EFFECT OF DESTRUCTION OF NTS AND PVN ON NEIGUAN (PC6)- ELECTROACUPUNCTURE-I NDUCED IMPROVEMENT OF ISCHEMIC MYOCARDIAL CELLULAR MEMBRANE POTENTIALS IN RABBITS

Objective: To observe the influence of electrolytic destruction of nucleus soli tary tract (NTS) and hypothalamic paraventricular nucleus (PVN) on the effect of electroacupuncture (EA) in improving ischemic myocardia cellular transmembrane action potential (TMAP). Methods: 38 Japanese breed big-ear wh ite rabbits (ane sthetized with 20% Urethane, 4 mL/kg) were randomly divided into acute myocardia l ischemia (AMI) group (n=8), PVN destruction group ( n=12) and PVN+NTS destructio n group (n=18). AMI model was established by occlusion of the descending anterio r branch (DAB) of the coronary artery. TMAP of myocytes was recorded by using a glass microelectrode which was fixed to a suspending spring silver wire. Bilater al "Neiguan"(PC 6) in all the 3 groups were punctured and stimulated electri call y by using parameters of continuous waves, frequency of 7 Hz, intensity of 6 mA a nd duration of 30 minutes. Results: After AMI, ECG-ST elevated significantly whil e APA lowered, APD50 and APD90 shortened clearly in comparison with those of pre -AMI in the 3 groups. Compared with AMI group, ECG-ST values of PVN destructi on group and PVN+NTS destruction group were significantly higher (P <0.05～0.01), whi le APA, APD50 and APD90 all significantly lower in all the recording time course s(P<0.05). The facts displayed that electrolytic destru ction of PVN and PVN+NT S could produce ischemic myocardial injury and reduce the protective effect of E A on ischemic myocardial cells. Comparison between PVN destruction and PVN+NTS g roups showed that all the 4 indexes of the later group were evidently worse than those of the former group (P<0.05), suggesting after des truction of these two n uclei, the effect of EA was worsened further. Conclusion: Electrolytic destru ction of PVN and NTS weakens the protective effect of EA on ischemic myocardial cells, both NTS and PVN take part in the effect of EA of "Neiguan"(PC 6) Point i n improving ischemic myocardium.

Effect of heartbeat perception on heartbeat evoked potential waves

Objective Early researches found that different heartbeat perceivers have different heartbeat evoked potential （HEP）waves.Two tasks were considered in our experiments to get more details about the differences between good and poor heartbeat perceivers at attention and resting state.Methods Thirty channels of electroencephalogram（EEG）were recorded in 22 subjects,who had been subdivided into good and poor heartbeat perceivers by mental tracking task. Principal component analysis（PCA）was applied to remove cardiac field artifact（CFA）from the HEP.Results（1）The good heart-beat perceivers showed difference between attention and resting state in the windows from 250 ms to 450 ms after R wave at C3 location and from 100 ms to 300 ms after R wave at C4 location;（2）The difference waveforms between good and poor heartbeat perceivers was a positive waveform at FZ from 220 ms to 340 ms after R wave,which was more significant in attention state.Conclusion Attention state had more effect on the HEPs of good heartbeat perceivers than that of poor heartbeat perceivers;and perception ability influenced HEPs more strongly in the attention state than in the resting state.

Diabetes-induced changes in cardiac voltage-gated ion channels

Diabetes mellitus affects the heart through various mechanisms such as microvascular defects,metabolic abnormalities,autonomic dysfunction and incompatible immune response.Furthermore,it can also cause functional and structural changes in the myocardium by a disease known as diabetic cardiomyopathy(DCM)in the absence of coronary artery disease.As DCM progresses it causes electrical remodeling of the heart,left ventricular dysfunction and heart failure.Electrophysiological changes in the diabetic heart contribute significantly to the incidence of arrhythmias and sudden cardiac death in diabetes mellitus patients.In recent studies,significant changes in repolarizing K+currents,Na+currents and L-type Ca^(2+)currents along with impaired Ca^(2+ )homeostasis and defective contractile function have been identified in the diabetic heart.In addition,insulin levels and other trophic factors change significantly to maintain the ionic channel expression in diabetic patients.There are many diagnostic tools and management options for DCM,but it is difficult to detect its development and to effectively prevent its progress.In this review,diabetes-associated alterations in voltage-sensitive cardiac ion channels are comprehensively assessed to understand their potential role in the pathophysiology and pathogenesis of DCM.

