慢性压力负荷性心衰大鼠心肌细胞肌动蛋白的免疫组化研究

目的：探讨慢性心衰时心肌细胞肌动蛋白的变化情况。方法：采用ＳＰ免疫组化方法,对升主动脉缩窄慢性心衰大鼠心肌细胞肌动蛋白进行定性及半定量分析。结果：慢性心衰时左心室心衰时左心室心肌细胞肌动蛋白免疫反应活性显著降低,反应产物排列不规则,而右心室心肌细胞肌动蛋白免疫反应活性无显著变化。结论：肌动蛋白活性降低是引起收心肌收缩力降低的原因之一。     

慢性压力负荷性心衰大鼠心肌细胞凋亡的研究

目的探讨慢性心衰时是否有心肌细胞凋亡。方法利用末端转移酶介导的切口末端标记法（ＴＵＮＥＬ）及ＴＥＭ法,检测慢性压力负荷性心衰大鼠左、右心室心肌的凋亡细胞。结果在心衰大鼠的左、右心室心肌组织中存在有凋亡的心肌细胞,而在对照组大鼠心肌组织中未见到心肌细胞调亡。结论慢性心衰与心肌凋亡之间有紧密联系。     

慢性心衰大鼠心肌细胞内雷尼丁受体及集钙蛋白的表达

目的:研究慢性心衰大鼠心肌细胞内雷尼丁受体(RyR2)及其调节蛋白集钙蛋白的表达,探讨心衰心肌细胞内钙容量降低的机制。方法:雄性SD大鼠被随机分为心衰组和假手术组,运用激光扫描共聚焦显微镜、透射电子显微镜、免疫印迹等方法研究2组大鼠心肌细胞肌浆网内钙容量、心肌细胞超微结构及心肌细胞内肌浆网钙释放通道RyR2和其调节蛋白集钙蛋白表达的变化。结果:慢性心衰大鼠心功能左心室舒张末期压力、左室压力最大上升速率均显著低于假手术组。假手术组大鼠心肌细胞的肌小节完整,肌丝排列整齐,线粒体结构正常;心衰组大鼠部分心肌细胞肌丝溶解,线粒体肿胀,嵴断裂。慢性心衰大鼠心肌细胞肌浆网内钙容量显著低于假手术组。慢性心衰大鼠心肌细胞内RyR2的表达量无明显变化,集钙蛋白表达明显下降。结论:慢性心衰大鼠心肌细胞内集钙蛋白表达下调,可能是导致心肌细胞肌浆网钙容量减少的原因之一。     

甲亢心脏病心肌细胞形态学改变(同龄对比)

应用甲状腺素的实验组和不用甲状腺素的对照组S.D鼠相比,用药一周和两周后,两组动物的体重无显著差异。而心脏重量差异非常显著。高甲状腺素用药一周,实验组S.D鼠的左、右心室壁心肌细胞的体积、长度、横切面积、表面积,宽度都显著增加。其中右心室心肌细胞厚度增加不显著而左心室心肌细胞厚度则明显增加;而在用药两周后,左心室心肌细胞和右心室心肌细胞厚度的增加均不显著。     

缺氧性肺动脉高压大鼠右心室重构

摘要目的：研究缺氧性肺动脉高压大鼠右心室重构情况。方法：常压间断缺氧法复制缺氧性肺动脉高压大鼠模型，采用右心导管法测定平均肺动脉压力，通过测量右心室流入及流出道长度、左心室壁和右心室壁厚度、右心室和左心室 室间隔重量对其右心室重构情况进行定性研究。结果：缺氧14d后大鼠平均肺动脉压力显著升高，右心室流出道长度及右心室肥大指数显著增加，缺氧21d后右心室游离壁重量显著增加；右心室流人道长度及左、右心室壁厚度与对照组无统计学差异。结论：缺氧性肺动脉高压大鼠右心室早期表现为离心性肥大。     

