犬冠状动脉脂肪栓塞引起慢/无血流模型的建立
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摘要
研究背景
冠状动脉硬化性心脏病(Coronary heart disease,CHD)是当今社会影响人们健康生活的主要原因之一。冠心病的治疗,由最初的仅限于药物治疗,到目前广泛应用的经皮冠状动脉介入治疗( Percutaneous coronary intervention ,PCI),对冠心病的临床预后和转归产生了跨时代的影响。但随之带来的问题:如血管腔内介入性治疗术后常见的慢/无复流(No-reflow,NR)现象可明显降低PCI术后左室功能恢复,增加再住院率及死亡率。有资料统计PCI术后无复流的发生率为13-37%之间。
《经皮冠状动脉介入治疗指南2009》中将慢/无复流定义为:冠状动脉狭窄解除,但远端前向血流明显减慢,〈TIMI (Thrombolysis in myocardial infarction) 2级,慢血流〉或丧失(TIMI0-1级,无复流)。无复流的出现反映了再通血管的相关区域仍部分或全部处于失灌注状态。目前对慢/无复流产生的原因推测很多。大致可其根据发生的机制不同分为2类:即再灌注无复流和介入性无复流。其中介入性无复流常发生在为较粗大的右冠脉行血管成形术的过程中,由于此过程机械刺激较大,如果此时血管内存在较大的粥样斑块,可造成冠状动脉粥样硬化斑块纤维帽破裂造成其中的脂质溢出,进而造成冠脉远端无复流。且有研究发现,在对急性心肌梗死(Acute myocardial infarction ,AMI)患者行血管成形或支架术后血管造影发现的无复流现象,与血管内超声(Intravascular ultrasound,IVUS)观察到的血管损伤的形态学表现有关。这些脂质池的形态学特点与病理学上的易损斑块相似,在行冠状动脉介入治疗时可人为的诱发斑块破裂、微栓塞产生。本实验基于临床观察到慢/无复流的发生背景,观察人为注入斑块内容物即脂肪栓子(Fat Embolus,FE)后是否可以产生慢/无血流现象,并探讨该栓子造成慢/无血流时的栓子量及其对微循环的损伤程度和机制。
实验方法
第一部分:
1.脂肪栓子的制备参考相关文献中脂滴栓子的制作方法,制作10 ml灭菌后脂肪栓子备用。
2.模型建立常规术前准备。记录术前心电图(Electrocardiograph,ECG)。采血留取心肌损伤标记物样本。同步进行心电监护。冠脉造影术:行左室造影,记录左室收缩压(Left ventricular systolic pressure,LVSP)和舒张末压(Left ventricular end-diastolic pressure,LVEDP)。同时进行左、右冠脉造影(Coronary arteriography ,CAG),超选优势动脉,自微导管将预先制备好的脂肪液缓慢注入动脉内,每次0.5 ml,注射时间为5 s。如未出现无复流表现,间隔5 min后可重复上述步骤。每次注射后,造影观察血流的变化,并监测LVEDP。使用可定量的校正的TIMI血流记帧法(Corrected TIMI frame count,CTFC),判断慢/无血流出现。观察到慢/无血流后,再次进行左室造影记录LVSP和LVEDP。
第二部分
1.术后监测:
术后继续观察犬的心脏电活动变化,每隔30 min记录1次心电图的变化,每隔1 h由犬股动脉鞘管内取血监测血液生化指标。
2.病理组织学检查和电镜观察
观察至10 h后将动物处死。开胸取出心脏,行心肌染色。取目标心肌行病理组织学检查和电镜观察。
结果
1.造模成功率为75%,平均脂滴微栓子注射次数为1.5次。
2.血流动力学的变化犬在冠脉脂肪栓塞造成慢/无血流前后,心率、血压、LVSP均出现明显变化。在注射栓子瞬间,即可观察到心电图变化,在其后的观察中,ECG异常呈演变性改变。
3.血液生化指标造模前后CK、CK-MB的水平自身比较有明显改变。
4.心肌的病理组织学及电镜观察均可观察到目标心肌损伤性改变。
结论
1.脂肪栓子可产生与临床一致的慢/无血流现象。
2.犬冠脉内脂肪栓塞模拟慢/无复流机械性阻塞现象是可行的,创伤小、存活率高。
3.脂肪栓子造成的机械栓塞为不完全性,可出现演变性变化,与临床观察到慢/无血流演变一致。
4.脂肪栓子对局部心肌的损伤除机械性栓塞外还可激活局部损伤机制,表现综合性作用。
Background
Atherosclerotic coronary heart disease is one of the main morbidities that affect people's health in today's society. The treatment of coronary heart disease have evolved from medication treatment to the widely application of percutaneous coronary intervention (PCI), which enabled fundamental breakthrough of the prognosis and outcome of CHD treatment. Albeit the significant improvement of CHD treatment by PCI, some complications occur from time to time and deeply annoy the cardiologists. One of the most frequent complications is the slow/no-reflow phenomenon, which greatly hampered the left ventricular function improvement after PCI and increased the re-hospitalization rate and the mortality. Some statistics show that the rate of no-reflow after PCI can be as high as 13-37%.
