尼群地平对豚鼠乳头状肌电生理特性的影响

目的：探讨尼群地平对心肌电生理特性的影响及药理学机制,为该药在临床应用上的推广提供基础理论依据,方法;采用常规微电极技术观察尼群地平对离体豚鼠乳头状肌快反应动作电位,收缩力的影响。结果：尼群地平对快Ｎａ＾＋,通道无作用,对平台期慢Ｃａ＾２＋,通道有双重效应。结论：尼群地平有抑制漫     

尼群地平对豚鼠乳头状肌电生理特性的影响

目的：探讨尼群地平对心肌电生理特性的影响及药理学机制,为该药在临床应用上的推广提供基础理论依据。方法：采用常规微电极技术观察尼群地平对离体豚鼠乳头状肌快反应动作电位、收缩力的影响。结果：尼群地平对快Ｎａ＋通道无作用（Ｐ＞０．０５）,对平台期慢Ｃａ２＋通道有双重效应（Ｐ＜０．０１）。结论：尼群地平有抑制慢Ｃａ２＋通道的作用同时对缺血性心肌有保护作用     

中药康心平对家兔在体心肌单相动作电位的影响

目的:观察中药康心平对家兔在体心肌单相动作电位的影响,以探讨其抗心律失常与否及其可能的作用机制。方法:12只健康家兔,随机分为康心平组和生理盐水组,分别给予康心平和生理盐水。观察给药前及给药后30、60、90、120min动作电位变化情况。采用心肌单相动作电位记录技术观察动作电位时程复极50%、90%(MAPD50、MAPD90),有效不应期(ERP),动作电位幅度(MAPA)及ERP/MAPD90比值。结果:中药康心平对家兔在体心肌单相动作电位时程MAPD90有缩短作用(P<0.05),能使MAPA降低(P<0.01),增大ERP/MAPD90比值(P<0.01),且上述指标无明显时间依赖性改变,但对MAPD50、ERP无明显影响。生理盐水组的各项观察指标给药前后均无明显改变。结论:康心平有抗心律失常作用,其机制可能与阻滞钠离子内流,促进钾离子外流有关,并具有心肌电稳定作用。     

盐酸哌替啶在足月胎儿分娩时对胎心和子宫收缩的影响及分析

1资料与方法 选择无合并症的正常足月初产妇,临产时精神紧张,睡眠不好,疲劳乏力,肛查子宫口开1～3 cm者40例,年龄22～32岁,平均26.2岁,孕周38～41周. 外阴、阴道消毒后,行人工破膜,然后置胎心内监测仪,用螺旋电极固定于胎儿头皮上,将子宫腔压力导管从子宫口进入,越过胎头,景于子宫腔内,导管用注射用水充满,并连接于监护仪上,监护子宫腔内压力,内监护时间为150 min以上,肌内注射盐酸派替啶前监护30 min,用药后连续监测120 min,观察用药后30,90,120 min胎心率变化.     

盐酸和氢氧化钠对豚鼠各段小肠平滑肌活动的影响

目的观察盐酸和氢氧化钠对豚鼠各段小肠平滑肌活动的影响。方法制备离体小肠平滑肌标本,放置于灌流浴槽中,观察其收缩活动的影响。结果与对照组相比,盐酸对十二指肠和空肠上段平滑肌自发收缩活动有增强效应(P<0.05),而对回肠下段平滑肌的自发收缩活动有抑制效应(P<0.05),氢氧化钠对空肠和回肠收缩活动均有抑制效应(P<0.05)。结论盐酸对豚鼠十二指肠和空肠平滑肌自发收缩活动有增强作用,而氢氧化钠对空肠和回肠的活动则有减弱作用。     

异丙酚、依托咪酯对兔离体气管平滑肌收缩力的影响

目的：研究异丙酚、依托咪酯对气道平滑肌张力的直接影响。方法：采用电刺激兔离体气管平滑肌的方法。结果：接近于临床有效血浆浓度的异丙酚（10-4mol/L)、依托咪酯（10－5mol/L)可显著抑制气道平滑肌的收缩,且呈剂量依赖性,其作用机制可能和外钙内流和内钙释放有关。结论：对有气道高反应的患者可安全地选用异丙酚、依托咪酯作为静脉麻醉药,并有可能起到一定的治疗作用。     

