改变在体兔左心室后负荷对其电生理参数的影响

目的：探讨改变在体兔左心室后负荷对室性心律失常发生情况及左心室电生理参数的影响。方法：改变左心室后负荷，观察室性心律失常发生情况，并测定左心室舒张阈值（ＶＤＴ），相对不应期（ＲＲＰ），有效不应期（ＥＲＰ）及其不应期离散和心室纤颤阈（ＶＦＴ）。结果：逐级增加左心室后负荷（ＡＢ级）可使左室空间ＲＲＰ，ＥＲＰ离散增加（Ｂ级，Ｐ＜００５），ＶＦＴ降低（Ｂ级，Ｐ＜００１）；各实验动物均出现室性心律失常（Ｂ级）；而逐级减小左室后负荷（ＣＤ级），心室电生理参数无变化（Ｐ＞００５），各实验动物亦无室性心律失常发生。结论：增加左心室后负荷诱发室性心律失常，与左室空间不应期离散增加有关。     

改变阈下串刺激参数特征对串刺激引起的心室不应期变化的影响

阈下条件单个刺激(S_s)和串刺激(S_t)可通过延长心脏受刺激局部的不应期,打断折返,终止快速性心律失常。本文使用心肌插入电极,观察了分别采用S_s法和S_t法测定的兔心室不应期强度间期关系特点及其关系,并观察了改变S_t的刺激参数特征对S_t引起的心室不应期变化的影响及S_s对心室有效不应期的影响。实验结果表明:低强度、高频、长持续时间的S_t能最大程度地延长心室不应期;具备以上刺激参数特征的S_t可能是用来终止折返性心动过速的最佳S_t。     

链霉素对兔左心室后负荷增加所致电生理变化的影响

目的:探讨左心室后负荷增加引起的心脏电生理变化及链霉素和维拉帕米对其的影响。方法:采用部分夹闭家兔升主动脉根部以增加左室后负荷的在体心脏模型,观察后负荷增加前后心肌相对不应期(RRP)、有效不应期(ERP)、单相动作电位时程(MAPD₉₀)和室颤阈(VFT)的变化,并比较了链霉素和维拉帕米对这些电生理参数变化的影响。结果:后负荷上升引起RRP、ERP和MAPD₉₀缩短,VFT下降(P<0.01);链霉素可有效抑制后负荷增加引起的心脏电生理变化;而维拉帕米除可提高VFT外(P<0.01),对后负荷增加引起RRP、ERP和MAPD90的缩短没有明显影响(P＞0.05)。结论:结果提示牵张激活性离子通道的活化可能参与后负荷增加引起的心脏电生理变化过程,且链霉素通过抑制这种离子通道的活化而发挥作用。     

非兴奋性电刺激对正常及心肌梗死兔心功能的影响及其作用的局部性

目的:观察于绝对不应期发放电刺激对正常和心肌梗死(MI)兔在体心脏心功能的影响及其对心肌作用的局部性。方法:64只家兔随机分为正常组和MI组两大组,每组又分为前壁和后壁两组。复制MI模型,4周后每组开胸,窦性心律下,分别于前壁组和后壁组的左心室前壁和后壁,发放绝对不应期方波电刺激(CCM)。观察左心室收缩压(LVSP)左心室舒张末压(LVEDP)及其微分(±dp/dt_max)的变化。结果:正常组前壁和后壁CCM刺激时LVSP及+dp/dt_max均显著大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值大于刺激前(P<0.05),且不同部位的CCM刺激对心功能的影响不同,左心室前壁的上述作用大于后壁(P<0.05);MI组前壁和后壁CCM刺激时LVSP及+dp/dt_max亦大于刺激前(P<0.05),LVEDP低于、-dp/dt_max负值亦大于刺激前(P<0.05),但前后壁两组之间无显著差别(P＞0.05)。结论:于绝对不应期发放电刺激能明显增强正常和MI后心肌的收缩和舒张功能,CCM刺激对心肌的作用是局部性的。     

