胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用的实验研究

目的分析胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用.方法采用标准玻璃微电极技术,观察胺碘酮、d,l-索他洛尔(即索他洛尔)与d-索他洛尔对犬心室肌细胞动作电位时程(APD)及跨壁复极离散(TDR)的作用,以研究三种药物不同的促心律失常发生率的机制.结果胺碘酮(5μM)对心室壁三层细胞APD作用不一,使M细胞的APD90缩短,而内、外膜的APD90延长,TDR降低.索他洛尔(100μM)使心室壁三层细胞APD90均延长,对M细胞APD延长更明显,使TDR增加.d-索他洛尔(100μM)使心室壁三层细胞APD90均增加,但以M细胞APD90增加最为显著,而且随着d-索他洛尔诱发早期后除极、APD交替变异发生,而在心室肌内、外膜细胞则未见上述变化.结论胺碘酮、索他洛尔及d-索他洛尔三种药物的不同促心律失常作用与其对心室TDR的作用不同有关.     

口服胺碘酮对家兔扩张型心肌病跨室壁复极不均一性的影响

目的　研究口服胺碘酮对扩张型心肌病 (DCM)跨室壁复极不均一性的影响及与抑制室性心律失常的关系。方法　用家兔进行实验研究 ,随机分成DCM治疗组、DCM对照组和正常对照组。用阿霉素制作DCM模型 ,DCM治疗组口服胺碘酮 ,然后离体灌流心脏 ,同步记录三层心肌的单相动作电位。结果　DCM对照组、DCM治疗组的三层心肌单相动作电位时程复极 90 %的时限 (APD90 )均较正常对照组相应延长 (P <0 0 0 1 ) ,DCM治疗组心外膜、心内膜APD90 又较DCM对照组延长 (P <0 0 5) ,但中层心肌APD90 与DCM对照组相似 (P >0 0 5) ,DCM治疗组ΔAPD90 的跨室壁复极离散度较DCM对照组明显缩小 (P <0 0 1 )。结论　口服胺碘酮能延长DCM心外膜、心内膜APD90 ,对中层心肌细胞APD90 无影响 ,缩小复极离散度 ,降低了三层心肌复极不均一性 ,所以致心律失常作用较小。     

钾通道开放剂与钙拮抗剂对长QT综合征LQT2模型的跨壁复极离散的作用

采用标准玻璃微电极技术 ,以d 索他洛尔 (Ikr阻断剂 )模拟长QT 2型 (LQT2 )模型观察其对犬心室肌细胞动作电位复极 90 %时程 (APD90 )及跨壁复极离散 (TDR)的作用 ,及钾通道开放剂 (吡那地尔 )和钙通道阻断剂 (硝苯地平 )对d 索他洛尔诱发的电生理变化的影响 ,为临床治疗LQT2的药物选择提供理论基础。结果 :d 索他洛尔 (10 0μmol/L)使三层心肌细胞APD90 均增加 ,但以中层心肌 (M)细胞APD90 增加最为显著 ,结果使TDR增加。d 索他洛尔作用于M细胞 ,诱发早期后除极 (EADs)和APD交替变异 ,而心内膜、外膜细胞则未见。吡那地尔 (2～ 6 μmol/L)和硝苯地平 (2～ 10 μmol/L)均呈浓度依赖性地缩短受d 索他洛尔而延长的三层细胞的APD ,以M细胞最为显著 ,因此明显降低TDR ,并且消除d 索他洛尔所产生的EADs及APD交替变异。结论 :对于Ikr缺陷所致的长QT综合征 ,钾通道开放剂和钙通道阻断剂可能有治疗作用。     

