高频超声及多普勒组织成像评价Sprague-Dawley大鼠心肌梗死模型的价值
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摘要
前言
冠状动脉粥样硬化性心脏病(CHD)是严重影响人类健康的心脏疾病，CHD的早期诊断、病变严重程度的评价和早期治疗有极其重要的作用。AMI作为CHD的急症之一，是人类心衰及死亡最常见的原因之一。动物实验在研究心肌梗死心功能方面有重要意义。由于大鼠与人类的基因高度同源，同时这种动物容易获取并且价格低廉，随着转基因技术的发展，可以作为良好的动物模型。研究者需要对大鼠心脏的形态、结构与功能有一种快速的检验和评价方法，无创性的心脏检查对这些小动物的活体评价有极其重要的作用。高频超声心动图、CT、MRI等方法可以对大鼠左室的形态、结构、功能等作出无创评价。但是CT、MRI价格高昂，操作复杂，并不是首选的评价方法。高频超声心动图能无创评价AMI大鼠的心脏的形态、结构、功能、血流情况。1990年De Simome、Pfeffer MA已开始应用多普勒超声心动图评价大鼠的心脏结构及功能。但是采用什么指标来评价大鼠心脏结构及功能的研究不多，不同时期与不同梗死面积的AMI大鼠心脏结构及功能的变化情况在文献上鲜有报道。DTI脉冲波技术(DTI-PW)在人类已证实是评价心肌运动及左室功能的良好技术，可以对心肌运动进行定量评价，但是能否评价大鼠节段心肌运动及功能，在文献中未见报道。我们通过不同时期正常与AMI大鼠的对照研究，旨在探讨①评价AMI大鼠的超声指标及不同时期AMI大鼠的左室重构情况。②DTI-PW能否评价大鼠节段心肌运动及功能。
浙江大学硕士学位论文
目的探讨高频超声心动图及DTI评价sP吨ue一Daw!ey大鼠(sD大鼠)心肌梗死模型心脏结
构、功能及心肌运动的价值。
方法
一、大鼠心肌梗死模型制备
SD大鼠腹腔麻醉，气管插管，人工呼吸机辅助呼吸，左侧开胸，左冠状动脉前降支结扎
致AMI。梗死面积)30%为大面积AMI组，梗死面积<30%为中小面积胡I组。
二、实验方案
(一)、AMI大鼠心脏结构及功能评价
1、不同梗死面积AMI大鼠心脏结构与功能的比较
正常大鼠、AMI大鼠制备成功后饲养2周或8周，高频超声心动图检查;根据Masson二色
染色分正常组、中小面积AMI组与大面积姗I组大鼠。比较不同梗死面积大鼠的心脏结构及功
能。
2、大面积AMI大鼠2周与8周时心脏结构与功能对照分析
胡I大鼠制备成功后饲养8周，2周时与8周时分别进行高频超声心动图检查心脏结构及功
能;根据Masson三色染色确定大面积胡I大鼠。比较大面积AMI大鼠2周与8周时心脏结构及功
能的改变。
(二)、正常大鼠与大面积AMI大鼠的心肌运动及二尖瓣口血流比较分析
正常大鼠、AMI大鼠制备成功后饲养8周，高频超声心动图检查，DTI检杏左室前壁与
左室后壁的心肌运动速度，多普勒血流成像测定二尖瓣口血流速度;根据Masson二色染色确
定大面积胡I组大鼠。比较正常大鼠与大面积AMI大鼠的心肌运动速度及二尖瓣口血流速度。
(三)、超声测量可重复性及差异性分析。
正常人鼠饲养8周，同一检查者进行两次高频超声心动图与DTI检查，另外不同检杳者亦
进行高频超声心动图与DTI检查，超声测量结果进行可重复性及差异性分析。
三、心脏超声检查
大鼠腹腔内注射麻醉后，使用Acuson Sequoia 512超声诊断仪进行心脏超声检查，采
用15L8w探头，探头频率为14姗z。左室短轴图像在乳头肌水平获得，以左室心外膜的弧状
轮廓显示出来为理想:左室长轴图像通过垂直于短轴获得，以左室长度最长，包含二尖瓣和
主动脉瓣为理想。舒张末期定义为左室容积最大时，收缩末期定义为左室容积最小时。测量
浙江大学硕士学位论文
左室长轴和左室短轴乳头肌水平M型曲线。测量左室内径、左室容量、左心功能、左心重
量、左房内径、室间隔和左室后壁收缩期与舒张期厚度及收缩期增厚百分比等指标。在胸骨
旁左室短轴乳头肌水平，用OTI一PW测定的左室前壁与左室后壁心肌运动频谱，记录土波
Sm、Em、Am的峰值速度。在心尖四腔心切面用PW测定二尖瓣口血流频谱，记录舒张早
期与舒张晚期的峰值速度。用MO储存资料供脱机分析。
四、形态学分析
五、统计学分析
Masson二色染色，所有SD大鼠AMI模型的梗死面积经Masson二色染色确定。
应用SPSS 11.0统计软件包进行统计分析处理。
结果
一、AMI大鼠心脏结构及功能评价
、不同梗死面积AMI大鼠心脏结构与功能的比较
1)、大鼠饲养2周组正常组、中小面积AMI组与大面积AMI组大鼠随着梗死面积的增人，
左室内径指标EDD、ESD增大，左室容量指标EDV、ESv增大，心功能指标EF、FS一卜降
(P<0.05，0.01)。
2)、大鼠饲养8周组正常组、中小面积阴I组与大面积胡I组大鼠随着梗死面积的增大，
左室内径指标EDD、ESD，左室容量指标EDV、ESV增大，心功能指标EF、FS一下降，室
间隔收缩期与舒张期厚度变薄，左房增大(P<0.05，0.01)。
2、大面积胡I大鼠2周与8周时心脏结构与功能对照分析
大面积AMI大鼠8周时较2周时心脏的结构及功能的改变:IVSd下降(P<0.01)。EDD、
ESD、EDV、ESV增加，FS、EF卜降，LA增大，IVSs卜降，LVPW%增大(P<0.05)。
二、正常大鼠与大面积AMI人鼠
Preface
CHD is one of heart diseases, which influence people's health seriously, so early diagnosis, evaluation of severity, and early treatment of CHD are very important. AMI is one of the most common causes of heart failure and death in human as emergency of CHD. Animal experiment plays an important role in evaluating of cardiac function of myocardial infarction. Rat can be used as an excellent animal model with the development of trans-gene technique because rat is cheap and easily obtained, and the gene of rat is