人参二醇组皂苷对心肌梗死后心室重构大鼠心脏形态学及血流动力学的影响

目的研究人参二醇组皂苷(Panaxadiol Saponins,PDS)对心肌梗死后心室重构大鼠心脏形态学及血流动力学的影响。方法通过结扎大鼠左冠状动脉前降支造成心肌梗死后心室重构模型。将W istar大鼠随机分成假手术组、模型组、PDS组及卡托普利组。假手术组及模型组腹腔注射生理盐水2ml.kg-1.d-1,PDS组腹腔注射人参二醇组皂苷50mg.kg-1.d-1,卡托普利组灌胃卡托普利100mg.kg-1.d-1。给药4w后观察各组大鼠心脏形态学,血流动力学及组织病理学等参数。结果 PDS能明显降低心室重构大鼠心室脏器指数,升高平均动脉压(MAP)、左心室内压最大上升和下降速率(±dp/dtmax),降低左心室舒张末压(LVEDP)。此外,PDS还可明显减轻心室重构大鼠心肌组织病理损伤。结论 PDS对大鼠心肌梗死后心室重构具有保护作用。     

充血性心力衰竭大鼠模型的制作及意义

目的：建立大鼠心肌梗死后心力衰竭的动物模型，深入心衰机制的研究。方法：通过结扎大鼠冠状动脉左主干，使心室壁发生梗死，长期饲养(6周)，建立心梗后慢性心力衰竭模型，并与同期的假手术组比较，观察术后大鼠临床表现、心电图、血液动力学变化及心梗区域大小。结果：手术组术后成活率52．5％，心梗后6周出现失代偿性心衰。结论：此方法有效且重复性好，可较理想地模拟心梗后慢性充血性心力衰竭的发生，对研究心衰机制有重要意义。     

益母草生物碱对心肌梗死大鼠心功能及肌浆网钙泵的活性及其蛋白水平的影响

目的 探讨益母草生物碱对大鼠心肌梗死后心功能保护作用的机制。方法 采用左冠状动脉前降支结扎制作大鼠心肌梗死模型，通过大鼠血流动力学指标以及心肌肌浆网钙泵的活性（SERCA2α）及其蛋白水平来反映益母草生物碱对大鼠心肌梗死后心功能的影响不明显（P〈0．05）。结果 益母草生物碱可以显著提高模型大鼠左室收缩压以及左室内压最大上升速率（P〈0．05），降低模型大鼠左室舒张末压以及明显提高左室内压最大下降速率（P〈0．05）；益母草生物碱对模型大鼠心肌组织SERCA2α活性及SERCA2α含量均有显著提高（P〈0．05）。结论 益母草生物碱能够提高冠状动脉结扎大鼠心肌收缩舒张功能，其可能机制是提高大鼠心肌组织SERCA2α活性及含量。     

心力衰竭大鼠ACE/ACE2相互负向调节及卡维地洛的作用

目的 探讨心肌梗死后心力衰竭大鼠心肌组织血管紧张素转化酶（angiotensin converting enzyme,ACE）与ACE2相互负向调节及卡维地洛的作用。方法 结扎大鼠左冠状动脉前降支复制心肌梗死后心力衰竭模型,随机分为心力衰竭组,卡维地洛组和假手术组;喂养2个月后检测血流动力学指标,计算左心室质量指数;放射免疫法测定心肌组织和血浆血管紧张素Ⅱ,逆转录聚合酶链反应检测心肌组织ACE和ACE2mRNA表达;蛋白质免疫印迹法检测心肌组织ACE和ACE2蛋白表达。结果 心力衰竭组大鼠循环和心肌组织血管紧张素Ⅱ水平明显升高（P〈0.01）,心肌组织ACE和ACE2的mRNA和蛋白表达均增强（P〈0.05,P〈0.01）,ACE/ACE2升高。卡维地洛组大鼠血流动力学指标改善（P〈0.01）,心肌组织血管紧张素Ⅱ水平下调（P〈0.05）,心肌组织ACE mRNA和蛋白表达下降（P〈0.01）,ACE2 mRNA和蛋白表达显著增强（P〈0.01）,ACE/ACE2降低。结论 心力衰竭大鼠心肌组织ACE和ACE2表达上调,ACE/ACE2升高;卡维地洛抑制ACE表达,增强ACE2表达,ACE/ACE2比值下降。     