In“Percutaneous coronary intervention Guideline 2009", the slow/no-reflow was defined as: Obvious distal forward flow reduction (Thrombolysis in myocardial infarction, TIMI grade 2, defined as slow-flow) or loss (TIMI grade 0-1, defined as no-reflow) after lifting of the coronary stenosis. Slow/no-reflow phenomenon reflects the partial or overall suboptimal perfusion of the target vessel related region. With regard to the mechanism of slow/no-reflow, there are currently multiple hypotheses. Generally, the mechanisms proposed can be attributed to 2 categories, i.e., no-reflow caused by reperfusion and no-reflow caused by intervention. The former is caused by fatty content of plaque that is squeezed out of the plaque through the erupted fibrous cap, which then blocks flow to the distal segment of the artery. This type of no-reflow more frequently occurs on the right coronary arteries. It is shown that, the no-reflow in acute myocardial infarction patients after PTCA or stenting was closely related with the morphological changes after vascular injury detected by IVUS. The fatty pool has similar morphology as the vulnerable plaque, and can be utilized to simulate the no-reflow phenomenon in the real setting. Based on the clinical problem of slow/no-reflow, the present study was designed to establish a practical animal model of slow/no-reflow, in which we firstly would investigate if manual injection of fat emboli (FE) could result in slow/no- reflow, and then explore the amount of emboli to be used and the severity and mechanism of microvascular injuries caused by this model.
Methods
Part I
1. Preparation of the fat emboli.
Ten milliliter of sterile fat emboli were prepared according to the literature for the subsequent experiment.
2. Establishment of the no-reflow animal model.
Routine pre-operation preparation was performed. The electrocardiograph (ECG) was recorded and the blood sample was drawn. Dynamic ECG monitoring was performed throughout the imaging procedure. The left ventricle was firstly imaged and the left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded. Then, coronary arteriography (CAG) of both the left and right coronary artery was performed. Fat emboli solution (0.5 ml) was slowly (5 seconds) infused into the dominant artery through the microcatheter. Coronary imaging was performed and LVEDP recorded after the injection. The corrected TIMI frame count (CTFC) was calculated to evaluate whether slow/no-reflow existed. If no signs of no-reflow appear, the emboli infusion was repeated after 5 minutes, until the success of the model. Finally, left ventricular imaging was performed again to record the LVSP and LVEDP.
Part II
1. Post-operational monitoring
The evolvement of ECG was monitored by recorded ECG every 30 minutes, and blood sample was taken every 1 hour from the femoral artery sheath catheter of the dog to measure the biochemical indices.
2. Histopathological examination and electronic microscopic observation
The animals were sacrificed 10 hours after the procedure. The heart was excised, and stained. The target region was examined by histopathological examinations and electronic microscopy.
Results
1. The success rate of the model was 75%, with average injections of 1.5 times.
2. Hemodynamic changes: Heart rate, blood pressure and LVSP all changed significantly after the model establishment. Changes of ECG can be observed as soon as the injection of the emboli. Dynamic evolvement of ECG was observed afterwards.
3. Blood examinations: The plasma levels of CK and CK-MB increased significantly after the establishment of the model.
4. Histopathology: Target region myocardial injuries were confirmed by both routine histopathology and electronic microscopy.
