苦参碱对心室肌细胞快速延迟整流钾电流的影响及致长QT综合征危险性探讨

目的 观察苦参碱对心肌细胞快速延迟整流钾电流(IKr)的作用并撂讨其诱发QT间期延长和致心律失常作用发生的危险性.方法 采用酶解法急性分离单个家兔、豚鼠心室肌细胞,全细胞膜片钳技术观察并苦参碱与胺碘酮对心肌细胞IKr的作用及对动作电位的影响.结果 苦参碱及胺碘酮均呈剂量依赖性押制家兔心室肌细胞IKr,胺碘酮浓度为0.1,1,10uM时,电流密度由(5.51±0.47)pA/pF分别下降到(4.00士0.30)pA/pF,(2.31士0.16)pA/pF和(1.43士0.21)pA/pF(n=8,P<0.05);苦参碱浓度为1,10,100 uM时,IKr电流密度由(5.80士0.57)pA/pF分别下降到(4.80士1.38)pA/pF、(3.34士O.59)pA/pF和(2.34士0.42)pA/pF(n=8,P<0.05).苦参碱、胺碘酮均可呈剂量依赖性明显延长豚鼠心室肌细胞动作电位而90%时程(APD90),在胺碘酮给药浓度为0.1,1,10 uM时,APD90分别由(239士11)ms延长至(280±9)ms、(390士20)ms和(573士14)ms(n=8,P<0.05);苦参碱给药浓度为1 uM时.APD90无明显变化,给药浓度为10 uM和100uM时,APD90分别由(226士19)ms延长至(251士20)ms和(283±24)ms(n=8,P相似文献   

心律失常与心肌外向延迟整流钾电流IK的改变

心肌外向延迟整流K^ 电流IK可分为IKr、IKs和IKur3种成分或亚电流，它的变化是在病理情况下引起心律失常的重要原因之一。心肌肥厚时IKr、IKs的减少导致动作电位时间(APD)延长，为早后除极(EAD)和RdP的产生创造了前提条件。缺血和交感神经兴奋时IKr、IKs和IKur，的增加可导致APD异质性加大，促发心律失常。多数Ⅲ类抗心律失常药物主要阻断IKs易导致APD过度延长，诱发EAD、TdP等心律失常。复合性Ⅲ类抗心律失常药对IKs的阻断不仅有利于抗心律失常，而且也能减少不良反应。     

兔肥厚心肌细胞内膜和外膜慢反应延迟整流钾电流和动作电位时程的变化

目的 探讨肥厚心肌的电生理重构机制,观察肥厚心肌细胞内膜和外膜慢反应延迟整流钾电流(IKs)和动作电位时程(APD)的变化.方法 家兔16只随机分为假手术组和心肌肥厚组.心肌肥厚组通过部分结扎腹主动脉的方法造成兔压力负荷性心肌肥厚模型,假手术组只暴露腹主动脉而不行缩窄术.实验以胶原酶分离兔心肌细胞,采用全细胞膜片钳记录IKs和APD.结果 ①假手术组和心肌肥厚组心内膜的IKs均显著小于心外膜.②与假手术组相比,心肌肥厚组心内膜和心外膜的IKs显著减小.③假手术组和心肌肥厚组心内膜的APD均显著长于心外膜.④与假手术组相比,心肌肥厚组心内膜和心外膜的APD显著延长.结论 肥厚心肌IKs存在跨室壁异质性,同时伴有心外膜和心内膜不均一的IKs减小,造成复极时程延长和跨室壁复极不均一性的增加.     

氟哌啶醇对豚鼠心室肌细胞IK的影响

目的 观察氟哌啶醇对豚鼠单个心室肌细胞延迟整流钾电流(IK)通道的作用,探讨氟哌啶醇致心律失常的离子基础.方法 应用全细胞膜片钳技术记录氟哌啶醇对豚鼠单个心室肌细胞IK的影响.结果 在获得单个细胞后,分别给予0.3、1.0 、3.0 μmol/L的氟哌啶醇.延迟整流钾电流在试验电压+70 mV时,从给药前的(16.660 4±1.571 7)分别减少至(5.025 5±1.937 2)、(9.857 2±3.900 2)、(7.179 4±1.816 0)pA/pF (n=7,P＜0.01).结论 氟哌啶醇可抑制IK,使动作电位时程延长而引发心律失常,其致心律失常作用可能与其对钾通道的作用有关.     