心肌梗塞致心力衰竭大鼠模型心脏NHE-1蛋白表达的改变

目的观察在结扎冠状动脉前降支心肌梗塞致心力衰竭大鼠缺血心脏Na+-H+交换蛋白-1(NHE-1)表达量的变化,探讨NHE-1在心力衰竭中的作用.方法应用左冠状动脉结扎制备慢性心力衰竭大鼠模型,术后第5周取左心室,分离心肌梗死区和心肌肥厚区,应用Western蛋白印记法检测左室心肌肥厚区NHE-1表达量的变化.结果在左室心肌肥厚区NHE-1表达量较对照组明显升高(P＜0.05),且大面积梗塞组光密度值(2.01±0.12)为小面积梗塞组(1.37±0.10)的1.5倍(P＜0.05).结论NHE-1不但在心肌细胞损害早期和心肌肥大、心室重塑的起始阶段起重要作用,而且在心力衰竭的进程(恶化)中也起重要作用.     

太子保心口服液防治心力衰竭后心律失常的作用机制

目的:探讨太子保心口服液防治心力衰竭后心律失常的作用机制。方法:采用冠状动脉结扎法建立大鼠心肌梗死后心力衰竭模型,术后次日将造模存活66只大鼠随机分为模型组、西药组、高剂量组、中剂量组、低剂量组,每组11只。灌胃给药4周,给药结束后采用电刺激方法诱发心室纤颤,检测大鼠心室纤颤阈值。采用血流动力学方法检测大鼠心功能;苏木精-伊红(HE)和Masson染色观察大鼠心肌病理组织变化和纤维化情况;采用荧光定量聚合酶链式反应(PCR)观察心力衰竭大鼠钙/钙调蛋白依赖的蛋白激酶Ⅱ(CaMKⅡ)mRNA相对表达情况。结果:与模型组比较,高剂量组、低剂量组大鼠心室纤颤阈值显著升高(P<0.05);低剂量组大鼠左室内压最大上升速率(+dp/dt_max)升高(P<0.05);中剂量组大鼠心肌组织中CaMKⅡmRNA相对表达量降低(P<0.01)。HE染色显示,太子保心口服液各剂量组心肌细胞坏死溶解减轻;Masson染色结果显示,太子保心口服液各剂量组心肌胶原容积分数降低。结论:太子保心口服液可降低心肌梗死后心力衰竭大鼠心室纤颤阈值,其作用机制可能与降低心肌组织CaM...     

促红细胞生成素对心肌梗死大鼠血流动力学及梗死面积的影响

目的探讨重组人促红细胞生成素(rhEPO)对大鼠急性心肌梗死(AMI)后24h血流动力学和左心室梗死面积的影响。方法 24只雄性SD大鼠随机分为假手术组、AMI组和EPO组,结扎左冠状动脉前降支建大鼠AMI模型,EPO组同时给予rhEPO5000U/kg腹腔内注射;24h后记录大鼠血流动力学参数并计算左心室梗死区与左心室质量比值。结果 AMI组各项血流动力学参数均明显下降;EPO组血流动力学参数均明显改善(P0.05,P0.01),尤其反映心肌舒张功能的指标改善更显著(P0.01);EPO明显降低左心室梗死区与左心室质量比值(P0.05)。结论 EPO急性干预缩小大鼠AMI后的梗死面积并明显改善其血流动力学参数,尤其对舒张功能改善更为明显。     

心复康口服液对心力衰竭大鼠心功能及心肌中链酰基辅酶A脱氢酶基因表达的影响

目的观察心复康口服液对心肌梗死后心力衰竭大鼠血流动力学、心功能及梗死周围心肌中链酰基辅酶A脱氢酶基因表达的影响。方法采用结扎SD大鼠左冠状动脉前降支致心肌梗死后心力衰竭大鼠模型,用心复康口服液于术后24h灌胃给药至6周,以卡托普利作为阳性对照药。给药4周后观察大鼠心脏功能、血流动力学及梗死周围心肌中链酰基辅酶A脱氢酶基因表达的变化。结果模型组与假手术对照组比较,左心室舒张末压升高,左心室收缩压、心排血量、左心室内压最大上升速率、左心室内压最大下降速率均显著降低,梗死周围心肌中链酰基辅酶A脱氢酶基因表达下调(P<0.01)。与模型组比较,心复康口服液和卡托普利皆可显著降低心梗后心衰大鼠左心室舒张末压(P<0.05),升高左心室收缩压、心排血量、左心室内压最大上升速率、左心室内压最大下降速率(P<0.05或P<0.01);梗死周围心肌中链酰基辅酶A脱氢酶基因表达上调(P<0.01)。结论心复康口服液可改善心肌梗死后心力衰竭模型大鼠心脏功能,并可上调心肌中链酰基辅酶A脱氢酶基因表达。     