Conclusion
1. Fat emboli can be used to induce slow/no-reflow phenomenon that resembles the clinical setting.
2. It is feasible to simulate slow/no-reflow phenomenon by injecting fat emboli into the canine coronary. The injuries were minor and animal survival rate was high.
3. Fat embolism causes incomplete mechanical obstruction, showing dynamic evolvement, which was in concordance with the slow/no-reflow phenomenon observed on patients.
4. Fat embolism activates additional local injury mechanisms besides the mechanical obstruction, demonstrating comprehensive myocardial injury effects.
冠状动脉硬化性心脏病(Coronary heart disease,CHD)是当今社会影响人们健康生活的主要原因之一。冠心病的治疗,由最初的仅限于药物治疗,到目前广泛应用的经皮冠状动脉介入治疗( Percutaneous coronary intervention ,PCI),对冠心病的临床预后和转归产生了跨时代的影响。但随之带来的问题:如血管腔内介入性治疗术后常见的慢/无复流(No-reflow,NR)现象可明显降低PCI术后左室功能恢复,增加再住院率及死亡率。有资料统计PCI术后无复流的发生率为13-37%之间。
《经皮冠状动脉介入治疗指南2009》中将慢/无复流定义为:冠状动脉狭窄解除,但远端前向血流明显减慢,〈TIMI (Thrombolysis in myocardial infarction) 2级,慢血流〉或丧失(TIMI0-1级,无复流)。无复流的出现反映了再通血管的相关区域仍部分或全部处于失灌注状态。目前对慢/无复流产生的原因推测很多。大致可其根据发生的机制不同分为2类:即再灌注无复流和介入性无复流。其中介入性无复流常发生在为较粗大的右冠脉行血管成形术的过程中,由于此过程机械刺激较大,如果此时血管内存在较大的粥样斑块,可造成冠状动脉粥样硬化斑块纤维帽破裂造成其中的脂质溢出,进而造成冠脉远端无复流。且有研究发现,在对急性心肌梗死(Acute myocardial infarction ,AMI)患者行血管成形或支架术后血管造影发现的无复流现象,与血管内超声(Intravascular ultrasound,IVUS)观察到的血管损伤的形态学表现有关。这些脂质池的形态学特点与病理学上的易损斑块相似,在行冠状动脉介入治疗时可人为的诱发斑块破裂、微栓塞产生。本实验基于临床观察到慢/无复流的发生背景,观察人为注入斑块内容物即脂肪栓子(Fat Embolus,FE)后是否可以产生慢/无血流现象,并探讨该栓子造成慢/无血流时的栓子量及其对微循环的损伤程度和机制。
实验方法
第一部分:
1.脂肪栓子的制备参考相关文献中脂滴栓子的制作方法,制作10 ml灭菌后脂肪栓子备用。
2.模型建立常规术前准备。记录术前心电图(Electrocardiograph,ECG)。采血留取心肌损伤标记物样本。同步进行心电监护。冠脉造影术:行左室造影,记录左室收缩压(Left ventricular systolic pressure,LVSP)和舒张末压(Left ventricular end-diastolic pressure,LVEDP)。同时进行左、右冠脉造影(Coronary arteriography ,CAG),超选优势动脉,自微导管将预先制备好的脂肪液缓慢注入动脉内,每次0.5 ml,注射时间为5 s。如未出现无复流表现,间隔5 min后可重复上述步骤。每次注射后,造影观察血流的变化,并监测LVEDP。使用可定量的校正的TIMI血流记帧法(Corrected TIMI frame count,CTFC),判断慢/无血流出现。观察到慢/无血流后,再次进行左室造影记录LVSP和LVEDP。
第二部分
1.术后监测:
术后继续观察犬的心脏电活动变化,每隔30 min记录1次心电图的变化,每隔1 h由犬股动脉鞘管内取血监测血液生化指标。
2.病理组织学检查和电镜观察
观察至10 h后将动物处死。开胸取出心脏,行心肌染色。取目标心肌行病理组织学检查和电镜观察。
结果
1.造模成功率为75%,平均脂滴微栓子注射次数为1.5次。
2.血流动力学的变化犬在冠脉脂肪栓塞造成慢/无血流前后,心率、血压、LVSP均出现明显变化。在注射栓子瞬间,即可观察到心电图变化,在其后的观察中,ECG异常呈演变性改变。
3.血液生化指标造模前后CK、CK-MB的水平自身比较有明显改变。
4.心肌的病理组织学及电镜观察均可观察到目标心肌损伤性改变。
结论
1.脂肪栓子可产生与临床一致的慢/无血流现象。
2.犬冠脉内脂肪栓塞模拟慢/无复流机械性阻塞现象是可行的,创伤小、存活率高。
3.脂肪栓子造成的机械栓塞为不完全性,可出现演变性变化,与临床观察到慢/无血流演变一致。
4.脂肪栓子对局部心肌的损伤除机械性栓塞外还可激活局部损伤机制,表现综合性作用。
Background
Atherosclerotic coronary heart disease is one of the main morbidities that affect people's health in today's society. The treatment of coronary heart disease have evolved from medication treatment to the widely application of percutaneous coronary intervention (PCI), which enabled fundamental breakthrough of the prognosis and outcome of CHD treatment. Albeit the significant improvement of CHD treatment by PCI, some complications occur from time to time and deeply annoy the cardiologists. One of the most frequent complications is the slow/no-reflow phenomenon, which greatly hampered the left ventricular function improvement after PCI and increased the re-hospitalization rate and the mortality. Some statistics show that the rate of no-reflow after PCI can be as high as 13-37%.