传统抗心律失常药物及苦参碱对家兔心室肌细胞快速延迟整流钾电流作用的比较

目的 比较传统的抗心律失常药物和苦参碱时心肌细胞快速延迟整流钾电流(IKr)的作用,以及其诱发QT间期延长和致心律失常作用发生的危险性.方法 采用酶解法急性分离单个家兔心室肌细胞,全细胞 膜片钳技术观察并比较奎尼丁、普萘洛尔、胺碘酮及苦参碱等药物对心肌细胞IKr的作用.结果 胺碘酮(0.1、1和10μM)及苦参碱(1、10和100μM)剂量依赖性抑制家兔心室肌细胞IKr,而苦参碱的抑制作用明显弱于胺碘酮;几种传统的抗心律失常药物中,在相同药物浓度下(1μM),奎尼丁和胺碘酮均表现为明显的IKr电流抑制作用,而普萘洛尔对IKr电流的抑制作用明显减轻(n=12,P<0.05).结论 中药苦参碱及β受体阻断药普荼洛尔对IKr电流的抑制作用较奎尼丁和胺碘酮为弱,其临床应用不易诱发QT间期延长和心律失常.     

缬沙坦对心房肌细胞钾电流的影响

目的:从心肌细胞电生理的角度探讨血管紧张素II受体阻断剂(ARB)类药物抗房颤的可能机制.方法:采用全细胞膜片钳技术的电压钳方法记录心房肌细胞的延迟整流钾电流(Ik).观察ARB类药物缬沙坦对豚鼠心房肌细胞离子通道电流的影响.结果:缬沙坦100μM明显抑制心房肌细胞IK的峰值电流,从(5.33±0.13)pA/pF减小至(4.49±0.48)pA/pF,P<0.05,并呈电压依赖性.结论:缬沙坦抑制心房肌细胞延迟外向钾电流,可能是引起其动作电位时程延长的一个重要因素.缬沙坦延长心房肌动作电位时程,可能在房颤的转复及房颤转复后窦性心律的维持中有价值.     

细胞膜磷脂PIP2对心肌HERG通道调节的研究进展

早在1990年Sanguinetti等[1]在观察E-4031对豚鼠单个心室肌细胞心肌延长整流钾电流(delyed rectifier K current,Ik)的影响时发现Ik有两个组分组成,并根据他们对E-4031敏感性的不同分别命名为快激活整流钾电流(rapid Ik,IKr),慢激活钾电流(slowIk,IKs)。HERG(human ether-a-gog     

甲状腺素诱导的豚鼠肥厚心肌中快速激活的延迟整流钾电流和内向整流钾电流

在甲状腺素诱导的豚鼠心肌肥厚模型上,采用膜片钳全细胞技术,研究病变心肌细胞ＡＰＤ,Ｉｋｒ及Ｉｋｌ离子通道特征,以及药物治疗后其离子通道的改变。结果表明,肥厚心肌细胞ＡＰＤ明显缩短,静息电位及动作电位幅度不变,Ｉｋｒ及Ｉｋｌ均显著增加,反转电位不变。经ｐｒｏｐｒａｎｏｌｏｌ治疗后,心肌ＡＰＤ,Ｉｋｒ及Ｉｋｌ均有明显改善,不影响Ｉｋｒ的反转电位,但使Ｉｋｌ反转电位向负的方向偏移。以上结果提示,甲状腺素诱发的心肌肥厚加重心律失常的严重性与增加Ｉｋｒ及Ｉｋｌ有关,作用多通道的复合型抗心律失常药有较好的治疗作用。     

