【作者】 籍振国；

【导师】 刘坤申；

【作者基本信息】 河北医科大学 ， 内科学， 2008， 博士

【摘要】 心力衰竭是由心脏的结构或功能异常损害了心室的充盈或射血能力而引起的一种复杂的临床综合症。随着生活条件的改善,人类平均寿命不断增加,慢性心力衰竭也正在成为重要的临床问题,尤其在老年人。它也是每年住院患者最常见的住院原因,其每年的医疗费开支超过心肌梗死。越来越多的证据表明,舒张功能不全是慢性心力衰竭的主要病理生理学表现,过去的研究偏重收缩功能不全。由于缺乏深入研究和循证医学证据,慢性心力衰竭的治疗指南对于舒张性心力衰竭人群尚无确切定义,也没有给出明确的治疗方法。舒张功能不全时,心室(左心室或右心室或两者)松驰和充盈延迟或不能完全恢复到收缩期前的长度和张力。舒张功能障碍常出现于收缩功能障碍之前。舒张性心力衰竭的最早期表现可能是劳力性呼吸困难和活动耐受力下降。通常是由于心肌肥厚、纤维化或缺血,左室充盈减慢或舒张不完全,引起肺静脉瘀血。冠心病伴无症状的左室舒张功能不全与临床上发生的症状性心力衰竭有一定的联系。由于从病史、体格检查、心电图和胸部X线检查来区分舒张功能不全与收缩功能不全是非常困难的,因此常常需要其他客观的检查手段。心导管检查是第一个用来诊断舒张功能不全的手段,但其具有一定的创伤性,且不利于长期随访。目前有关冠心病病变程度与左室舒张功能的关系以及导管法与超声应变率显像对舒张功能所测指标的关系报道较少。为尽早对此类患者进行强化干预治疗,改善预后,有必要采用不同方法探讨冠状动脉病变程度与左室舒张功能的关系。应变率显像易于被患者接受,是一种可靠及实用的心室舒张功能障碍的检查方法。肾素-血管紧张素-醛固酮系统(RAAS)不仅在心室收缩功能不全的病理生理过程中起着重要的作用,而且在心室舒张功能不全中也有重要作用。由于RAAS在心肌间质纤维化的独特作用,已经确立了血管紧张素转换酶(ACE)抑制剂及醛固酮受体拮抗剂在收缩功能不全治疗中的地位。基于RAAS分子水平的研究发现,RAAS中血管紧张素Ⅱ和醛固酮有明确的致心肌纤维化作用,而干预RAAS的一类神经内分泌拮抗剂在心室舒张功能不全也应有较大的治疗价值。到目前为止,仅有血管紧张素Ⅱ型受体拮抗剂针对舒张性心力衰竭患者的死亡率进行了研究,而其他神经内分泌拮抗剂在舒张功能不全的研究正在进行,尚未有最后结果。本研究分为三部分。首先应用心导管及超声心动图检查研究了不同冠状动脉病变程度的冠心病患者心室舒张功能的变化。第二部分应用超声应变率显像从临床上分析了ACE抑制剂、β受体阻滞剂以及加用醛固酮受体拮抗剂螺内酯对冠心病心室舒张功能障碍患者的影响。第三部分从基础研究的角度分析了大鼠左室损伤模型应用ACE抑制剂、β受体阻滞剂及醛固酮受体拮抗剂对血流动力学和心室重构的影响。第一部分左心导管法与超声心动图检查对比评价冠状动脉病变对左心室舒张功能的影响目的:探讨冠心病患者冠状动脉病变程度对左心室舒张功能的影响。资料与方法:应用心导管法及超声心动图检查对75例经选择性冠状动脉造影确诊的冠心病患者进行了研究。根据冠状动脉造影结果将冠心病患者按病变狭窄所累及的动脉支数分为四组:轻度冠状动脉狭窄组(冠状动脉狭窄程度≥50%且≤75%,轻度病变组)、单支病变组(单支血管狭窄>75%)、双支病变组(两支血管狭窄>75%)及三支病变组(三支血管狭窄>75%)。另外,根据Gensini积分进行分组,比较不同积分与心室舒张功能的关系。应用导管法测定主动脉内的收缩压、舒张压、心率、左心室舒张末期压力(LVEDP),收缩期及舒张期左室压力最大变化率(dp/dtmax, dp/dtmin)及等容舒张期压力衰减时间常数(T)。比较不同的冠状动脉狭窄程度与心室舒张功能的关系。应用心导管法与超声心动图检查分析左心房内径(LAD)、左心室舒张末期容量(EDV)、收缩末期容量(ESV)、每搏量(SV)、舒张期前1/3充盈量(1/3V)及舒张早期充盈分数(1/3FF),并计算左心室射血分数(EF)。应用超声应变率显像(SRI)分别测量左心室各壁不同节段收缩期(SRs)、快速充盈期(SRe)及舒张晚期(SRa)的峰值应变率,对各峰值应变率与导管法所测的相应指标进行相关性分析。结果:常规超声心动图指标比较,在不同冠状动脉狭窄病变组,仅LAD在三支病变组(38.74±4.57mm)较轻度冠脉病变组(33.87±3.80mm)及单支血管病变组(33.77±3.94mm)显著增加。左心导管测定的LVEDP、dp/dtmax、dp/dtmin、EDV、ESV各组比较均未发现有显著的统计学差异。而轻度冠脉病变组的时间常数T(30.31±6.50ms)低于其他各组(单支病变、双支病变与三支病变组分别为40.92±11.79、43.02±15.83、50.32±23.57ms, P<0.05),反映了显著狭窄各组的左室舒张早期,尤其是等容舒张期功能受损。舒张早期充盈的1/3V(轻度冠脉病变组、单支病变组、双支病变组及三支病变组分别为55.69±24.87、31.44±21.17、24.29±14.79、19.15±13.01ml)及1/3FF%(分别为45.95±19.90、33.29±20.49、25.52±15.06、24.22±15.29),冠状动脉显著狭窄组低于轻度冠脉病变组。而反映左室收缩功能指标的SV及EF在三支病变组降低,与轻度冠脉病变组比较出现了统计学差异(P<0.05)。不同Gensini积分的患者比较,常规超声心动图的LAD在积分较高的“15~”及“30~”两组显著高于“<15”组,导管法测得的EF值、1/3V及1/3FF仅在“30~”组与“<15”组有显著的统计学差别。等容舒张时间常数T及LVEDP在以Gensini积分分组的各组间未发现显著的统计学差异。16例患者同时进行了超声应变率与心导管血流动力学的检查。导管法所测各项心功能指标与超声所测指标的相关性分析发现,两种方法测得的EF相关性良好,相关系数为0.89(P<0.01);导管法所测的EF与SRI的平均SRs相关系数为-0.74(P<0.01);SRe与舒张期前1/3充盈分数的相关系数为0.61(P=0.01),与等容舒张时间常数T的相关系数为-0.66(P<0.01);而未发现E峰与舒张早期峰值应变率、E峰与T有显著的相关性。结论:不同程度的冠状动脉病变对心室的舒张功能具有一定的影响,而且随着病变程度的加重影响增大。无论以冠状动脉的狭窄动脉支数还是以冠状动脉狭窄的Gensini积分法比较都反映了冠状动脉显著狭窄影响左心室舒张功能,但前者更能敏感地反映舒张功能的受损;超声应变率显像技术可以准确判断冠心病患者的心室舒张功能。第二部分血管紧张素转换酶抑制剂、β受体阻滞剂及螺内酯对冠心病左室舒张功能的影响目的:应用超声应变率成像(SRI)技术观察冠心病舒张功能障碍患者应用血管紧张素转换酶(ACE)抑制剂、β受体阻滞剂及醛固酮受体拮抗剂螺内酯对左心室舒张功能的影响。方法:34例无心肺疾病的对照组与连续在本科住院符合入选条件的75例冠心病患者,年龄25~83岁。所有患者无ACE抑制剂、β受体阻滞剂及醛固酮受体拮抗剂应用的禁忌证。