In“Percutaneous coronary intervention Guideline 2009", the slow/no-reflow was defined as: Obvious distal forward flow reduction (Thrombolysis in myocardial infarction, TIMI grade 2, defined as slow-flow) or loss (TIMI grade 0-1, defined as no-reflow) after lifting of the coronary stenosis. Slow/no-reflow phenomenon reflects the partial or overall suboptimal perfusion of the target vessel related region. With regard to the mechanism of slow/no-reflow, there are currently multiple hypotheses. Generally, the mechanisms proposed can be attributed to 2 categories, i.e., no-reflow caused by reperfusion and no-reflow caused by intervention. The former is caused by fatty content of plaque that is squeezed out of the plaque through the erupted fibrous cap, which then blocks flow to the distal segment of the artery. This type of no-reflow more frequently occurs on the right coronary arteries. It is shown that, the no-reflow in acute myocardial infarction patients after PTCA or stenting was closely related with the morphological changes after vascular injury detected by IVUS. The fatty pool has similar morphology as the vulnerable plaque, and can be utilized to simulate the no-reflow phenomenon in the real setting. Based on the clinical problem of slow/no-reflow, the present study was designed to establish a practical animal model of slow/no-reflow, in which we firstly would investigate if manual injection of fat emboli (FE) could result in slow/no- reflow, and then explore the amount of emboli to be used and the severity and mechanism of microvascular injuries caused by this model.
Methods
Part I
1. Preparation of the fat emboli.
Ten milliliter of sterile fat emboli were prepared according to the literature for the subsequent experiment.
2. Establishment of the no-reflow animal model.
Routine pre-operation preparation was performed. The electrocardiograph (ECG) was recorded and the blood sample was drawn. Dynamic ECG monitoring was performed throughout the imaging procedure. The left ventricle was firstly imaged and the left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded. Then, coronary arteriography (CAG) of both the left and right coronary artery was performed. Fat emboli solution (0.5 ml) was slowly (5 seconds) infused into the dominant artery through the microcatheter. Coronary imaging was performed and LVEDP recorded after the injection. The corrected TIMI frame count (CTFC) was calculated to evaluate whether slow/no-reflow existed. If no signs of no-reflow appear, the emboli infusion was repeated after 5 minutes, until the success of the model. Finally, left ventricular imaging was performed again to record the LVSP and LVEDP.
Part II
1. Post-operational monitoring
The evolvement of ECG was monitored by recorded ECG every 30 minutes, and blood sample was taken every 1 hour from the femoral artery sheath catheter of the dog to measure the biochemical indices.
2. Histopathological examination and electronic microscopic observation
The animals were sacrificed 10 hours after the procedure. The heart was excised, and stained. The target region was examined by histopathological examinations and electronic microscopy.
Results
1. The success rate of the model was 75%, with average injections of 1.5 times.
2. Hemodynamic changes: Heart rate, blood pressure and LVSP all changed significantly after the model establishment. Changes of ECG can be observed as soon as the injection of the emboli. Dynamic evolvement of ECG was observed afterwards.
