重组生长激素及其与氯沙坦联用对缺血性坏死心肌模型心功能和心肌的影响

生长激素对心脏的发育、形态及功能的维持均具有重要作用。本研究单用重组生长激素 (ｒＧＨ)或与血管紧张素Ⅱ受体拮抗剂氯沙坦联用 ,治疗实验性心肌缺血坏死模型 ,了解两药对心功能及缺血坏死心肌的影响。1.材料与方法 :(1)心肌坏死模型的制备与分组 :参照Ｂｌａｓｉｎｇ方法用异丙基肾上腺素制备雄性ＳＤ大鼠心肌缺血坏死模型 ,随机分 3组 ,每组 9只。Ａ组 :对照组 ,生理盐水每日皮下注射 0 3ｍｌ ,灌胃 1ｍｌ ,共 15ｄ。Ｂ组 :ｒＧＨ组 ,皮下注射ｒＧＨ (安徽安科药业公司提供 ,4Ｕ/支 ) 2ｍｇ·ｋｇ-1·ｄ-1,生理盐水 1ｍｌ灌胃 ,共 15…     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系.方法用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF).结果①与正常对照组相比,DCM组大鼠心脏LVED(cm)和LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0.05).②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原CVF及Ⅰ、Ⅲ型胶原的含量明显增加.结论 DCM大鼠心肌间质胶原网络重塑影响左室功能.     

扩张型心肌病大鼠模型心肌结构与心功能的变化

目的　探讨扩张型心肌病大鼠胶原重塑及其与心功能的关系。方法 用呋喃唑酮饲养Wistar大鼠建立扩张型心肌病(DCM)大鼠模型, 超声心动图检测大鼠左心室舒张期末内径(LVED)、左心室收缩期末内径(LVES)、左心室内径缩短率(FS)及左心室射血分数(LVEF);右心导管测压,HE染色观察大鼠心肌细胞形态学变化;VG和免疫组化染色检测心肌胶原纤维及胶原容积分数(CVF)。结果 ①与正常对照组相比,DCM组大鼠心脏 LVED(cm)和 LVES(cm)均明显增大、FS(%)和LVEF(%)均明显下降,左心室内径增大、游离壁变薄,心脏重量/体重比值增加,右房压明显增高(均P>0 .05)。②DCM大鼠心肌细胞肥大,变性,间质胶原纤维明显增多,间质胶原 CVF及Ⅰ、Ⅲ型胶原的含量明显增加。结论 DCM大鼠心肌间质胶原网络重塑影响左室功能。     

探索迪谢内肌营养不良及贝克肌营养不良与扩张型心肌病共同的基因特征和生物学机制

目的 通过生物信息学分析发现迪谢内肌营养不良（Duchenne muscular dystrophy, DMD）、贝克肌营养不良（Becker muscular dystrophy, BMD）与扩张型心肌病（dilated cardiomyopathy, DCM）之间共有的基因特征和相关的发病机制。方法从基因表达综合数据库（Gene Expression Omnibus, GEO）中下载DMD(GSE6011)、BMD(GSE13608)和DCM(GSE116250)的数据集。分别识别DMD与DCM、BMD与DCM的共同差异表达基因（differentially expressed genes, DEGs）。并对共同的DEGs进行富集分析、构建蛋白质相互作用（protein-protein interactions, PPI）网络、筛选中心基因,并在GEO下载的数据集GSE109178(DMD、BMD)和GSE141910(DCM)中验证表达水平。构建关键转录因子-中心基因调控网络。结果DMD与DCM共有60个共同的DEGs。富集分析强调了细胞外基质结构成分、MHCⅡ类蛋白复合物结合、...     