75例冠心病患者随机分为两组,即干预1组共38例应用ACE抑制剂+β受体阻滞剂(C+M),干预2组共37例,在上述治疗的基础上加用螺内酯40mg/d(C+M+S)。用药前及用药后1个月、3个月及6个月时采用超声心动图测量左房内径(LAD)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT),并计算左室质量指数(LVMI)。应用Simpson双平面面积长度法测量左室舒张末期容量、左室收缩末期容量,并计算左室射血分数;应用脉冲多普勒测定二尖瓣口舒张早期左室充盈峰速度( E)、心房收缩期左室充盈峰速度(A),并计算E/A比值。启动组织多普勒测量左心室各壁不同节段收缩期、快速充盈期及房缩期的峰值应变率(SRs、SRe及SRa)。结果:对照组与冠心病患者的常规超声心动图指标比较,治疗后6个月无论是两药合用(C+M组,36.84±3.50mm),还是三药合用(C+M+S组,34.86±3.18mm)除LAD冠心病组高于对照组(30.40±2.92mm)而有显著的统计学差异(P<0.01)外,其余各项指标均无显著的统计学差异。三药合用组的LAD较ACE抑制剂+β受体阻滞剂合用组缩小,但仍达不到对照组水平。对照组与冠心病各组超声应变率显像指标比较,对照组各项指标均显著好于冠心病各组,无论是ACE抑制剂+β受体阻滞剂合用还是在此基础上再加用螺内酯。但加用螺内酯6个月后,反映心室舒张功能的指标SRe可进一步改善。冠心病的C+M组与C+M+S组治疗前各项超声心动图指标比较无显著的统计学差别。治疗前与治疗后6个月两组组内比较,E/A比值均增大(P<0.05),两组E/A比值的均值分别为0.74及0.75,说明了舒张早期经二尖瓣血流的增加,间接反映了左室舒张早期快速充盈功能的改善。6个月的治疗后三药合用(C+M+S)组IVST、LVPWT及LVMI也较治疗前好转(P<0.05),说明心室质量的下降。治疗前后不同治疗方案的冠心病两组组内比较,各项应变率指标(包括收缩功能指标SRs及舒张早期的SRe)均有不同程度的改善。但在C+M+S组反映舒张早期左室快速充盈功能的SRe在各心室节段的改善更为显著。治疗后的组间比较表明,SRe在C+M+S组的基底段后间隔(PS)、侧壁(LW)及前间隔(AS),心室中段的侧壁(LW)、前壁(AW)、前间隔(AS)和后壁(PW)较C+M组有显著的统计学意义的增加。长期应用三种药物的联合治疗,未发现严重的影响治疗的副作用。结论:ACE抑制剂及β受体阻滞剂可以显著改善冠心病患者的心室舒张功能,醛固酮受体拮抗剂在ACE抑制剂和β受体阻滞剂合用的基础上应用,能使单纯舒张功能障碍患者的心室舒张功能得到更好的改善,而且长期应用的安全性良好。第三部分螺内酯、卡托普利及卡维地洛对左室损伤大鼠血流动力学及心室重构的影响目的:探讨应用卡托普利、卡维地洛和醛固酮拮抗剂螺内酯对大鼠急性左室损伤后血流动力学及左室重构的影响。方法:雄性健康、Wistar大鼠,超低温冷冻左室游离壁15秒建立大鼠急性心肌坏死模型。24小时存活者96只,12只为假手术组,其余84只随机分为4组,即损伤对照组22只、螺内酯组22只、卡托普利+卡维地洛组20只、卡托普利+卡维地洛+螺内酯组20只。给予不同的药物14周时,存活76只,死亡20只。假手术组12只,心室肌坏死面积符合要求的共54只,即损伤对照组12只、螺内酯组14只、卡托普利+卡维地洛组16只、卡托普利+卡维地洛+螺内酯组12只。测定主动脉收缩压、舒张压、平均压、心率、左室舒张末压、左室内压最大上升和下降速率、等容舒张压力衰减时间常数。之后处死大鼠,称重全心质量、左室质量、测量左室横径及心肌坏死面积,同时测定非坏死区心肌胶原含量及Ⅰ/Ⅲ型胶原比值。结果:不同药物处理组的死亡数无显著的统计学差异。与损伤对照组(2.94±0.30mg/g)比较,假手术组(2.33±0.27mg/g)与三药合用组(2.43±0.17mg/g)心脏相对质量的降低有显著的统计学差异。用药各组的左室舒张末期压力和时间常数与假手术组无统计学差别,但均低于对照损伤组(P<0.05),假手术组和三药联合应用组的时间常数低于单用螺内酯组与卡托普利+卡维地洛组(P<0.05),而假手术组及用药各组的非梗塞区心肌胶原含量及Ⅰ/Ⅲ型胶原比值低于损伤对照组,三药合用组低于螺内酯单用及卡托普利与卡维地洛合用组。结论:卡托普利、卡维地洛和螺内酯改善受损左室的血流动力学及心室重构,螺内酯与其他神经内分泌拮抗剂的联合应用对血流动力学的改善及心肌胶原增生的抑制有协同作用。综上所述,我们的研究结果表明:1.冠心病患者的冠状动脉狭窄程度与左室舒张功能障碍有关,随着病变范围的增大,对舒张功能的影响增加,且在一定程度时影响心室收缩功能。2.从临床观察及动物模型的研究证明,应用ACE抑制剂及β受体阻滞剂可以改善左室舒张功能障碍,在此基础上加用醛固酮拮抗剂螺内酯可进一步改善左室舒张功能,减轻心室重构。更多还原

【Abstract】 Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. With the improvement of life enviroment and increase of the life-span in human being, chronic heart failure (CHF) is becoming an important and growing clinical problem, especially in the elderly. CHF is the most common inpatient diagnosis. The annual hospital cost of treating these patients is more than the cost of treating patients with myocardial infarction. Increasingly, many evidences indicate that diastolic dysfunction is a major contributor to the pathophysiology of CHF, which traditionally has been identified with systolic dysfunction. Interestingly, because of the lack of evidence-based data, many guidelines for treatment of CHF either do not address diastolic heart failure or do not give definitive therapeutic recommendations. Diastolic dysfunction refers to abnormalities in ventricular relaxation