心复康口服液对心力衰竭大心功能及心肌中链酰基辅酶A脱氢酶基因表达的影响

目的 观察心复康口服液对心肌梗死后心力衰竭大鼠血流动力学、心功能及梗死周围心肌中链酰基辅酶A脱氢酶基因表达的影响.方法 采用结扎SD大鼠左冠状动脉前降支致心肌梗死后心力衰竭大鼠模型,用心复康口服液于术后24 h灌胃给药至6周,以卡托普利作为阳性对照药.给药4周后观察大鼠心脏功能、血流动力学及梗死周围心肌中链酰基辅酶A脱氢酶基因表达的变化.结果 模型组与假手术对照组比较,左心室舒张末压升高,左心室收缩压、心排血量、左心室内压最大上升速率、左心室内压最大下降速率均显著降低,梗死周围心肌中链酰基辅酶A脱氢酶基因表达下调(P＜0.01).与模型组比较,心复康口服液和卡托普利皆可显著降低心梗后心衰大鼠左心室舒张末压(P＜0.05),升高左心室收缩压、心排血量、左心室内压最大上升速率、左心室内压最大下降速率(P＜0.05或P＜0.01);梗死周围心肌中链酰基辅酶A脱氢酶基因表达上调(P＜0.01).结论 心复康口服液可改善心肌梗死后心力衰竭模型大鼠心脏功能,并可上调心肌中链酰基辅酶A脱氢酶基因表达.     

他克莫司在大鼠心肌梗死后心力衰竭中的作用

目的探讨他克莫司(FK506)在大鼠心力衰竭中所起的作用。方法 SD大鼠随机分组,以结扎大鼠左冠状动脉前降支建立心肌梗死模型,胃灌注给药方式饲养30 d,采用心脏彩超检查左心室前壁运动情况及左心室射血分数;处死大鼠后,测量心肌梗死面积权衡心室梗死重量指数。结果给予心肌梗死后心力衰竭大鼠FK506,可改善左心室前壁运动减弱趋势(P<0.05),缩小左心室梗死面积(P<0.05)。结论 FK506可降低心肌梗死后大鼠心肌梗死面积,减轻发生心力衰竭的趋势,对衰竭心肌的左室功能有改善作用。     

Converting enzyme inhibition after experimental myocardial infarction in rats: comparative study between spirapril and zofenopril.

STUDY OBJECTIVE--The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor. DESIGN--Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined. SUBJECTS--Normotensive male Wistar rats (220-240 g) were used. MEASUREMENTS AND MAIN RESULTS--Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals. CONCLUSIONS--Both spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings.     

利用超声心动图评定大鼠心脏功能的可行性研究

目的 :通过与血流动力学检测比较 ,确定 M-型超声心动图是否可用来评价正常和心肌梗死大鼠左心室功能和结构变化。方法　利用冠状动脉左前降支结扎术制备大鼠大面积心肌梗死模型后 ,术后 3 d和 3 0 d进行 M-型超声心动图测定、血流动力学检测和取材称左心室重量 ;同时也对心脏功能正常大鼠进行上述研究。结果　用 M-型超声心动图测定心脏功能正常大鼠 ( NOR组 )、心肌梗死急性心力衰竭大鼠 ( AHF组 )和慢性充血性心力衰竭大鼠( CHF组 )的 EF和 FS值与用血流动力学方法测得的 LVdp/ dtmax值呈良好的正相关 ( r=0 .811-0 .972 ,均 P<0 .0 1) ;心肌梗死后 3 d和 1月 EF值与 FS值变化趋势与 L Vdp/ dtmax值变化趋势一样 ,均明显低于 NOR组 (均 P<0 .0 1) ,而且 CHF组各值也明显低于 AHF组 (均 P<0 .0 1)。同时还观察到应用超声心动图测得的三种心功能状态大鼠左心室重量与精密天平检测结果基本一致 (均 P>0 .5 )。结论　无创性经胸壁二维引导 M-型超声心动图可用来动态评价心肌梗死引起的大鼠心脏功能和结构改变     

Effects of chronic glyceryl trinitrate on left ventricular haemodynamics in a rat model of congestive heart failure: demonstration of a simple animal model for the study of in vivo nitrate tolerance