快速起搏心衰犬心室扩张及其逆转时心肌胶原重构及心功能的变化

本文观察右室快速起搏心肌病犬心室扩张及其逆转时心肌间质胶原和伴随的血液动力学及神经内分泌的变化。17只犬，随机分为3组：P组（n=6）：以250次／分频率右心室持续起搏4周。R组（n=6）：持续右室起搏4周后，停止起搏，恢复4周。C组（n=5）对照组。与C组比较，起搏后P组左室舒张末内径（Dd）和平均肺楔压（MPCWP）明显增高，左室射血分数（EF）和心排量（CO）显著降低；血浆NE、AⅡ、ALD增高；心肌胶原含量及Ⅰ／Ⅲ型胶原比值明显降低。R组动物随着扩张心室的恢复和心功能与神经内分泌指标的改善，心肌胶原含量及其表型也有相应的恢复。以上表明，这种动物模型的心肌间质胶原重构与心功能、神经内分泌的改变有一定关系。     

激光心肌血运重建术与VEGF基因治疗犬心肌缺血心功能的变化

目的　观察 TML R联合 VEGF1 65c DNA治疗心肌缺血犬后心功能的变化。方法　健康杂种犬 36只 ,随机分为 VEGF1 65基因组、空质粒组 ,激光心肌打孔为对照组 (n=12 ) ,结扎冠状动脉造成急性心肌缺血后 6 0 min分别行CO2 激光心肌打孔和基因转染。采用热稀释法和彩色多谱勒超声心动图检测心排量 (CO)和左心室射血分数(L VEF)。结果　治疗后 6周和 12周 VEGF1 65c DNA组 L VEF和 CO显著高于激光打孔组 (P<0 .0 5 ) ,以治疗后 12周最为显著。结论　犬急性心肌缺血后采用激光心肌打孔联合 VEGF1 65基因治疗可显著改善心功能。     

Lamin A/C基因敲除小鼠核结构和功能缺陷导致扩张型心肌病

核纤层病是-类由编码核纤层蛋白lamin A和lamin C的LMN A基因突变引起的疾病，其发病机制不明。本文报道了laminA／C基因敲除（bnna-／-）小鼠表现出快速进行性的扩张型心肌病（DCM），其特征为左心室（LV）扩张及其收缩功能降低。分离出的Dnna-／-小鼠心肌显示，正常基线水平和钙离子瞬变峰值时射血分数均降低。Dnna-／-小鼠左心室心肌细胞核的形状和大小上均发生显著改变，并伴有异染色质的核中心转移及破裂。这些变化亦出现在左心房细胞核内，但是其程度要轻微的多。电子显微镜观察Lmna-／-心肌细胞显示，desmin纤维结构被破坏，与核内膜表面分离，并伴随着胞浆骨架的desmin网进行性分裂。核骨架的改变与核功能的损伤密切相关，这为SREBP1入核减少、PPA取表达减少、肥厚基因活性缺失所证实。上述发现提出了-个模型，该模型认为lamin与横纹肌特异的desmin网络的相互作用障碍使力传导受损以及细胞骨架牵张力丧失是Lmna-／-小鼠的主要稿理学机制。尽管有严重的扩张型心肌病，但是核功能的缺陷阻止了Lmna-／-心肌细胞发展为代偿性肥厚和病程的加速。     

儿童和成人心肌肥厚患者具有同样的致病基因

[英]/Morita H…//N Engl J Med.-2008,358.-1899-1908.没有家族心肌病史的儿童特发性心肌肥厚病往往预示着预后不良,尽管其心肌形态学和成人阶段发病的遗传性心肌病非常相似,但基因遗传在该病中的具体作用仍不清楚。为探讨一些儿童左心室肥厚患者和成人肥厚性心肌病是否具有共     

Neuromuscular implications in left ventricular hypertrabeculation/noncompaction

This review focuses on recent advances in the association between left ventricular hypertrabeculation/noncompaction (LVHT), a form of unclassified cardiomyopathy, and neuromuscular disorders (NMD). So far, LVHT has been found in single patients with dystrophinopathy, dystrobrevinopathy, laminopathy, zaspopathy, myotonic dystrophy, infantile glycogenosis type II (Pompe's disease), myoadenylate-deaminase deficiency, mitochondriopathy, Barth syndrome, Friedreich ataxia, and Charcot–Marie–Tooth disease. Most frequently LVHT is found in patients with Barth syndrome and mitochondrial disorders. The prevalence of LVHT in NMD patients is not known. On the contrary, NMD can be detected in up to four fifths of the patients with LVHT. Because LVHT is associated with an increased risk of rhythm abnormalities and heart failure, it is essential to detect LVHT as soon as possible. Because of adequate therapeutic options, all patients with NMD should undergo a comprehensive cardiological examination as soon as their neurological diagnosis is established. In reverse, all patients with LVHT should undergo a comprehensive neurological investigation following the detection of LVHT.     