3. Blood examinations: The plasma levels of CK and CK-MB increased significantly after the establishment of the model.
4. Histopathology: Target region myocardial injuries were confirmed by both routine histopathology and electronic microscopy.
Conclusion
1. Fat emboli can be used to induce slow/no-reflow phenomenon that resembles the clinical setting.
2. It is feasible to simulate slow/no-reflow phenomenon by injecting fat emboli into the canine coronary. The injuries were minor and animal survival rate was high.
3. Fat embolism causes incomplete mechanical obstruction, showing dynamic evolvement, which was in concordance with the slow/no-reflow phenomenon observed on patients.
4. Fat embolism activates additional local injury mechanisms besides the mechanical obstruction, demonstrating comprehensive myocardial injury effects.
引文
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29. Nakamoto S, Kaneda T, Inoue T, et al. Disseminated cholesterol embolism after coronary artery bypass grafting. J Card Surg 2001;16:410-13.
30. Stone GW,Webb J , Cox DA , et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction : a randomized controlled trial. JAMA ,2005 ,293 :1063-1072.
31. Paul D. Stein,Abdo Y.Yaekoub,Fat embolism syndrome,THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES,2008;336:472-477
32. Jouven X , Charles MA , Desnos M , et al . Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population [J ] . Circulation ,2001 ,104 (7) :7562-761
33. Katsuomi Iwakura, Hiroshi Ito*, Shigeo Kawano, Atsushi Okamura, Toshiya Kurotobi, Motoo Date,Koichi Inoue, and Kenshi Fujii Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction European Heart Journal ,2006,27, 534-539
34. Abbo KM, Dooris M, Glazier S. Features and outcome of no-reflow after percutaneous coronary intervention. Am J Cardiol. 1995;75:778-782.
35. Piana RN, Paik GY, Moscucci M, et al. Incidence and treatment of“no-reflow”after percutaneous coronary intervention. Circulation. 1994; 89:2514-2518.
36. Atsushi Tanaka, MD; Takahiko Kawarabayashi, No-Reflow Phenomenon and Lesion Morphology in PatientsWith Acute Myocardial Infarction.Circulation. 2002;105:2148-2152
37. Webb JG, Carere RG, Virmani R, et al. Retrieval and analysis of particulate debris after saphenous vein graft intervention. J Am Coll Cardiol. 1999;34:468-475
38. Sutsch G, Kiowiski W, Bossard A, et al. Use of an emboli containment and retrieval system during percutaneous coronary angioplasty in native coronary arteries. Schweiz Med Wochenschr. 2000;130:1135-1145.
39. Xiaofan Wu,Akiko Maehara,Gary S Mintz, Attenuated Plaque Identified by Intravascular Ultrasound Predicts No-Reflow After Stenting in Acute Myocardial Infarction: The HORIZONS-AMI Trial , Circulation. 2009;120:1000-1001
40. Burzotta F, Trani C, Romagnoli E, Mazzari MA, Rebuzzi AG, De Vita M, Garramone B, Giannico F, Niccoli G. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary andrescue angioplasty (REMEDIA) trial. J Am Coll Cardiol 2005;46:371-376.
41. Maden,O;Kacmaz,F;Selcuk,MT. Relation of admission QRS duration with development of angiographic no-reflow in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous interventions. Journal of Electrocardiology.2008vol.41
42. Fukuda D, Kawarabayashi T, Tanaka A, et al. Lesion characteristics of acute myocardial infarction: an investigation with intravascular ultrasound. Heart.2001;85:402-406.
43. Fishbein MC , Siegel RJ . How big are atherosclerotic plaques thatrup- ture ?Circulation , 1996 , 94 :2662-2666.
44. J H Bae,T-G Kwon,D-W Hyun,Predictors of slow flow during primary percutaneous coronary intervention: an intravascular ultrasound-virtual histology study.Heart 2008;94:1559-1564
45.马长生.冠状动脉造影的血流与灌注评价[M]/马长生.冠心病介入治疗技术与策略.第2版.北京:人民卫生出版社,2004:15-l6.
46. Gibson C M,Cannon C P.TIMI frame count:a quantitative method of assessing coronary artery flow[J].Circulation,1996,93(5):879-888.