急性心肌梗塞早期心室易损性的电生理实验研究

本文采用Ｓ１－Ｓ２程控电刺激方法同时测定心室易期和室颤阈，并结合其它有关电生理指标，评价了急性心肌梗塞早期心室易损性。结果表明，急性心肌梗塞早期，心室易损期明显延长，室颤阈显著下降，起搏阈值降低，有效不应期缩短，强度间期曲线下移，心室易损期外缘向Ｔ波方向延伸，联律间期与折回间期呈负相关。根据上述指标分析了急性心肌梗塞早期室性心动过速和／或心室颤动产生的电生理机制以及心室易损期在ｒｏｎＴ室性早搏触发     

犬右心室M细胞复极1期瞬间外向钾电流特性的研究

目的:探讨犬右心室M细胞复极1期瞬间外向钾电流(Ito₁)的电生理特性。方法:应用膜片钳技术,对犬右心室M细胞复极1期Ito₁离子流的电流强度、动力学过程和动作电位切迹进行定量观察。结果:(1)犬右心室M细胞Ito₁离子流的激活过程呈明显的电压依赖性,在37℃、刺激周长为5000ms、去极化电压为0mV和+70mV时,其峰值Ito₁离子流的强度和密度分别为(690±380)pA和(3130±1910)pA,差异显著(P＜0.01);(2)犬右心室M细胞Ito₁离子流具有明显的频率依赖性,在37℃、去极化试验电压为+70mV和基础刺激周长为500ms及5000ms时,Ito₁离子流的强度分别为(1690±830)pA和(3130±1910)pA,差异显著(P＜0.01),并与动作电位的"尖峰-和穹隆"幅度的增加相对应。结论:强大的Ito₁离子流及其介导的"尖峰-和穹隆"状动作电位图形是犬右心室M细胞一个突出的电生理特点之一。     

膈神经传导时间在麻醉复苏中的应用

目的:探讨膈神经传导时间(PNCT)在麻醉复苏过程中对膈肌功能的监测作用。方法: 对8例手术病人观察全麻使用肌松药前后颤搐性跨膈压(Pdi_(t))和PNCT的变化。结果: 8例手术病人在全麻前:Pdi(t)为(23.7±2.4) cmH₂O,左、右侧PNCT分别为(5.7±1.3) ms和(5.6±0.9) ms;全麻使用肌松药后:Pdi_(t)下降到(11.5±3.4) cmH2O(下降率51.5%,P＜0.01),而左、右侧PNCT则分别延长为(6.1±1.3)ms和(6.4±0.6)ms,并随Pdi_(t)的恢复而逐步缩短。结论:肌松药诱发膈肌无力和引起双侧PNCT延长,且PNCT随着Pdi_(t)的恢复而缩短; PNCT的测定有助于间接监测全麻使用肌松药期间膈肌肌力的动态变化。     

慢性心力衰竭兔心室结构重构导致心功能和电生理异常及其意义探讨

目的:探讨慢性心力衰竭(心衰)兔心室结构重构导致心功能和电生理异常及其意义。方法:25只雄性新西兰大耳白兔,其中14只制备慢性心衰模型(心衰组),最终造模成功10只,另11只作为对照组(手术时1只气胸致兔死亡,余10只进入实验)。利用Masson染色技术观察各组心室肌组织间质胶原纤维并计算间质胶原容积系数(CVF),透射电镜观察心室肌细胞超微结构改变。监测各组兔M型超声心动图和Ⅱ导心电图,观察左心室射血分数(LVEF)、主动脉最大流速(Av_(max))、左心室舒张末期内径(LVEDd)和室间隔厚度(IVST)以及心率、PR间期、QT间期和ST段,评价心功能和电生理变化。程控刺激方法观察刺激周长(BCL)为150ms和200ms时心室有效不应期(ERP_(150)和ERP_(200))以及各自有效不应期离散度(dERP_(150)和dERP_(200))。评价Burst-pacing诱发室性心律失常(VA)的BCL和诱发率。结果:与对照组比较,心衰组心室肌组织中胶原纤维明显增多,CVF显著升高(P0.01)。心室肌细胞排列不规则,出现断裂坏死,且超微结构异常改变,心房肌细胞核固缩,线粒体排列杂乱、肿胀或出现空泡,肌小节损伤严重。心衰组LVEF和Av_(max)显著下降(P均0.05),LVEDd明显延长,IVST变薄(P均0.01),且心率明显减慢,PR和QT间期均显著延长(P均0.01),ST段明显下移(P0.05)。与对照组比较,心衰组兔ERP_(150)和ERP_(200)均显著延长, dERP_(150)和dERP_(200)均明显增大,且心衰兔被诱发VA的BCL显著延长,VA诱发率明显加大(P均0.01)。结论:心衰兔心室组织发生明显的病理性改变和超微结构异常的结构重构,造成心室功能下降和电生理紊乱,易于诱发VA。     