辛伐他汀对慢性心力衰竭大鼠左室重构的影响

目的:探讨辛伐他汀对慢性心力衰竭大鼠心肌纤维化及心肌超微结构的影响.方法:利用腹主动脉缩窄法建立雄性Wistar大鼠心衰模型,随机分为心衰假手术组、模型组和辛伐他汀组.观察各组大鼠左心室肌质量指数(LVMI),H-E和Massion染色观察左心室心肌形态结构变化,电镜下观察左心室心肌的超微结构,SP免疫组织化学检测左心室心肌中结缔组织生长因子(CTGF)表达情况,RT-PCR测定各组大鼠左心室心肌CTGF mRNA水平.结果:与假手术组相比,模型组LVIM、心肌胶原容积分数(CVF)、CTGF蛋白及mRNA表达明显上升.与模型组相比,辛伐他汀组LVMI、CVF、CTGF蛋白及mRNA表达均明显下降.光镜和电镜结果显示,辛伐他汀组心肌损害程度较模型组明显减轻.结论:辛伐他汀能显著改善慢性心力衰竭大鼠心肌肥厚,逆转心肌纤维化和超微结构的异常方面,其机制可能与下调CTGF的表达有关.     

慢性缺氧致大鼠右心室心肌细胞调亡及其机制研究

目的:通过建立大鼠慢性缺氧心肌肥大模型,探讨慢性缺氧致大鼠心肌细胞凋亡的发生规律及其机制.方法:将大鼠随机分为慢性缺氧组和正常对照组,每组30只,慢性缺氧组置于氧浓度为(10.0±0.5)%的大型玻璃舱中,分别持续缺氧14、21、28 d,分别于第14、21、28 d处死大鼠,取心脏称重,留右心室,进行形态学观察,分析心肌细胞凋亡形态及计量,检测肌球蛋白β重链(B-MHC)、原癌基因B淋巴细胞瘤-2(bcl-2)、Bad等mRNA及Bcl-2、Bad蛋白的表达水平.结果:(1)慢性缺氧14、21、28 d组大鼠右心室/(左心室+室间隔)[RV/(LV+s)]、右心室/体重(RV/BW)比值及右心室β-MHC mRNA和蛋白表达均明显高于正常对照组(均P<0.01),并且随时间延长而增高(均P<0.01).(2)慢性缺氧心肌细胞凋亡指数14、21、28 d组大鼠均明显高于正常对照组(均P<0.01),且随着时间的延长而增加(均P<0.01).(3)慢性缺氧14、21、28 d组大鼠右心室bcl-2 mRNA表达和Bcl-2蛋白表达均明显低于正常对照组(均P<0.05),缺氧28 d组bcl-2 mRNA表达和Bcl-2蛋白表达较缺氧14 d组显著降低(均P<0.05).慢性缺氧14、21、28 d组大鼠右心室bad mRNA表达和Bad蛋白表达与正常对照组比较无明显改变(均P>0.05).(4)慢性缺氧14、21、28 d组大鼠右心室bcl-2/bad比值均明显低于正常对照组(均P<0.05),缺氧28 d组bcl-2/bad比值较缺氧14 d组显著降低(P<0.05).结论:慢性缺氧可以诱导大鼠右心室心肌细胞凋亡和心肌肥大,且大鼠右心室心肌细胞凋亡和心肌肥大程度随着缺氧时间的延长而增加.慢性缺氧通过抑制大鼠右心室心肌细胞抗凋亡基因bcl-2表达,使bcl-2/bad比值下调,打破原有的平衡,导致心肌细胞凋亡.     

