Modulation of heart activity during withdrawal reflexes in the snail <Emphasis Type="Italic">Helix aspersa</Emphasis>

The beating activity of the molluscan heart is myogenic, but it is influenced by nervous signals of central origin. Previous studies have demonstrated changes in cardiac output during feeding and other behaviors. Here, we describe a short latency, transient cardiac response that accompanies withdrawal reflexes. When evoked by electrical stimulation of peripheral nerves, the response was detected within one or two heartbeats. Beat amplitudes increased on average 11.6%, and inter-beat intervals decreased on average 2.1%. The mean duration of the response was 28.1 s. A transient inhibitory phase often preceded the excitatory response. Results from testing various nerves and tissues show that the cardiac responses invariably occur whenever contractions of the tentacle retractor muscle are elicited. Even stimulation of the ovotestis and the kidney elicit responses despite their protected locations within the mantle cavity. Three excitatory cardioactive neurons are identified in the central nervous system of Helix aspersa, and their involvement in the reflex response is documented. The results suggest that the heart output is initially inhibited to relax the hydroskeleton and thereby aid withdrawal movements. A delayed increase in cardiac output then facilitates the re-inflation, hence eversion, of the withdrawn body parts.     

High-sensitivity cardiac troponin T for diagnosis of NSTEMI in the elderly emergency department patient: a clinical cohort study

Purpose: The aim of this study is to evaluate the impact of age on the diagnostic performance of high-sensitivity troponin T (hsTnT) under routine conditions.

Materials and methods: Data of 4118 consecutive emergency department (ED) patients who underwent a routine TnT measurement between 11 October 2012 and 30 November 2013 were analysed. Diagnostic accuracy of hsTnT was compared in four age categories (<50, 50–64, 65–74, ≥75 years of age) for different cut-off values. Primary endpoint was a main hospital diagnosis of NSTEMI.

Results: The median age of the study population (n?=?4118) was 61 years (IQR: 45–75 years). NSTEMI was diagnosed in 3.3% (n?=?136) of all patients. There were significant differences in hsTnT concentrations between age-groups (p?p?=?0.297). 72.2% of all patients ≥75 years of age (583/808) without NSTEMI had hsTnT concentrations above the 99th percentile of a healthy reference population. Specificity at 14?ng/L was 93.6% (95% CI: 92.12–94.87) in patients below 50 years of age and 27.9% (95% CI: 24.78–31.08) in patients 75 years of age and older.

Conclusions: Patients’ age needs to be considered at least one influencing factor on hsTnT concentrations at admission and should be included in the clinical interpretation of hsTnT concentrations for further clinical workup beneath other influencing factors like comorbidities and symptom onset time. The implementation of age-specific cut-off values could be considered for single troponin testing at admission but is associated with an increased risk of underdiagnosis of NSTEMI.     

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N^ω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.     

参附注射液联合新活素对老年慢性心力衰竭患者心功能及血清BNP、MMP-9、CypA水平的影响

目的:研究参附注射液联合新活素对老年慢性心力衰竭患者心功能及血清B型利钠肽(Brain natriuretic peptide,BNP)、基质金属蛋白酶-9(matrix metalloprotein-9,MMP-9)、亲环素(cyclophilin,CypA)水平的影响。方法:选择2015年6月至2017年5月在我院进行治疗的慢性心力衰竭患者100例,根据治疗方案不同分为观察组和对照组,对照组给予新活素治疗,观察组以对照组为基础联合参附注射液治疗。治疗后,观察和比较两组的临床疗效、不良反应的发生情况及治疗前后血清BNP、MMP-9、CypA、SCr和BUN水平、LVEF、SV、LVEDD的变化。结果:观察组总有效率显著高于对照组(P0.05),治疗后,观察组血清BNP、MMP-9、CypA、SCr、BUN、LVEDD水平及不良反应发生率均显著低于对照组(P0.05),LVEF、SV均明显高于对照组(P0.05)。结论:参附注射液联合新活素治疗慢性心力衰竭可有效改善患者心功能,降低血清BNP、MMP-9、CypA水平,提高临床疗效,减少不良反应。     