卡托普利对兔急性心肌梗塞早期再灌注心室肌易损性的影响

目的：观察卡托普利对兔急性心肌梗塞（AMI）早期再灌注心室易损性的改变，探讨卡托普利对AMI早期再灌注心律失常的影响。方法：采用S1-S2程控电刺激方法同时测定开胸不阻断冠脉的无心肌缺血组（假手术对照组）、无心肌缺血用卡托普利灌流组（卡托普利组）、AMI早期缺血-再灌注对照组（再灌注对照组）和用卡托普利灌流早期缺血-再灌注组（再灌注卡托普利组）对家兔心室易损期（VVP）、室颤阈（VFT）、舒张阈（DT）、有效不应期（ERP）、T波顶点与VVP外缘处的时间关系（T_T-VVP）等电生理指标，卡托普利灌流速度0.1 mg·kg^-1·min^-1。结果：VVP、VFT、DT、ERP和T_T-VVP在假手术对照组和卡托普利组分别为(8.12±2.43) ms、(2.49±0.76) μJ、(3.62±0.59) V、(178.67±16.43) ms、(51.32±8.76) ms和(8.64±2.85) ms、(2.41±0.80) μJ、(3.85±0.58) V、(180.25±14.87) ms、(50.35±8.91) ms，组间比较皆无显著差异（P>0.05），再灌注对照组分别为(85.37±20.65) ms、(0.16±0.13) μJ、(2.25±0.48) V、(112.65±13.61) ms和(10.72±4.81) ms，再灌注卡托普利组分别为(56.34±15.21) ms、(0.26±0.14) μJ、(2.91±0.61) V、(137.83±15.24) ms和(14.84±7.89) ms；假手术对照组与再灌注对照组和再灌注卡托普利组比较有显著差异（P<0.01），再灌注对照组与再灌注卡托普利组比较亦有显著差异（P<0.01）。结论：卡托普利对无缺血心肌影响不明显；缺血-再灌注能明显增加急性心肌梗塞早期再灌注室性心动过速和/或心室颤动的发生，卡托普利对再灌注室性心动过速和/或心室颤动的发生有抑制作用。     

心通胶囊对心肌缺血大鼠心室肌亚硝酸盐和cGMP含量的影响

目的:探讨心通胶囊对实验性大鼠心肌缺血的预防效果及其与一氧化氮形成的相关机制。方法:应用垂体后叶素致大鼠急性心肌缺血模型,以心电图上ST段的抬高作为心肌缺血的指标。测定大鼠心肌缺血心室肌组织一氧化氮(NO)代谢产物(NO₂^-/NO₃^-)和cGMP含量。结果:急性心肌缺血组大鼠的心室肌组织NO₂^-/NO₃^-和cGMP含量分别为(486±59)nmol/gprotein和(0.38±0.08)nmol/gprotein,明显低于正常对照组大鼠的NO₂^-/NO₃^-和cGMP含量,有显著差异(P＜0.01);急性心肌缺血前使用心通胶囊组的心室肌组织NO₂^-/NO₃^-和cGMP含量为(845±105)nmol/gprotein和(0.51±0.10)nmol/gprotein明显高于缺血组(P＜0.01)。与正常组比较,缺血组的心电图ST段抬高明显抬高(P＜0.05);心肌缺血前使用心通胶囊,可使心肌缺血得以改善。结论:心通胶囊提高急性心肌缺血大鼠心室肌组织的NO含量,进而使cGMP含量升高,达到改善心肌缺血的作用。     