心肌收缩力调节器的研究进展

心肌收缩力调节器（CCM）是应用于心力衰竭患者的一种新的治疗方法,其通过调节心肌细胞中钙离子的浓度以及调节自主神经功能来增强心肌收缩力,从而改善心力衰竭患者的症状、运动耐受性、生活质量、心肌收缩力以及心室重塑,并且不增加心肌耗氧量,CCM尤其适用于LVEF为35%～45%的患者。CCM的广泛应用可以给心力衰竭患者带来新的希望。该文对CCM的作用机制、适用人群、临床疗效及安全性进行综述,以期为临床医师提供参考。     

豚鼠离体右心房自律性及收缩特性与葛根素的影响

目的:观察葛根素对豚鼠离体右心房自律性及收缩特性的影响,并探讨其作用机制。方法:实验于2005-07在赣南医学院药理实验室(省级重点实验室)完成。健康豚鼠6只,用锤子击打头部至昏迷,剖开胸腔迅速取出心脏,在持续充纯氧的条件下,分离右心房。将右心房肌悬挂在含20mLKrebs液的麦氏浴槽中,恒温(37±0.5)℃,持续通入纯氧。右心房稳定45min后,测定其正常自动节律、收缩幅度、收缩速度和舒张速度作为给药前对照,然后累积加入葛根素(终浓度为0.0036,0.012,0.036,0.12,0.36,1.2,3.6mmol/L),每次给药间隔5min,测定其自动节律、收缩幅度、收缩速度、舒张速度的变化。结果:葛根素可降低豚鼠离体右心房的自律性、收缩幅度、收缩速度、舒张速度,且有明显的剂量依赖性。结论:葛根素可抑制豚鼠离体右心房的自律性,明显降低豚鼠离体右心房的收缩幅度、收缩速度、舒张速度,且有明显的剂量依赖性,其作用机制可能与抑制钙离子通道及钠离子通道有关。     

红景天对心脏血液动力学及心肌收缩力的影响

背景：红景天具有抗衰老、抗疲劳、提高人体免疫力的作用，并可缓解心绞痛。目的：研究红景天对心脏的血液动力学及心肌收缩力的影响，并探讨其机制。设计：以实验动物为研究对象的观察对比研究。单位：一所医科大学的生理学教研室。材料：实验于2001—01／2001—04在广西医科大学生理学教研室心血管研究实验室进行。新西兰大白兔30只，雌雄不限，体质量1．9～2．3kg，随机分为2组，对照组(生理盐水4mL／kg)和红景天(诺迪康)组(0．5g／4mL&;#183;kg^-1)，每组15只。普通野生青蛙100只，体质量120～160g，随机分为4组，即生理盐水对照组、诺迪康小剂量组(血药浓度209mg／L)、诺迪康中剂量组(血药浓度418mg／L)和诺迪康大剂量组(血药浓度627mg／L)，每组25只。方法：运用ms2000多媒体生物信号分析系统，经Straub法制备离体蛙心灌流标本并检测心脏活动，利用血液动力学方法检测大白兔的心室活动等相关指标。主要观察指标：两组家兔心脏血液动力学变化的比较，不同剂量诺迪康对离体蛙心工作影响的比较。结果：各诺迪康组的心肌收缩力比对照组的明显增强(F=8．939，P&;lt;0．01)，209，418，627mg／L诺迪康组的心肌收缩力呈现递增趋势，分别增强52．3％，70．1％，86．4％，但各实验组间未达显著差异(P&;gt;0．05)；各组之间的蛙心心率也无显著性差异(P&;gt;0．05)。大白兔血液动力学方面，诺迪康组的左室内压最大上升速率增加了22．1％(F=6．259，P&;lt;0．05)，平均动脉压降低了8．2％(F=5．688，P&;lt;0．05)．其他各指标在对照组与诺迪康组之间均未见显著变化。结论：诺迪康能增强心肌收缩力，加速心肌的收缩速度但对心肌舒张无明显影响，同时有降低平均动脉压的作用。     