甲状腺素性心肌病时左右心室瞬时外向钾电流的不均一性研究

目的:以正常心肌为对照,研究甲状腺素心肌病左右心室瞬时外向钾电流(Ito)不均一性变化。方法:SD大鼠以0.5mg/kgipL-甲状腺素10d后造成心肌病,以急性酶解法消化大鼠心脏,得到左右心室单个心肌细胞,用全细胞膜片钳技术分别记录Ito。结果:正常心肌细胞中左右心室的Ito存在一定差异,但不明显,然而在甲状腺素心肌病模型中这种差异显著增大。去极化电压为+40mV时,Ito右心室的电流密度从(9.23±0.84)pA/pF增强至(11.19±1.73)pA/pF,而左心室的电流密度从(6.99±1.14)pA/pF降至(4.95±1.84)pA/pF,且离散度增大。病变的右心室细胞半失活电压V1/2从(-68.85±1.37)mV右移至(-49.86±0.69)mV;正常心肌细胞的左右心室失活后恢复常数τ相当,而在病变心肌左右心室的τ值离散度显著增大,分别为(79.16±7.04)ms和(53.19±3.72)ms。结论:在心脏病变中左右心室Ito的不均一性增大可能是肥厚心脏导致心律失常的重要离子基础之一。     

致心律失常性右室心肌病心力衰竭期的病理特点分析

目的 通过分析致心律失常性右室心肌病(ARVC)心力衰竭期的病理改变,以进一步了解其临床分期与病理表型的关系.方法 从2004-2007 年在阜外心血管病医院接受心脏移植的心力衰竭病例中,收集病理诊断为ARVC的受体心脏8例,测量心脏重量,评价左右心室心腔扩张、心肌细胞肥大、脂肪浸润、纤维化、附壁血栓和伴发心肌炎等指标,注意左心室受累情况,并进行病理分型.结果 8例中的7例为经典型(即右心室改变为主),1例为左优势型(左心室改变为主),未见双室型病例.组织学均为纤维脂肪型,未见单纯脂肪型病例.经典型病例的右心室中、重度扩张,少数有室壁瘤形成,其中6例伴左心室受累,受累左心室轻、中度扩张,心肌广泛间质纤维化,部分病例伴替代性疤痕,而脂肪浸润量小,多局限于心外膜下.左心室心肌细胞肥大普遍.而左优势型的左心室重度扩张,弥漫间质纤维化和局部透壁性脂肪浸润.8例中3例左心室明显肥厚,3例查见双室附壁血栓,1例伴局灶性心肌炎.结论 ARVC心力衰竭期的左心室受累多见而严重,左心室间质纤维化突出,心肌细胞肥大明显,但脂肪替代少见和局限.左、右心室多扩张,可见附壁血栓,应注意与扩张型心肌病等鉴别.     

慢性缺氧致大鼠右心室心肌细胞凋亡及其机制研究

目的：通过建立大鼠慢性缺氧心肌肥大模型,探讨慢性缺氧致大鼠心肌细胞凋亡的发生规律及其机制。方法: 将大鼠随机分为慢性缺氧组和正常对照组,每组30只,慢性缺氧组置于氧浓度为(10.0±0.5)％的大型玻璃舱中,分别持续缺氧14、21、28 d,分别于第14、21、28 d处死大鼠,取心脏称重,留右心室,进行形态学观察,分析心肌细胞凋亡形态及计量,检测肌球蛋白β重链(β-MHC)、原癌基因B淋巴细胞瘤-2（bcl-2）、Bad 等mRNA及Bcl-2、Bad蛋白的表达水平。结果: (1)慢性缺氧14、21、28 d组大鼠右心室/（左心室+室间隔）［RV/(LV+S)］、右心室/体重（RV/BW）比值及右心室β-MHC mRNA和蛋白表达均明显高于正常对照组(均Ｐ<0.01),并且随时间延长而增高(均Ｐ<0.01)。(2) 慢性缺氧心肌细胞凋亡指数14、21、28 d组大鼠均明显高于正常对照组(均Ｐ<0.01),且随着时间的延长而增加(均Ｐ<0.01)。（3）慢性缺氧14、21、28 d组大鼠右心室bcl-2 mRNA表达和Bcl-2蛋白表达均明显低于正常对照组(均Ｐ<0.05),缺氧28 d组bcl-2 mRNA表达和Bcl-2蛋白表达较缺氧14 d组显著降低 (均Ｐ<0.05)。慢性缺氧14、21、28 d组大鼠右心室bad mRNA表达和Bad蛋白表达与正常对照组比较无明显改变 (均Ｐ>0.05)。（4）慢性缺氧14、21、28 d组大鼠右心室bcl-2/bad比值均明显低于正常对照组(均Ｐ<0.05),缺氧28 d组bcl-2/bad比值较缺氧14 d组显著降低 (Ｐ<0.05)。结论: 慢性缺氧可以诱导大鼠右心室心肌细胞凋亡和心肌肥大,且大鼠右心室心肌细胞凋亡和心肌肥大程度随着缺氧时间的延长而增加。慢性缺氧通过抑制大鼠右心室心肌细胞抗凋亡基因bcl-2表达,使bcl-2/bad比值下调,打破原有的平衡,导致心肌细胞凋亡。     

Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia-induced cardiac hypertrophy in rats.

