厄贝沙坦对高血压左室肥厚家兔跨心室壁Cx43蛋白异质性的影响

目的观察血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)厄贝沙坦对高血压左室肥厚(left ventricular hypertrophy,LVH)家兔左心室心肌跨室壁复极不均一性及Cx43蛋白分布异质性的影响,探讨ARB在LVH恶性室性心律失常(malignant ventricular arrhythmias,MVA)治疗中的作用。方法将20只家兔随机分成LVH实验组和厄贝沙坦治疗组,每组10只。两组均采用传统的腹主动脉缩窄术制备家兔LVH模型。对照组继续喂养8周,厄贝沙坦治疗组手术后除普通喂养外还给予经口喂服厄贝沙坦片,每次10mg·kg-1,每天1次,连续8周,然后进行实验。分别检测两组家兔的室颤阈值(ventricular fibrillation threshold,VFT)及心外膜下、中层心肌和心内膜下心肌细胞的单相动作电位复极90%时程(APD90)、跨室壁复极离散度(transmural dispersion of repolarization,TDR)以及三层心肌Cx43蛋白表达的差异。结果厄贝沙坦治疗组的平均动脉压、心质量/体质量指数和左心室壁厚度与LVH实验组对比明显下降(P<0.05)。厄贝沙坦治疗组的VFT明显高于LVH实验组(P<0.05),TDR和△APD90则显著缩小(P<0.05)。与LVH实验组比较,厄贝沙坦治疗组中层心肌、心外膜下心肌和心内膜下心肌的Cx43蛋白表达均有明显增加(P<0.05),但以中层心肌的增加更为明显,△Cx43缩小。结论厄贝沙坦能改善高血压左室肥厚的跨室壁Cx43表达异质性,使左心室心肌跨室壁复极不均一性增大,VFT下降,减少MVA的发作。     

七氟烷对离体兔心室肌单相动作电位及跨室壁复极不均一性的影响

目的观察七氟烷对离体兔心室肌单相动作电位及跨室壁复极不均一性的影响。方法选取1.5~2.0kg健康家兔24只,随机分为对照组(C组)、七氟烷0.65MAC组(S1组)和七氟烷1.3MAC(S2组)。肝素化后3%戊巴比妥钠30mg/kg经耳缘静脉麻醉,迅速开胸取心,于37℃恒温条件下予K-H液进行非循环式Langendorff离体心脏灌注,心脏平衡灌注15min后采用自制单相动作电位电极同步记录左心室前壁外膜、中层、内膜三层心肌单相动作电位(MAP)。计算MAP复极90%的时程(MAPD90)及跨室壁复极离散度(TDR),观察有无早期后除极(EAD)及延迟后除极(DAD)。结果(1)与C组比较,三层心肌MAPD90与TDR差异无统计学意义(P>0.05);(2)三组均未发现EAD及DAD。结论七氟烷不增加兔离体心脏跨室壁不均一性,不延长动作电位时程,未引起触发活动及触发性心律失常。     

奎尼丁相关性尖端扭转型室性心动过速机制的实验研究

目的　在低钾时观察不同浓度QUI对 3层心肌细胞复极和跨室壁复极离散度 (TDR)的影响及致EAD ,TdP的情况 ,以探讨QUI致TdP的发生机制。方法　采用Langen dorff技术离体兔心脏灌流。于不同起搏周长同步记录不同浓度QUI(1、5、1 0 μmol·L- 1 ) +低钾 (1 5mmol·L- 1 )作用时3层心肌MAP ,观察并记录EAD及诱发TdP的情况。结果　 (1 )QUI浓度依赖性地延长三层心肌MAPD90 ,其中对中层心肌作用最明显。 (2 )QUI逆浓度依赖性、逆频率依赖性地增大TDR。在 1 50 0ms起搏频率 ,低、中、高浓度QUI组及对照组TDR分别为 (83± 1 1 )、(74± 1 2 )、(68± 1 1 )及 (47± 7)ms。 (3)各浓度QUI组均频繁出现EAD ,各组间对比无差异 (P >0 0 5)。而低、中、高浓度QUI组TdP发生率分别为 5/1 0、3/9、1 /9。TDR的变化与TdP的发生相关。结论　QUI导致兔心脏跨室壁复极离散的增大 ,是其诱发TdP产生的主要机制     