Cardiac Electrophysiological Differences Between Kunming and C57BL6/J Mice

Objective To investigate the alterations of cardiac electrophysiological properties and substantial mechanism and find the stable arrhythmia mouse model in Kunming （KM） and C57BL6/J （C57） mice. Methods Electrocardiogram recordings were used to analyze the QT interval in vivo, and mono- phasic action potential of right and left ventricular epicardium was recorded to elicit changes of action potential duration （APD） in conventional and programmed electrical stimulation （PES）. Transient outward potassium current （Its,） was recorded via whole-cell patch-clamp technique in single right and left epicardial myocytes. Results QT interval was prolonged in KM mice relative to C57 mice （62.51±4.47 ms vs. 52.59±4.85 ms, P〈0.05）. The APD at 50% repolarization of the left ventricular epicardium （18.60±0.91 ms vs. 12.90±0.35 ms）, and APDs at 50% （17.31±6.05 ms vs. 12.00±3.24 ms） and 70% repolarization （36.13±5.32 ms vs. 2 1.95±8.06 ms） of the right ventricular epicardium in KM mice were significantly pro- longed compared with C57 mice, respectively （all P〈0.05）. KM mice were more sensitive to PES-induced ventricular tachycardia （25%, 3 of 12 hearts）, and especially to Burst-induced ventricular tachycardia （50%, 6 of 12 hearts） compared with C57 mice, which were 20% （2 of 10 hearts） and 30% （3 of 10 hearts） respec- tively. It,, densities both in the left and right ventricular epicardial myocytes from KM mice were significantly decreased compared with C57 mice, respectively （all P〈0.01）. Conclusion Our data showed that KM mice with tile prolonged QT interval and APD are ruiner- abilities to ventricular arrhythmia, which are attributed to lower Ito densities in ventricular myocytes ob- tained from KM mice than that from C57 mice.

Fetal cardiac mesenchymal stem cells express embryonal markers and exhibit differentiation into cells of all three germ layers

AIM:To study the expression of embryonal markers by fetal cardiac mesenchymal stem cells(fC-MSC)and their differentiation into cells of all the germ layers. METHODS:Ten independent cultures of rat fCMSC were set up from cells derived from individual or pooled fetal hearts and studies given below were carried out at passages 3,6,15 and 21.The phenotypic markers CD29,CD31,CD34,CD45,CD73,CD90, CD105,CD166 and HLA-DR were analyzed by flow cytometry.The expression of embryonal markers Oct-4, Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4,TRA-1-60 and TRA 1-81 were studied by immunocytochemistry.The fC-MSC treated with specific induction medium were evaluated for their differentiation into(1)adipocytes and osteocytes(mesodermal cells)by Oil Red O and Alizarin Red staining,respectively,as well as by expression of lipoprotein lipase,PPARγ2 genes in adipocytes and osteopontin and RUNX2 genes in osteocytes by reverse-transcription polymerase chain reaction(RT- PCR);(2)neuronal(ectodermal)cells by expression of neuronal Filament-160 and Glial Fibrillar Acidic Protein by RT-PCR and immunocytochemistry;and(3)hepa- tocytic(endodermal)cells by expression of albumin by RT-PCR and immunocytochemistry,glycogen deposits by Periodic Acid Schiff staining and excretion of urea into the culture supernatant. RESULTS:The fC-MSC expressed CD29,CD73,CD90, CD105,CD166 but lacked expression of CD31,CD34, CD45 and HLA-DR.They expressed embryonal markers,viz.Oct-4,Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4, TRA-1-81 but not TRA-1-60.On treatment with specific induction media,they differentiated into adipocytes and osteocytes,neuronal cells and hepatocytic cells. CONCLUSION:Our results together suggest that fCMSC are primitive stem cell types with a high degree of plasticity and,in addition to their suitability for cardiovascular regenerative therapy,they may have a wide spectrum of therapeutic applications in regenerative medicine.