and filling (right ventricle, left ventricle, or both) with prolonged or incomplete return to presystolic length and force. In the progression of most cardiac diseases, diastolic dysfunction typically precedes systolic impairment. One of the earliest signs of diastolic dysfunction is exercise intolerance due to exertional dyspnea. Because of increased chamber stiffness, the end-diastolic volume in patients with diastolic dysfunction cannot increase during exercise. Usually as a result of myocardial hypertrophy, fibrosis, or ischemia, left ventricular filling is slowed or incomplete, causing pulmonary venous congestion.The presence of asymptomatic left ventricular diastolic dysfunction is related to the symptomatic heart failure in the patients with coronary heart disease. Diastolic dysfunction is difficult to differentiate from systolic dysfunction on the basis of history, physical examination, electrocardiographic and chest radiographic findings. Objective diagnostic testing is required. Cardiac catheterization was the first method used to diagnose diastolic dysfunction. However, the catheterization is invasive and impractical for long-term follow-up. A few reports investigated the severity of impaired LV diastolic function in patients with coronary artery disease and its relationship to the number and coronary score in coronary artery lesions visualized at coronary angiography. It is necessary to evaluate the effect of the severity of coronary stenosis on the left ventricular diastolic function by catheterization and echocardiographic strain rate imaging method in order to carry out the intensive treatment for the patients with diastolic dysfunction and improve the patients’prognosis. Strain rate imaging is an accepted, reliable, and practical method for diagnosing diastolic dysfunction.The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of both systolic dysfunction as well as diastolic dysfunction. The beneficial role of angiotensin-converting enzyme (ACE) inhibitors as well as aldosterone antagonists in systolic dysfunction has been well established. Because of its unique role of the RAAS in establishing fibrosis at a molecular level, RAAS blockade provides an opportunity to expand the therapeutic options for diastolic dysfunction. Thus far, in patients with primary diastolic dysfunction only the angiotensin receptor type 1 antagonist has been reported to decrease morbidity. Other kinds of neuroendocrine blockers are currently underway to establish the role in patients with diastolic dysfunction.Our current research included three parts. In the part 1, we aimed to investigate the severity of impaired left ventricular diastolic function in patients with coronary heart disease and its relationship to the number and coronary score of coronary artery lesions visualized at coronary angiography and echocardiography. The part 2 was designed to assess the effects of spironolactone on left ventricular diastolic dysfunction on the