临床同种原位心脏移植进展(3)
6.影响长期存活主要因素
随着心脏移植近期疗效的提高，移植后远期并发症的防治显得更为重要。移植远期主要致死原因有移植物冠状血管病(Cardiac Allograft Vasculopathy，CAV)、恶性肿瘤、感染，分别占术后5年死亡原因的25%、18.6%、7.9%。其中CAV是移植后中远期发病和死亡的主要原因(1)。CAV发病后进展迅速，除再次移植以外内、外科治疗效果均较差。因此，研究其发病机制并探索有效的预防措施势在必行。CAV的发病机制尚不清楚。目前认为存在免疫学因素和非免疫学因素。一般认为与免疫反应有关，且细胞免疫和体液免疫都参与血管内膜的损伤，引起CAV。国外较多研究认为，免疫学因素和抗排异反应药物的应用是CAV
发病的重要因素。
供心缺血性损伤可能是移植后CAV的发病原因：内皮对调节血管和凝血机制的稳定性发挥重要作用，它可以产生前列环素、纤维蛋白原激活因子、抗血栓素Ⅲ和内皮依赖性舒张因子等。内皮的中断可影响其正常功能，对心肌的灌注、通透性、内皮与血小板间的反应都会产生有害的作用(20)；移植后CAV有别于普通冠心病，其发病较早，病理学特点为冠状血管弥漫性病变、内膜呈同心园样增厚，血管内粥样改变少见，坏死改变、胆固醇结晶、钙质沉重较少发生，这与心肌缺血导致的弥漫性血管内膜病理改变相似(21)；供心保护液的临床研究发现，钾离子对冠状血管内皮具有损害作用(24)，高浓度钾离子的UW液保存移植后的供心，CAV的发病率是用Stanford液保存后的二倍(20)；Gaudin等(22)对50例患者移植后前3次心内膜心肌活检资料研究发现，50%患者存在冠状血管的病理改变，通过多元回归分析证明，心肌缺血性损伤在移植后CAV的发病过程中起重要作用，并认为移植早期心内膜心肌活检的组织学改变可作为术后CAV的高危因素；研究证明，随供心缺血时间的延长，心肌超微结构受到损害的同时，冠状血管内皮也受到一定程度的损害甚至是不可逆的，这对移植后的CAV可能是一个重要因素(23)。CAV可能是各种原因造成血管内膜损害后机体愈合反应的结果，它的发生与发展也随损害的严重性而不同。改进供心保护方法，改善供心保护效果不仅可以提高移植成活率，也可以有助于移植后的远期存活率和生活质量。
, 百拇医药
参考文献
1Hosenpud JD,Bennett LE,Keck BM,et al.The Registry of the International Society for Heart and Lung Transplantation: sixteenth official report--1999. J Heart Lung Transplant, 1999,18:37-105.
2Fower MB. Evaluating and selecting patients for cardiac transplantation.In:Smith JA eds. The Stanford manual of cadiopulmonary transplanptation.Futura Publishing Company Inc,1996,4-5.
3Defraigne JO, Demoulin JC, Beaujean MA,et al.Cardiac transplantation beyond 55 years of age. Transpl Int,1990 ,3(2):59-61.
, 百拇医药
4Frazier OH, Macris MP, Duncan JM, et al.Cardiac transplantation in patients over 60 years of age. Ann Thorac Surg, 1988,45:129--32.
5Chen JM, Levin HR, Michier RE, et al. Reevaluating the significance of pulmonary hypertension before cardiac transplantation: Determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality. J Thorac Cardiovasc Surg, 1997,114:627-34
6Goarin JP, Cohen S, Jacquens Y, et al.Left ventricular function in brain dead donor :Assessment using transesophageal echocardiography. Anesthesiology, 1990,73:A84
, http://www.100md.com
7Vedrinne JM, Vedrinne C,Dorez D,et al. Transesophageal echocardiography assessent of heart in brain dead patients befor harvesting. Transplantation proceedings,1995,27:1655.
8Yeh TJR,Wechsler AS,Graham LJ,et al.Acute braith alters left ventricular myocardial gene expression. J Thoracic Cardiovasc Surg,1999,117:65-74.
9Novitzky D, Rose AG, Cooper DK ,Injury of myocardial conduction tissue and coronary artery smooth muscle following brain death in the baboon. Transplantation 1988 ,45(5):964-6
, 百拇医药
10Takahashi A,Hearse DJ,Braimbridge MV, et al. Harvesring hearts for long-term preservation: Dtermental effects of intial hyperthermic infusion o cardioplegic solutions. J Thoracic Cardiovasc Surg, 1990,100:371-8.
11Stringham JC,Love RB,Welter D,et al . Impact of University of Wisconsin solution on clinical heart transplantation. A comparision with Stanford solution for extended preservation. Circulation, 1998,10:Ⅱ157-61.