养心颗粒含药血清对豚鼠心室肌细胞外向延迟整流K电流的影响

目的观察养心颗粒含药血清对单个豚鼠心室肌细胞动作电位、外向延迟整流K电流的影响,探讨养心颗粒在离子通道水平的药理机制。方法胶原酶急性酶解法分离单个豚鼠心室肌细胞,实验分为空白对照组、养心颗粒含药血清2%、4%、8%组,采用全细胞膜片钳的方法,记录养心颗粒对动作电位、外向延迟整流K电流的影响。结果养心颗粒4%、8%组可延长APD 50和APD 90,其对应峰值钾电流分别为(15.33±1.56)、(14.33±1.11)PA/PF,与对照组比较,差异有统计学意义。养心颗粒2%组则无明显影响。结论养心颗粒通过抑制延迟整流K+通道来延长ADP50,ADP90,从而延长有效不应期,发挥其抗心律失常的作用,且可能有一定的浓度依赖性。     

机械牵张对缺血预适应心肌动作电位的影响

目的 研究在模拟缺血-再灌流条件下机械牵张对缺血预适应(ischemic preconditioning，IPC)的离体豚鼠乳头肌动作电位的影响。方法 应用细胞内标准玻璃微电极技术，记录并观察一定牵张力(200mg强度)作用下IPC乳头肌细胞动作电位(AP)的变化。结果牵张可使单纯缺血-再灌流(IR)组和IPC组在整个缺血期除兴奋传导时间(cT)明显延长外，Vmax、RP、APA、APD50、APD90等参数明显减小，但对IPC组的影响较小。IPC限制了复氧再灌流时APD50、APD90的过度延长，并导致RP和CT增大；而牵张可使两组动作电位的Vmax、RP、APA、APD50降低，CT和APD90延长，但对IPC组的影响较小。链霉素可抑制机械牵张对IPC组上述参数的影响。结论 在模拟缺血一再灌流条件下，IPC乳头肌对机械牵张的耐受性增强，可能具有抗心律失常效应；链霉素可抑制牵张对IPC心肌动作电位的影响。     

TMB-8 as a pharmacologic tool in guinea pig myocardial tissues. I. Effects of TMB-8 on force of contraction and on action potential parameters in atrial and papillary muscles.

The compound 8-)N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) had been introduced as an intracellular Ca++ antagonist. We have studied the effects of TMB-8 on electrical and mechanical activity of isolated cardiac tissues in order to estimate its spectrum of action in heart muscle. In spontaneously beating right atria of the guinea pig, TMB-8 (1-100 microM) had a negative chronotropic effect. In left atria, TMB-8 (1-100 microM) induced a frequency-dependent biphasic inotropic effect: A transient increase in force of contraction was followed by a sustained decrease; the latter could be antagonized partially by an increase in [Ca++]o. TMB-8 prolonged the time-to-peak force. At high concentrations of TMB-8 (greater than 10 microM), the electrical stimulation threshold was elevated. TMB-8 (20 microM) competitively inhibited the positive inotropic effect of Bay K 8644 and reduced the magnitude of the positive inotropic and/or chronotropic effects of veratridine, (-)-isoproterenol, forskolin, histamine and (-)-phenylephrine. TMB-8 (30 microM) prolonged the action potential duration (APD) [in particular at 90% of repolarization (APD90)] and the refractory period, and decreased the AP amplitude and Vmax. In right ventricular papillary muscles, TMB-8 (30 microM) shortened the APD (APD20 = APD50 greater than APD90) and the refractory period but hardly affected the AP amplitude and Vmax. The resting membrane potential remained unchanged in both tissues. These findings suggest that in addition to interference with the Ca++ release from the sarcoplasmic reticulum, TMB-8 also affects the membrane conductances for cations.     