Effect of Cerium on Cardiac Muscle of Rat and Guinea Pig

The effect of Ce3+ on cardiac muscle of rat and guinea pig was studied. In vitro, 0.05 mmol·L-1 solution of Ce3+ inhibited the contraction of guinea pig atria. The change of action potential duration(APD) of guinea pig papillary muscle exposed to 0.4 mmol·L-1 Ce3+ was significant, and those exposed to 0.1 and 0. 2 mmol·L-1 Ce3+ were not significant. In vivo, compared with the control group, the APD for rat cardiac muscle after long-term feed on Ce3+ was significantly delayed in high dose, and that was not significantly delayed in low dose. The results suggest that Ce3+ with long-term high dose intake might affect the influx of Ca2+, Na+ and outflow of K+ for rat cardiac muscle.

Dynamical modelling of cardiac electrical activity using bidomain approach: The effects of variation of ionic model parameters

This work presents the dynamical modelling of cardiac electrical activity using bidomain approach. It focuses on the effects of variation of the ionic model parameters on cardiac wave propagation. Cardiac electrical activity is governed by partial differential equations coupled to a system of ordinary differential equations. Numerical simulation of these equations is computationally expensive due to their non-linearity and stiffness. Nevertheless, we adopted the bidomain model due to its ability to reflect the actual cardiac wave propagation. The derived bidomain equations coupled with FitzHugh-Nagumo’s ionic equations were time-discretized using explicit forward Euler method and space-discretized using 2-D network modelling to obtain linearized equations for transmembrane potential Vm, extracellular potential φe and gating variable w. We implemented the discretized model and performed simulation experiments to study the effects of variation of ionic model parameters on the propagation of electrical wave across the cardiac tissue. Time characteristic of transmembrane potential, Vm, in the normal cardiac tissue was obtained by setting the values of ionic model parameters to 0.2, 0.2, 0.7 and 0.8 for excitation rate constant ε1, recovery rate constant ε2, recovery decay constant γ and excitation decay constant β respectively. Changing the values of ε1, ε2 to 0.04 and 0.28 respectively, the obtained Vm showed a time dilation at 0.04 indicating cardiac arrhythmia but no significant change to Vm was observed at 0.28. Also, changing β to 0.3 and 1.1 and γ to 0.4 and 1.2 sequentially, there was no significant change to the time characteristic of Vm. The obtained results revealed that only decrease in ε1, ε2 impacted significantly on the cardiac wave propagation.

Long-term potentiation in autonomic ganglia:Potential role in cardiovascular disorders

Ganglionic long-term potentiation(gLTP) is an activitydependent,enduring enhancement of ganglionic transmission.This phenomenon may be induced in autonomic ganglia of an organism under certain conditions whererepetitive impulses surge from the central nervous system(CNS) to the periphery.Chronic stress,repetitive epileptic seizure or chronic use of CNS stimulants could induce gL TP,which would result in a long lasting heightening of sympathetic tone to the cardiovascular system causing hypertension and disturbed cardiac rhythm that may lead to sudden cardiac death.These conditions are briefly reviewed in this article.

