缺血预适应对犬在体三层心肌单向动作电位和不应期的影响

探讨缺血预适应(IPC)抗急性缺血心律失常的部分电生理机制。12只犬随机分为对照组(n=6)和IPC组(n=6),采用特制电极记录和测量三层心肌单相动作电位(MAP)及有效不应期(ERP),测量并分析MAP时程(MAPD),MAPD跨室壁离散(TDR)及ERP跨室壁离散(TDE)。结果:对照组缺血时MAPD缩短,ERP延长且三层心肌延长的幅度不一致,IPC组缺血时MAPD缩短与ERP延长均不明显,两者相比具有显著差别(P<0.05)。两组三层心肌之间的MAPD变化一致,不存在TDR,对照组缺血时ERP变化明显不一致,TDE增大,与IPC组相比较具有显著差别(P<0.05或<0.01)。结论:IPC减少急性缺血时MAPD缩短、ERP延长及TDE,这可能是其抗心律失常的部分机制。     

2-甲硫基三磷酸腺苷对心力衰竭兔心室电生理的影响

目的观察2-甲硫基三磷酸腺苷(2-MeS ATP)对充血性心力衰竭(CHF)心室电生理的影响。方法 45只雄性新西兰大耳白兔分为对照组、CHF组和2-MeS ATP组。CHF组和2-MeS ATP组均行CHF模型制备。CHF模型制备是经兔耳缘静脉注射异丙肾上腺素(每天每公斤体重0.3 mg,连续注射3周)诱导。喂养6个月后。记录在体心脏左心室单相动作电位(MAP)和程控以及短阵快速刺激方法观察静息膜电位(RMP)、动作电位幅度(APA)、最大上升速率(V_(max))、复极化到20%和50%以及90%时程(APD_(20)、APD_(50)、APD_(90))以及有效不应期(ERP)和室性心律失常诱发率等指标。2-MeS ATP组于CHF免静脉滴注2-MeS ATP(10 mg/kg)20 min,然后维持静脉滴注过程中完成上述指标检测。酶解法分离各组单个心室肌细胞全细胞膜片钳技术记录心室肌细胞瞬时外向钾电流(I_(to)),以各自指令电位为横坐标,相对应的电流密度为纵坐标,绘制电流-电压(I-V)曲线。2-MeS ATP组分离单个心室肌细胞后用含有2-MeS ATP(25μmol/L)的细胞外液灌流CHF心室肌细胞10 min完成上述试验。结果最后各组均入选10只兔。与对照组比较,CHF组RMP和APA明显降低,V_(max)减慢,APD均显著延长(P均0.05);与CHF组比较,2-MeS ATP组RMP和APA增加,V_(max)增快,各APD都显著缩短(P均0.05)。CHF组较对照组ERP显著延长,与APD_(90)的比值严重降低,诱发室性心律失常的刺激周长(BCL)明显增加,室性心律失常的诱发率上升,持续时间更长(P均0.01);而2-MeS ATP组较CHF组ERP明显缩短,和APD_(90)的比值显著增加,被诱发室性心律失常的BCL严重缩短,室性心律失常的诱发率和持续时间均降低(P均0.01)。与CHF组比较,2-MeS ATP组I_(to)的电流密度增加,当钳制电位为+50 mV时,2-MeS ATP能够使I_(to)的电流密度由CHF组的(7.94±3.53)pA/pF增加到(11.79±4.51)pA/pF(P0.01),2-MeS ATP组较CHF组心室肌细胞I_(to)的I-V曲线明显上抬,接近对照组。结论 2-MeSATP可以使CHF心肌APD缩短,室性心律失常的易感性降低,起到抗CHF后室性心律失常作用。     

益气复脉合剂抗心律失常作用机制研究

目的利用膜片钳技术阐述益气复脉合剂抗心律失常作用机制。方法采用胶原酶法急性分离大鼠左心室肌细胞,利用膜片钳技术,记录心室肌细胞动作电位。结果异丙肾上腺素(Iso)灌流前,中药组动作电位时程(APD)、APD50、APD90较空白对照组明显延长(P0.05);Iso灌流后,空白对照组与中药组APD较灌流前显著延长(P0.05或P0.01),空白对照组APD50、APD90较灌流前亦显著延长(P0.01);给Iso后,中药组APD、APD50、APD90较空白对照组显著缩短(P0.01)。结论益气复脉合剂可以缩短Iso引起的APD的延长,可能与抑制平台期Ca2+电流和复极后期K+电流有关。     