冲击波对兔复合肌肉动作电位及肌组织形态学的影响

目的:评估单侧小腿后方放散式体外冲击波(radial extracorporeal shock wave treatment,rESWT)处理后兔的双侧腓肠肌复合肌肉动作电位和肌组织形态学。方法:体重2±0.2kg雄性新西兰兔63只,其中3只兔进行预实验确定rESWT强度,对剩余60只兔左小腿三头肌肌腹最粗大的位置稍偏外侧行强度1.5bar,频率10Hz的2000次冲击。分为6组,在放散式体外冲击波处理当天和处理后第1、2、4、6、8周在麻醉情况下用日本光电MEB-9100K肌电图仪记录双侧腓肠肌外侧头复合肌肉动作电位,比较两侧波幅、潜伏期,每组抽取一个样本对其双侧腓肠肌外侧头行重复电刺激,记录不同频率刺激后波幅衰减情况。肌电图检查完成立即取下双侧腓肠肌外侧头肌组织,冰冻切片后进行HE染色,观察肌肉组织形态学变化。结果:前三组实验兔(处理当天和处理后第1、2周)实验侧动作电位波幅降低,与对照侧比较差异显著(P0.05),后三组实验兔实验侧动作电位波幅与对照侧无明显差异。所有实验兔双侧动作电位潜伏期差异不明显,HE染色未见肌组织形态学明显异常。结论:运用rESWT对兔小腿三头肌肌腹最肥大处行强度1.5bar,频率10Hz的2000次冲击可降低其复合肌肉动作电位的波幅但作用持续时间较短且对肌组织形态学不会产生较大影响。     

Effects of acebutolol and other structurally related beta adrenergic blockers on transmembrane action potential in guinea-pig papillary muscles

The effects of acebutolol (13-134 microM), pindolol (10-50 microM), oxprenolol (16-66 microM) and (+) and (-)-K?592 (39-193 microM) on action potentials were investigated in isolated guinea-pig papillary muscles. All the drugs reduced Vmax at 1 Hz, dose-dependently. The reduction was less prominent with prolongation of the interstimulus interval until there was virtually no reduction. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.1 Hz or in responses after interrupting driving stimuli at 1 Hz. Time constants of recovery thus estimated were 12 to 14 sec for acebutolol and pindolol, 3 to 6 sec for oxprenolol and 0.7 to 1 sec for (-)-K?592. The reduction of Vmax was rate dependent for all the drugs, and at 5 Hz, the order of potency was oxprenolol > pindolol > acebutolol congruent to (-)- and (+)-K?592. The most potent was alprenolol (3.5-17.5 microM), which we have already studied in detail. At 1 Hz or lower, the action potential duration was shortened by application of all the compounds mentioned except acebutolol, but tended to be longer than in control, at higher rates for all the drugs. We conclude that molecular bulkiness and dimension may be associated with the time constant of recovery, whereas the potency at high driving rates may be correlated roughly linearly with the lipid solubility of the agents.     

Electrophysiological Effects of Intrapericardial Infusion of Endothelin-1

Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients undergoing open-heart surgery. ET-1 has been suggested to have direct arrhythmogenic effect on myocardium. The aim of the present study was to examine the putative arrhythmogenic effect of intrapericardial infusion of ET-1 in anesthetized dogs (n=15).
In preliminary experiments, ET-1 (0.125–1.0 nmol/min, n=7) was infused into the closed pericardial sack for 40 min. ET-1 induced non-sustained and/or sustained ventricular tachyarrhythmias in all but the lowest dose. For detailed arrhythmia analysis in addition to standard ECG ventricular endocardial and epicardial monophasic action potentials (MAP) were recorded. ET-1 (0.250 nmol/min, n=7) induced mono- and polymorphic ventricular tachycardias, which (degenerated into ventricular fibrillation in two instances. Moderate if any ischemic signs could be detected before the onset of arrhythmias. The arrhythmias spontaneously disappeared in all instances with the exception when ventricular fibrillation terminated the experiment. QT interval (260±23ms vs. 317±31ms, P < 0.05), and endo- and epicardial MAPD₉₀ (at 300 ms cycle length) prolonged significantly (in average 182±12ms vs. 224±25ms, P < 0.05). Using MAP recording afterdepolarizations were detected in three instances. In control animals (n=3) arrhythmias were not observed and all electrophysiological parameters remained unchanged.
The present results show that intrapericardial administration of ET-1 can induce ventricular arrhythmias in dogs. The arrhythmogenic effect of ET-1 may be based on prolongation of MAP duration and development of afterdepolarizations. However, the elucidation of the precise mechanism needs further investigation.     