索他洛尔对兔在体心脏左心室壁心肌复极不均一性影响的实验研究

目的　观察索他洛尔对兔在体心脏左心室壁各层心肌复极的影响 ,以证实在体心肌 M细胞的存在 ,探讨其与心律失常的关系。　方法　采用单相动作电位 (m onophasic action potential,MAP)记录技术 ,同步记录 12只开胸兔左心室外膜心肌 (epicardium ,Epi)、中层心肌 (m id- myocardium ,Mid)和心内膜心肌 (endocardium ,Endo)的 MAP,静脉注射索他洛尔后 ,测量 3层心肌 MAP的复极时限和跨心室壁心肌复极离散度 (transm ural dispersion of repolarization,TDR)。　结果　 1用药前 Epi、Mid、Endo的 MAP10 0 %复极时限 (APD1 0 0 )分别为 (136± 16 )、(15 2± 19)、(15 0± 2 0 ) m s,TDR为 (17± 8) m s。每间隔 30 m in静脉注射索他洛尔 0 .5、1.0、1.5和 2 .0 m g· kg- 1后发现 ,索他洛尔剂量依赖性延长 3层心肌的 APD1 0 0 ,其中以延长 Mid的 APD1 0 0 更为明显 ,对 Epi和 Endo的 APD1 0 0 延长程度相近 ,使 TDR增加 ;至静脉注射 2 .0 mg· kg- 1 后 ,Epi、Mid、Endo的 APD1 0 0 分别为 (177± 30 )、(2 34± 32 )、(194± 30 ) ms,TDR为 (5 7± 15 ) ms(P <0 .0 5 ) ;2索他洛尔剂量依赖性地增加尖端扭转性室性心动过速 (torsade depointes,TDP)的发生率。　结论　在体兔心肌存在 M细胞。索他洛尔增加兔     

胺碘酮对肥厚心肌钙调蛋白激酶活性的影响

目的观察口服胺碘酮对肥厚心肌细胞钙调蛋白激酶(CaMK)活性的影响,探讨胺碘酮抗心律失常的作用机制。方法30只家兔随机分为假手术组、心肌肥厚组和胺碘酮组,每组10只,喂养3个月,制备兔左室楔形心肌块。同步记录楔形心肌块容积心电图和内、外膜心肌细胞跨膜动作电位(TAP),程序电刺激诱发室性心律失常,并观察各组QT间期、跨室壁复极离散度(TDR)、早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的诱发率。利用放射免疫法测定心肌细胞CaMK活性。结果胺碘酮组和心肌肥厚组QT间期、内外膜心肌细胞TAP复极90%时程(APD90)和TDR均较假手术组明显延长(P<0.01),胺碘酮组QT间期和内、外膜心肌细胞APD90与心肌肥厚组相比进一步延长(P<0.05),但对TDR无明显影响。与假手术组比较,心肌肥厚组EAD和Tdp的发生率较假手术组明显升高(P<0.01),胺碘酮组EAD和Tdp的发生率较心肌肥厚组降低(P<0.05)。心肌肥厚组心肌细胞CaMK活性较假手术组明显升高,胺碘酮组CaMK活性较心肌肥厚组降低(P均<0.05)。结论胺碘酮抗心律失常的作用机制可能部分与抑制CaMK活性有关。     

硫酸镁对家兔在体心脏跨室壁心肌复极不均一性的影响

目的：观察静脉注射索他洛尔后，硫酸镁对家兔跨室壁心肌复极不均一性的影响，探讨其治疗室性心律失常的机制。方法：采用单相动作电位（monophasic action potential,MAP)记录技术，同步记录12只开胸兔左室心外膜心肌、中层心肌和心内膜心肌的MAP，在静脉注射索他洛尔基础上，静脉滴注硫酸镁后观察其对心肌得极不均一性的影响。结果：（1）索他洛尔剂量依赖性地显延长中层心肌的MAP复极100％时程，增加跨室壁复极离散度（transmural dispersion of repolarization,TDR)；静脉滴注硫酸镁后TDR明显减少。（2）索他洛尔剂量依赖性地诱发早期后除极（early afterdepolarization,EAD)和尖端扭转型室性心动过速（torsade de pointes,TdP)的发生率；硫酸镁抑制索他洛尔诱导的EAD和TdP。结论：硫酸镁逆转索他洛尔所致的TDR增加，抑制索他洛尔诱导产生EAD，其治疗TdP的机制可能与此有关。     