槲寄生黄酮苷对大鼠心室肌细胞钾离子通道的作用

目的观察槲寄生黄酮苷对大鼠心室肌细胞钾离子通道的作用,探讨槲寄生黄酮苷抗心律失常作用机制。方法应用全细胞膜片钳技术记录槲寄生黄酮苷对大鼠单个心室肌细胞内向整流钾电流(IK1)、瞬时外向钾电流(Ito)的影响。结果应用50μg/ml和250μg/ml两种浓度的槲寄生黄酮苷分别使大鼠单个心室肌细胞内向整流钾电流(IK1)在实验电压-120mV时从给药前(-26.23±9.52)pA/pF减少到(-20.82±7.88)pA/pF,(-18.11±7.89)pA/pF(n=7,P<0.05);使大鼠心室肌细胞瞬时外向钾电流(Ito)在实验电压+50mV时,从给药前(26.14±6.67)pA/pF减少到(16.41±6.23)pA/pF,(13.25±3.78)pA/pF(n=4,P<0.05)。结论槲寄生黄酮苷抑制大鼠心室肌细胞IK1,Ito可能是其抗心律失常作用的一个机制。     

肥厚左心室肌中层细胞Na+/Ca2+交换体电流及钾电流重构特征

目的 探讨肥厚左心室肌中层细胞Na⁺/Ca²⁺交换体电流(Na⁺/Ca²⁺ exchanger current,I_Na⁺/Ca²⁺)及钾电流重构特征,揭示心肌肥厚时心律失常发生的离子基础。方法 新西兰兔分为正常对照组及手术组各10只,手术组通过肾上腹主动脉次全缩窄诱发左室肥厚。采用全细胞膜片钳技术分别记录对照组及手术组左心室肌中层细胞的动作电位、I_Na⁺/Ca²⁺、慢激活的延迟整流钾电流(slowly activating delayed rectifier potassium current,I_Ks)、快激活的延迟整流钾电流(rapidly activating delayed rectifier potassium current,I_kr)等。结果 在基础刺激周长为2 s时,对照组和手术组的90%动作电位时程(90% action potential duration,APD90)分别为522.0±19.5 ms(n=6)、664.7±32.7 ms(n=7);在测试电位为+40 mV时,外向I_Na⁺/Ca²⁺密度在对照组及手术组分别为0.94±0.11 pA/pF(n=9)、1.30±0.11 pA/pF(n=8);在测试电位为-100 mV时,内向I_Na⁺/Ca²⁺密度在对照组及手术组分别为0.40±0.05 pA/pF(n=9)、0.56±0.02 pA/pF(n=8);在测试电位为+50 mV时,对照组及手术组的I_Ks尾电流密度分别为0.26±0.03 pA/pF(n=8),0.17±0.01 pA/pF(n=9);在测试电压为+50 mV时,对照组及手术组的I_kr尾电流密度分别为0.34±0.02 pA/pF(n=8),0.23±0.02 pA/pF(n=9),以上二者相比均有统计学意义。结论肥厚左心室肌中层细胞的电生理特性发生改变,表现为动作电位时间延长、I_Na⁺/Ca²⁺上调、I_Ks及I_kr下调。     

Long-term effects of imidapril on calcium and potassium currents in rabbit left ventricular hypertrophic myocytes

Cardiachypertrophy ,inducedby pressureoverload ,isassociatedwithalterationsintheelectrophysiologicpropertiesoftheheart,whichmaycontributetotheincreasedincidenceofventriculararrhythmias 1,2 Amongmanyfactorsinducinghearthypertrophy ,therenin angiotensinsystem (RAS) playsanimportantroleintheregulationofcardiaccellsandmatrixgrowth AngiotensinⅡlevelcanbepartiallyreducedafteradministrationofangiotensinconvertingenzyme (ACE)inhibitors ACEinhibitorshavebeenshowntodecreaseventricularhypertrophyandr…     

Na+/Ca2+ exchanger current and K+ current remodeling in midmyocardial cells of hypertrophic left ventricle]