basis of ACE inhibitor andβblocker in patients with coronary heart disease by echocardiographic strain rate imaging. In the part 3, we established rat model of left ventricular injury. The effect of ACE inhibitor,βblocker and spironolactone on hemodynamics and remodeling of injury left ventricles in rats were analyzed.Part 1 Relationship between severity of coronary lesions and left ventricular diastolic function in patients with coronary heart disease by cardiac catheterization and echocardiographic imagingObjective:We aimed to investigate the severity of impaired LV diastolic function in patients with coronary heart disease(CHD) and its relationship to the number and coronary score in coronary artery lesions visualized at coronary angiography and echocardiography.Methods:Seventy-five consecutive patients with CHD confirmed by coronary angiography were divided into 4 groups according to extent of coronary lesions(the degree of stenosis≥50% and≤75% defined as mild stenosis, stenosis in one vessel>75% as single branch lesion, in two vessels >75% as double branch lesion and in three vessels>75% as triple branch lesion ) and the diseased coronary artery Gensini score was evaluated. The systolic pressure and diastolic pressure in aorta, heart rate, left ventricular end-diastolic pressure (LVEDP), maximum and minimum value of the first derivative of left ventricular pressure (dp/dtmax, dp/dtmin), ejection fraction in left ventricles(EF) were measured and then, the time constant of isovolumic pressure decay in early period of left ventricular relaxation(T) was calculated. The left atrial dimension(LAD), left ventricular end-diastolic volume(EDV), left ventricular end-systolic volume(ESV), stroke volume(SV), the early 1/ 3 filling volume (1/3V) and filling fraction (1/ 3 FF) of left ventricle were measured by left ventriculography and echocardiography. Peak systolic strain rate (SRs), peak early diastolic strain rate (SRe) and peak late diastolic strain rate( SRa) in each segment of left ventricles were measured. The correlation of the peak strain rates and other diastolic parameters was analyzed.Results:The significant difference in echocardiographic study was only the diameter of LAD which in triple branch lesion group(38.74±4.57mm)was more than in mild stenosis group(33.87±3.80mm) and in single branch lesion group(33.77±3.94mm). There was no significant difference in LVEDP, dp/dtmax, dp/dtmin among those groups. The time constant(T) was better in mild stenosis group(30.31±6.50 ms) than in single vessel lesion(40.92±11.79), double vessel lesion(43.02±15.83ms) and triple-vessel lesion group(50.32±23.57ms, P<0.05). The increase in time constant in obvious stenosis showed the impaired diastolic function of left ventricle, especially for the isovolumic diastole. The early filling 1/3V (55.69±24.87、31.44±21.17、24.29±14.79、19.15±13.01ml in mild stenosis group, single, double and triple branch lesion group, respectively ) and 