胺碘酮慢性作用对兔心室肌细胞L型钙通道电流和跨壁动作电位相关性研究

目的 从单个心室肌细胞L型钙通道电流时间常数(τ)和组织块跨壁动作电位复极90%时程(APD90),探讨胺碘酮慢性作用抗心律失常的可能细胞电生理机制.方法 健康兔口服胺碘酮80 mg·kg-1·d-1共4周,记录离体兔带血管心室肌组织块跨膜心室肌细胞动作电位后分离心室肌细胞,记录单细胞L型钙通道电流τ,比较对照组、胺碘酮组及索他洛尔组干预下τ与APD90比值(τ/APD90)变化.结果 对照组τ为(98±8)ms(n=10)、APD90为(220±10)ms(n=5)、τ/APD90为0.44±0.03.与对照组相比,胺碘酮组τ明显延长[为(164±8)ms,n=8,P＜0.05],APD90亦明显延长[为(321±12)ms,n=5,P＜0.05],τ/APD90较对照组增加(分别为0.51±0.03与0.44±0.03,P＜0.05).索他洛尔(3×10-5mmoL/L)组与对照组相比,τ明显延长[为(128±7)ms,n=8,P＜0.05],但因APD90延长较著[为(405±13)ms,n=4,P＜0.01],使τ/APD90较对照组明显减少(分别为0.32±0.05与0.44±0.03,P＜0.05).索他洛尔+胺碘酮组的τ为(150±12)ms、APD90为(355±11)ms(n=4),与索他洛尔组比较,τ/APD90增加(为0.44±0.02,P＜0.05),与对照组相比,差异无统计学意义(P＞0.05).结论 心室肌细胞膜L型钙通道电流的τ/APD90大小与胺碘酮慢性作用相关,这为胺碘酮慢性作用的安全性提供了一种可能解释.     

索他洛尔对兔心肌电生理的影响

目的探讨索他洛尔口服后对兔左心室心肌细胞电生理的影响及其发生机制。方法建立冠状动脉灌注的兔左心室楔形心肌模型,应用心电图同步记录技术和浮置玻璃微电极技术,观察索他洛尔口服后兔内外两层心肌动作电位时程(action potential duration,APD)、Q-T间期及跨壁复极离散度(transmural dispersion of repolarization,TDR)的变化以及心律失常的发生。结果索他洛尔组兔内、外膜心肌细胞的APD、Q-T间期及TDR在不同刺激周长下均较对照组延长,且以内膜延长为主(均P0.05)。索他洛尔组兔心律失常发生率较对照组升高(P0.05)。结论索他洛尔可明显延长兔内、外膜心肌细胞的APD、Q-T间期,并可增大兔心肌细胞的TDR,在兔子模型中,应用索他洛尔容易导致心律失常发生。     

钾通道开放剂对长QT综合征LQT2模型的跨壁复极离散作用的实验研究

目的观察钾通道开放剂(吡那地尔)对LQT2模型心室肌细胞动作电位时程(APD)及跨壁复极离散(TDR)的作用及电生理变化的影响,为临床治疗LQT2的药物选择提供理论基础。方法采用标准玻璃微电极技术,以d-索他洛尔(Ikr阻断剂)模拟LQT2模型。结果d-索他洛尔(100μmol/L)使三层心肌细胞APD90均增加,但以M细胞APD80增加最为显著,结果使TDR增加。d-索他洛尔作用于M细胞,诱发早期后除极(EADs)和APD交替变异,而心内膜、外膜细胞则未见。吡那地尔(2-6μmol/L)呈浓度依赖性地缩短受d-索他洛尔影响而延长的三层细胞的APD,以M细胞为著,因此明显降低TDR,并且消除d-索他洛尔所产生的EADs及APD交替变异。结论对于Ikr缺陷所致的LQTs,钾通道开放剂可能有治疗作用。     