慢性心力衰竭患者彩色多普勒超声心功能参数与血清同型半胱氨酸水平的相关性研究

目的:探讨慢性心力衰竭(CHF)患者彩色多普勒超声的心功能参数与血清同型半胱氨酸水平的相关性。方法:选取2016年2月至2017年6月期间我院收治的CHF患者73例作为研究组,选取同期体检的健康志愿者70例作为对照组。检测两组血清同型半胱氨酸(Hcy)及氨基末端B型利钠肽前体(NT-proBNP)水平,采用彩色多普勒超声测定两组心脏左室射血分数(LVEF)及左室舒张末期内径(LVEDd)。分析CHF患者血清Hcy水平与NT-proBNP、LVEF、LVEDd的相关性,观察不同血清Hcy水平CHF患者心血管事件发生情况。结果:研究组血清Hcy、NT-proBNP及LVEDd显著高于对照组,LVEF显著低于对照组(P0.05)。Ⅳ级患者血清Hcy、NT-proBNP、LVEDd水平高于Ⅱ级与Ⅲ级,且Ⅲ级高于Ⅱ级(P0.05);Ⅳ级患者LVEF水平低于Ⅱ级与Ⅲ级,且Ⅲ级低于Ⅱ级(P0.05)。由Pearson相关性分析可得,CHF患者血清Hcy水平与血清NT-proBNP、LVEDd呈正相关,与LVEF呈负相关(P0.05)。血清Hcy水平高于25μmol/L的患者心血管事件发生率为31.43%,血清Hcy水平在15μmol/L-25μmol/L范围内的患者心血管事件发生率为10.53%,差异有统计学意义(P0.05)。结论:CHF患者血清Hcy、NT-proBNP、LVEDd随心功能恶化程度增加而升高,LVEF随之降低,且Hcy水平越高,患者预后越差。     

通心络胶囊对急性心梗PCI术后心肌微循环及心功能的影响

目的:探讨通心络胶囊对急性心梗经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后心肌微循环及心功能的影响。方法:选取2014年1月-2017年6月我院收治的ST段抬高型急性心肌梗死需经PCI患者200例,按照治疗方法分为对照组、观察组,每组100例。对照组进行常规药物治疗,观察组联合通心络胶囊进行治疗。比较两组PCI后心肌梗死溶栓(thrombolysis in myocardial infarction,TIMI)血流分级与计帧值(corrected thrombolysis in myocardial frame count,CTFC)、ST段回落情况、肌酸磷酸激酶同工酶(creatine phosphokinase-isoenzyme-MB,CK-MB)峰值及峰值时间,治疗前后心功能相关指标的变化。结果:PCI术后,两组冠脉TIMI血流分级比较差异不显著(P0.05),观察组CFTC显著低于对照组(P0.05),观察组ST段回落50%比例显著高于对照组(P0.05),CK-MB峰值及CK-MB峰值时间显著低于对照组(P0.05)。治疗后,两组左室射血分数(left ventricular ejection fraction,LVEF)、心脏指数(cardiac index,CI)均显著升高(P0.05)左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDD)、左心室收缩末期内径(left ventricular end-systolic dimension,LVESD)均显著降低(P0.05),且观察组的以上指标的改善明显优于对照组(P0.05)。结论:通心络胶囊在急性心梗PCI后患者的应用中临床疗效良好,能够改善心肌微循环和心功能。     

促甲状腺激素对大鼠心肌成纤维细胞影响的研究

目的:探讨促甲状腺激素(TSH)对SD乳鼠心肌成纤维细胞(CFs)的影响及机制。方法:新生1-3 d的SD乳鼠15只,处死后进行CFs的分离与培养,倒置显微镜对原代培养细胞形态进行鉴定,免疫组织化学染色法对CFs胞浆内波动蛋白进行染色并鉴定。后续实验过程中,按照使用b TSH工作液的稀释浓度分为A组(1μmol·L~(-1))、B组(2μmol·L~(-1))、C组(4μmol·L~(-1))。MTT法检测心肌成纤维细胞增殖率。酶联免疫吸附法(ELISA)检测培养细胞的上清液中Ⅰ、Ⅲ型胶原蛋白含量。荧光定量PCR反应测定培养细胞上清液中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)m RNA的相对表达量。Western-blot法检测培养细胞上清液中MMP-2、MMP-9的蛋白表达水平。结果:CFs的形态学变化及纯度鉴定结果显示乳鼠CFs培养成功。MTT试验结果显示,24 h时后,A、B、C组CFs的增殖率分别为112.91±10.23、123.22±9.34、132.56±9.36;48 h时后,A、B、C组CFs的增殖率分别为124.4±8.34、133.5±9.02、139.6±11.36。随着b TSH浓度的增加,CFs增殖率呈逐渐增加趋势。ELISA检测结果显示,A、B、C组I型胶原蛋白表达水平分别为(2.61±0.31)μg·L~(-1)、(5.53±0.66)μg·L~(-1)、(7.91±0.74)μg·L~(-1);A、B、C组Ⅲ型胶原蛋白表达水平分别为(3.96±0.25)μg·L~(-1)、(6.72±0.52)μg·L~(-1)、(8.11±0.65)μg·L~(-1)。随着b TSH浓度的升高,I型和Ⅲ型胶原蛋白表达水平呈升高趋势。荧光定量PCR法检测结果显示,A、B、C组MMP-2的m RNA表达量分别为9.124±1.021、15.223±1.536、18.678±1.742;A、B、C组MMP-9的m RNA表达量分别为16.447±1.664、17.402±1.881、24.247±2.364。随着b TSH浓度的增加,MMP-2、MMP-9的m RNA相对表达量呈增加趋势。Western-blot法检测结果显示,A、B、C组MMP-2灰度值分别为165.41±16.57、198.25±21.34、223.41±19.08;A、B、C组MMP-9灰度值分别为140.30±15.09、190.47±20.06、230.14±21.45。随着b TSH浓度的增加,MMP-2、MMP-9的蛋白表达水平呈增加趋势。结论:TSH能够促进乳鼠CFs细胞增殖及I、Ⅲ型胶原蛋白表达增加,导致细胞外基质成分降解及合成过程失调。     