OBJECTIVE: To investigate the characteristics of Na+/Ca2+ exchanger current (INa+ /Ca2+) and K+ current remodeling in midmyocardial cells of hypertrophic left ventricle for understanding the ionic basis of arrhythmia of the hypertrophic heart. METHODS: Twenty New Zealand rabbits were divided equally into normal control group and operation group, and in the latter, left ventricular hypertrophy was induced in the rabbits by partial ligation of the abdominal aorta. Action potentials, INa+/Ca2+, slowly activating delayed rectifier K+ current (IKs) and rapidly activating delayed rectifier K+ current (IKr) were recorded in the two groups by using whole-cell patch-clamp technique. RESULTS: At the basic cycle length of 2 s, 90% action potential duration (APD90) in control and operation groups was 522.0+/-19.5 ms (n=6) and 664.7+/-32.7 ms (n=7) respectively; at the testing potential of +40 mV, outward INa+/Ca2+ density in the two groups was 0.94+/-0.11 pA/pF (n=9) and 1.30+/-0.11 pA/pF (n=8) respectively; the testing potential of -100 mV elicited inward INa+/Ca2+ density of 0.40+/-0.05 pA/pF (n=9) and 0.56+/-0.02 pA/pF (n=8) respectively. The testing potential of +50 mV induced IKs tail current density of 0.26+/-0.03 pA/pF (n=8) and 0.17+/-0.01 pA/pF (n=9), and IKr tail current density of 0.34+/-0.02 pA/pF (n=8) and 0.23+/-0.02 pA/pF (n=9) respectively. Statistically significant differences were identified between the control and operation groups in all the above indices measured. CONCLUSION: The characteristics of electrical remodeling changes in midmyocardial cells of hypertrophic left ventricle, exhibited by prolonged action potential, up-regulated INa+/Ca2+ and down-regulated IKs and IKr.     

Verapamil modulating arsenic trioxide-induced QT interval rolongation in guinea pig

Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide (As2O3) in guinea pig and to further explore its possible mechanism. Methods Different doses of As2 O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram (ECG) at different times in guinea pig. Patchclamp technique and laser scanning confocal microscopy were utilized to study the action of As2 O3 on action potential duration (APD),L-type calcium current (ICa-L ), rapid delayed rectifier potassium current (IKr) and intracellular calcium concentration ([Ca2+]i) of guinea pig myocytes. At the same time, verapamil was applied preliminarily to evaluate effects of verapamil on changes of the above index induced by As2O3. Results Intravenous administration of As2 O3 at the dose of 1.6mg/kg and 0.8mg/kg prolonged QT interval on ECG obviously in guinea pig hearts dose dependently and time dependently. QTc (corrected QT interval) was progressively prolonged in the 2-hour period of intravenous infusion of 1.6mg/kg As2O3 from (328.5 ± 30.9)ms of control to (388.4 ± 31.3)ms at 2h following As2O3 ( P ＜ 0.01) .When verapamil was pretreated for 5min, then 1.6mg/kg As2 O3 was added, the results showed that QTe was shorter in verapamil-treatment group (357.3±21.4)ms than that in As2O3 group (388.4±31.3)ms (P＜0.05) at 2h. Confocal experiments showed that in normal Tyrode solution, As2 O3 (1μmol/L and 10μmol/L) had no obvious effects on resting [Ca2+]i (P＞0.05) in guinea pig cardiomyocytes, however, 10μmol/L As2 O3 could markedly enhance [Ca2+]i increase induced by KCl 60mmol/L and the peak value increased from 903.4±369.4 to 1674.6±563.2 ( P＜0.05). The action of elevating [Ca2+]icould be blocked by 10μmol/L verapamil incompletely. The patch-clamp studies indicated that As2 O3 at concentration of 10μmol/L prolonged APD50 from (263.6 -±75.2)ms to (523.9±47.8)ms (P＜0.01) and APD90 from (277.5 ± 77.5)ms to (536.3 ±49.6)ms (P ＜0.01) ,and increased ICa-L from (- 6.0±1.5)pA/pF to (-8.7±2.0)pA/pF (P＜0.01) at 0mV and also reduced IKr from (6.7±1.8)pA/pF to (4.5±1.8)pA/pF (P＜0.05). However, 10μmol/L verapamil could modulate prolonging APD50 from (523.9 ± 47.8) ms to (340.4±83.8) ms ( P＜0.01) and APD90 from (536.3 ±49.6)ms to (348.9 ± 85.5)ms (P＜0.01) and correct increasing Ica-L induced by 10μmol/L As2O3 from (-8.7±2.0)pA/pF to ( - 6.6±1.4)pA/pF (P＜0.05) at 0mV. Conclusion As2O3 could induce prolongation of the QT interval on the ECG in guinea pig hearts and the ionic mechanism is associated with increasing Ica-L and inhibiting IKr/HERG. Verapamil may be useful in normalizing QT prolongation during As2 O3 therapy by decreasing Ica-L and [Ca2+]iof ventricular myocytes in guinea pig.     