1/3FF%(45.95±19.90、33.29±20.49、25.52±15.06、24.22±15.29 in mild stenosis group, single, double and triple branch lesion group, respectively) was more in mild stenosis group than in obvious stenosis groups. The level of EF and SV in mild stenosis group was more than in triple branch lesion group. The comparison of LAD, EF, early 1/3V and 1/3FF of different coronary Gensini score was significant difference in score“<15”and“15~”,“30~”group. The parameters of“<15”group was better than in“15~”and“30~”group. There was no significant difference of the time constant (T) and LVEDP among the groups by coronary Gensini score. The catheterization and strain rate image of echocardiography were carried out in sixteen patients. A strong correlation between the EF by echocardiogram and by invasive catheter(r=0.89, P<0.01) was existed. Invasive EF was significantly related to SRs( r=-0.74, P<0.01). SRe was also correlated to the time constant of left ventricular pressure decay (r=-0.66, P<0.01) and early 1/3FF(0.61, P=0.01), whereas a lack of significant correlation was found between the time constant and the peak of mitral early diastolic velocity(E), and SRe and E.Conclusions: The different severity of coronary lesion affected ventricular diastolic function at a certain extent. Whether by the lesion numbers or the coronary Gensini score, the more the severity of coronary lesion was, the more serious ventricular diastolic dysfunction was. The grouping by the lesion numbers was more sensitive than the grouping by Gensini score in predicting diastolic dysfunction. Strain rate imaging in echocardiogram is reasonable accuracy for evaluating diastolic dysfunction in patients with CAD. Part 2 Effect of angiotensin-converting enzyme inhibitor,βblocker and spironolactone on left ventricular diastolic function in patients with coronary heart diseaseObjective: This study was designed to assess the effects of angiotensin-converting enzyme inhibitor (ACEI),βblocker and spironolactone on left ventricular diastolic dysfunction in patients with coronary heart disease (CHD) by echocardiographic strain rate imaging (SRI).Methods: Thirty-four subjects without heart and lung disease (control group) and seventy-five patients with CHD between 25 and 83 years of age with isolated diastolic dysfunction and no contraindications for ACEI,βblocker and spironolactone were enrolled in this study. The patients with CHD were randomized to combination of ACEI andβblocker (C+M group, 38 patients) or combination of ACEI,βblocker and spironolactone (C+M+S group, 37 patients, spironolactone 40mg/d) for 6 months. Left atrial dimension(LAD), left ventricular end diastolic and systolic dimension, interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT) were measured by echocardiography. Left ventricular mass index (LVMI) was calculated from the above mentioned left ventricular parameters. Measurements of left ventricular end-diastolic volume ,end-systolic volume and ejection fraction was obtained by