Rate-dependent electrical, contractile and restitution properties of isolated left ventricular myocytes in guinea-pig hypertrophy

Left ventricular hypertrophy predisposes to sudden cardiac death (SCD) and studies of human SCD suggest that the antecedent heart rate (HR) is usually < 100 beats min(-1). This is surprising in view of the known association between adrenergic receptor stimulation and SCD which by itself would suggest that it is more likely to occur from high rather than low HR. We therefore hypothesized that there may be electrical or mechanical abnormalities present in myocytes isolated from animals with left ventricular hypertrophy that predispose to SCD at low stimulation frequencies but which may not be present at high HR. Mild left ventricular hypertrophy was induced in guinea-pigs by infra-renal aortic banding. Electrical and mechanical properties of isolated myocytes were studied at different stimulation frequencies between 0.1 and 3 Hz. Action potential duration (APD) is prolonged in hypertrophy at stimulation frequencies < 1 Hz but not at faster rates. Contraction size, time-to-peak contraction (TTPC) and half-relaxation time are greatly enhanced in hypertrophy at all frequencies between 0.1 and 3 Hz. Electrical (50.3 +/- 5.2 ms in hypertrophy and 78.4 +/- 12.1 ms in control, P < 0.03) and mechanical (205 +/- 16 ms for hypertrophy and 266 +/- 24 ms for control cells, P < 0.03) restitution time constants are quicker in hypertrophy. The finding of APD prolongation at low but not at high frequencies is consistent with the finding that SCD arises from low and not high HR. This data supports the role of abnormal repolarization in SCD.     

Influence of right ventricular pre- and afterload on right ventricular ejection fraction and preload recruitable stroke work relation.

When right ventricular (RV) afterload is abnormally increased, it correlates inversely with right ventricular ejection fraction (RVEF). We tested, whether this would be different with normal afterload. Additionally, we investigated whether previous studies on the slope of RV preload recruitable stroke work (SW) relation, which used rather non-physiological measures to change RV preload, could be transferred to more physiological loading conditions. RV volumes were determined by thermodilution in 16 patients with stable coronary artery disease and normal pulmonary artery pressure (PAP) at rest. Pre- and afterload were varied by body posture, nitroglycerin (NTG) application and by exercise at different body positions. At rest, the change from recumbent to sitting position decreased PAP, cardiac index (Ci), RV diastolic and systolic volumes, and RVEF. Additionally, mean pulmonary artery pressure (MPAP) correlated positively with both RVEF and cardiac index. After correction for mathematical coupling, the RV preload recruitable SW relation was: right ventricular stroke work index (RVSWi) (103 erg m-2)= 8.1 x (RV end-diastolic volume index -4.9), with n=96, r=0.57, P< or =0.001. Exercise abolished this correlation and led to an inverse correlation between RV end-systolic volume (ESV) and RVSW. In conclusion, (i) RVEF correlates positively with RV afterload when afterload varies within normal range; (ii) the slope of the RV preload recruitable SW relation, which is obtained at steady state under normal loading conditions, is substantially flatter than previously described for dynamic changes of RV preload. With increasing afterload, preload loses its determining effect on RV performance, while afterload becomes more important. This puts earlier assumptions of an afterload independent RV preload recruitable SW relation into question.     

Sarcomere length during contraction of isolated guinea-pig ventricular myocytes

 An improved method was developed for measuring sarcomere length (SML) during twitch contractions of single cardiac ventricular myocytes, using a charge-coupled photodiode array self-scanning at a rate of 1.5 ms/element. The average resting SML of 111 cells was 1.88±0.04 μm (mean ±SD). When contractions were triggered by action potentials under perforated-patch conditions, the time course of SML shortening closely followed changes in cell length. A large variation was observed in contraction time course between myocytes, some cells having a phasic component with a duration at 50% shortening (full-width at half-maximum; FWHM) of approximately 40 ms, while others shortened more slowly (FWHM of phasic component @100 ms). FWHM was highly correlated with relaxation half-time, but with neither action potential duration nor resting SML. The kinetics of slowly contracting cells could not be converted to the rapid type by using conditioning trains or applying isoprenaline. The steady-state SML/pCa relation in ventricular myocytes was measured by applying solutions of various pCa immediately after localized punctures of the surface membrane using a focal laser beam. The Hill coefficient, n _H, was @4–5 and K _1/2@400–500 nM, but there was no evidence of two populations of cells with different Ca²⁺ sensitivities. Received: 28 September 1998 / Received after revision: 11 December 1998 / Accepted: 14 December 1998     