12Drinkwater D,Ziv ET,Lais H,et al. Extracellular and standard University of Wisconsin solution provide equivalent preservation of myocardial function. J Thoracic Cardiovasc Surg,1995,110:738-45.
, 百拇医药
13Argenziano M, Oz MC, Rose EA. The continuing evolution of mechanical ventricular assist devices. Curr Probl Surg 1997;34:317--86.
14DiSesa VJ. Cardiac Xenotransplantation.Ann Thorac Surg, 1997,64:1858—65.
15Shumway NE, Lower RR, Stofer RC. Transplantation of the heart .Adv Surg, 1966,2:255-84.
16Gamel AEL,Yonan NA,Grant S,et al.Orthotopic heart trnsplantation:a comparison of standard and bicaval Wythenshawe techniques. J Thorac Cardiovasc Surg,1995;109:721-730.
, http://www.100md.com
17Bhatia SJS, Kirshenbaum JM,Shernin RJ,et al.Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac trnsplantation. Circulation,1987;8:819-26.
18Sievers HH,Legh R,Jahnke A,et al.Bicaval versus atrial anastomoses in cardiac transplantation. J Thorac Cardiovasc Surg,1994;108:780-89.
19Aziz T, Burgess M, Khafagy. Bicaval and standard techniques in orthotopic heart transplantation: Medium-term experience in cardiac performance and survival.J Thorac Cardiovasc Surg 1999;118:115-122.
, http://www.100md.com
20Demertziis S,Wippermann J,Schaper J,et al.University of Wisconsin versus St.Thomas hospital solution for human donor heart preservation. Ann Thorac Surg 1993;55:1131-7.
21Le Biois J,Ladeia A,Vouhe P,et al.Risk of coronary graft disease following heart transplantation.Noppon Kyobu Gakkai Zasshi 1993;42(10):20-40.
22Gaudin PB,Raybura BK,Hutchins,et al.Peritransplant injury to the myocardium associated with the developmet of accelerated arteriosclerosis in heart transplant recipients.Am Surg Pathol 1994;18(4):338-46.
23臧旺福，韩振，夏求明，等。改善供心保护对移植后冠状血管病的影响. 哈尔滨医科大学学报，1999，2：113.
24Sorajjia P,Cable DG,Schaff HV,et al.Hypothermic storage with UW solution preserves edothelial and vascular smooth-muscle function. Circulation, 1997,(supplI)II-297-308., http://www.100md.com
随着心脏移植近期疗效的提高，移植后远期并发症的防治显得更为重要。移植远期主要致死原因有移植物冠状血管病(Cardiac Allograft Vasculopathy，CAV)、恶性肿瘤、感染，分别占术后5年死亡原因的25%、18.6%、7.9%。其中CAV是移植后中远期发病和死亡的主要原因(1)。CAV发病后进展迅速，除再次移植以外内、外科治疗效果均较差。因此，研究其发病机制并探索有效的预防措施势在必行。CAV的发病机制尚不清楚。目前认为存在免疫学因素和非免疫学因素。一般认为与免疫反应有关，且细胞免疫和体液免疫都参与血管内膜的损伤，引起CAV。国外较多研究认为，免疫学因素和抗排异反应药物的应用是CAV
发病的重要因素。
供心缺血性损伤可能是移植后CAV的发病原因：内皮对调节血管和凝血机制的稳定性发挥重要作用，它可以产生前列环素、纤维蛋白原激活因子、抗血栓素Ⅲ和内皮依赖性舒张因子等。内皮的中断可影响其正常功能，对心肌的灌注、通透性、内皮与血小板间的反应都会产生有害的作用(20)；移植后CAV有别于普通冠心病，其发病较早，病理学特点为冠状血管弥漫性病变、内膜呈同心园样增厚，血管内粥样改变少见，坏死改变、胆固醇结晶、钙质沉重较少发生，这与心肌缺血导致的弥漫性血管内膜病理改变相似(21)；供心保护液的临床研究发现，钾离子对冠状血管内皮具有损害作用(24)，高浓度钾离子的UW液保存移植后的供心，CAV的发病率是用Stanford液保存后的二倍(20)；Gaudin等(22)对50例患者移植后前3次心内膜心肌活检资料研究发现，50%患者存在冠状血管的病理改变，通过多元回归分析证明，心肌缺血性损伤在移植后CAV的发病过程中起重要作用，并认为移植早期心内膜心肌活检的组织学改变可作为术后CAV的高危因素；研究证明，随供心缺血时间的延长，心肌超微结构受到损害的同时，冠状血管内皮也受到一定程度的损害甚至是不可逆的，这对移植后的CAV可能是一个重要因素(23)。CAV可能是各种原因造成血管内膜损害后机体愈合反应的结果，它的发生与发展也随损害的严重性而不同。改进供心保护方法，改善供心保护效果不仅可以提高移植成活率，也可以有助于移植后的远期存活率和生活质量。
, 百拇医药
参考文献
1Hosenpud JD,Bennett LE,Keck BM,et al.The Registry of the International Society for Heart and Lung Transplantation: sixteenth official report--1999. J Heart Lung Transplant, 1999,18:37-105.