Verapamil modulating arsenic trioxide-induced QT interval prolongation in guinea pig

Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide （As2O3） in guinea pig and to further explore its possible mechanism. Methods Different doses of As2O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram （ECG） at different times in guinea pig. Patchclamp technique and laser scanning confocal microscopy were utilized to study the action of As2O3 on action potential duration （APD）,     

Left ventricular hypertrophy amplifies the QT, and Tp-e intervals and the Tp-e/ QT ratio of left chest ECG

Objective： To evaluate the changes in Tp-e interval （an interval from the peak to the end of the T wave）, QT interval and Tp-e/QT ratio of the body surface ECG in patients with left ventricular hypertrophy （LVH）. Methods： The Tp-e interval and QT interval were measured on body surface ECGs in 42 patients without either hypertension or LVH （control group）, 41 patients having hypertension but not LVH （non-LVH group）, and 38 patients with both hypertension and LVH （LVH group）. Results： The mean corrected QT （QTc） interval, and mean corrected Tp-e[T（p-e）c] interval were significantly longer in the LVH group （0.430±0.021s vs. 0.409±0.019s, p 〈 0.01; 0.098±0.013s vs. 0.088±0.011s, respectively） than those in the control group. The Tp-e/QT ratio was also amplified in LVH group （0.232± 0.028 vs.0.218± 0.027） （p 〈 0.05）. Conclusion： LVH increased the QT interval, Tp-e interval and Tp-e/QT ratio of the body surface ECG.     

应变率成像评价原发性高血压患者左心室心肌的舒缩功能障碍

目的:探讨应变率成像技术(SRI)为临床无创评估原发性高血压患者心脏舒缩功能障碍的价值。方法:将90例原发性高血压患者依据左心室心肌质量指数(LVMI)分为两组:左室肥厚(LVH)组46例和无左室肥厚(NLVH)组44例。行常规超声心动图检查并测量左房、左室大小,室间隔和左室后壁厚度,同时测定LVEF和LVFS、E/A比值等参数。应用应变率成像技术,对左心室纵向各室壁心肌在整个心动周期中SR参数进行分析测定,并与45例正常人(对照组)对照比较。结果:⑴与对照组及NLVH组相比,LVH组左房较大,室壁增厚,心肌收缩期SR参数绝对值均明显降低(P<0.05),而LVEF、LVFS无差异(P>0.05);并且室壁收缩期SR的绝对值与室壁的肥厚程度呈负相关(P<0.05)。⑵LVH组心肌快速充盈期SR参数同E/A比值都显著降低(P<0.05)。而室壁的厚度与室壁的快速充盈期SR无相关性(P>0.05)。3组心室肌的心房收缩期SR参数无明显差别(P>0.05)。⑶LVH组收缩后收缩(PSC)的出现率(59.8%)显著高于Normal组(21.0%)和NLVH组(36.6%)(P<0.05)。LVH组收缩后收缩的SR绝对值、收缩后收缩与收缩期SR的比值均大于其他两组(P<0.05)。结论:SR能反映不同程度原发性高血压患者左心室心肌舒缩功能障碍。     