胺碘酮急性灌流对左室肌3层心肌细胞动作电位和L-型钙离子流异质性的影响

目的:研究正常兔心室内膜心肌(Endo)细胞、心外膜心肌(Epi)细胞及中层心肌(M)细胞的动作电位时程(APD)、跨壁离散度(TDR)和3层心肌细胞的L-型钙通道(Ica-L)电流的异质性,以及胺碘酮急性灌流对上述生理指标的影响.方法:以混合气-二型胶原酶解法分离30只兔左室游离壁3层心肌,采用全细胞膜片钳记录生理台氏液和10μmol/L浓度胺碘酮急性灌流时的动作电位(AP)和Ica-L电流,并记录APD20、APD50及APD90.结果:(1)生理台式液下APD以M细胞最长,Endo细胞最短;胺碘酮处理后Endo细胞的APD20、APD50及APD90,Epi细胞的APD20、APD50与生理台式液比较均延长(P＜0.05),M细胞的APD20、APD50、APD90缩短(P＜0.05);胺碘酮处理后3层心肌细胞的APD20、APD50及APD90比较,差异无统计学意义(P＞0.05).胺碘酮处理后TDR较生理台氏液下明显减小,差异有统计学意义(P＜0.001).(2)生理台式液下各组电流密度差异有统计学意义(P＜0.05);胺碘酮急性灌流对3层心肌细胞的Ica-L均有所抑制,但只有M细胞处理前后差异有统计学意义(P＜0.05),胺碘酮对3层心肌细胞的电流电压(Ⅰ-Ⅴ)曲线形态和Ica-L电压依赖性无显著影响.结论:兔3层心肌细胞的动作电位存在明显的异质性,应用胺碘酮后APD减小,但不影响3层心肌细胞的Ica-L形态.     

CX43蛋白在低温联合右美托咪啶增加心室复极不均一性中的作用的研究

目的 探讨CX43蛋白在低温联合右美托咪啶处理影响心室复极不均一性中的作用.方法 成年家兔18只,体质量2.0～2.5 kg,制备Langendorff离体心脏灌注模型,取模型制备成功的心脏18个,采用随机数字表法分为3组(n=6):正常对照组(C组)、低温组(H组)、低温+右美托咪定组(HD组).C组继续灌注37℃K-H液60 min,H组灌注32℃K-H液60 min,HD组灌注32℃含右美托咪啶25 ng/mL K-H液60 min.于平衡灌注末(T0)、灌注K-H液15 min(T1)、30 min (T2)和60min(T3)时记录3层心肌单相动作电位,测量单相动作电位复极90％时程(MAPD90),计算跨室壁复极离散度(TDR),记录完毕后取左心室前壁心肌组织进行western blot检测CX43蛋白表达.结果 与C组比较,H组和HD组MAPD90延长,TDR增大,CX43蛋白表达下降;H组与HD组相比较各 项指标,差异无统计学意义(P＞0.05).结论 CX43蛋白的表达下降可能是低温造成心室复极不均一性增大的原因,而右美托咪啶既不影响CX43蛋白表达,也不加重低温对TDR的影响.     

比索洛尔对高血压左室肥厚患者心室跨壁离散度及室性心律失常的影响

目的观察比索洛尔对高血压左室肥厚患者心室跨壁离散度及室性心律失常的影响。方法选择高血压病并经过M型超声心动图确定有左室肥厚的患者120例,随机分为治疗组和对照组各60例,予除β受体阻滞剂以外的常规降压治疗,治疗组加比索洛尔口服治疗,2.5 mg·d-1开始,根据病情每周调整一次服药量,达到最大耐受量10 mg·d-1为止,疗程为8周。通过测量治疗前后心电图V2导联T波峰—末间期(T peak-end interval,Tp-e间期)和QT离散度(QT dispersion,QTd)及采用心律失常Lown分级标准评价心室跨壁离散度和室性心律失常的变化。结果治疗前两组Tp-e间期、QTd及室性心律失常比较差异无统计学意义(P>0.05),治疗8周后治疗组与对照组相比Tp-e间期和QTd指标差异有统计学意义(P<0.05),比索洛尔治疗组Tp-e间期和QTd明显缩短,室性心律失常减少。结论比索洛尔可降低高血压左室肥厚患者的心室跨壁离散度,防治恶性心律失常,减少猝死。     