Effects of ventricular pacing protocol on electrical restitution assessments in guinea-pig heart

The steep slope of the rate adaptation of ventricular action potential duration (APD) is thought to indicate profibrillatory tendency. In cardiac patients, APD restitution is commonly assessed by extrasystolic (S(1)-S(2)) stimulations rather than dynamic pacing, because the latter may provoke myocardial ischaemia. In this study, ventricular APD and effective refractory period (ERP) were measured in perfused guinea-pig hearts to determine whether S(1)-S(2) stimulations and dynamic pacing may have similar value in APD restitution assessments aimed to predict arrhythmic risk. The maximal restitution slope was greater upon S(1)-S(2) stimulation than dynamic pacing at the epicardium (S(1)-S(2), 1.2 ± 0.08; dynamic, 0.72 ± 0.06; P = 0.0004) and endocardium (S(1)-S(2), 1.45 ± 0.08; dynamic, 0.95 ± 0.06; P = 0.0003). This difference was partly accounted for by an effect of the previous pacing history, as evidenced by flattening of APD restitution upon reductions in the regular beating interval prior to S(2) application. Furthermore, shorter ERP than APD relationships enabled ventricular capture at shorter diastolic intervals during S(1)-S(2) stimulation than dynamic pacing at the epicardium (S(1)-S(2), -1 ± 3 ms; dynamic, 35 ± 3 ms; P < 0.0001) and endocardium (S(1)-S(2), -1 ± 7 ms; dynamic, 38 ± 3 ms; P < 0.0001), thereby contributing to greater maximal restitution slope values. Flecainide, a Na(+) channel blocker, increased the ERP-to-APD ratio and eliminated early premature beats (diastolic interval of ～0 ms), thereby flattening the S(1)-S(2) restitution curve, but had no effect on dynamic restitution. In hypokalaemia-induced arrhythmogenicity, a reduction in ventricular fibrillation threshold was paralleled by increased steepness of dynamic APD restitution, while no change in the maximal restitution slope was revealed by S(1)-S(2) stimulations. In summary, changes in electrical restitution obtained from extrasystolic stimulations may dissociate from those revealed by dynamic pacing. These findings therefore challenge the value of electrical restitution assessments based on extrasystolic stimulation alone, as commonly performed in the clinical setting.     

Electrical restitution in rat ventricular muscle

The mechanism of electrical restitution was studied in isolated rat ventricular muscle using drugs that inhibit specific ion currents. The effect of transient changes in cytosolic Ca concentration and Na/Ca exchange in relation to the restitution process was also studied in single ventricular cardiomyocytes. Conventional microelectrode techniques were applied to record action potentials having gradually increasing coupling intervals, each evoked following a train of stimuli with a frequency of 1 Hz. Ion currents were recorded from enzymatically isolated cells using the whole cell patch clamp technique. Ca transients were monitored in myocytes loaded with the fluorescent dye, indo-1. The electrical restitution process in multicellular rat ventricular preparations at 37 °C was described as a sum of three exponential components: an early positive component, a subsequent fast negative component and a late negative component, having time constants of 21.9±1.9, 73.1±6.0 and 1053±61 ms, respectively (n=9). Inhibition of the transient outward K current, the delayed rectifier K current, or the chloride current did not substantially alter these time constants. The early positive and fast negative components were fully abolished by nifedipine or MnCl₂. In the presence of caffeine, the fast negative component was absent, while the time constant of the early positive component increased to 39.5±5.8 ms (n=5). In single myocytes loaded with indo-1, the Ca transients decayed with a time constant of 151±12 ms at room temperature (n=5). These Ca transients were accompanied by inward current tails, identified as a Na/Ca exchange current, having a decay time constant of 140±4.5 ms. It is concluded that electrical restitution in rat ventricular muscle is relatively little affected by recovery from voltage-dependent inactivation of ion channels, it is rather governed by transient changes in cytosolic Ca concentration possible via Ca-dependent inactivation of the L-type Ca current and activation of the Na/Ca exchange current.     