心肌肌球蛋白结合蛋白C磷酸化与慢性心力衰竭关系的研究进展

心肌肌球蛋白结合蛋白C是心肌粗肌丝中的重要组成部分,它的磷酸化水平可影响心肌的收缩和舒张功能。由于其磷酸化水平的改变与慢性心力衰竭的发生发展密切相关,近年来逐渐成为慢性心力衰竭研究中的一个关键位点。现就心肌肌球蛋白结合蛋白C磷酸化与慢性心力衰竭的关系及其作为治疗靶点的可能性进行综述。

冰片通过TRPM8减轻小鼠心肌梗死后炎症反应并抑制心脏重构

目的:研究冰片(borneol)对小鼠心肌梗死(myocardial infarction,MI)后炎症反应和心脏重构的作用及可能机制。方法:8周龄野生型(wild-type,WT)C57BL/6小鼠和瞬时受体电位阳离子通道M亚家族成员8(transient receptor potential cation channel subfamily M member 8,TRPM8)基因敲除(TRPM8 gene knockout,TRPM8−/−)小鼠随机分为假手术组和MI组,再分别用生理盐水(对照组)或冰片(冰片组)灌胃。绘制小鼠MI后生存曲线,28 d后超声心动图检测心脏功能,多导生理记录仪测量血流动力学参数,病理染色观察MI面积、心肌肥大和间质纤维化,并检测梗死交界区心肌中炎症反应情况。结果:在WT小鼠中,梗死交界区心肌组织中TRPM8表达显著增加(P<0.05),冰片对心脏中TRPM8表达无影响(P>0.05),但可提高小鼠生存率,缩小MI面积,抑制MI后心脏重构,改善心脏功能(P<0.05或P<0.01);在TRPM8−/−小鼠中,冰片对小鼠生存率、MI面积、心肌肥大、心肌纤维化和心脏功能未见明显影响(P>0.05)。在WT小鼠中,冰片可减少中性粒细胞和巨噬细胞的浸润(P<0.01),抑制炎症因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、IL-6和单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)过度表达(P<0.05或P<0.01);而在TRPM8−/−小鼠中,冰片对炎症细胞数量和炎症因子表达未见明显影响(P>0.05)。结论:TRPM8可能是冰片在心脏的作用靶点;冰片可能通过TRPM8减轻MI后炎症反应和抑制心脏重构,改善小鼠MI后的心脏功能。

兔骨髓间充质干细胞心脏移植治疗扩张型心肌病的实验研究

目的探讨骨髓间充质干细胞(mesenchymal stem cells,MSCs)心脏移植后对兔扩张型心肌病(dilated cardio-myopathy,DCM)心功能、心肌结构及心内膜单相动作电位(monophasic action potential durations,MAP)的影响。方法新西兰兔分为正常对照组(n=12),DCM实验组(n=13),DCM对照组(n=13),DCM模型通过静脉注射阿霉素诱导。DCM实验组移植骨髓MSCs,DCM对照组注射培养基,移植后4周采用超声心动图和MAP参数评价心功能和电生理的改变;并取移植区心肌组织行免疫荧光染色以观察移植细胞的增殖分化情况,另选部分心肌组织做HE染色和透射电镜查看心肌组织形态学改变。结果与正常组相比,DCM各组心功能明显受损、MAP时程延长、心肌细胞变性坏死,且实验组受损较对照组轻;移植的细胞有肌钙蛋白T(cardiac troponin T,cTnT)和缝隙连接蛋白43(connexin 43,Cx43)的表达。结论体内移植骨髓MSCs后在一定程度上可改善DCM心功能,使病损心肌组织病变减轻,并可能抑制心电紊乱的进一步发展。

西红花酸对去甲肾上腺素所致原代培养心肌细胞能量代谢和凋亡的影响

目的 研究西红花酸对去甲肾上腺素(NE)诱导原代培养心肌细胞能量代谢障碍和细胞凋亡的保护作用。方法 1μmol·L-1NE损伤原代培养的心肌细胞,检测细胞培养上清液的LDH、心肌细胞ATPase、线粒体琥珀酸脱氢酶(MSDH)的活力,线粒体膜电位的变化,流式细胞仪检测细胞凋亡,观察西红花酸保护作用。结果 模型组细胞培养上清液LDH增加,心肌细胞MSDH和ATPase的活力降低,线粒体膜电位降低,心肌细胞凋亡率增加。西红花酸明显降低培养上清液LDH增加,提高MSDH和ATPase的活力、线粒体膜电位的水平,对心肌细胞的凋亡具有明显的保护作用。结论 西红花酸对NE所致的心肌细胞能量代谢障碍和凋亡具有明显的保护作用。