To determine the effects of chronic anemia on the functional and structural characteristics of the heart, 1-month-old male rats were fed a diet deficient in iron and copper, which led to a hemoglobin concentration of 4.63 g/dl, for 8 weeks. At sacrifice, under fentanyl citrate and droperidol anesthesia, systolic, diastolic, and mean arterial blood pressures were decreased, whereas differential pressure was increased. Left ventricular systolic pressure and the ventricular rate of pressure rise (mmHg/s) were reduced by 9% and 14%, respectively. Moreover, developed peak systolic ventricular pressure and maximal dP/dt diminished 14% and 12%. After perfusion fixation of the coronary vasculature and the myocardium, at a left ventricular intracavitary pressure equal to the in vivo measured end diastolic pressure, a 10% thickening of the left ventricular wall was measured in association with a 13% increase in the equatorial cavitary diameter and a 44% augmentation in ventricular mass. The 52% hypertrophy of the right ventricle was characterized by an 11% thicker wall and a 37% larger ventricular area. The 33% expansion in the aggregate myocyte volume of the left ventricle was found to be due to a 14% myocyte cellular hypertrophy and a 17% myocyte cellular hyperplasia. These cellular parameters were calculated from the estimation of the number of myocyte nuclei per unit volume of myocardium in situ and the evaluation of the distribution of nuclei per cell in enzymatically dissociated myocytes. Myocyte cellular hyperplasia provoked a 9% increase in the absolute number of cells across the left ventricular wall. In contrast, myocyte cellular hypertrophy (42%) was responsible for the increase in myocyte volume of the right ventricle. The proliferative response of left ventricular myocytes was not capable of restoring diastolic cell stress, which was enhanced by the changes in ventricular anatomy with anemia. In conclusion, chronic anemia induced an unbalanced load on the left ventricle, which evoked a hyperplastic reaction of preexisting myocytes, in an attempt to normalize diastolic wall and myocyte stress.     

Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.     

Normal Right Ventricular Three‐Dimensional Architecture,as Assessed with Diffusion Tensor Magnetic Resonance Imaging,is Preserved During Experimentally Induced Right Ventricular Hypertrophy

The three‐dimensional architecture of the right ventricular myocardium is a major determinant of function, but as yet no investigator‐independent methods have been used to characterize either the normal or hypertrophied state. We aimed to assess and compare, using diffusion tensor magnetic resonance imaging, the normal architecture with the arrangement induced by chronic hypertrophy. We randomized 20 female 5 kg piglets into pulmonary trunk banding (N = 16) and sham operation (N = 4). Right ventricular hypertrophy was assessed after 8 weeks. The excised and fixed hearts were subject to diffusion tensor imaging to determine myocyte helical angles, and the presence of any reproducible tracks formed by the aggregated myocytes. All banding animals developed significant right ventricular hypertrophy, albeit that no difference was observed in terms of helical angles or myocardial pathways between the banded animals and sham group animals. Helical angles varied from ～70 degrees endocardially to ?50 degrees epicardially. Very few tracks were circular, with helical angles approximating zero. Reproducible patterns of chains of aggregated myocytes were observed in all hearts, regardless of group. The architecture of the myocytes aggregated in the walls of the right ventricle is comparable to that found in the left ventricle in terms of endocardial and epicardial helical angles, however the right ventricle both in the normal and the hypertrophied state lacks the extensive zone of circular myocytes seen in the mid‐portion of the left ventricular walls. Without such beneficial architectural remodelling, the porcine right ventricle seems unsuited structurally to sustain a permanent increase in afterload. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Myocyte transdifferentiation: a possible pathogenetic mechanism for arrhythmogenic right ventricular cardiomyopathy