欧前胡素通过ERK1/2信号保护心肌细胞低氧性损伤

目的:研究欧前胡素对低氧诱导的大鼠心肌细胞损伤的保护作用和机制。方法:采用CO2-95%和N2-5%的细胞培养箱诱导H9c2大鼠心肌细胞建立心肌细胞低氧损伤模型,采用不同浓度的欧前胡素孵育细胞12、24 h,检测上清液中乳酸脱氢酶(lactate dehydrogenase,LDH)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde MDA)的含量。采用MTT方法检测细胞的存活率,Annexin V/PI双标记流式细胞术检测细胞凋亡比例,蛋白质印迹法检测检ERK1/2蛋白的表达。结果:低氧处理H9c2心肌细胞12 h后,上清中LDH和MDA的含量分别为(523.28±90.29)U/L和(5.59±0.33)U/L,均明显高于对照组(P0.05),而SOD的含量[(12.23±1.38)U/mg]明显低于对照组(P0.05)。低、高浓度欧前胡素孵育12 h后,细胞存活率分别为(64.51±2.78)%和(73.22±3.56)%,低、高浓度欧前胡素孵育24 h后,细胞存活率分别为(80.21±4.67)%和(87.38±5.41)%,均较与模型组显著升高(P0.05)。高浓度欧前胡素孵育12 h和24 h后凋亡细胞比例分别为(39.67±4.11)%和(49.61±3.39)%,均较模型组显著降低(P0.05),10μmol/L的PD98059阻断ERK1/2信号通路后细胞存活率均较高浓度欧前胡素组显著降低,凋亡细胞比例较高浓度欧前胡素明显升高(P0.05)。高浓度欧前胡素孵育12 h和24 h后,ERK1/2蛋白相对表达量分别为(1.92±0.09)和(2.42±0.21),与模型组相比均显著增加(P0.05)。结论:欧前胡素可能通过活化ERK1/2信号通路保护低氧诱导的心肌细胞损伤。     

心房钠尿肽通过上调OPA1表达抑制心衰小鼠心肌线粒体分裂并改善心脏功能

目的:探讨心房钠尿肽(Atrial natriuretic peptide,ANP)对后负荷增加引起的心脏功能下降的保护作用及其机制。方法:选择雄性C57小鼠30只,将其随机分为假手术组(sham)、主动脉弓结扎(Transverse aortic constriction,TAC)手术组和主动脉弓结扎手术ANP干预组(TAC+ANP)。ANP通过皮下注射4周,随后超声检测心脏功能、四腔心切片观察心肌重构,电镜观察心肌线粒体的形态与数量,Western-Blot检测心肌组织中融合分裂相关分子的表达。结果:同sham组相比,TAC组射血分数(Ejection fraction,EF)降低,且左室舒张末内径(End-diastolic left ventricular internal diameter,LVIDd)、左室舒张期后壁厚度(End-diastolic left ventricular posterior wall thickness,LVPWd)、左室质量(LV mass)、心肌质量/胫骨长度(Heart weight/tibial length,HW/TL)显著增加(P0.05),线粒体面积减小伴数量增加(P0.05),且线粒体融合相关蛋白OPA1表达量下降(P0.05)。同TAC组相比,TAC+ANP组EF显著增加,且LVIDd、LV mass、HW/TL均显著下降(P0.05),线粒体面积增加伴数量减少(P0.05),且线粒体融合相关蛋白OPA1表达量上调(P0.05)。在离体培养的心肌细胞中,给予ANP处理可减轻H_2O_2诱导的OPA1表达下降,给与ANP竞争性多肽抑制剂anantin后该作用消失。结论:ANP通过上调OPA1的表达抑制线粒体分裂改善后负荷增加导致的心脏功能下降。     

The role of the unfolded protein response in arrhythmias

Human heart failure is characterized by arrhythmogenic electrical remodeling consisting mostly of ion channel downregulations. Reversing these downregulations is a logical approach to antiarrhythmic therapy, but understanding the pathophysiological mechanisms of the reduced currents is crucial for finding the proper treatments. The unfolded protein response (UPR) is activated by endoplasmic reticulum (ER) stress and has been found to play pivotal roles in different diseases including neurodegenerative diseases, diabetes mellitus, and heart disease. Recently, the UPR is reported to regulate multiple cardiac ion channels, contributing to arrhythmias in heart disease. In this review, we will discuss which UPR modulators and effectors could be involved in regulation of cardiac ion channels in heart disease, and how the understanding of these regulating mechanisms may lead to new antiarrhythmic therapeutics that lack the proarrhythmic risk of current ion channel blocking therapies.