心脏记忆现象及其产生机制的研究现状

心脏记忆是近20年来才被人们开始认识的一种正常的生理现象。在未出现心力衰竭、心肌缺血等疾病,心电图未见异常的情况下,若给心脏施加易位电刺激一段时间,如心室起搏在恢复为正常窦性节律后心电图T波仍与起搏时QRS波同向及起搏停止后T波记住了起搏时QRS波形态,且这种记忆维持一段时间后才会消失。由于T波的记忆现象会影响心室复极和动作电位的不应期,有诱发或抑制心律失常发生的作用,且由它引起的T波形态的改变,与许多病理状态下,如心肌缺血时T波的形态相似,容易产生混淆等特点,使心脏记忆的研究越来越受到人们的关注。本文重点介绍了心脏记忆现象及其产生的电生理离子通道机制,并总结了当前的主要研究结果。

西洋参茎叶皂甙对大鼠培养心肌细胞氧化损伤的保护作用

黄嘌呤-黄嘌呤氧化酶可引起大鼠培养心肌细胞电参数变小、心肌细胞起搏比例减少及心肌细胞超微结构破坏。西洋参茎叶皂甙可使上述指标明显改善,说明其有抗氧化损伤作用。

槐果碱的心脏电生理效应

目的研究中药单体槐果碱对心脏快、慢反应动作电位和离体心脏心电图的影响,初步探讨其抗心律失常的机制。方法应用细胞内微电极技术和Langendorff离体心脏灌流的方法,研究槐果碱对心肌细胞快、慢反应动作电位和离体心脏心电图的影响。结果槐果碱可使豚鼠心室乳头肌快反应动作电位的时程(APD50,APD90)和有效不应期(ERP)延长,0期上升速率(Vmax)降低,且呈剂量依赖性变化;可使家兔窦房结慢反应动作电位4期自动除极速率(SDVP4)、自律性兴奋频率(SEF)和动作电位幅值(APA)明显减小,此效应亦呈浓度依赖性;在豚鼠离体心电图实验中,槐果碱能对抗肾上腺素诱发的快速性心律失常。结论根据槐果碱对动物心脏电生理活动的影响,初步推测其可能通过抑制钠、钾和钙离子通道而产生抗心律失常效应。

心源性猝死的病因、诱因及预防——附178例法医病理学解剖分析

目的:探讨心源性猝死(SCD)不同年龄、性别的病因、诱因特点及相关预防措施。方法:对2000～2005年在四川华西法医学鉴定中心进行尸体解剖的178例SCD案例资料进行回顾性分析。研究SCD与年龄、性别、诱因、潜伏病变的关系,并提出预防措施。结果:本组资料显示,精神性因素、过度劳累、轻微外伤在各类诱因中所占比例较高,不同年龄组潜伏病变有差别。负性生活事件可看作SCD一个潜在的诱因,在不同性别与年龄组中起着不同的作用。结论:心源性猝死多数有诱因或伴发于负性生活事件,减少此类事件的发生对预防心源性猝死有一定帮助。