Pathomorphologic findings in left ventricular hypertrabeculation/noncompaction of adults in relation to neuromuscular disorders

Background

Aim of this study was to assess pathomorphologic findings (PATHO) in patients with echocardiographically (ECHO) diagnosed left ventricular hypertrabeculation/noncompaction.

Methods

ECHO-criteria for LVHT were: > 3 trabeculations, moving synchronously with the compacted myocardium, and forming the noncompacted part of a two-layered myocardium. At autopsy, the hearts were investigated according to the pathologists' preferences.

Results

Twelve patients (2 females, age 27–81 years) were included. Seven suffered from neuromuscular disorders, 5 patients were not investigated neurologically. The specimens were acquired after explantation during heart transplantation (n = 1), death due to heart failure (n = 6), sudden death (n = 2), pneumonia (n = 2) and stroke (n = 1). Eight hearts were investigated without fixation and 4 after formaldehyde fixation. The hearts were opened along the long-axis, in 3 hearts additional short-axis cuts were carried out.At PATHO the trabecular meshwork was better visible in the formaldehyde-fixed hearts than in the fresh hearts. Differentiation from papillary muscles was easier on the long-axis cuts, whereas the two-layered structure was better visible on short-axis cuts. The trabecular pattern was similar in patients with neuromuscular disorders and those who did not undergo neurologic investigation. Subendocardial fibrosis was found in each case. Due to the complex three-dimensional geometry, it was impossible to count the number of trabeculations.

Conclusion

Formaldehyde-fixation should be performed when comparing ECHO with PATHO findings in LVHT. Long-axis as well as short-axis cuts should be carried out in order to assess the course of trabeculations and the extent of the two-layered structure. Subendocardial fibrosis in LVHT deserves further research.     

Prognostic impact of left ventricular noncompaction in patients with Duchenne/Becker muscular dystrophy — Prospective multicenter cohort study

Background

The reported prevalence of left ventricular noncompaction (LVNC) varies widely and its prognostic impact remains controversial. We sought to clarify the prevalence and prognostic impact of LVNC in patients with Duchenne/Becker muscular dystrophy (DMD/BMD).

Methods

We evaluated the presence of LNVC in patients with DMD/BMD aged 4–64 years old at the study entry (from July 2007 to December 2008) and prospectively followed-up their subsequent courses (n = 186). The study endpoint was all-cause death and the presence of LVNC was blinded until the end of the study (median follow-up: 46 months; interquartile range: 41–48 months).

Results

There were no significant differences in baseline characteristics between patients with LVNC (n = 35) and control patients without LVNC (n = 151), with the exception of LV function. Patients with LVNC showed, in comparison with patients without LVNC, a significant negative correlation between age and LVEF (R = − 0.7 vs. R = − 0.4) at baseline; and showed a significantly greater decrease in absolute LVEF (− 8.6 ± 4.6 vs. − 4.3 ± 4.5, p < 0.001) during the follow-up. A worse prognosis was observed in patients with LVNC (13/35 died) than in patients without LVNC (22/151 died, Log-rank p < 0.001). Multivariate Cox analysis revealed that LVNC is an independent prognostic factor (relative hazard 2.67 [95% CI: 1.19–5.96]).

Conclusion

LVNC was prevalent in patients with DMD/BMD. The presence of LVNC is significantly associated with a rapid deterioration in LV function and higher mortality. Neurologists and cardiologists should pay more careful attention to the presence of LVNC.     