STUDY OBJECTIVE--The aim of the study was to investigate the problem of pharmacological tolerance to nitrate therapy in congestive heart failure, using an animal model. DESIGN--The effects of chronic glyceryl trinitrate infusions were studied in a rat model of congestive heart failure, induced by myocardial infarction, wherein surgical procedures have been developed to permit continuous monitoring of ventricular pressures in conscious animals for up to 4-5 d. SUBJECTS--male Sprague-Dawley rats were used, weight 300-325 g, n = 3-7 per experiment. MEASUREMENTS AND MAIN RESULTS--Glyceryl trinitrate infusion (18 micrograms.kg-1.min-1) in rats with congestive heart failure caused by a 28.5(SEM 3.5)% infarction induced a rapid fall in left ventricular end diastolic pressure from 12.0(0.8) mm Hg to a peak effect of 5.5(0.6) mm Hg within 30 min (n = 7), but rapid attenuation developed beginning about 4 h after the start of the infusion. Complete abolition of the haemodynamic effects of glyceryl trinitrate was observed after 8 h of infusion. After a 12 h wash out period, responsiveness to a new infusion of glyceryl trinitrate (same dose) was restored. Withdrawal of nitrovasodilator dose led to rapid return to baseline left ventricular end diastolic pressure values. Infusion of vehicle to control animals (infarct size not different from treatment group) caused no haemodynamic effects. CONCLUSIONS--The haemodynamic changes caused by glyceryl trinitrate resemble those seen in man and suggest a possible use for this animal model in examining the mechanisms of nitrate action and tolerance.     

Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril

Although vasodilator therapy has been shown to improve functional capacity in patients with congestive heart failure, there is no evidence that such therapy can prolong survival. Coronary artery ligation in the rat was used to produce a wide range of myocardial infarct sizes and a resultant spectrum of left ventricular dysfunction. To determine the relationship between size of myocardial infarction and long-term survival and to test the hypothesis that long-term therapy with captopril could improve survival after myocardial infarction, 302 rats were randomly assigned to either placebo or captopril therapy 14 days after coronary artery ligation. The animals were kept in a laminar flow unit and followed daily for a 1 year period or until spontaneous death. Size of myocardial infarction was determined by planimetry of serial histologic sections of the left ventricle. One year survival in placebo-treated rats decreased markedly in direct relation to increasing size of infarction (from 71% in noninfarcted rats to only 8% in rats with large infarcts). Long-term captopril therapy prolonged the survival of rats with infarcts (p less than .02). The most marked improvement in survival was noted in the animals with infarcts of moderate size, in which 1 year survival was 21% in the placebo-treated rats and 48% in the captopril-treated rats. Thus, in this experimental preparation of myocardial infarction and left ventricular dysfunction, survival was inversely related to size of infarction. Long-term therapy with captopril, which we had previously shown to improve left ventricular function and lessen dilatation in the chronic phase of infarction, also had a pronounced effect on prolonging survival in this preparation of chronic infarction.     

Clinical characteristics of postinfarction left ventricular aneurysm with extensive calcification]

The authors experienced 4 cases of calcified postinfarction aneurysm of the left ventricle. They were all male, aged 55 to 71 (mean 64). Risk factor for coronary artery disease was only smoking in 2 patients, but there was none in the others. They had had acute anteroseptal or extensive anterior infarction at age 41-57 years (mean 49.3), and associated major cardiac events 10-22 years (mean 14.5) after acute myocardial infarction. Ventricular tachycardia, congestive heart failure and systemic thromboembolism were seen in 4, 2 and 1 patients respectively. However, none developed angina pectoris. In the 2 patients in whom signal-averaged electrocardiogram was performed, late potential was detected, so it was suspected that ventricular tachycardia could be due to reentry. Left ventricular end-diastolic pressure was elevated in all patients except one and ranged from 11 to 22 mmHg. Left ventricle was dilated in all cases and the end-diastolic volume index ranged from 143 to 503 ml/m2. The left ventricular ejection fraction ranged from 11 to 24%. However, in 2 of the 4 patients, the cardiac index was within normal limits, and evidence of congestive heart failure was absent. In 2 other patients with associated congestive heart failure, cardiac indices were 2.32, 1.56 l/min/m2 respectively. Coronary arteriogram showed a total occlusion in the left anterior descending (LAD) artery in all cases, and only the LAD artery was affected in 2 patients. In the remaining 2 patients, the right coronary arteries also were significantly stenotic or totally occluded, i.e., they had 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular basis of ventricular remodeling after myocardial infarction.