水飞蓟宾对异丙肾上腺素引起的大鼠乳鼠心肌细胞损伤的保护作用及其机制

水飞蓟宾(silibinin)为从菊科植物水飞蓟(Silybum marianum)的种子和果实中提取得到的黄酮类单体成分。本研究观察水飞蓟宾对β-肾上腺素受体激动剂异丙肾上腺素对培养乳鼠心肌细胞损伤的影响,并对其机制进行研究。采用MTT法测定细胞存活率,酶联法测定细胞丙二醛(maleic dialdehyde,MDA)和细胞培养液中乳酸脱氢酶(lactate dehydrogenase,LDH)的含量以及超氧化物歧化酶(superoxide dismutase,SOD)的活性,流式细胞仪测定线粒体膜电位(ΔΨ),以及Western blotting检测与线粒体相关蛋白的表达。与模型组相比,水飞蓟宾使细胞受损伤的程度降低,并且增加SOD的活性,抑制了细胞膜电位的降低,并且改善Bcl-2家族蛋白中Bax/Bcl-2的表达比率,上调Bax上游去乙酰化酶SIRT1蛋白的表达。水飞蓟宾通过上调线粒体上游Bax/Bcl-2的表达比率与SIRT1蛋白的表达,改善了线粒体的功能,从而对由异丙肾上腺素引起的培养乳鼠心肌细胞损伤有明显的保护作用。

瑞芬太尼对兔心肌动作电位及跨室壁复极离散度的影响

目的：观察瑞芬太尼对兔心肌动作电位及跨室壁复极离散度的影响。方法：成年家兔18只，体重2.0～2.5 kg，制备Langendorff离体心脏灌注模型，K-H液平衡灌注15 min后随机分为3组（n＝6）：正常对照组（C组）继续灌注37℃K-H液60 min；瑞芬太尼组（ R组）灌注含12μg／L瑞芬太尼的K-H液60 min；瑞芬太尼＋氨茶碱组（ RA组）灌注含12μg／L瑞芬太尼＋30 mg／L氨茶碱的K-H液60 min。记录平衡灌注15 min （ T0）、继续灌注15 min （ T1）、30 min （ T2）和60 min （ T3）时心率（ HR）和左心室前壁3层心肌单相动作电位（ MAP），计算单相动作电位复极90％的时程（ MAPD90）和跨室壁复极离散度（ TDR）。记录早期后除极、延迟后除极及心律失常的发生情况。结果：与T0比较，R组T1～T3时HR减慢，MAPD90延长，TDR增大（ P＜0.05）。与C组和RA组比较，R组HR减慢时，MAPD90延长，TDR增大（P＜0.05）。结论：瑞芬太尼减慢HR时，MAPD90延长，TDR增大，折返激动易于发生；氨茶碱增快HR，缩短MAPD90，从而使TDR减小。

“缺血”引起的绵羊浦肯野纤维跨膜电位与离子流变化

以低氧、高钾、低pH、无能量供应的模拟缺血溶液灌流离体绵羊心脏浦肯野纤维,观察“缺血”对心肌跨膜电位和离子流的影响。实验共24例。跨膜电位的变化过程如下:模拟缺血液灌流后2-3min,首先出现最大舒张电位(MDP)轻度除极,4期舒张除极速率减慢,随后动作电位时程(APD)缩短(n=13)或先缩短、后延长、再缩短的变化(n=11),平台逐渐消失,最后MDP进一步除极,动作电位波幅(APA)减小,兴奋性逐渐降低,以致不能引出动作电位(AP)。其中6例即使MDP高于-60mV时AP已不能引出。以上变化过程历时长短不等,在不同标本为30-160min。跨膜离子流方面,当APD缩短时,在所有膜电位水平即时外向电流都明显增加。稳态电流-电压关系曲线由正常的S形变成直线,内向整流现象消失。慢内向离子流由“缺血”前的6.74±4.48nA减少到0.86±1.39nA,(M±SD,P<0.01,n=8),在多数测试电位水平都有显著减少,其电流-电压关系曲线向较负电位方向移位。以上结果提示:心肌“缺血”时浦肯野细胞起搏功能受抑制,细胞内大量K^+外流,Ca^(2+)内流减少,心肌细胞除极,以上多种变化可能为心肌缺血时心律失常发生的原因。