Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

普拉固和鱼油对高胆固醇血症患者血脂与心脑血管事件影响的比较

目的:比较普拉固和鱼油对高胆固醇血症患者的血脂、血粘度、血管内皮功能和心脑血管事件的影响。方法:对266例原发性高胆固醇血症患者经2周洗脱期后,随机分为两组,普拉固组,初服10mg,每晚一次,8周后若TC仍>5.2mmol/L,LDL—ch>3.12mmol/L,则加量至20mg/d,每8周再查血脂,以达到TC<5.2mmol/L,LDL—ch<3.12mmol/L的量作治疗量继续服用。鱼油组,服美国深海鱼油一日三次,一次3g,均于服药8周复查血脂、血粘度及血管内皮功能等并作16月随访。结果:治疗8周,TC,普拉固组下降26％,鱼油组下降12％(P<0.01)。LDL—ch,普拉固组下降31％,鱼油组下降11％(P<0.01),肱动脉流量介导的舒张与硝酸甘油介导的舒张,普拉固组分别增加104％和19％,鱼油组无明显改变。全血低切粘度,普拉固组减少23％,鱼油组减少10％(P<0.01)。平均随访16月,普拉固组中脑出血1例(0.8％),鱼油组发生心脑血管事件7例(5.3％),死亡1例(P<0.05)。两组均无明显的不良反应。结论:普拉固是一个安全有效的降脂药,能改善血管内皮功能,降低血粘度,减少高胆固醇血症病人心脑血管事件发生。     

牛磺酸对大鼠缺血心肌Bcl-2和Bax蛋白表达的影响

目的：探讨大鼠心肌缺血损伤与凋亡相关基因bcl-2和bax表达的关系及牛磺酸的影响。方法：结扎大鼠冠状动脉左前降支建立心肌缺血模型。检测心肌线粒体中超氧化物歧化酶（SOD）、Ca^2 -ATPase活性及MDA（丙二醛）含量，用免疫组化法检测Bcl-2和Bax蛋白在心肌中的表达量。结果：结扎冠脉左前降支可致心肌线粒体MDA含量升高，SOD和Ca^2 －ATPase活性下降；缺血心肌Bax蛋白表达呈显著升高；牛磺酸能明显减少缺血心肌线粒体MDA的生成，降低心肌Bax蛋白的表达，增加Bcl-2蛋白的表达。结论：结扎大鼠冠状动脉左前降支导致的心肌缺血损伤与Bcl-2和Bax蛋白的表达有关。     

Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 tmol/L) (P1 and P2) and depolarized arrest St. Thomas‘ solution (S1 and S2) subjected to 15 C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest.Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.     

抑肽酶预处理防护大鼠肝脏缺血再灌注损伤的实验研究

目的 探讨抑肽酶预处理对肝脏缺血再灌注损伤的防护作用。方法 SD大鼠80只，随机分为抑肽酶预处理和生理盐水预处理两组，观察肝脏缺血再灌注损伤引起及抑肽酶预处理的影响。结果 拟肽酶预处理组大鼠缺血再灌注损伤引起的血清谷丙转氨酶（ALT），谷草转氨酶（AST）活性及肝组织丙二醛（MDA）含量变化均显著低于生理盐水预处理组（P＜0．01）；肝细胞形态学异常改变也明显较生理盐水预处理组轻。结论 抑肽酶预处理对大鼠肝脏缺血再灌注损伤有明显的防治作用。     

高温、亚低温对大鼠脑缺血再灌注损伤的作用及其机制研究

目的：研究轻度高温、亚低温对大鼠脑缺血再灌注损伤组织兴奋性氨基酸（EAA）与氧自由基的相互关系及病理损伤程度的影响。方法：60只Wistar大鼠按不同脑温条件随机分为生化组（n=28）和病理组（n=32)，采用改良Nagasawa局灶脑缺血再灌注模型，观察脑缺血再灌注损伤组织谷氨酸（Glu），超氧化物歧化酶（SOD）、丙二醛（MDA）的变化及光镜，电镜下的病理变化。结果：轻度高温明显加重常温脑缺血再灌注损伤组织Glu、MDA的升高（P＜0．01）及SOD的下降（P＜0．05），加重常温脑缺血再灌注组织病理损伤程度，亚低温的作用则相反，结论：轻度高温可能通过同时促进EAA合成，释放和氧自由基生成系统活化，造成大鼠脑缺血再灌注损组织损伤加重；亚低温可能通过同时抑制EAA合成，释放和氧自由基生成系统活化，减轻大鼠脑缺血再灌注组织损伤程度，对大鼠脑缺血再灌注损伤组织起保护作用。     

强心通脉灵对大鼠急性心肌梗死后心室重构的影响

目的探讨强心通脉灵对急性心肌梗死(AMI)大鼠心室重构(VR)的干预机制。方法选择Wistar大鼠85只,随机分为强心通脉灵大剂量组(QXLmax组)12只、强心通脉灵小剂量组(QXLmin组)14只、卡托普利组11只、模型组15只和假手术组13只,采取冠状动脉结扎造成AMI模型,术后均予口服给药治疗,模型组及假手术组予以相应的生理盐水。4周后处死,放射免疫法测血浆血管紧张素Ⅱ(AngⅡ)和超氧化物歧化酶(SOD)含量,计算左心室质量指数,光镜下观察心尖组织病理形态学改变,采用ABC染色测TGF-β1的表达量。结果模型组及各给药组AngⅡ水平较高,各给药组较模型组有下降趋势,其中QXLmax组较卡托普利组及QXLmin组更低。模型组及各给药组SOD水平较假手术组降低,QXLmax组及QXLmin组较模型组有升高趋势,左心室质量指数模型组较假手术组显著升高,各给药组较假手术组有升高趋势,QXLmax组较QXLmin组及卡托普利组低。卡托普利组及QXLmin组健存心肌细胞周围胶原组织明显减少,QXLmax组病理改变最轻,偶有少量胶原纤维增生。TGF-β1表达QXLmax组较QXLmin组及卡托普利组低(P<0.01)。结论强心通脉灵可降低AMI后大鼠血浆AngⅡ水平,增加SOD活性,降低左心室质量指数及心肌组织TGF-β1表达,从而平稳AMI后VR的进程。     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.