Lubeluzole-induced prolongation of cardiac action potential in rabbit Purkinje fibres

Lubeluzole, a novel neuroprotective compound, has been associated with cases of QT interval prolongation but its effects on the cardiac action potential have not been described to date. Thus, the electrophysiological effects of lubeluzole were studied in rabbit isolated Purkinje fibres. The results demonstrate that lubeluzole (0.001-1 microM) concentration-dependently lengthened action potential duration at 50% and 90% of repolarization (APD50 and APD90) without significantly modifying other parameters. Furthermore, APD lengthening induced by lubeluzole was not significantly decreased by reducing the basic cycle length (from 3,000 to 1,000 ms). The results demonstrate that lubeluzole potently and concentration-dependently increases APD from 0.01 microM, consistent with class III-type antiarrhythmic actions, which is likely to underlie QT interval prolongation induced by the drug.     

The effect of acoustic cavitation on the contraction force and membrane potential of rat papillary muscle

In experiments on isolated rat papillary muscles an acoustic cavitation induced by continuous wave focused ultrasound (543 kHz with intensity up to 3 W/cm2) was found to result in reversible membrane depolarization by 54.0 +/- 1.4 mV (n = 5), loss of excitability and rise in resting tension up to 53.1 +/- 4.3% (n = 15) of contractile response in the control. It was supposed that the rapid recovery of excitability (69.3 +/- 10.3 s, n = 15) might be a result of Ca2+ pump activation and/or alterations of intercellular coupling when cavitation ends.     

Protective effects of ranolazine and propranolol,alone or combined,on the structural and functional alterations of cardiomyocyte mitochondria in a pig model of ischemia/reperfusion

Preventing the consequences of ischemia/reperfusion (I/R)‐induced lesions in the clinic requires the administration of pharmacological agents prior to restoring coronary vascularization. The aim of this study was to evaluate the effects of ranolazine and propranolol when administered either alone or combined prior to I/R induction in a pig model. Thirty domestic pigs were randomly assigned to five groups of six animals including (i) sham animals; (ii) untreated animals with 45‐min ischemia and 1‐min reperfusion; animals administered intravenously with (iii) ranolazine, or (iv) propranolol, or (v) both combined, prior to 45‐min ischemia and 1‐min reperfusion. The heart rate (HR), duration of monophasic action potentials (dMAP), and peak of the time derivative of left ventricular pressure (LV dP/dt max) were measured during ischemia and after 1 min of reperfusion. Structural and functional parameters of mitochondria were analyzed in tissue samples taken from the left ventricle ischemic area at the end of the experiment. I/R induced expected effects, namely accelerated HR, decreased dMAP and LV dP/dt max, and altered mitochondrial structural and functional parameters including decreased oxygen consumption, increased reactive oxygen species (ROS) production, and reduced calcium retention capacity resulting in the opening of mitochondrial permeability transition pores (mPTP). Ranolazine and propranolol administered either alone or combined prior to I/R significantly decreased all of these deleterious consequences. The protective effects of ranolazine and propranolol are seemingly due to the prevention of calcium overload and resulting lesions in mitochondria.     

急性心房压力增高对心房肌电生理性质的影响

目的:探讨急性心房压力增高对心房肌电生理性质的影响及其与房性心律失常的关系。方法:12只杂种成年犬,在阻断自主神经状态下行心外膜电生理检查,分成基础对照组,单纯升压组及胺碘酮 升压组,分别测量心房不同位点的单相动作电位(MAP)及房颤诱发率。结果:与基础对照相比,单纯升压组MAPD90明显延长,MAPD90离散度(△MAPD90)增大,RT离散度(△RT)增大,房颤诱发率增加。胺碘酮 升压组MAPD90延长,但△MAPD90减小,△RT在慢频率起搏时减小,但起搏频率增快时逐渐增大,房颤诱发率虽高于对基础对照,但与单纯升压组相比无统计学差异。结论:1)急性心房压力增高后△RT增大,这可能是此时房颤诱发率增高的电生理基础;2)胺碘酮静脉制剂在房压增高时不能有效降低房颤诱发率,推测与这时△RT在快频率起搏时增大有关。