To determine whether acute left ventricular failure associated with myocardial infarction leads to architectural changes in the spared nonischemic portion of the ventricular wall, large infarcts were produced in rats, and the animals were sacrificed 2 days after surgery. Left ventricular end-diastolic pressure was increased, whereas left ventricular dP/dt and systolic pressure were decreased, indicating the presence of severe ventricular dysfunction. Absolute infarct size, determined by measuring the fraction of myocyte nuclei lost from the left ventricular free wall, averaged 63%. Transverse midchamber diameter increased by 20%, and wall thickness diminished by 33%. The number of mural myocytes in this spared region of the left ventricular free wall decreased by 36% and the capillary profiles by 40%. Thus, side-to-side slippage of myocytes in the myocardium occurs acutely in association with ventricular dilation after a large myocardial infarction. In order to analyze the chronic consequences of myocardial infarction on ventricular remodeling, a second group of experiments was performed in which the left coronary artery was ligated and the functional and structural properties of the heart were examined 1 month later. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), a 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased 9-fold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Thus, decompensated eccentric ventricular hypertrophy develops chronically after infarction and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistence of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

免疫球蛋白对心梗后心衰大鼠心功能及非梗死区胶原的影响

目的 研究免疫球蛋白对心肌梗死后心衰大鼠心功能的影响及非梗死区胶原的抑制作用.方法 将结扎左冠状动脉前降支并饲养6 w的24只存活雌性Wistar大鼠,分为假手术组、模型组及免疫球蛋白组,每组8只.连续腹腔注射给药4 w后测定大鼠血流动力学参数,Masson染色观察非梗死区心肌胶原的沉积.结果 免疫球蛋白能明显升高左心室内压最大上升和最大下降速率(+dp/dtmax及-dp/dtmax),能明显升高左心室收缩压(LVSP),降低左心室舒张末压(LVEDP)(P＜0.05或P<0.01),但对心率(HR)、收缩压(SBP)、舒张压(DBP)无明显影响(P>0.05).Masson染色可见非梗死区心肌胶原沉积明显减轻.结论 免疫球蛋白对梗死后心衰大鼠非梗死区心肌间质胶原重构有显著的抑制作用,其作用机制与减轻胶原沉积有关.     

Clinico-morphological and echocardiographic parallels in myocardial hypertrophy in patients with ischemic heart disease]

Left ventricular myocardial hypertrophy was found in patients with repeated myocardial infarctions, the greatest weight of the left ventricle being noted in those with congestive heart failure. A high correlation (r = 0.78) was established between the mass of the left ventricular myocardium calculated with the aid of echocardiography and the actual weight of the left ventricle. The important compensatory role of the ventricular septum is emphasized for the cases of myocardial infarction occurring in the free wall of the left ventricle. Left ventricular hypertrophy was detected by ECG in only 25% of those ischaemic heart disease cases in whom signs of myocardial hypertrophy were revealed by echocardiography.     

Urinary cyclic guanosine monophosphate as an indicator of experimental congestive heart failure in rats

STUDY OBJECTIVE--The aim was to investigate the relationship between urinary cyclic guanosine monophosphate (GMP) excretion and activation of the heart endocrine function in two rat models of cardiac failure. DESIGN--Left ventricular infarction and aging in spontaneously hypertensive rats (SHR) are two models that could lead to congestive heart failure. In the first the degree of failure depends on the length of the infarcted area. In the second the degree of failure depends on time. Urinary cyclic GMP, plasma atrial natriuretic factor (ANF), and degree of congestive heart failure were evaluated in both models. EXPERIMENTAL ANIMALS--31 male Wistar rats were used for myocardial infarction and sham operated controls. Spontaneously hypertensive (SHR) rats (2, 6, 12 and 24 months old, n = 10 per group) were used for the age overload studies. MEASUREMENTS AND MAIN RESULTS--In myocardial infarction, the amount of left ventricular ANF mRNA, plasma ANF concentration, and urinary cyclic GMP excretion were correlated and were proportional to the degree of cardiac failure, as assessed by the increase in right ventricular mass and the decrease in blood pressure. In male SHR (aged 6-24 months), plasma ANF and urinary cyclic GMP were correlated, increased with age, and were proportional to the heart to body weight ratio. These correlations between plasma ANF, daily urinary cyclic GMP excretion, and left ventricular hypertrophy persisted in two year old SHR. The presence of pleural extravasation in these old animals was also characterised by significant increases in both plasma ANF and urinary cyclic GMP. The plasma ANF and the daily urinary cyclic GMP excretion were negative prognostic indicators of life expectancy in two year old SHR. CONCLUSIONS--Urinary cyclic GMP excretion, correlated with the plasma ANF level, is a non-invasive indicator of congestive heart failure in two models of overloaded left ventricle in rats.