biplane Simpson’s method. E/A ratio were calculated according to the early diastolic peak filling velocity of mitral inflow (E) and to late diastolic peak filling velocity (A). Peak systolic strain rate (SRs), peak early diastolic strain rate (SRe) and and peak late diastolic strain rate (SRa) in each segment of left ventricle were measured by tissue Doppler mode. The parameters mentioned above were determined at baseline 1st month, 3rd month and 6th months after randomization.Results: LAD at 6-month follow-up was 36.84±3.50mm in two-drug combination (C+M) group, 34.86±3.18mm in three-drug combination (C+M+S) group and 30.40±2.92mm in control group. The difference of LAD among the groups was significant (P<0.01). There was no significant difference in other conventional echocardiographic parameters. Although LAD in the group of three-drug combination was smaller than in the group of two-drug combination, LAD in three-drug combination (C+M+S) group was larger than in control group at 6th month. The parameters of SRI in control group were better than (C+M) and (C+M+S) group. However, compared with the (C+M) group, SRe reflecting the early ventricular diastolic function was improved in C+M+S group six months later(P<0.05).The baseline characteristics of the two groups with coronary heart disease were equally distributed. The E/A ratio averaged 0.74 in the (C+M) group and 0.75 in the (C+M+S) group at 6th month. There was significant difference within groups (P<0.05). The increase in E/A ratio implicated that the left ventricular inflow and filling function in the early diastole was improved. The decrease of IVST, LVPWT and LVMI in (C+M+S) group showed that the ventricular mass became less after six-month treatment.The indexes related to the systolic (SRs) and diastolic (SRe) functions were improved after treatment in two groups with coronary heart disease. However, the SRe was significantly higher in ventricular basal segments of posterior septum, lateral wall, anterior septum and mid segments of lateral wall, anterior wall, anterior septum and posterior wall in (C+M+S) group than in (C+M) group.No serious side-effect which influenced continued treatment was found in the combinative use of ACE inhibitor,β-blocker and spironolactone in long term.Conclusions: The combination of ACE inhibitor andβ-blocker significantly improved the ventricular diastolic function in patients with coronary heart disease. The additive aldosterone inhibitor spironolactone in the background of combination of ACE inhibitor andβ-blocker made the isolated diastolic dysfunction better and the safety was promotive in the long term application. Part 3 Effect of spironolactone, captopil and carvedilol on hemodynamics and remodeling after left ventricular injury in ratsObjective: To evaluate the effect of spironolactone, captopil and carvedilol on hemodynamics and remodeling of injury left ventricles in rats.Methods: Wistar rats (male) were cryoinjuried on the free left ventricular wall for 15 seconds to establish the myocardial necrosis model. There were 96 survived rats after 24 hours of the operation. Except 12 rats which were enrolled in Sham group, 84 rats were randomly divided into control group(22 rats), spironolactone group(22 rats), captopil and carvedilol group(20 rats), combinative group (20 rats, captopil+ carvedilol+spironolactone). There were 76 rats survived and 20 death after 14 weeks. 