similar with human. Researchers need a means to examine and evaluate quickly the cardiac structure and function of rat. Cardiac examination non-invasively plays an important role in vivo-evaluation of these small animals. High frequency echocardiography, MR1 and CT can be used to evaluate non-invasively left ventricular morphology, structure, and function of rat. MRI and CT, which are limited by high price and complicated operation, are not preferred. High frequency echocardiography can evaluate left ve
ntricular morphology, structure, function, and flow of AMI rat. De Simome and Pfeffer began to evaluate cardiac structure and function of rat with echocardiography in 1990.But there is little research about which echocardiographic index can be used to evaluate the cardiac structure and function of rat. The change of cardiac structure and function of rat in different phases of AMI is seldom reported in literature. DTI pulse wave technique (DTI-PW) has been proved a good index to evaluate myocardial movement and left ventricular function in human. Whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat is seldom reported. We explore by the control research between normal and AMI rat in different phases: How to evaluate AMI rat with echocardiographic index and the process of left ventricular remodeling of AMI rat in different phases; whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat.
Objective
To explore the value of High frequency echocardiography and DTI-PW to evaluate cardiac structure and function and myocardial movement of Sprague-Dawley Rat models with AMI.
Methods
Production of Rat Models with Acute Myocardial Infarction
Sprague-Dawley rats were anesthetized and intubated and ventilated with ventilator. Through a thoracotomy on the left side, Left anterior descending coronary artery was ligated proximally. Infarct area no less than 30% was large, and infarct area less than 30% was mild or moderate. Study Designs
1. Evaluation of cardiac structure and function of AMI rat A) Comparison of AMI rats of different infarct area
Cardiac structure and function of normal and AMI rats were examined with high frequency echocardiography in 2 weeks or 8 weeks after induction successfully. Normal and mild/moderate infarct and large infarct group rats were divided by infarct area, which was ascertained by Masson trichrome staining. The cardiac structure and function of three groups were compared. B Comparison of AMI rats of the large infarct area in different phases
Cardiac structure and function of AMI rats were examined with high frequency echocardiography in 2 weeks and 8 weeks after induction successfully. Infarct area was ascertained by Masson trichrome staining. The cardiac structure and function in 2 weeks and 8 weeks of large infarct rats were compared.