卡托普利对缺血豚鼠心肌电生理的作用

目的 :探讨卡托普利对缺血豚鼠乳头肌的直接电生理作用。方法 :采用标准玻璃微电极技术 ,记录缺血豚鼠离体乳头肌的单细胞动作电位。结果 :卡托普利治疗组与对照组比较动作电位幅度 (APA) ,复极至30 %、5 0 %时动作电位的时程 (APD3 0 、APD50 ) ,静息膜电位 (RMP) ,有效不应期 (ERP)差异有显著性意义 ,分别为(10 6 .8± 11.2 )∶(94 .0± 2 5 .4 )mV (1min) ,(75 .6± 2 3.4 )∶(4 9.0± 2 8.8)ms(3min) ,(12 9.5± 33.2 )∶(81.6±4 4 .6 )ms(10min) ,(14 8.0± 4 8.5 )∶(6 6 .6± 9.4 )mV(10min) ,(2 11.0± 4 7.2 )∶(172 .2± 39.0 )ms(10min) ,P <0 .0 5。卡托普利治疗组心律失常的发生率较对照组显著减少 (P <0 .0 5 )。结论 :卡托普利拮抗缺血导致APA降低 ,APD缩短 ,RMP降低 ,ERP缩短 ,减少缺血性心律失常的发生 ,提示它对缺血损伤有直接的电生理作用     

糖尿病心肌钾离子通道改变研究进展

心肌细胞短暂外向钾电流(Ito)、延迟整流性外向钾电流(IK)、超快速激活型钾电流(IKur)、ATP敏感性钾通道(KATP)等钾离子通道在糖尿病(DM)模型中均发生异常改变,可引起动作电位(AP)、动作电位时程(APD)、QT间期、有效不应期(ERP)改变,以及折返、触发等活动,导致心律失常发生。DM心肌电生理改变可能与体内糖代谢紊乱造成心肌细胞葡萄糖利用障碍、ATP供给下降有关,这些改变可导致细胞骨架稳定性的破坏、基因转录的抑制和蛋白翻译水平的下降。但机制远不止这些,还需要大量的研究工作来探索心肌电生理发生的改变及其机制。     

预处理对缺血再灌注时心肌电生理的影响

目的探讨缺血预适应（IPC）对缺血/再灌注心律失常的影响及其机制。方法12只犬随机分为对照组（n=6）和IPC组（n=6）,采用特制电极记录技术,观察和测量三层心肌单相动作电位（MAP）及有效不应期（ERP）,分析室性心律失常发生率、MAP时程（MAPD）、MAPD跨室壁离散（TDR）及ERP跨室壁离散（TDE）。结果对照组6只中有4只发生室速/室颤,而IPC组6只中仅1只发生室速/室颤。对照组缺血时MAPD同步缩短,而ERP延长且三层心肌延长的幅度不一致,再灌注时逐步恢复。IPC组缺血时MAPD缩短与ERP延长均不明显,与对照组相比,具有显著差异（P<0.05）。各组三层心肌之间的MAPD是一致的。对照组缺血/再灌注时ERP明显不一致,TDE增大,而IPC组TDE小,两者相比较具有显著差异（P<0.05或P<0.01）。结论IPC减少缺血/再灌时MAPD、ERP的变化及TDE,这可能是其抗心律失常的部分机制。     

低渗性肿胀对豚鼠心室肌细胞动作电位及延迟整流钾电流的影响

观察单个豚鼠心室肌细胞动作电位和主要复极期电流延迟整流钾电流(IK)的变化,探讨急性心肌缺血再灌注室性心律失常发生的离子机制。采用全细胞膜片钳记录技术,观察低渗液(200mOsm/kg)灌流胶原酶分离的单个豚鼠心室肌细胞发生肿胀后的动作电位各参数的变化,同时记录IK及其快、慢两种激活成分(IKr及IKs)的变化。结果:低渗液灌流后心室肌细胞迅速发生肿胀,动作电位幅度(APA)、静息膜电位(RMP)及阈电位水平无明显变化;而动作电位时程(APD)在600,1000和3000ms三种基础起搏周长(BCL)刺激时均缩短(P<0.05),尤以APD复极达50%和90%时缩短更为明显。APD生理性频率适应性消失且离散度增大。低渗性肿胀状态下IK电流幅度在3000ms长去极化保持时间(主要成分为IKs)刺激时从1134.33±150.17pA增加至1621.98±234.95pA(P<0.001,n=10);而在100ms短去极化保持时间(主要成分为IKr)刺激时从693.44±96.44pA降低至294.06±71.79pA(P<0.05,n=8);并且使IK的IV曲线向上移位。结论:低渗性肿胀的心室肌细胞IK特别是IKs的增加是引起APD缩短的重要因素,是急性心肌缺血再灌注室性心律失常发生的离子机制之一。     