47. Fearon WF, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2008;51:560-564.
48. Lenoarda Galiuto,Barbara Garramone,The Extent of Microvascular Damage During Myocardial Contrast Echocardiography Is Superior to Other Known Indexes of Post-Infarct Reperfusion in Predicting Left Ventricular Remodeling, Journal of the American College of Cardiology,2008;51:552-559.
49. Iwakura,K;Ito,H;Okamura,A,Comparison of Two- Versus Three-Dimen-sional Myocardial Contrast Echocardiography for Assessing Subendocardial Perfusion Abnormality After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction,The American Journal of Cardiology , 2007; 85:781-786
50.谷新顺,傅向华。小型猪急性心肌梗死-经皮冠状动脉再通后无复流模型的建立,中国介入心脏病学杂志。2006,1214:357-360
51. D.D.LIU,N-K.Hsieh Histopathological and biochemical changes followingfat embolism with administration of corn oil micelles Journal of Bone and Joint Surgery;2008,90:1571-1576
52. Santoro GM ,Valenti R ,Buomamici P,et a1.Relation between ST-segment changes and myocardial pefusion evaluated by myocardial contrastechocardiography in patients with acute myocardial infarction treated with direct angioplasty[J].Am J Cardiol,1998,82:932-936.
53.杨成明,王旭开,王红勇.ST段抬高心肌梗死冠脉介入术后冠状动脉无复流患者左室功能的探讨[J].重庆医学,2008,37(6)
54. Yang TS. Experimental diagnosis of coronary heart disease[M] .Beijing : Scientific and Technical Documents Publishing House ,2002 :275-287
55. Walter S,Carlsson J,Enzymatic markers of reperfusion in acute myocardial infarct.With data from the ISAM study.Herz,1999,24(6):430-439
56. Thorsten Reffelmann, Sharon L. Hale, Joan S. Dow and Robert A. Kloner. No-Reflow Phenomenon Persists Long-Term After Ischemia/Reperfusion in the rat and Predicts Infarct Expansion Circulation 2003;108;2911-2917;
57. Thorsten Reffelmann Robert A. KlonerThe no-reflow phenomenon:A basic mechanism of myocardial ischemia and reperfusionBasic Res Cardiol 2006 ;101:359-372
58. Thorsten Reffelmann, Sharon L,Hale,Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusionAm J Physiol Heart Circ Physiol 2002;282: 766-772,
59. Ku DD. Coronary vascular reactivity after acutemyocardial ischemia.Science, 1982, 218: 576-578.
60. KaefferN, Richard V, Franois A, et al. Preconditioning prevents chronic reperfusion2induced coronary endothelial dysfunction in rats.Am J Physiology, 1996, 271: 842-849.
61. Richard V, Kaeffer N, Tron C, et al. Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation, 1994, 89: 1254-1261.
62. Kloner RA, Ganote CE, Jennings RB. The no-reflow phenomenon after temporary coronary occlusion in the dog. J Clin Invest, 1974,54: 1498-1508.
63. 1wakura K,Ito H,Ikushima M ,et a1.Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction.J Am Coll Cardiol,2003;41(1):1106-11
64. Tadamichi Sakuma, MD, Howard Leong-Poi, MD, Further Insights Into the No-reflow Phenomenon After Primary Angioplasty in Acute Myocardial Infarction: The Role of Microthromboemboli。Journal of the American Society of Echocardiography,2003;44:15-21
65.张成,王伟.远端保护装置在冠心病介入治疗中的应用[J].中国心血管杂志,2007,12(1)
66. Svilaas T, Vlaar PJ, van der Horst IC,Diercks GF, de Smet BJ, van den Heuvel AF, Anthonio RL, Jessurun GA, Tan ES, Suurmeijer AJ, Zijlstra F. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008;358:557-567.
67. Stone GW,Webb J ,Cox DA , et al. For the Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (E-MERALD) Investi- gatons[J ] . JAMA ,2005 ,293 :1063-1072.
68. Richard E, KuntzMD,Donald S, et al. Percutaneous coronary intervention induced emboli during p rimary PCI for STEMI: too little, too much, too late? [ J ]. Am Heart J, 2005, 150: 4-6.
