Cognitive impairments in the STOP null mouse model of schizophrenia.

Cognitive dysfunction is a primary and persisting core deficit of schizophrenia that is marginally improved by antipsychotic treatment. Adult mice that lack the stable tubule-only polypeptide (STOP) have neurochemical and behavioral abnormalities that model some features of schizophrenia. Recognition and long-term memory in the STOP null mouse were tested with the novel object recognition task and an olfactory discrimination task, respectively. Researchers examined the brains from STOP null mice to determine whether differences in task performance were associated with alterations in brain morphology. STOP null mice displayed deficits in both recognition and long-term memory. These behavioral deficits were accompanied by a massive enlargement of the cerebral ventricular system as well as by reductions in volume of cortical and diencephalic structures. In addition to deficits in recognition and long-term memory, STOP null mice displayed exaggerated neuroanatomical deficits somewhat reminiscent of those observed among individuals with schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measurements of left ventricular dimensions using real-time acquisition in cardiac magnetic resonance imaging: comparison with conventional gradient echo imaging

This study investigates the use of real-time acquisition in cardiac magnetic resonance imaging (MRI) for measurements of left ventricular dimensions in comparison with conventional gradient echo acquisition. Thirty-one subjects with a variety of left ventricular morphologies to represent a typical clinical population were studied. Short-axis data sets of the left ventricle (LV) were acquired using a conventional turbo-gradient echo and an ultrafast hybrid gradient echo/echo planar sequence with acquisition in real-time. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and left ventricular mass (LV mass) were measured. The agreement between the two acquisitions and interobserver, intraobserver and interstudy variabilities were determined. The bias between the two methods was 5.86 ml for EDV, 0.23 ml for ESV and 0.94% for EF. LV mass measurements were significantly lower with the real-time method (mean bias 14.38 g). This is likely to be the result of lower spatial resolution and chemical shift artefacts with the real-time method. Interobserver, intraobserver and interstudy variabilities were low for all parameters. In conclusion, real time acquisition in MRI can provide accurate and reproducible measurements of LV dimensions in subjects with normal as well as abnormal LV morphologies, but LV mass measurements were lower than with conventional gradient echo imaging. Presented in abstract form at the International Society of Magnetic Resonance in Medicine meeting in Denver, Colorado in April 2000.     

白花前胡提取物对腹主动脉缩窄大鼠心室重构及Bcl-2、Bax 蛋白表达的影响

目的:研究白花前胡提取物(PdE) 对腹主动脉缩窄术后大鼠心室重构及心肌组织凋亡相关蛋白Bcl-2、Bax 表达的影响。方法:部分缩窄大鼠腹主动脉术制作心肌肥厚模型。称重法检测左室心肌重量, 计算心系数;观察细胞组织结构改变, 测量左心室内径;免疫组织化学法检测凋亡相关基因及Bcl-2、Bax 蛋白表达。结果:腹主动脉缩窄术后, 大鼠左室重量及心系数明显增加;400 %PdE 可明显减轻大鼠腹主动脉术所致左室重量增加(用药组0.49 ±0.07 g, 模型组0.57 ±0.16 g, P <0.05) 及心系数的升高(用药组2.44 %, 模型组2.82 %, P <0.05);200 % PdE 亦可明显降低大鼠腹主动脉术后心系数的升高(用药组2.51 %, 模型组2.82 %, P <0.05);腹主动脉缩窄术后大鼠心肌细胞明显肥大,胞核呈浓染、增大, 细胞间距增大, 组织横断面心肌纤维增多;400 % PdE 及200 % PdE 可有效改善因腹主动脉缩窄所致心肌组织结构变化;腹主动脉缩窄术后, 大鼠左室腔内径明显缩小, 而400 % PdE 及200 % PdE 可显著改善大鼠腹主动脉术后左室腔内径缩小(P <0.05);模型组Bcl-2 与Bax 蛋白表达率与伪手术组、各浓度PdE 组比较均有显著性差异(P<0.05), 但伪手术组, 400 %及200 % PdE 组Bcl-2/Bax 表达比例均较模型组有明显增加(P <0.05) 。结论:PdE 能有效改善因腹主动脉缩窄所致的心室重构过程中的左心室壁肥厚和心系数增加, 调节心肌细胞凋亡相关蛋白Bcl-2 与Bax 的表达。     

人参皂苷Rg1治疗性给药的抗心肌肥厚作用

目的 观察人参皂苷Rg1 治疗性给药对缩窄腹主动脉所致大鼠左心室肥厚的影响。 方法 SD 大鼠随机分为假手术组、模型组、Rg1 (3.75,15 mg/kg) 组以及左旋精氨酸(L-arg) 200 mg kg组。后4 组用腹主动脉缩窄术(AAC) 造模, 手术3周后腹腔注射给药共4 周。给药末监测大鼠血流动力学, 称心脏质量以计算左室肥厚指标(即左室肥厚指数, LVHI =左室重 体重) 和左室重 右室重(LVW/VW), 用实时荧光定量PCR (Real-Time PCR) 法检测心房利钠因子(ANF) 和钙调神经磷酸酶(CaN) mRNA 的表达。 结果 与假手术组比较,模型组的血压、左室内收缩压、左室舒张期末压、LVHI 和LVW/RVW 均显著升高, ±dp/d tmax 降低,ANF 和CaN mRNA 表达明显上调。Rg1 和L-arg给药不影响血压及左室内收缩压, 但显著降低左心室舒张期末压(LVEDP) 而增加±dp/dtmax, 并使LVHI 和LVW/RVW 减低, ANF 和CaN mRNA 表达下调。 结论 Rg1 具有抗压力超负荷所致左心室肥厚作用, 并可能与其抑制CaN 信息通路有关。     