12 rats were in Sham group and 54 rats in control group or other treated groups complying with the requirement of myocardial necrosis. Systolic pressure, diastolic pressure and mean pressure in aorta, heart rate, left ventriclular end-diastolic pressure (LVEDP), maximum and minimum dp/dt in left ventricles were measured after 14 weeks of the drug administration. Then, the time constant of isovolumic pressure decay was calculated. The collagen content and the ratio of typeⅠandⅢcollagen in non-necrosis zone were determined. Cardiac actual weight, left ventricular actual weight, the diameter and area of left ventricular necrosis were measured after the rats were killed.Results: Compared with control group(2.94±0.30mg/g), relative cardiac weight in Sham group(2.33±0.27mg/g) and three-drug administration group(2.43±0.17mg/g) was lower (P<0.05). There were not significantly different in LVEDP and the time constant between Sham group and the drug administration groups, but the parameters in these groups were better than in control group(P<0.05). The time constant in Sham group and three-drug combination group were better than in spironolactone group and captopil+carvedilol group(P<0.05). The collagen content and the ratio of typeⅠandⅢcollagen in non-necrosis zone were lower in Sham group and each of treated groups than control group. The levels of the collagen content and the ratio of typeⅠandⅢcollagen in non-necrosis zone in three-drug combined group were lower than spironoloactone group and captopil+carvedilol group.Conclusion: The cardiac hemodynamic parameters and ventricular remodeling in rats with the myocardiac injury are improved by the use of spironolactone, captopil and carvedilol. Spironolactone cooperates with other neurohormonal antagonists in the improvement of cardiac function and remodeling.In conclusion, our research results indicated that:1. The left ventricular dysfunction was related to the severity of coronary artery stenosis in patients with coronary heart disease. The more the severity of coronary lesion was, the more serious ventricular diastolic dysfunction was. The serious and wide range of stenosis may impair the systolic function.2. Our research from both clinical observation and animal models demostrated that ACE inhibitor andβ-blocker contributed to the improvement of left ventricular diastolic dysfunction. Adding spironolactone to ACE inhibitors andβ-blocker made further ventricular diastolic function improvement and reduced ventricle remodeling in coronary heart disease.更多还原