69. Ito H , Tomooka T, Sakai N , et al. Lack of myocardial perfusion immediately after successful thrombolysis : a predictor of poor recovery of left ventricularfunction in anterior myocardial infarction. Circulation , 1992 , 85 : 1699-1705
70. Lin MS,Wu LS,Cheng NJ,Thrombus Aspiration Complicated by Systemic Embolization in Patients With Acute Myocardial Infarction Circ J. 2009 Jul;73(7):1356-8.
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29. Nakamoto S, Kaneda T, Inoue T, et al. Disseminated cholesterol embolism after coronary artery bypass grafting. J Card Surg 2001;16:410-13.
30. Stone GW,Webb J , Cox DA , et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction : a randomized controlled trial. JAMA ,2005 ,293 :1063-1072.
31. Paul D. Stein,Abdo Y.Yaekoub,Fat embolism syndrome,THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES,2008;336:472-477
32. Jouven X , Charles MA , Desnos M , et al . Circulating nonesterified fatty acid level as a predictive risk factor for sudden death in the population [J ] . Circulation ,2001 ,104 (7) :7562-761
33. Katsuomi Iwakura, Hiroshi Ito*, Shigeo Kawano, Atsushi Okamura, Toshiya Kurotobi, Motoo Date,Koichi Inoue, and Kenshi Fujii Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction European Heart Journal ,2006,27, 534-539
34. Abbo KM, Dooris M, Glazier S. Features and outcome of no-reflow after percutaneous coronary intervention. Am J Cardiol. 1995;75:778-782.
35. Piana RN, Paik GY, Moscucci M, et al. Incidence and treatment of“no-reflow”after percutaneous coronary intervention. Circulation. 1994; 89:2514-2518.
36. Atsushi Tanaka, MD; Takahiko Kawarabayashi, No-Reflow Phenomenon and Lesion Morphology in PatientsWith Acute Myocardial Infarction.Circulation. 2002;105:2148-2152
37. Webb JG, Carere RG, Virmani R, et al. Retrieval and analysis of particulate debris after saphenous vein graft intervention. J Am Coll Cardiol. 1999;34:468-475
38. Sutsch G, Kiowiski W, Bossard A, et al. Use of an emboli containment and retrieval system during percutaneous coronary angioplasty in native coronary arteries. Schweiz Med Wochenschr. 2000;130:1135-1145.
39. Xiaofan Wu,Akiko Maehara,Gary S Mintz, Attenuated Plaque Identified by Intravascular Ultrasound Predicts No-Reflow After Stenting in Acute Myocardial Infarction: The HORIZONS-AMI Trial , Circulation. 2009;120:1000-1001
40. Burzotta F, Trani C, Romagnoli E, Mazzari MA, Rebuzzi AG, De Vita M, Garramone B, Giannico F, Niccoli G. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary andrescue angioplasty (REMEDIA) trial. J Am Coll Cardiol 2005;46:371-376.
41. Maden,O;Kacmaz,F;Selcuk,MT. Relation of admission QRS duration with development of angiographic no-reflow in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous interventions. Journal of Electrocardiology.2008vol.41
42. Fukuda D, Kawarabayashi T, Tanaka A, et al. Lesion characteristics of acute myocardial infarction: an investigation with intravascular ultrasound. Heart.2001;85:402-406.
43. Fishbein MC , Siegel RJ . How big are atherosclerotic plaques thatrup- ture ?Circulation , 1996 , 94 :2662-2666.
44. J H Bae,T-G Kwon,D-W Hyun,Predictors of slow flow during primary percutaneous coronary intervention: an intravascular ultrasound-virtual histology study.Heart 2008;94:1559-1564
45.马长生.冠状动脉造影的血流与灌注评价[M]/马长生.冠心病介入治疗技术与策略.第2版.北京:人民卫生出版社,2004:15-l6.
46. Gibson C M,Cannon C P.TIMI frame count:a quantitative method of assessing coronary artery flow[J].Circulation,1996,93(5):879-888.
47. Fearon WF, Shah M, Ng M, et al. Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2008;51:560-564.
48. Lenoarda Galiuto,Barbara Garramone,The Extent of Microvascular Damage During Myocardial Contrast Echocardiography Is Superior to Other Known Indexes of Post-Infarct Reperfusion in Predicting Left Ventricular Remodeling, Journal of the American College of Cardiology,2008;51:552-559.