美西律对兔楔形心肌动作电位时程、跨壁复极离散及索他洛尔口服后改变的影响

目的探讨美西律、索他洛尔、索他洛尔十美西律口服后对家兔左心室楔形心肌组织块电生理特性的影响。方法建立冠状动脉灌注的家兔左心室楔形心肌组织块模型。应用浮置玻璃微电极和心电图同步记录技术,观察美西律、索他洛尔、索他洛尔＋美西律口服后对家兔内外层心肌细胞的动作电位时程（APD）、跨壁复极离散（TDR）的影响。结果美西律组内、外膜心肌细胞的APD、Q—T间期及TDR在不同刺激周长下均较对照组缩短,索他洛尔组均较对照组延长,且以内膜延长为主（均P〈0．05）,索他洛尔＋美西律组较对照组仅轻微延长,差异无统计学意义,但较索他洛尔组缩短（P〈005）。美西律组、索他洛尔＋美西律组心律失常发生率与对照组比较差异无统计学意义,索他洛尔组心律失常发生率高较对照组升高（P〈005）。,结论美西律可明显缩短内、外膜心肌细胞的APD、Q—T问期,并可减小心肌细胞的TDR。索他洛尔相反,抗心律失常同时容易导致心律失常,联合应用美西律可逆转索他洛尔对兔心肌电生理的不利作用,从而提高安全性。     

Cardiovascular,diabetes, and cancer strips: evidences,mechanisms, and classifications

Objectives

To report and name firstly that there are cardiovascular disease (CVD), diabetes mellitus (DM) and cancers (CDC) strips; and disclose their mechanisms, classifications, and clinical significances.

Study design

Narrative and systematic review study and interpretive analysis.

Methods

Data sources and study selection: to collect and present related evidences on CDC strips from evidence-based, open-access, both Chinese- and English-language literatures in recent 10 years on clinical trials from PubMed according to keywords “CVD, DM and cancers” as well as authors’ extensive clinical experience with the treatment of more than fifty thousands of patients with CVD, diabetes and cancers over the past decades, and analyze their related mechanisms and categories which based on authors’ previous works. Data extraction: data were mainly extracted from 48 articles which are listed in the reference section of this review. Qualitative, quantitative and mixed data were included, narratively and systematically reviewed.

Results

With several conceptual and technical breakthrough, authors present related evidences on CDC strips, these are, CVD and DM, DM and cancers, cancers and CVD linked, respectively; And “Bad SEED” +/– “bad soil” theory or doctrine may explain this phenomenon due to “internal environmental injure, abnormal or unbalance” in human body resulting from the role of risk factors (RFs) related multi-pathways and multi-targets, which including organ & tissue (e.g., vascular-specific), cell and gene-based mechanisms. Their classifications include main strips/type B, and Branches/type A as showed by tables and figures in this article.

Conclusions

There are CDC strips and related mechanisms and classifications. CDC strips may help us to understand, prevent, and control related common non-communicable diseases (NCDs) as well as these high risk strips.     

Trust,benefit, satisfaction,and burden

BACKGROUND: Community-based participatory research (CBPR) approaches that actively engage communities in a study are assumed to lead to relevant findings, trusting relationships, and greater satisfaction with the research process. OBJECTIVE: To examine community members' perceptions of trust, benefit, satisfaction, and burden associated with their participation. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial tested a cancer prevention intervention in members of African-American churches. Data were collected at baseline and 1-year follow-up. MEASUREMENTS: Subscales measured perception of trust in the research project and the project team, benefit from involvement with the project, satisfaction with the project and the team, and perception of burden associated with participation. MAIN RESULTS: Overall, we found high levels of trust, perceived benefit, and satisfaction, and low perceived burden among community members in Partnership to Reach African Americans to Increase Smart Eating. In bivariate analyses, participants in the intervention group reported more perceived benefit and trust (P <.05). Participants in smaller churches reported more benefit, satisfaction and trust, while participants from churches without recent health activities perceived greater benefit, greater satisfaction, and lower burden with the project and the team (P <.05). Participants whose pastors had less educational attainment noted higher benefit and satisfaction; those whose pastors were making personal lifestyle changes noted higher benefit and satisfaction, but also reported higher burden (P <.05). CONCLUSIONS: A randomized clinical trial designed with a CBPR approach was associated with high levels of trust and a perceived benefit of satisfaction with the research process. Understanding variations in responses to a research partnership will be helpful in guiding the design and implementation of future CBPR efforts.     