2Fower MB. Evaluating and selecting patients for cardiac transplantation.In:Smith JA eds. The Stanford manual of cadiopulmonary transplanptation.Futura Publishing Company Inc,1996,4-5.
3Defraigne JO, Demoulin JC, Beaujean MA,et al.Cardiac transplantation beyond 55 years of age. Transpl Int,1990 ,3(2):59-61.
, 百拇医药
4Frazier OH, Macris MP, Duncan JM, et al.Cardiac transplantation in patients over 60 years of age. Ann Thorac Surg, 1988,45:129--32.
5Chen JM, Levin HR, Michier RE, et al. Reevaluating the significance of pulmonary hypertension before cardiac transplantation: Determination of optimal thresholds and quantification of the effect of reversibility on perioperative mortality. J Thorac Cardiovasc Surg, 1997,114:627-34
6Goarin JP, Cohen S, Jacquens Y, et al.Left ventricular function in brain dead donor :Assessment using transesophageal echocardiography. Anesthesiology, 1990,73:A84
, http://www.100md.com
7Vedrinne JM, Vedrinne C,Dorez D,et al. Transesophageal echocardiography assessent of heart in brain dead patients befor harvesting. Transplantation proceedings,1995,27:1655.
8Yeh TJR,Wechsler AS,Graham LJ,et al.Acute braith alters left ventricular myocardial gene expression. J Thoracic Cardiovasc Surg,1999,117:65-74.
9Novitzky D, Rose AG, Cooper DK ,Injury of myocardial conduction tissue and coronary artery smooth muscle following brain death in the baboon. Transplantation 1988 ,45(5):964-6
, 百拇医药
10Takahashi A,Hearse DJ,Braimbridge MV, et al. Harvesring hearts for long-term preservation: Dtermental effects of intial hyperthermic infusion o cardioplegic solutions. J Thoracic Cardiovasc Surg, 1990,100:371-8.
11Stringham JC,Love RB,Welter D,et al . Impact of University of Wisconsin solution on clinical heart transplantation. A comparision with Stanford solution for extended preservation. Circulation, 1998,10:Ⅱ157-61.
12Drinkwater D,Ziv ET,Lais H,et al. Extracellular and standard University of Wisconsin solution provide equivalent preservation of myocardial function. J Thoracic Cardiovasc Surg,1995,110:738-45.
, 百拇医药
13Argenziano M, Oz MC, Rose EA. The continuing evolution of mechanical ventricular assist devices. Curr Probl Surg 1997;34:317--86.
14DiSesa VJ. Cardiac Xenotransplantation.Ann Thorac Surg, 1997,64:1858—65.
15Shumway NE, Lower RR, Stofer RC. Transplantation of the heart .Adv Surg, 1966,2:255-84.
16Gamel AEL,Yonan NA,Grant S,et al.Orthotopic heart trnsplantation:a comparison of standard and bicaval Wythenshawe techniques. J Thorac Cardiovasc Surg,1995;109:721-730.
, http://www.100md.com
17Bhatia SJS, Kirshenbaum JM,Shernin RJ,et al.Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac trnsplantation. Circulation,1987;8:819-26.
18Sievers HH,Legh R,Jahnke A,et al.Bicaval versus atrial anastomoses in cardiac transplantation. J Thorac Cardiovasc Surg,1994;108:780-89.
19Aziz T, Burgess M, Khafagy. Bicaval and standard techniques in orthotopic heart transplantation: Medium-term experience in cardiac performance and survival.J Thorac Cardiovasc Surg 1999;118:115-122.
, http://www.100md.com
20Demertziis S,Wippermann J,Schaper J,et al.University of Wisconsin versus St.Thomas hospital solution for human donor heart preservation. Ann Thorac Surg 1993;55:1131-7.
21Le Biois J,Ladeia A,Vouhe P,et al.Risk of coronary graft disease following heart transplantation.Noppon Kyobu Gakkai Zasshi 1993;42(10):20-40.
22Gaudin PB,Raybura BK,Hutchins,et al.Peritransplant injury to the myocardium associated with the developmet of accelerated arteriosclerosis in heart transplant recipients.Am Surg Pathol 1994;18(4):338-46.
23臧旺福，韩振，夏求明，等。改善供心保护对移植后冠状血管病的影响. 哈尔滨医科大学学报，1999，2：113.
24Sorajjia P,Cable DG,Schaff HV,et al.Hypothermic storage with UW solution preserves edothelial and vascular smooth-muscle function. Circulation, 1997,(supplI)II-297-308., http://www.100md.com