2. Comparison of myocardial movement and mitral valve orifice flow between normal and large infarct rats
The left ventricular anterior and posterior wall myocardial movement of normal and AMI rats were examined with high frequency echocardiography and DTI in 8 weeks after induction successfully. Mitral valve orifice flow velocity was recorded by Doppler flow imaging. Infarct area was ascertained by Masson trichrome staining. Mitral orifice flow
velocity and myocardial movement were compared between the normal and the large infarct rats. 3. Reproducibility and variability analysis
Normal rats were examined with high frequency echocardiography and DTI in
冠状动脉粥样硬化性心脏病(CHD)是严重影响人类健康的心脏疾病，CHD的早期诊断、病变严重程度的评价和早期治疗有极其重要的作用。AMI作为CHD的急症之一，是人类心衰及死亡最常见的原因之一。动物实验在研究心肌梗死心功能方面有重要意义。由于大鼠与人类的基因高度同源，同时这种动物容易获取并且价格低廉，随着转基因技术的发展，可以作为良好的动物模型。研究者需要对大鼠心脏的形态、结构与功能有一种快速的检验和评价方法，无创性的心脏检查对这些小动物的活体评价有极其重要的作用。高频超声心动图、CT、MRI等方法可以对大鼠左室的形态、结构、功能等作出无创评价。但是CT、MRI价格高昂，操作复杂，并不是首选的评价方法。高频超声心动图能无创评价AMI大鼠的心脏的形态、结构、功能、血流情况。1990年De Simome、Pfeffer MA已开始应用多普勒超声心动图评价大鼠的心脏结构及功能。但是采用什么指标来评价大鼠心脏结构及功能的研究不多，不同时期与不同梗死面积的AMI大鼠心脏结构及功能的变化情况在文献上鲜有报道。DTI脉冲波技术(DTI-PW)在人类已证实是评价心肌运动及左室功能的良好技术，可以对心肌运动进行定量评价，但是能否评价大鼠节段心肌运动及功能，在文献中未见报道。我们通过不同时期正常与AMI大鼠的对照研究，旨在探讨①评价AMI大鼠的超声指标及不同时期AMI大鼠的左室重构情况。②DTI-PW能否评价大鼠节段心肌运动及功能。
浙江大学硕士学位论文
目的探讨高频超声心动图及DTI评价sP吨ue一Daw!ey大鼠(sD大鼠)心肌梗死模型心脏结
构、功能及心肌运动的价值。
方法
一、大鼠心肌梗死模型制备
SD大鼠腹腔麻醉，气管插管，人工呼吸机辅助呼吸，左侧开胸，左冠状动脉前降支结扎
致AMI。梗死面积)30%为大面积AMI组，梗死面积<30%为中小面积胡I组。
二、实验方案
(一)、AMI大鼠心脏结构及功能评价
1、不同梗死面积AMI大鼠心脏结构与功能的比较
正常大鼠、AMI大鼠制备成功后饲养2周或8周，高频超声心动图检查;根据Masson二色
染色分正常组、中小面积AMI组与大面积姗I组大鼠。比较不同梗死面积大鼠的心脏结构及功
能。
2、大面积AMI大鼠2周与8周时心脏结构与功能对照分析
胡I大鼠制备成功后饲养8周，2周时与8周时分别进行高频超声心动图检查心脏结构及功
能;根据Masson三色染色确定大面积胡I大鼠。比较大面积AMI大鼠2周与8周时心脏结构及功
能的改变。
(二)、正常大鼠与大面积AMI大鼠的心肌运动及二尖瓣口血流比较分析
正常大鼠、AMI大鼠制备成功后饲养8周，高频超声心动图检查，DTI检杏左室前壁与
左室后壁的心肌运动速度，多普勒血流成像测定二尖瓣口血流速度;根据Masson二色染色确
定大面积胡I组大鼠。比较正常大鼠与大面积AMI大鼠的心肌运动速度及二尖瓣口血流速度。
(三)、超声测量可重复性及差异性分析。
正常人鼠饲养8周，同一检查者进行两次高频超声心动图与DTI检查，另外不同检杳者亦
进行高频超声心动图与DTI检查，超声测量结果进行可重复性及差异性分析。
三、心脏超声检查
大鼠腹腔内注射麻醉后，使用Acuson Sequoia 512超声诊断仪进行心脏超声检查，采
用15L8w探头，探头频率为14姗z。左室短轴图像在乳头肌水平获得，以左室心外膜的弧状
轮廓显示出来为理想:左室长轴图像通过垂直于短轴获得，以左室长度最长，包含二尖瓣和
主动脉瓣为理想。舒张末期定义为左室容积最大时，收缩末期定义为左室容积最小时。测量
浙江大学硕士学位论文
左室长轴和左室短轴乳头肌水平M型曲线。测量左室内径、左室容量、左心功能、左心重
量、左房内径、室间隔和左室后壁收缩期与舒张期厚度及收缩期增厚百分比等指标。在胸骨
旁左室短轴乳头肌水平，用OTI一PW测定的左室前壁与左室后壁心肌运动频谱，记录土波
Sm、Em、Am的峰值速度。在心尖四腔心切面用PW测定二尖瓣口血流频谱，记录舒张早
期与舒张晚期的峰值速度。用MO储存资料供脱机分析。
四、形态学分析
五、统计学分析
Masson二色染色，所有SD大鼠AMI模型的梗死面积经Masson二色染色确定。
应用SPSS 11.0统计软件包进行统计分析处理。
结果
一、AMI大鼠心脏结构及功能评价
、不同梗死面积AMI大鼠心脏结构与功能的比较