49. Iwakura,K;Ito,H;Okamura,A,Comparison of Two- Versus Three-Dimen-sional Myocardial Contrast Echocardiography for Assessing Subendocardial Perfusion Abnormality After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction,The American Journal of Cardiology , 2007; 85:781-786
50.谷新顺,傅向华。小型猪急性心肌梗死-经皮冠状动脉再通后无复流模型的建立,中国介入心脏病学杂志。2006,1214:357-360
51. D.D.LIU,N-K.Hsieh Histopathological and biochemical changes followingfat embolism with administration of corn oil micelles Journal of Bone and Joint Surgery;2008,90:1571-1576
52. Santoro GM ,Valenti R ,Buomamici P,et a1.Relation between ST-segment changes and myocardial pefusion evaluated by myocardial contrastechocardiography in patients with acute myocardial infarction treated with direct angioplasty[J].Am J Cardiol,1998,82:932-936.
53.杨成明,王旭开,王红勇.ST段抬高心肌梗死冠脉介入术后冠状动脉无复流患者左室功能的探讨[J].重庆医学,2008,37(6)
54. Yang TS. Experimental diagnosis of coronary heart disease[M] .Beijing : Scientific and Technical Documents Publishing House ,2002 :275-287
55. Walter S,Carlsson J,Enzymatic markers of reperfusion in acute myocardial infarct.With data from the ISAM study.Herz,1999,24(6):430-439
56. Thorsten Reffelmann, Sharon L. Hale, Joan S. Dow and Robert A. Kloner. No-Reflow Phenomenon Persists Long-Term After Ischemia/Reperfusion in the rat and Predicts Infarct Expansion Circulation 2003;108;2911-2917;
57. Thorsten Reffelmann Robert A. KlonerThe no-reflow phenomenon:A basic mechanism of myocardial ischemia and reperfusionBasic Res Cardiol 2006 ;101:359-372
58. Thorsten Reffelmann, Sharon L,Hale,Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusionAm J Physiol Heart Circ Physiol 2002;282: 766-772,
59. Ku DD. Coronary vascular reactivity after acutemyocardial ischemia.Science, 1982, 218: 576-578.
60. KaefferN, Richard V, Franois A, et al. Preconditioning prevents chronic reperfusion2induced coronary endothelial dysfunction in rats.Am J Physiology, 1996, 271: 842-849.
61. Richard V, Kaeffer N, Tron C, et al. Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation, 1994, 89: 1254-1261.
62. Kloner RA, Ganote CE, Jennings RB. The no-reflow phenomenon after temporary coronary occlusion in the dog. J Clin Invest, 1974,54: 1498-1508.
63. 1wakura K,Ito H,Ikushima M ,et a1.Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction.J Am Coll Cardiol,2003;41(1):1106-11
64. Tadamichi Sakuma, MD, Howard Leong-Poi, MD, Further Insights Into the No-reflow Phenomenon After Primary Angioplasty in Acute Myocardial Infarction: The Role of Microthromboemboli。Journal of the American Society of Echocardiography,2003;44:15-21
65.张成,王伟.远端保护装置在冠心病介入治疗中的应用[J].中国心血管杂志,2007,12(1)
66. Svilaas T, Vlaar PJ, van der Horst IC,Diercks GF, de Smet BJ, van den Heuvel AF, Anthonio RL, Jessurun GA, Tan ES, Suurmeijer AJ, Zijlstra F. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med. 2008;358:557-567.
67. Stone GW,Webb J ,Cox DA , et al. For the Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (E-MERALD) Investi- gatons[J ] . JAMA ,2005 ,293 :1063-1072.
68. Richard E, KuntzMD,Donald S, et al. Percutaneous coronary intervention induced emboli during p rimary PCI for STEMI: too little, too much, too late? [ J ]. Am Heart J, 2005, 150: 4-6.
69. Ito H , Tomooka T, Sakai N , et al. Lack of myocardial perfusion immediately after successful thrombolysis : a predictor of poor recovery of left ventricularfunction in anterior myocardial infarction. Circulation , 1992 , 85 : 1699-1705
70. Lin MS,Wu LS,Cheng NJ,Thrombus Aspiration Complicated by Systemic Embolization in Patients With Acute Myocardial Infarction Circ J. 2009 Jul;73(7):1356-8.