心脏神经节丛在诱发房颤中的作用

目的:心脏自主神经系统包括内在神经系统和外在神经系统。心房颤动(房颤)是最常见的持续性心律失常之一,心脏内在神经系统是否能独立诱发房颤尚不十分清楚。本实验旨在观察心脏内在神经系统在房颤诱发中的独立作用。方法:采用10只实验用犬,建立Langenfroff离体灌流心脏模型,在基础状态下,刺激心脏神经节丛时,分别测量心房有效不应期、肺静脉有效不应期以及房颤诱发率。结果:刺激心脏神经节丛能够缩短心房有效不应期(基线:(129±11)ms;刺激:(105±17)ms;P<0.05),以及缩短肺静脉有效不应期(基线:(136±12)ms;刺激:(112±14)ms;P<0.05)。同时能显著增加房颤的诱发率(基线:7%;刺激:93%;P<0.05)。结论:在完全去除心脏外在神经支配的情况下,心脏内在神经系统张力增高,能够独立诱发房颤。心脏内在神经系统组成的局部环路在房颤的产生中起重要作用。     

西洋参茎叶总皂苷通过抑制内质网应激相关细胞凋亡减轻大鼠急性心肌梗死后心室重构

 目的： 研究西洋参茎叶总皂苷 (Panax quinquefolium saponin, PQS)对大鼠急性心肌梗死(AMI)后心室重构的作用及其机制。方法： 健康雄性SD大鼠90只,随机分为假手术 (sham) 组、AMI组、牛磺酸 (300 mg·kg-1·d-1) 组及PQS (50、100和200 mg·kg-1·d-1) 组 (n=15)。结扎大鼠左冠状动脉前降支复制AMI模型。术后第2天开始,各用药组用饮用水10 mL·kg-1·d-1溶解药物灌胃,sham组及AMI组予等量饮用水灌胃。术后4周,超声心动图检测左室结构及功能变化;TTC染色法测定心肌梗死范围;比色法测定非梗死区心肌组织羟脯氨酸含量;TUNEL法检测非梗死区心肌细胞凋亡率,Western blotting检测内质网应激分子葡萄糖调节蛋白78 (GRP78)、钙网蛋白 (CRT)、C/EBP同源蛋白 (CHOP) 及凋亡相关蛋白Bcl-2、Bax的表达。结果： 与AMI组比较,PQS低、中、高剂量组左室收缩末期内径分别降低17.2%、20.3%和38.8%,左室舒张末期内径分别降低8.9%、9.0%和17.2%,左室收缩末期容积分别降低31.4%、38.5%和66.9%左室舒张末期容积分别降低18.2%、18.8%和34.2%,射血分数分别升高44.9%、60.1%和118.0%,左室短轴缩短率分别升高55.4%、71.0%和148.0%,梗死范围分别降低4.6%、39.5%和55.8% (均P<0.05);非梗死区心肌组织羟脯氨酸含量分别降低34.5%、35.9%和48.7% (P<0.01)。与AMI组比较,PQS 200 mg·kg-1·d-1组心肌细胞凋亡率降低27.3% (P<0.05),GRP78和CRT蛋白表达分别降低79.9%和80.8% (P<0.01),CHOP和Bax分别降低42.5%和53.1% (P<0.01),Bcl-2表达升高1.1倍 (P<0.01);上述保护作用的程度与内质网应激抑制剂牛磺酸相近 (P>0.05)。Spearman相关分析发现CHOP蛋白表达与心肌细胞凋亡率显著正相关 (r=0.797, P<0.01)。结论： PQS剂量依赖性减轻大鼠心肌梗死后心室重构,其机制与抑制CHOP介导的内质网应激凋亡通路有关。