1)、大鼠饲养2周组正常组、中小面积AMI组与大面积AMI组大鼠随着梗死面积的增人，
左室内径指标EDD、ESD增大，左室容量指标EDV、ESv增大，心功能指标EF、FS一卜降
(P<0.05，0.01)。
2)、大鼠饲养8周组正常组、中小面积阴I组与大面积胡I组大鼠随着梗死面积的增大，
左室内径指标EDD、ESD，左室容量指标EDV、ESV增大，心功能指标EF、FS一下降，室
间隔收缩期与舒张期厚度变薄，左房增大(P<0.05，0.01)。
2、大面积胡I大鼠2周与8周时心脏结构与功能对照分析
大面积AMI大鼠8周时较2周时心脏的结构及功能的改变:IVSd下降(P<0.01)。EDD、
ESD、EDV、ESV增加，FS、EF卜降，LA增大，IVSs卜降，LVPW%增大(P<0.05)。
二、正常大鼠与大面积AMI人鼠
Preface
CHD is one of heart diseases, which influence people's health seriously, so early diagnosis, evaluation of severity, and early treatment of CHD are very important. AMI is one of the most common causes of heart failure and death in human as emergency of CHD. Animal experiment plays an important role in evaluating of cardiac function of myocardial infarction. Rat can be used as an excellent animal model with the development of trans-gene technique because rat is cheap and easily obtained, and the gene of rat is similar with human. Researchers need a means to examine and evaluate quickly the cardiac structure and function of rat. Cardiac examination non-invasively plays an important role in vivo-evaluation of these small animals. High frequency echocardiography, MR1 and CT can be used to evaluate non-invasively left ventricular morphology, structure, and function of rat. MRI and CT, which are limited by high price and complicated operation, are not preferred. High frequency echocardiography can evaluate left ve
ntricular morphology, structure, function, and flow of AMI rat. De Simome and Pfeffer began to evaluate cardiac structure and function of rat with echocardiography in 1990.But there is little research about which echocardiographic index can be used to evaluate the cardiac structure and function of rat. The change of cardiac structure and function of rat in different phases of AMI is seldom reported in literature. DTI pulse wave technique (DTI-PW) has been proved a good index to evaluate myocardial movement and left ventricular function in human. Whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat is seldom reported. We explore by the control research between normal and AMI rat in different phases: How to evaluate AMI rat with echocardiographic index and the process of left ventricular remodeling of AMI rat in different phases; whether DTI-PW can be used to evaluate segmental myocardial movement and function of rat.
Objective
To explore the value of High frequency echocardiography and DTI-PW to evaluate cardiac structure and function and myocardial movement of Sprague-Dawley Rat models with AMI.