丹参酮ⅡA对自发性高血压大鼠左心室谷胱甘肽-s-转移酶μ2表达的影响

目的 观察丹参酮ⅡA 对自发性高血压大鼠(SHR) 左心室谷胱甘肽-s-转移酶μ2(glutathiones-transferase μ2, GSTμ2) 表达的影响, 探讨丹参酮ⅡA 防治左心室肥厚的机制。方法 实验分3 组:(1) 正常对照组;(2) SHR 组;(3) 丹参酮ⅡA 组。处理后检测血流动力学指标、左室重量指数及大鼠左心室GSTμ2 的活性, 采用共聚焦显微镜检测左心室O2^- 的产生情况, Western blotting 检测GSTμ2 的表达情况。结果 SHR 组血压与左室重量指数均显著高于正常对照组, 左心功能明显下降;丹参酮ⅡA 显著逆转了SHR 的左心室肥厚,但未明显改善高血压。SHR 组左心室O2^-的产生较正常对照组显著增多, 而丹参酮ⅡA 治疗后,O2^-产生较SHR 组显著减少。GSTμ2 的表达及活性在SHR 组显著降低, 而丹参酮ⅡA 显著增加了GSTM2 的表达及活性。结论 丹参酮ⅡA 能逆转SHR 的左心室肥厚, 这可能与其增加GSTμ2 表达, 减少活性氧产生, 消除氧化应激有关。     

Unstable eigenmodes are possible drivers for cardiac arrhythmias

The well-organized contraction of each heartbeat is enabled by an electrical wave traversing and exciting the myocardium in a regular manner. Perturbations to this wave, referred to as arrhythmias, can lead to lethal fibrillation if not treated within minutes. One manner in which arrhythmias originate is an ill-fated interaction of the regular electrical signal controlling the heartbeat, the sinus wave, with an ectopic stimulus. It is not fully understood how and when ectopic waves are generated. Based on mathematical models, we show that ectopic beats can be characterized in terms of unstable eigenmodes of the resting state.     

高血压左心功能常规指标与声学定量技术比较

为了将反映高血压患者心功能的常规指标与声学定量技术（Acoustic Quantification,AQ）指标进行比较分析,评价高血压左心功能变化,将实验对象分为对照组30例和高血压病组45例,将高血压组分成非肥厚组和肥厚组;对各组进行了常规心功能指标及AQ检测。各组间DBP、LVM、LVMI、IVS、IVPW、LA有显著性差异（P〈0.05）。与对照组相比,非肥厚组与肥厚组的VE/VA及RF/AF降低,AFF及LVESV增加（P〈0.05）。与对照组相比,肥厚组RFF降低,PAFR、LVEDV及OAFV增加（P〈0.05）。常规心功能指标中EF同AQ指标中EF进行非配对T检验,显示前者低于后者（P〈0.05）。实验结果表明,AQ技术作为一种新的能评价舒张功能障碍的新方法,可视为常规超声心动图指标的补充,结合此两种方法可有效提高临床诊断左心室舒张功能异常。     

Inhibitory Effects of Nobiletin on Voltage-Gated Na+ Channel in Rat Ventricular Myocytes Based on Electrophysiological Analysis and Molecular Docking Method

Nobiletin (NOB) has attracted much attention owing to its outstanding bioactivities. This study aimed to investigate its anti-arrhythmic effect through electrophysiological and molecular docking studies. We assessed the anti-arrhythmic effects of NOB using aconitine-induced ventricular arrhythmia in a rat model and the electrophysiological effects of NOB on rat cardiomyocytes utilizing whole-cell patch-clamp techniques. Moreover, we investigated the binding characters of NOB with rNav1.5, rNav1.5/QQQ, and hNa_V1.5 via docking analysis, comparing them with amiodarone and aconitine. NOB pretreatment delayed susceptibility to ventricular premature and ventricular tachycardia and decreased the incidence of fatal ventricular fibrillation. Whole-cell patch-clamp assays demonstrated that the peak current density of the voltage-gated Na⁺ channel current was reversibly reduced by NOB in a concentration-dependent manner. The steady-state activation and recovery curves were shifted in the positive direction along the voltage axis, and the steady-state inactivation curve was shifted in the negative direction along the voltage axis, as shown by gating kinetics. The molecular docking study showed NOB formed a π-π stacking interaction with rNav1.5 and rNav1.5/QQQ upon Phe-1762, which is the homolog to Phe-1760 in hNa_V1.5 and plays an important role in antiarrhythmic action This study reveals that NOB may act as a class I sodium channel anti-arrhythmia agent.     

Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate

Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs.     

磁悬浮离心式左心室辅助装置溶血实验研究

通过体外以及在体溶血实验, 探讨磁悬浮驱动离心式心室辅助装置血液相容性能.将左心室辅助装置置于充满新鲜羊血的模拟循环通路中, 在输出流量为5 L/min、后负荷压力为100 mmHg的条件下, 检测血泵体外溶血性能.在8只健康绵羊体内植入血泵进行在体辅助实验, 通过定期抽血检验血浆游离血红蛋白值, 测定其在体溶血性能.结果表明:可植入磁悬浮驱动离心式左心室辅助装置的体外标准溶血指数(normal index of hemolysis, NIH)为(0.075±0.017) mg/L.在体实验中, 2例存活超过20 d, 循环辅助后实验羊血浆游离血红蛋白(free hemoglobin, FHB)呈现上升趋势, 2例实验FHB最大值分别达0.846和1.09 g/L, 之后逐渐下降到术前水平.本实验血泵同其他国产血泵比较, 具有较好的体外和在体血液相容性, 具备好的长期动物在体辅助实验基础.