Adipose substitution of ventricular myocardium is characteristic of arrhythmogenic right ventricular cardiomyopathy, but is also found in other heart conditions. It is thought to be a consequence of myocyte loss due to myocarditis or other noxious stimuli. We describe a unique case of cardiomyopathy with a morphologic pattern suggestive of transdifferentiation from myocytes to mature adipocytes. Gross, histologic, and ultrastructural examination were performed on the heart of a female transplant patient with a clinical diagnosis of familial dilated cardiomyopathy. Gross examination showed fibroadipose substitution of the left ventricle and adipose replacement of the right. Histology, immunohistochemistry, and ultrastructure were highly suggestive of transdifferentiation from cardiac muscle to adipose tissue. Myocyte transdifferentiation could represent an alternative pathogenetic pathway to the myocyte-loss and adipose-replacement mechanism in arrhythmogenic right ventricular cardiomyopathy, or it could be the basis of a new type of familial cardiomyopathy.     

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.     

Xq28-linked noncompaction of the left ventricular myocardium: Prenatal diagnosis and pathologic analysis of affected individuals

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24–30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located. Am. J. Med. Genet. 72:257–265, 1997. © 1997 Wiley-Liss, Inc.     

Sudden arythmogenic death in hospitals after heart surgery

29 cases of sudden heart death (SHD) which occurred in hospital after heart surgery within 1989-1998 are reported. More than 50% were SHD after aortocoronary shunting, it occurred in stenosing atherosclerosis of more than 3 arteries. An important role in tanatogenesis belongs to ischemic heart disease (IHD) with complications (chronic aneurysm of the left ventricle, postinfarction failure of the mitral valve) and combination of IHD with aortal heart deficiency which is followed by pronounced hypertrophy of the left ventricle which is an important factor of SHD risk. Interventricular defects and Fallot's tetrad are most frequent among heart malformations with SHD after heart surgery. Cardiomegaly, myocardial fibrosis, dilatation of the heart cavities, fibroelastosis of ventricular endocardium, anomalous chordal arrangement in the left ventricle, right ventricular lipomatosis are main factors of SHD of the arrhythmogenic type after heart surgery. Introduction of the new notion "sudden heart death at the hospital stage after heart surgery" is suggested.     

Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants.

Chronic adriamycin (ADR) intoxication was produced in three groups of beagle dogs by weekly intravenous injections (1 mg/kg body weight) for 20 weeks (cumulative dose 400 mg/sq m). Group A (6 dogs) received ADR only; Group B (6 dogs) were given ADR and weekly doses of vitamin E (17 mg/kg body weight) as alpha-tocopherol acetate; and Group C (6 dogs) received ADR and weekly doses of vitamin E as did Group B and selenium (0.06 mg/kg body weight as selenite). Each of the 18 dogs developed ADR-induced cardiomyopathy (CMY), and death occurred in 11 dogs during Weeks 17-20. Mortality was lowest in Group B (2 of 6), but no differences between groups were seen either in survival time of the dogs that died or in severity of CMY. Cardiomyopathy was more severe in dogs that died than in survivors. Congestive heart failure with transudation was present in 4 of 11 dogs that died. Cardiac histopathology was characterized by vacuolar degeneration of myocytes. Myocardial damage was most severe in the left ventricle and the ventricular septum, intermediate in the right ventricle and the left atrium, and least in the right atrium. Ultrastructural study showed that an early alteration in damaged myocytes was distention of sarcoplasmic reticulum to form sarcoplasmic vacuoles. Occasional damaged fibers had myofibrillar lysis and focal proliferation of sarcoplasmic reticulum. This study demonstrates that the dog offers a suitable model for studies of chronic ADR cardiotoxicity in man. The lack of cardioprotection from vitamin E and selenium supplementation fails to support the proposed role of lipoperoxidative damage in the development of chronic ADR-induced CMY.