The heart in Duchenne muscular dystrophy: a non-invasive longitudinal study.

Sixteen boys with Duchenne muscular dystrophy (DMD) underwent serial investigations of echocardiographic left ventricular dimensions, systolic time intervals (STI), ECG and vectorcardiography (VCG). Spirometry with measurement of vital capacity and forced expiratory volume was also performed, as well as tests of muscle function. ECG was abnormal with high right precordial R-amplitudes even in the youngest patients. In contrast, VCG QRS area progressively diminished with age. STI and echocardiographic contractility indices decreased with increasing age. There was no clinically useful relationship between the various non-invasive variables on the one hand and results from skeletal muscle tests or lung function tests on the other, or between the different cardiac investigation methods. It is concluded that several non-invasive tests are needed during follow-up studies of Duchenne patients to evaluate the effects of treatment or assess prognosis.     

五例心脏淀粉样变的临床表现及诊断分析

目的探讨心脏淀粉样变的临床特点及诊断.方法对5例心脏淀粉样变患者的临床特点、辅助检查及确诊方法进行分析.结果全部患者均为多系统病变伴心力衰竭,可伴限制型心肌病表现、体位性低血压、心律失常,超声心动图示心室壁增厚而心腔大小正常.结论对出现以上症状、体征及辅助检查结果者,拟诊为心脏淀粉性变性,确诊靠病理学检查.     

The Cryopreservation of Leukaemia Cells: Morphological and Functional Changes

Stored autologous haemopoietic cells may be used to repopulate the bone marrow of patients in the advanced stages of different leukaemias who have received cytotoxic drugs. We have used a continuous flow blood cell separator to collect peripheral blood leucocytes from patients with chronic granulocytic leukaemia (CGL) before treatment. We also collected bone marrow cells from patients with CGL and from patients with acute myeloid leukaemia in complete remission. The collected cells were frozen at I degree C per minute using dimethyl sulphoxide as cryoprotective agent and stored in liquid nitrogen. For reconstitution of frozen cells we found that the use of dextran II0 inhibited leucoagglutination. The viability and function of the reconstituted leucocytes were assessed by their morphological appearance, their capacity to phagocytose and kill Candida albicans organisms, their ability to reduce the dye nitroblue tetrazolium (NBT) in vitro and to incorporate tritiated thymidine into DNA and by the growth of colony forming units (CFUc) in agar culture. With this method of cryopreservation the phagocytic function of mature neutrophils is retained to some extent but their capacity to reduce NBT and their microbicidal activity are completely lost. In contrast CFUc may remain after storage for periods of at least 2 years.     

Taste Reactivity to Alcohol and Basic Tastes in Outbred Mice

The taste reactivity test was used to determine the response of out-bred mice to orally infused taste solutions. For the initial measures, mice ( n = 10) were tested with 3%, 6%, 9%, and 12% (v/v) alcohol and four taste solutions: sucrose, sodium chloride, hydrochloric acid, and quinine hydrochloride (a single concentration of each). A second group of naive mice ( n = 16) was tested with 5%, 10%, 20%, 30%, and 40% alcohol. The final set of measures with naive mice ( n = 26) was taken with a range of sucrose concentrations: 0.01 M, 0.05 M, 0.1 M, 0.5 M, and 1.0 M. In general, mice made similar reactivity responses to all solutions tested. A predominant component of the mouse response to all infused fluids was forelimb flailing; gaping was also a common response to all solutions. Despite the large number of aversive-type responses, mice rejected very little fluid via passive drip or fluid expulsion. The single, significant difference in responding to the four taste stimuli was that mice made fewer aversive responses to sucrose. Differential responding to the 5 to 40% alcohol concentrations and sucrose concentrations was observed. Mice increased ingestive responding as the concentration of alcohol and sucrose increased. Aversive responding decreased reliably only with increases in the sucrose concentration. Data provide the first reported taste reactivity responses of mice to orally infused taste solutions. These results can be compared with the extant data available in rats and can also be used as a basis for exploring taste factors in genetically defined mouse populations.