Ventricular arrhythmias: Q-T prolongation and left ventricular hypertrophy in adult Nigerians with hypertensive heart disease

Seventy adult Nigerians with hypertensive heart disease (HHD) and 68 healthy controls were studied for ventricular arrhythmias (VA). The roles of QT prolongation and left ventricular hypertrophy in these arrhythmias were received. The mean age of the study population was 49.9 +/- 6.0 years. 14 (20.0%) patients had cardiac arrhythmias with 3 patients having premature ventricular contractions (PVC). Ten (14.3%) cases had QTc prolongation out of which 1 patient had PVC. Some factors that were found to be associated with QT prolongation in HHD include: left ventricular hypertrophy, persistently elevated systolic blood pressure and female gender. There was a positive correlation between left ventricular hypertrophy and QTc prolongation and also between QTc prolongation and frequency of ventricular arrhythmias.     

1-磷酸鞘氨醇对豚鼠心室肌细胞单通道延迟整流钾电流的影响

目的： 观察1-磷酸鞘氨醇（S1P）对豚鼠心室肌细胞单通道延迟整流钾电流的影响,探讨S1P在室性心律失常中的作用。方法： Langendorff离体心脏逆向灌流法分离豚鼠心室肌细胞,随机选取心室肌细胞分为正常对照组、S1P(2.2 μmol·L^-1)组及S1P(2.2 μmol·L^-1)+Suramin（200 μmol·L^-1）组。应用细胞贴附式记录方式记录心室肌细胞延迟整流钾电流（I_K）。结果：细胞贴附式记录及通道动力学分析 ,S1P组心室肌细胞通道开放时间及开放概率明显低于正常对照组(P<0.05),关闭时间明显高于正常对照组（P<0.05）;S1P+Suramin组通道开放时间、开放概率以及关闭时间与正常对照组比较差异无显著性（P>0.05）。结论： S1P抑制心室肌细胞延迟整流钾电流外流,该作用通过缩短开放时间、延长关闭时间、降低开放概率实现,且通过膜受体介导。     

原发性高血压左室肥厚心率变异性与室性心律失常分析

目的:分析72例有或无左室肥厚(LVH)原发性高血压患者心率变异性(HRV)时域指标和室性心律失常的关系。方法:连续记录24h动态心电图通过计算机算出72例原发性高血压病人HRV时域指标(白天、夜间SDNN)及室性心律失常发生率。结果:高血压LVH组(HRV)时域指标小于高血压不伴LVH组,P<0.01,室性心律失常的发生率与高血压不伴LVH组比较明显增加,P<0.01。结论:HRV时域指标对于预测高血压左室肥厚患者发生室性心律失常有一定的参考价值。     

老年SD大鼠前列腺上皮细胞膜钾离子通道变化及意义

目的探讨雄性SD大鼠前列腺上皮细胞膜钾离子通道电流的变化和对钾通道阻断剂的反应。方法分别取3个月龄成年和12个月龄的老年SD大鼠的背外侧叶前列腺组织,剪成1—2mm^3大小,经消化、培养、免疫组鉴别,将形态正常、贴壁良好的腺上皮细胞用全细胞膜片钳模式记录钾通道电流。结果成年和老年SD大鼠的前列腺上皮细胞膜＋80mV钾电流密度分别为（10．84±1．54）pA／pF vs（18．48±1．7）pA／pF（n=20,P〈0．01）;钙激活型钾通道抑制剂（KCa通道）四乙胺（TEA）对老年大鼠峰电流阻断从19．1±2．9到7．2±3．2,KCa电流被抑制约63％;成年大鼠为9．5±1．8到5．4±3．1,KCa通道电流被抑制约44％。电压依赖型钾通道抑制剂4-AP（四氨基吡啶）对大鼠前列腺上皮细胞膜钾电流有显著阻断效应。结论老年大鼠的前列腺上皮细胞膜钾通道电流比成年大鼠显著增强,同时老年大鼠KCa通道电流对TEA更敏感。由此结果可推论老年大鼠的前列腺上皮细胞分泌功能是降低的。