Methods
Production of Rat Models with Acute Myocardial Infarction
Sprague-Dawley rats were anesthetized and intubated and ventilated with ventilator. Through a thoracotomy on the left side, Left anterior descending coronary artery was ligated proximally. Infarct area no less than 30% was large, and infarct area less than 30% was mild or moderate. Study Designs
1. Evaluation of cardiac structure and function of AMI rat A) Comparison of AMI rats of different infarct area
Cardiac structure and function of normal and AMI rats were examined with high frequency echocardiography in 2 weeks or 8 weeks after induction successfully. Normal and mild/moderate infarct and large infarct group rats were divided by infarct area, which was ascertained by Masson trichrome staining. The cardiac structure and function of three groups were compared. B Comparison of AMI rats of the large infarct area in different phases
Cardiac structure and function of AMI rats were examined with high frequency echocardiography in 2 weeks and 8 weeks after induction successfully. Infarct area was ascertained by Masson trichrome staining. The cardiac structure and function in 2 weeks and 8 weeks of large infarct rats were compared.
2. Comparison of myocardial movement and mitral valve orifice flow between normal and large infarct rats
The left ventricular anterior and posterior wall myocardial movement of normal and AMI rats were examined with high frequency echocardiography and DTI in 8 weeks after induction successfully. Mitral valve orifice flow velocity was recorded by Doppler flow imaging. Infarct area was ascertained by Masson trichrome staining. Mitral orifice flow
velocity and myocardial movement were compared between the normal and the large infarct rats. 3. Reproducibility and variability analysis
Normal rats were examined with high frequency echocardiography and DTI in
引文
1. Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E, Amouyel P: Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet 1999, 353(9164): 1547-1557.
2. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (l). N Engl J Med 1992, 326(4):242-250.
3. Iwanaga Y, Hoshijima M, Gu Y, lwatate M, Dietetic T, Ikeda Y, Date MO, Chrast J, Matsuzaki M, Peterson KL et al: Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 2004, 113(5):727-736.
4. Charreau B, Tesson L, Soulillou JP, Pourcel C, Anegon l: Transgenesis in rats: technical aspects and models. Transgenic Res 1996, 5(4):223-234.
5. Clark MS: Comparative genomics: the key to understanding the Human Genome Project. Bioessays 1999, 21(2): 121-130.
6. Burley SK, Almo SC, Bonanno JB, Capel M, Chance MR, Gaasterland T, Lin D, Sali A, Studier FW, Swaminathan S: Structural genomics: beyond the human genome project. Nat Genet 1999, 23(2): 151-157.
7. Bentley DR: The Human Genome Project-an overview. Med Res Rev 2000, 20(3): 189-196.
8. Jorgensen SM, Demirkaya O, Ritman EL: Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT.Am J Physiol 1998, 275(3 Pt 2):H1103-1114.
9. Rehwald WG, geeder SB, McVeigh ER, Judd RM: Techniques for high-speed cardiac
magnetic resonance imaging in rats and rabbits. Magn Resort Med 1997, 37(1): 124-130.
10. Moises VA, Ferreira RL, Nozawa E, Kanashiro RM, Campos O, Andrade JL, Carvalho AC, Tucci PJ: Structural and functional characteristics of rat hearts with and without myocardial infarct. Initial experience with Doppler echocardiography. Arq Bras Cardiol 2000, 75(2):125-136.
11. de Simone G, Wallerson DC, Volpe M, Devereux RB: Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats. Necropsy validation. Am J Hypertens 1990, 3(9):688-696.
12. Pfeffer MA, Braunwald E: Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 1990, 81(4):1161-1172.
13. Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A, Iuchi A, Fukuda N, Ito S: Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997, 79(7):921-928.
14. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA: Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures, J Am Coll Cardiol 1997, 30(6): 1527-1533.
15. Garcia-Fernandez MA, Azevedo J, Moreno M, Bermejo J, Perez-Castellano N, Puerta P, Desco M, Antoranz C, Serrano JA, Garcia E et al: Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging. Eur Heart J 1999, 20(7):496-505.
16. Brachfeld N: Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. Am J Cardiol 1976, 37(4):528-532.
17. Tzanidis A, Hannan RD, Thomas WG, Onan D, Autelitano DJ, See F, Kelly DJ, Gilbert RE, Krum H: Direct actions of urotensin Ⅱ on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res 2003, 93(3):246-253.