从索他洛尔电生理作用评价其抗心律失常作用

从索他洛尔 (sotalol)电药理和电生理作用探索其抗心律失常机制。方法 :①采用经典的微电极方法和膜片钳技术观察sotalol对豚鼠心肌细胞动作电位时程 (APD)和膜离子流的作用 ;②运用心内膜单相动作电位 (MAP)技术观察sotalol对狗APD、有效不应期 (ERP)的影响 ;③监测药物浓度与QT间期关系。结果 :①索他洛尔对内向整流性钾流、钠内流、慢钙内流无影响 ,仅对延迟整流性钾流 (IK)有抑制作用 ;②索他洛尔可延长APD ,呈反转使用依赖 ;③静脉注射索他洛尔后 ,QTc ,APD90 和心室ERP均延长 ,缺血区心肌与非缺血区心肌对索他洛尔的反应一致 ;④QT间期随血药浓度升高而延长 ,血药浓度随剂量增大而上升。结论 :索他洛尔阻滞IK 外流、延长APD ,呈反转使用依赖。索他洛尔延长QTc与血药浓度呈正相关。因此 ,如能掌握索他洛尔特性 ,本药还不失为一安全有效的Ⅲ类抗心律失常药物。     

缺血预适应抗心律失常机制的实验研究（摘要）

研览缺血预适应抗心律失常的电生理基础。采用大鼠乳头肌离体灌注技术和标准玻璃徽电极记录技术，观察缺血预适应形成过程中及其对继后模拟缺血一复氧灌注时动作电位、有效不应期等参效的影响，井使用Glibenclimide阻滞ATP敏感性钾通道，探讨该通道的开放在缺血预适应形成中的作用。     

兔界嵴细胞离子通道特性研究

目的研究生理状态下及异丙肾上腺素灌流对兔界嵴(CT)与梳状肌(PM)细胞动作电位(AP)及钠电流(INa)、短暂外向钾电流(Ito)、L型钙电流(ICa-L)、延迟整流钾电流(IK)及内向整流性钾电流(IK1)的影响,探讨CT与房性心律失常的关系。方法酶解法分离兔CT及PM细胞,利用全细胞膜片钳技术,记录生理状态下及异丙肾上腺素灌流后CT与PM细胞AP及INa、Ito、ICa-L、IK及IK1的变化。结果①生理状态下,CT细胞动作电位时程(APD)较长,可见明显的平台期;PM细胞AP形态与普通心房肌细胞相似,1期复极迅速,平台期短,类似三角形。②生理状态下,CT细胞Ito电流密度比PM细胞明显降低(7.13±0.38 pA/pF vs 10.70±0.62 pA/pF,n=9,P<0.01),而INa、Ito、ICa-L、IK及IK1则无明显差别。③异丙肾上腺素灌流时CT与PM细胞APD20、APD50、APD90均延长(n=8,P<0.01);指令电位+50 mV时,CT与PM细胞Ito电流密度均减少(n=9,P<0.01)而IK均增加(n=8,P<0.05);指令电位+10 mV时,CT与PM细胞ICa-L电流密度均增加(n=9,P<0.01);IK1在两种心肌细胞均无明显差异。结论 CT与PM细胞AP差异与Ito有关。异丙肾上腺素灌流时ICa-L与IK增强,Ito抑制使CT与PM细胞APD延长,触发机制可能是CT参与房性心律失常的机制之一。     

银杏叶提取物对模拟缺血条件下兔心室肌细胞动作电位及ATP敏感性钾通道的影响

研究银杏叶提取物 (EGb)对模拟缺血条件下兔心室肌细胞三磷酸腺苷敏感性钾通道电流 (IKATP)及跨膜动作电位时程 (APD)的影响 ,以探讨其抗缺血性心律失常作用的电生理机制。采用酶解法分离获取兔心室肌细胞 ,将其分为正常对照、持续缺血、缺血预处理以及含EGb液 (15 ,30 ,6 0 ,12 0 μg/L)灌流 4组。用全细胞膜片钳技术 ,记录不同条件下的IKATP和跨膜动作电位。结果 :①与持续缺血组比较 ,缺血预处理以及EGb(12 0 μg/L)可使单个心室肌细胞APD50 、APD90 明显缩短 (n =5 ,P <0 .0 5 )。EGb处理组与缺血预处理组相比较 ,对APD的影响无显著差异 ;②与持续缺血组比较 ,缺血预处理和EGb(12 0 μg/L)均可以使IKATP由 112 4± 15 3pA增至 344 0± 2 0 5和 2 95 9± 12 9pA(n =5 ,P <0 .0 5 ) ,使得IKATPI V曲线抬高 ;③增大的电流均可被Glibenclimide阻断。结论 :EGb可开放细胞膜ATP敏感性钾通道、缩短APD ,产生类似心肌缺血预适应的病理生理过程。     

