thorac Surg, 1998, 66(3): 768-773.
    144. Tanaka H, Okazzaki K, Shigenobu K. Cardioprotective effects of N1P-121, a novel ATP-sensitive potassium channel opener, during ischemia and reperfusion in coronary perfused guinea pig myocardium. J Cardiovasc Pharmacol,1996, 27(5):695-701.
    145. Jayawant AM, Stephenson ES, Mattw GS, et al. Potassium-channel opener cardioplegia is superior to St. Thomas' solution in the intact animal. Ann Thorac
    
    Surg, 1999,68(1):67-74.
    146. Behling RW, Malong HJ. KATP-channel openers protect against increased cytosolic calcium during ischaemia and reperfusion. J Mol Cell Cardial, 1995,27: 1809-1817.
    147. Monticello TM, Sargent CA, McGill JR, et al. Amelioration of ischemia/reperfusion injury in isolated rats hearts by the ATP-sensitive potassium channel opener BMS-180448. Cardiovasc Res, 1996, 31(1): 93-101.
    148.王莉莎,张育才。补体系统与心肌缺血再灌注损伤。《国外医学》麻醉学与复苏分册,2001,22(6):358—360。
    149. Nakano A, Cohen MV. Ischemic preconditioning: from basic mechanisms to clinical applications. Pharmacol Ther,2000,86:263-275.
    150. Lapace M, Guenoun T, Montagne O, et al. Cytosolic myocardial calcium modulation by ATP-dependent potassium channel openers and NO donors. J Cardiovasc Pharmacol. 1999; 33(3):394-400。
    151. Jovanovic A, Jovanovic S, Lorenz E, et al. Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to chemical hypoxia-reoxgenation injury. Circulation, 1998; 98(15):1548-1555.
    152. Lopez JR, Jahangir R, Jahangir A. Potassium channel openers preven potassium-induced calcium loading of cardiac cell:possible implications incardioplegia. J Thorac Cardiovasc Surg. 1996, 112(3):820-831.
    153. Behliing RW, Malone HJ. KATP-channel openers protect against increased cytosolic calcium during ischemia and reperfusion. J Mol Cell Cardiol. 1995,27(9):1809-1817.
    154. Yellon DM, Baxter GF, Garcia Dorado D. Ischemic preconditioning: present position and future direction. Cardiovasc Res. 1998,37(1):21-33.
    155. Piper HM, Siegmund B, Schluter KD. Prevention of the oxygen paradox in the isolated cardiocyte and the whole heart. Am J Cardiovasc Pathol, 1992,4:115-122.
    156. Kaplan P, Lehotsky J, Racay P. Role of sarcoplasmic reticulum in the contractile dysfunction during myocardial ischemia and reperfusion. Physiol Res. 1997,46(5):333-339.
    157. Jovanovic A, Alekseev AE, Lopez. JR. Adenosine prevents hperkalemia-induced calcium loading in cardiac cells: relevance for cardioplegia. Ann Thorac Surg,1997,63(1): 153-161.
    
    
    158. Cleveland JC JR, Meldrum DR, Rowland RT. Adenosine preconditioning of human myocardium is depent upon the ATP-sensitive K+ channel. J Mol Cell Cardil. 1997,29(1): 175-182.
    159. Geshi E, Ishioka H, Nomizo A, et al. Biochemical and ultrastructural evaluations of the effect of ischemic preconditioning on ischemic myocardial injury-role of the adenosine triposphate-sensitive potassium channel. Jpn Circ J, 1998,62(12):915-924.
    160. Koyama T, Zhu MY, Kinjo M et al. Dynamic microstructure of mitochondrial membrane from rabbit heart subjected to reperfusion after ischemia.Jpn Heart J 1991;32:247.
    161. Krumins SA, Characterization of dermorphin binding to membranes of rat brain and heart. Neuropeptides, 1987,9: 93-102.
    162. Jin WQ, Tai KK, Chan TK, Wong TM. Further characterization of [3H]U69593 binding sites in the rat heart. J Mol Cell Cardiol, 1995,27: 1507-1511.
    163. Tai KK, Jin WQ, Chan TK, Wong TM. Characterization of [3H]U69593 binding sites in the rat heart by receptor binding assays. J Mol Cell Cardiol, 1991,23: 1297-1302.
    164. Ventura C, Bastagli L, Bernardi P, Caldarera CM, Guarnieri C. Opioid receptors in rat cardiac sarcolemma: effect of phenylephrine and isoproterenol. Biochim Biophys Acta, 1989,987: 69-74.
    165. Tai KK, Bian CF, Wong TM. kappa-Opioid receptor stimulation increases intracellular free calcium in isolated rat ventricular myocytes. Life Sci, 1992,51: 909-913.
    166. Schultz JE, Rose E, Yao Z, Gross GJ. Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol, 1995,268: H2157-H2161.
    167. Schultz JJ, Hsu AK, Gross GJ. Ischemic preconditioning is mediated by a peripheral opioid receptor mechanism in the intact rat heart. J Mol Cell Cardiol, 1997,29: 1355-1362.
    168. Bell SP, Sack MN, Patel A, Opie LH, Yellon DM. Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle. J Am Coll Cardiol, 2000,36: 2296-2302.
    169. Miki T, Cohen MV, Downey JM. Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits. Mol Cell Biochem, 1998,186: 3-12.
    