18. Tsujita Y, Witt S: 用高分辨率超志心动描记术对小鼠扩张性心肮病进行增强评价， Glascock B: Medical solutions 2004, 1(3):39-42.
19. Ad N, Oron U: Impact of low level laser irradiation on infarct size in the rat following myocardial infarction, Int J Cardiol 2001, 80(2-3): 109-116.
20. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM, Tikkanen I: Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 2001, 280(6):H2726-2731.
21. Litwin SE, Katz SE, Morgan JP, Douglas PS: Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat. Circulation 1994, 89(1):345-354.
22. Sutton MG, Sharpe N: Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000, 101(25):2981-2988.
23. Spadaro J, Fishbein MC, Hare C, Pfeffer MA, Maroko PR: Characterization of myocardial infarcts in the rat. Arch Pathol Lab Med 1980, 104(4):179-183.
24. McDicken WN, Sutherland GR, Moran CM, Gordon LN: Colour Doppler velocity imaging of the myocardium. Ultrasound Med Biol 1992, 18(6-7):651-654.
25. Waggoner AD, Bierig SM: Tissue Doppler imaging: a useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function, J Am
Soc Echocardiogr 2001, 14(12): 1143-1152.
26. Trambaiolo P, Tonti G, Salustri A, Fedele F, Sutherland G: New insights into regional systolic and diastolic left ventricular function with tissue Doppler echocardiography: from qualitative analysis to a quantitative approach. J Am Soc Echocardiogr 2001, 14(2):85-96.
27. Fedele F, Trambaiolo P, Magni G, De Castro S, Cacciotti L: New modalities of regional and global left ventricular function analysis: state of the art. Am J Cardiol 1998, 81(12A):49G-57G
28. Isaaz K, Thompson A, Ethevenot G, CIoez JL, Brembilla B, Pernot C: Doppler echocardiographic measurement of low velocity motion of the left ventricular posterior wall. Am J Cardiol 1989, 64(1):66-75.
29. Ommen SR: Echocardiographic assessment of diastolic function. Curr Opin Cardiol 2001, 16(4):240-245.
30. Yamada E, Garcia M, Thomas JD, Marwick TH: Myocardial Doppler velocity imaging-a quantitative technique for interpretation of dobutamine echocardiography. Am J Cardiol 1998, 82(6):806-809, A809-810.
31. Mishiro Y, Oki T, Yamada H, Onose Y, Matsuoka M, Tabata T, Wakatsuki T, Ito S: Use of angiotensin Ⅱ stress pulsed tissue Doppler imaging to evaluate regional left ventricular contractility in patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr 2000, 13(12): 1065-1073.
32. Bach DS, Armstrong WF, Donovan CL, Muller DW: Quantitative Doppler tissue imaging for assessment of regional myocardial velocities during transient ischemia and reperfusion. Am Heart J 1996, 132(4):721-725.
33. Prunier F, Gaertner R, Louedec L, Michel JB, Mercadier J J, Escoubet B: Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats. Am J Physiol Heart Circ Physiol 2002, 283(1):H346-352.
2. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes (l). N Engl J Med 1992, 326(4):242-250.
3. Iwanaga Y, Hoshijima M, Gu Y, lwatate M, Dietetic T, Ikeda Y, Date MO, Chrast J, Matsuzaki M, Peterson KL et al: Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 2004, 113(5):727-736.
4. Charreau B, Tesson L, Soulillou JP, Pourcel C, Anegon l: Transgenesis in rats: technical aspects and models. Transgenic Res 1996, 5(4):223-234.
5. Clark MS: Comparative genomics: the key to understanding the Human Genome Project. Bioessays 1999, 21(2): 121-130.
6. Burley SK, Almo SC, Bonanno JB, Capel M, Chance MR, Gaasterland T, Lin D, Sali A, Studier FW, Swaminathan S: Structural genomics: beyond the human genome project. Nat Genet 1999, 23(2): 151-157.
7. Bentley DR: The Human Genome Project-an overview. Med Res Rev 2000, 20(3): 189-196.
8. Jorgensen SM, Demirkaya O, Ritman EL: Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT.Am J Physiol 1998, 275(3 Pt 2):H1103-1114.
9. Rehwald WG, geeder SB, McVeigh ER, Judd RM: Techniques for high-speed cardiac
magnetic resonance imaging in rats and rabbits. Magn Resort Med 1997, 37(1): 124-130.