楸毒素抗E-4031所致豚鼠离体心脏和心肌细胞LQT2作用的研究

目的观察楸毒素(mallotoxin,MTX)对E-4031诱发豚鼠离体心脏和心肌细胞LQT2的作用。方法采用Langendorff逆行主动脉灌流法对豚鼠离体心脏进行灌流,采集离体心脏表面Ⅱ导联心电图以考察低、中、高3个浓度MTX及其在应用hERG通道阻断剂E-4031条件下,对QT/QTc间期、跨室壁离散度、电生理平衡指数的影响;酶解法分离豚鼠单个心室肌细胞,应用全细胞膜片钳技术分别在正常和hERG通道阻断剂E-4031存在条件下,记录低、中、高3个浓度的MTX对动作电位时程的影响。结果 MTX缩短豚鼠离体心脏QT间期,降低跨室壁离散度,减小电生理平衡指数。MTX可逆转E-4031诱发的QT间期延长、跨室壁离散度增加和电生理平衡指数增大。MTX缩短豚鼠心室肌细胞动作电位复极时程,降低APD90、APD60、APD30,加速复极。MTX可逆转E-4031诱发的动作电位复极时程延长。结论MTX缩短QT间期,降低复极跨室壁离散度,减小电生理平衡指数和缩短动作电位复极时程,具有抗E-4031所致LQT2的作用。     

幼猪心肌梗死后植入骨髓间充质干细胞对心室肌细胞复极活动的影响

目的调查心肌梗死后植入骨髓间充质干细胞(mes-enchymal stem cells,MSCs)对心室肌细胞复极活动的影响。方法取10只苏中幼猪作正常对照组(Control),另取23只通过球囊导管堵闭左前降支法建立心肌梗死(myocardial in-farction,MI)模型,并分别移植MSCs悬液(MSCs组,n=13)或等量生理盐水(MI组,n=10),6周后记录左室心内膜心肌细胞的单相动作电位(MAP),分析动作电位复极90%的时间(APD90)、复极时间(RT)、APD和RT离散度(APDd和RTd),APD重整曲线斜率及APD交替的阈值周长。结果(1)MI组和MSCs组APD90、RT、APDd和TRd值较Control组均延长(P均<0.01),但MSCs组较MI组缩短(P<0.05或0.01);(2)Control组APD重整曲线斜率<1(正常),而MSCs组和MI组重整曲线斜率均>1(异常),但前者斜率明显小于后者;(3)MSCs诱发APD交替的阈值周长虽高于Control组(P<0.01),却低于MI组(P<0.05)。结论 MI后心室复极离散度增大,MSCs可以减轻MI引起的复极紊乱,提示MSCs移植有助于降低MI后室性心律失常的风险。     

比索洛尔治疗慢性充血性心力衰竭的临床分析

目的研究比索洛尔治疗慢性充血性心力衰竭(CHF)的临床观察。方法比索洛尔与强心、利尿剂等配合使用治疗CHF,判定比索洛尔是否明显改善CHF患者的心功能及提高患者的生活质量。结果采用比索洛尔与强心、利尿扩血管等药物联合使用,比索洛尔治疗组有效率(95.83%)明显高于常规治疗组(77.08%)(P<0.05)。结论常规抗心力衰竭治疗基础上加用比索洛尔治疗能提高疗效,显著改善CHF患者的心功能,降低患者的病死率。     

普鲁卡因胺对绵羊心室跨壁复极时间的影响

目的研究普鲁卡因胺对心室跨壁复极时间的影响。方法对6只绵羊用苯巴比妥麻醉后,开胸,用4个针状(p lunge need les)电极分别插入到左心室的基底部和心尖部,测量室壁激动-恢复间期(AR I)。静脉注射普鲁卡因胺20mg.m in-1后观察AR I的变化。结果窦性心律时,心外膜、中层心肌和心内膜的AR I差异无显著性,[分别为(266.0±30.5)m s、(265.0±28.9)m s和(265.7±28.1)m s,P>0.05]。普鲁卡因胺对各层心肌的AR I均有延长作用,心外膜、中层心肌和心内膜的AR I分别延长了(66.8±18.3)m s、(70.3±14.7)m s和(65.3±15.7)m s(P>0.05)。结论钠通道阻滞剂普鲁卡因胺对左室的心外膜、中层心肌和心内膜复极的延长程度相似。     

Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

Aim： To study the effects of carvedilol on the transmural heterogeneity of ventricular repolarization in rabbits with congestive heart failure （CHF）. Methods： Rabbits were randomly divided into 3 groups： control, CHF and carvedilol treated CHF group. Monophasic action potential duration （MAPD） in the 3 myocardial layers was simultaneously recorded. Results： All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resistance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold （VFT） was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization （TDR） was significantly increased in CHF. Low-dose carvedilol （0.25 mg/kg, twice daily） had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Although the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. Conclusion： In the present study, the transmural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological property rather than its effect on ventricular remodeling.     

Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90% (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of ICa_L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of     

Effects of imidapril on heterogeneity of action potential and calcium current of ventricular myocytes in infarcted rabbits.

AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90 % (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of I(Ca-L) [was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measured. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.     

兔左室肌三层细胞动作电位和L型钙离子流异质性以及胺碘酮急性灌流作用的研究

摘要 目的 本实验用膜片钳技术研究正常兔心室内、外膜层及M细胞的动作电位时程（APD）跨壁离散度（TDR）和三层细胞的L-型钙通道电流的异质性,以及胺碘酮急性灌流对上述生理指标的影响。方法 以混合气-二型胶原酶消化法分离兔左室游离壁内、中、外三层心肌,继而对其采用全细胞膜片钳记录生理台氏液和10μmol/L浓度胺碘酮急性灌流测量AP和Ica-L离子电流。结果：(1)APD以M细胞为最长,内膜细胞最短,外膜细胞居中,APD 90分别为488.13±22.88 ms、326.36±14.51 ms和391.1±23 ms,P<0.05;TDR为185 ms。存在显著的l相切迹和2相驼峰。(2)应用胺碘酮后的三层细胞动作电位的APD 20,50和90在M细胞显著缩短（P<0.05）,Edno显著延长（P<0.05）,TDR明显减小。胺碘酮对动作电位的形态无影响。(3)正常兔三层心肌细胞的ICa-L电流密度存在明显差异,外膜细胞和内膜细胞的ICa-L电流密度分别为：6.21±1.35 和 7.20±0.83 pA／pF。M细胞的ICa-L电流密度较大为11.59±3.71pA／pF, P <0.05。三层细胞的ICa-L 电压-电流曲线形态和电压依赖性无差异。(4)10μmol/L胺碘酮急性灌流对ICa-L的影响,在内、外细胞和M均有所抑制,但只有M细胞有统计学意义11.59±3.71 vs 7.28±2.01,（P<0.05）。胺碘酮对三层细胞的ICa-L的电压-电流（I-V )曲线形态和电压依赖性无差异。结论 (1)兔三层心肌细胞的AP存在明显的异质性,M细胞拥有明显大的APD,Endo细胞的APD最短,三层细胞的TDR较大。外膜细胞的AP形态有大的2相穹窿,M细胞拥有小的穹窿和尖锐的0时相上升支,呈尖峰圆顶型。M细胞明显大的ICa-L,外膜细胞和内膜细胞的ICa-L大小相仿,三层细胞的ICa-L的形态无差异。(2)胺碘酮延长Endo细胞的APD,缩短M细胞的APD,使得TDR减小。胺碘酮能显著抑制M细胞的ICa-L,但不影响三层细胞的ICa-L的形态。     

Potential cellular mechanisms of hydrogen peroxide-induced cardiac arrhythmias.

The electrophysiologic effects of hydrogen peroxide on the isolated guinea pig right ventricular free wall were studied using simultaneous recordings of action potentials from the epicardium and the endocardium. Exposure to hydrogen peroxide caused a time- and concentration-dependent change in action potential characteristics. Action potential durations at 50 and 90% of repolarization (APD50 and APD90, respectively) were significantly prolonged by hydrogen peroxide in both the epicardium and the endocardium. Although prolongation occurred at lower concentrations (0.5 mM) in the epicardium, increases in APD in response to higher concentrations of hydrogen peroxide (1 or 4 mM) were maintained for a longer period of time in the endocardium. In addition, hydrogen peroxide (1 or 4 mM) caused significant depolarization in the epicardium after 10 min, although this effect was observed only in the endocardium exposed to 4 mM hydrogen peroxide. Ventricular arrhythmias were observed in 5 of 7, 6 of 7, and 7 of 7 preparations exposed to 0.5, 1, and 4 mM hydrogen peroxide, respectively. The most frequently observed electrophysiologic abnormalities were associated with increased automaticity. Coupled beats, including clearly identifiable early and delayed depolarizations, were also observed. Verapamil (2 microM) and amiloride (0.1 mM) reduced both the incidence and the duration of hydrogen peroxide-induced arrhythmias but did not influence the effects on APD. This study is the first demonstration of hydrogen peroxide-mediated transmural dispersion in APD that could play an important role in the development of ventricular arrhythmias. In addition, our results demonstrate that hydrogen peroxide can induce ventricular arrhythmias through several cellular mechanisms, including increased automaticity, coupled beats, and triggered activity.     

Effect of amiodarone on dispersion of ventricular repolarization in a canine congestive heart failure model

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胺碘铜对快速右心室起搏致心力衰竭犬心室电生理特性的影响

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