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity,Pathogenicity, and Transmissibility in Avians,Mice, Swine,Seals, Ferrets,and Humans

Genetically diverse influenza A viruses (IAVs) circulate in wild aquatic birds. From this reservoir, IAVs sporadically cause outbreaks, epidemics, and pandemics in wild and domestic avians, wild land and sea mammals, horses, canines, felines, swine, humans, and other species. One molecular trait shown to modulate IAV host range is the stability of the hemagglutinin (HA) surface glycoprotein. The HA protein is the major antigen and during virus entry, this trimeric envelope glycoprotein binds sialic acid-containing receptors before being triggered by endosomal low pH to undergo irreversible structural changes that cause membrane fusion. The HA proteins from different IAV isolates can vary in the pH at which HA protein structural changes are triggered, the protein causes membrane fusion, or outside the cell the virion becomes inactivated. HA activation pH values generally range from pH 4.8 to 6.2. Human-adapted HA proteins tend to have relatively stable HA proteins activated at pH 5.5 or below. Here, studies are reviewed that report HA stability values and investigate the biological impact of variations in HA stability on replication, pathogenicity, and transmissibility in experimental animal models. Overall, a stabilized HA protein appears to be necessary for human pandemic potential and should be considered when assessing human pandemic risk.     

Correlations between lipid levels and age, gender, glycemia, obesity, diabetes, and smoking

A low level of high-density lipoprotein cholesterol (HDL-C) is an important cardiovascular risk factor. Dietary measures and pharmacological agents are often not sufficient to reach the HDL-C target level of 40 mg/dl in patients with low baseline HDL-C. This study assesses the association between lipid levels and age, gender, body mass index (BMI), glycemia, diabetes and smoking and focuses on the parameters influencing HDL-C. In the town of Lede (Belgium) all patients aged between 45 and 64 years were invited during 1999 for a free of charge health check-up and blood test. Blood pressure, weight, length and smoking habits were recorded. Serum levels for glycemia and lipoproteins were determined. In total, 629 subjects attended for the check-up. In a logistic regression analysis age above 50 years was correlated with low HDL-C (OR = 2.27 CI = 1.10-4.68). Male gender was correlated with low HDL-C (OR = 3.85 CI = 1.77-8.43) and with high triglycerides (TG) (OR = 1.94 CI = 1.14-3.30). From the level of 90 mg/dl glycemia was correlated with low HDL-C (OR = 2.56 CI = 1.02-6.39) and high TG (OR = 2.12 CI = 1.16-4.06). Obesity was correlated with low HDL-C (OR = 2.36 CI = 1.18-4.71) and high TG (OR = 2.17 CI = 1.88-5.23). This study provides some evidence to sharpen the target levels for glycemia and BMI among patients with low HDL-C and high TG. For these patients, the target glycemia should be around 90 mg/dl and BMI around 25 kg/m2. Physical activity and diet are also important in the achievement of these target levels.     

Lipoxins,Resolvins, Protectins,Maresins, and Nitrolipids: Connecting Lipids,Inflammation, and Cardiovascular Disease Risk

Essential fatty acids and their metabolites (γ-linolenic acid [GLA], dihomo-GLA, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; prostaglandin E₁; prostacyclin [PGI₂]; PGI₃; lipoxins; resolvins; protectins; maresins; and nitrolipids) prevent platelet aggregation, produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, possess peroxisome proliferator-activated receptor-γ ligand activity, and release nitric oxide. Thus, they lower blood pressure, are anti-arrhythmic and anti-inflammatory in nature, reduce low-density lipoprotein cholesterol, ameliorate the adverse actions of homocysteine, activate telomerase, and have cytoprotective properties—actions that prevent atherosclerosis and cardiovascular disease. Because coronary heart disease (CHD) and atherosclerosis are low-grade systemic inflammatory conditions, it is likely that reduced formation of lipoxins, resolvins, protectins, maresins, and nitrolipids plays a significant role in the pathogenesis of CHD. Hence, development of stable synthetic analogues of lipoxins, resolvins, protectins, and maresins may form a new therapeutic approach to CHD and other low-grade systemic inflammatory conditions.