10. Moises VA, Ferreira RL, Nozawa E, Kanashiro RM, Campos O, Andrade JL, Carvalho AC, Tucci PJ: Structural and functional characteristics of rat hearts with and without myocardial infarct. Initial experience with Doppler echocardiography. Arq Bras Cardiol 2000, 75(2):125-136.
11. de Simone G, Wallerson DC, Volpe M, Devereux RB: Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats. Necropsy validation. Am J Hypertens 1990, 3(9):688-696.
12. Pfeffer MA, Braunwald E: Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 1990, 81(4):1161-1172.
13. Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A, Iuchi A, Fukuda N, Ito S: Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997, 79(7):921-928.
14. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA: Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures, J Am Coll Cardiol 1997, 30(6): 1527-1533.
15. Garcia-Fernandez MA, Azevedo J, Moreno M, Bermejo J, Perez-Castellano N, Puerta P, Desco M, Antoranz C, Serrano JA, Garcia E et al: Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging. Eur Heart J 1999, 20(7):496-505.
16. Brachfeld N: Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. Am J Cardiol 1976, 37(4):528-532.
17. Tzanidis A, Hannan RD, Thomas WG, Onan D, Autelitano DJ, See F, Kelly DJ, Gilbert RE, Krum H: Direct actions of urotensin Ⅱ on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res 2003, 93(3):246-253.
18. Tsujita Y, Witt S: 用高分辨率超志心动描记术对小鼠扩张性心肮病进行增强评价， Glascock B: Medical solutions 2004, 1(3):39-42.
19. Ad N, Oron U: Impact of low level laser irradiation on infarct size in the rat following myocardial infarction, Int J Cardiol 2001, 80(2-3): 109-116.
20. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM, Tikkanen I: Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 2001, 280(6):H2726-2731.
21. Litwin SE, Katz SE, Morgan JP, Douglas PS: Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat. Circulation 1994, 89(1):345-354.
22. Sutton MG, Sharpe N: Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000, 101(25):2981-2988.
23. Spadaro J, Fishbein MC, Hare C, Pfeffer MA, Maroko PR: Characterization of myocardial infarcts in the rat. Arch Pathol Lab Med 1980, 104(4):179-183.
24. McDicken WN, Sutherland GR, Moran CM, Gordon LN: Colour Doppler velocity imaging of the myocardium. Ultrasound Med Biol 1992, 18(6-7):651-654.
25. Waggoner AD, Bierig SM: Tissue Doppler imaging: a useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function, J Am
Soc Echocardiogr 2001, 14(12): 1143-1152.
26. Trambaiolo P, Tonti G, Salustri A, Fedele F, Sutherland G: New insights into regional systolic and diastolic left ventricular function with tissue Doppler echocardiography: from qualitative analysis to a quantitative approach. J Am Soc Echocardiogr 2001, 14(2):85-96.
27. Fedele F, Trambaiolo P, Magni G, De Castro S, Cacciotti L: New modalities of regional and global left ventricular function analysis: state of the art. Am J Cardiol 1998, 81(12A):49G-57G
28. Isaaz K, Thompson A, Ethevenot G, CIoez JL, Brembilla B, Pernot C: Doppler echocardiographic measurement of low velocity motion of the left ventricular posterior wall. Am J Cardiol 1989, 64(1):66-75.
29. Ommen SR: Echocardiographic assessment of diastolic function. Curr Opin Cardiol 2001, 16(4):240-245.
30. Yamada E, Garcia M, Thomas JD, Marwick TH: Myocardial Doppler velocity imaging-a quantitative technique for interpretation of dobutamine echocardiography. Am J Cardiol 1998, 82(6):806-809, A809-810.
31. Mishiro Y, Oki T, Yamada H, Onose Y, Matsuoka M, Tabata T, Wakatsuki T, Ito S: Use of angiotensin Ⅱ stress pulsed tissue Doppler imaging to evaluate regional left ventricular contractility in patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr 2000, 13(12): 1065-1073.
32. Bach DS, Armstrong WF, Donovan CL, Muller DW: Quantitative Doppler tissue imaging for assessment of regional myocardial velocities during transient ischemia and reperfusion. Am Heart J 1996, 132(4):721-725.
33. Prunier F, Gaertner R, Louedec L, Michel JB, Mercadier J J, Escoubet B: Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats. Am J Physiol Heart Circ Physiol 2002, 283(1):H346-352.