    
    170. Schultz JE, Hsu AK, Nagase H, Gross GJ. TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels. Am J Physiol, 1998;274:H909-H914.
    171. Huh J, Gross GJ, Nagase H, Liang BT. Protection of cardiac myocytes via delta(1)-opioid receptors, protein kinase C, and mitochondrial K(ATP) channels. Am J Physiol Heart Circ Physiol, 2001,280: H377-H383.
    172. Fryer, RM, Hsu AK, Eells JT, Nagase H, Gross GJ. Opioid-induced second window of cardioprotection: potential role of mitochondrial KATP channels. Circ Res, 1999,84: 846-851.
    173. Wu S, Li HY, Wong TM. Cardioprotection of preconditioning by metabolic inhibition in the rat ventricular myocyte. Involvement of kappa-opioid receptor. Circ Res, 1999, 84: 1388-1395.
    174. Schultz JJ, Hsu AK, Gross GJ. Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide sensitive mechanism in the rat heart. Cire Res,1996, 78:1100-1104
    175. Miki T, Cohen M, Downey J. Opioid receptor contributes to ischemic preconditioning through pritenin kinase C activation in rabbits. Mol Cell Biochem, 1998,186:3-12.
    176. Schultz J, Hsu A, Gross G. Ischemic preconditioning is mediated by a peripheral opioid receptor mechanism in the intact rat heart. J Mol Cell Cardiol, 1997,29:1355-136
    177. Imagawa J, Baxter GF, Yellon DM. Myocardial protection afforded by nicorandil and ischaemic preconditioning in a rabbit infarct model in vivo. J Cardiovasc Pharmacol, 1998,31: 74-79,
    178. Tai KK, Jin WQ, Chen T, et al. Characterization of [3H] U69593 Binding sites in the rat heart by receptor binding assays.J Mol Cell Cardiol, 1991,23:1297-1302.
    179. Jin WQ, Tai KK, Chen T, et al. Further characterization of[3H] U69593 Binding sites in the rat heart. J Mol Cell Cardiol,1995,27:1507-1511.
    180. Sheng JZ,Dong H, Wang TM. Effect of U50488H,a k-agonist,on action poteotials of isolated ventricular papillary muscle of guinea pigs. Acta Pharmacol Sin,1994,15:36-38.
    181.王欣,李玉光,张元春等。阿片受体在缺血预处理中的作用。中华胸心血管外科杂志,2001,17(2):93-95。
    
    
    182. Wang GY, Wu S, Pei JM. k-opioid receptor mediates cardioprotection of ischemic preconditioning-role of PKC and KATP. Am J Physiol,2001,280: H384-H391.
    183. Weinbrenner C, Liu GS, Cohen MV, Downey JM. Phosphorylation of tyrosine 182 of p38 mitogen-activated protein kinase correlates with the protection of preconditioning in the rabbit heart. J Mol Cell Cardiol,1997,29: 2383-2391,
    184. Ela C, Barg J, Vogel Z. Distinct components of morphine effects on cardiac myocytes are mediate by the rand δ opioid receptors. J Mol Cell Cardiol,1997,29:711-720.
    185. Ventura C, Spurgeon H, Lakatta EC. rand δopioid receptor stimulation effects cardiac myocytes function and Ca2+ release from an intracellular pool in myocytes and neurons. Circ Res, 1992,70:66-81.
    186. Sheng JZ, Wong NS, Wang HX, Wong TM. Pertussis toxin, but not tyrosine kinase inhibitors, abolishes effects of U-50488H on [Ca2+]i in myocytes. Am J Physiol, 1997,272: C560-C564.
    187. Bian JS, Zhang WM, Xia Q, Wong TM. Phospholipase C inhibitors attenuate arrhythmias induced by kappa-receptor stimulation in the isolated rat heart. J Mol Cell Cardiol, 1998,30:2103-211,.
    188. Sheng JZ, Wong NS, Tai KK, Wong TM. Lithium attenuates the effects of dynorphin A(1-13) on inositol 1,4,5-trisphosphate and intracellular Ca2+ in rat ventricular myocytes. Life Sci, 1996,59: 2181-2186.
    189. Bian JS, Wang HX, Zhang WM, Wong TM. Effects of kappa-opioid receptor stimulation in the heart and the involvement of protein kinase C. Br J Pharmacol, 1998,124: 600-606.
    190. Wong TM, Sheng JZ, Wong NS, Tai KK. Signal transduction in the cardiac k-receptor. Biol Signals, 1995, 4: 174-178,.
    191. Wong TM, Lee AY, Tai KK. Effects of drugs interacting with opioid receptors during normal perfusion or ischemia and reperfusion in the isolated rat heart--an attempt to identify cardiac opioid receptor subtype(s) involved in arrhythmogenesis. J Mol Cell Cardiol 1990,22:1167-75
    192. Gross GJ, Fryer RM. Sarcolemmal versus mitochondrial ATP-sensitive K~+ channels and myocardial preconditioning. Circ Res,1999.84: 973-979.

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