Interaction of the effects of hypoxia, substrate depletion, acidosis and hyperkalaemia on the class III antiarrhythmic properties of sotalol

The effects of hypoxia on the actions of dl-sotalol 10(-4) mol . litre-1 were studied in rabbit papillary muscles at 32 degrees C. Superfusion for 30 min with a hypoxic solution (95% N2, 5% CO2) in the presence of 5 mmol . litre-1 glucose caused moderate shortening of control action potential duration from 208 +/- 3 to 138 +/- 9 ms (mean +/- SEM). In the presence of sotalol, hypoxia caused shortening of APD90 from 399 +/- 9 ms to 249 +/- ms, but the value after 30 min was still significantly greater than in controls (p less than 0.001). Superfusion with a hypoxic, glucose-free solution, however, caused profound shortening of APD90 in controls to 80 +/- 7 ms at 30 min. The highly significant lengthening of APD90 produced by sotalol in control conditions was abolished after 5 min hypoxia. The effects of hypoxia on the effective refractory period (ERP) paralleled those on APD90. Exposure to a hypoxic, acidotic, hyperkalaemic solution (80% N2, 20% CO2, pH 6.8; K+ 12 mmol . litre-1) produced moderate shortening of APD90 with convergence of the two groups. There was an increase in ERP, with the development of an equal degree of post-repolarisation refractoriness in the control and sotalol groups. The Class III effect of sotalol is preserved under mild but lost under severely hypoxic conditions. Using "simulated ischaemic" conditions, with controlled extracellular potassium concentrations, there was no difference in the relationship between APD90 and ERP in the control and sotalol groups.     

慢性充血性心力衰竭时K_(ATP)通道与心室肌电生理特性变化的关系

探讨慢性充血性心力衰竭 (CHF)时三磷酸腺苷敏感性钾通道 (KATP通道 )在心室肌电生理特性改变和室性心律失常发生中的意义。采用阿霉素制作CHF兔模型。 2 9只兔分为健康对照组 (HC组 )和CHF实验组 ,后者包括CHF对照组 (CHFC组 )、CHF +KATP通道开放剂组 (P组 )、CHF +KATP通道阻断剂组 (G组 )、CHF +KATP通道开放剂和阻断剂组 (P +G组 )四个亚组。每组均予心房快速起搏 30min ,分别测定起搏前后 90 %单相动作电位时程(MAPD90 )、心室有效不应期 (VERP)及其离散度和兴奋时间 (AT)离散度 ,测定毕程序刺激诱发室性心动过速或心室颤动。结果 :快速起搏使MAPD90 、VERP延长 ,在CHFC组较HC组显著 (11.82± 10 .2 0vs 8.18± 6 .97ms,P <0 .0 5和14 .95± 12 .82vs 9.0 7± 8.79ms,P <0 .0 1) ,而G组和P +G组的MAPD90 、VERP延长更明显。各组快速起搏均未引起MAPD90 、VERP离散度变化 ,但CHFC组和P组都有AT离散度显著增大 (2 8.5 3± 8.6 3vs 36 .80± 6 .97ms ,P <0 .0 1和 2 6 .33± 5 .82vs 33.80± 9.5 0ms,P <0 .0 5 ) ,阻断剂可对抗AT离散度的增大。结论 :快速心房起搏可开放CHF心室肌KATP通道 ,一方面阻止MAPD90 、VERP的延长 ,另一方面又加大AT的非同步性 ,使室性心动过速易于诱发。     

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.     

Prolonged action potential durations,increased dispersion of repolarization,and polymorphic ventricular tachycardia in a mouse model of proarrhythmia

Introduction: In the congenital long QT syndrome, inhomogeneously prolonged action potentials, bradycardia, and hypokalemia can cause afterdepolarizations and torsade de pointes. Other genetic factors may contribute to similar forms of ventricular tachycardias in hypertrophied or failing hearts, especially if the outward current I_Kr is blocked pharmacologically. We sought to develop a mouse heart model for such arrhythmias in order to identify the proarrhythmic potential in transgenic animals. Methods and results: Hearts of adult wild-type (CD1) mice were isolated and the aorta was retrogradely perfused. Three monophasic action potentials and a volume-conducted ECG were simultaneously recorded. Sotalol (10^-5M and 2 × 10^-5M) prolonged action potential duration (APD) in a concentration-dependent and reverse frequency-dependent fashion (from 34 ± 1 to 48 ± 2 ms at 100 ms basic cycle length (BCL), from 38 ± 2 to 54 ± 3 ms at 180 ms BCL for APD90, p < 0.05). Sotalol did not alter the relation between refractoriness and APD (ERP/APD ratio = 0.76 - 0.93). AV nodal block caused ventricular bradycardia and doubled dispersion of APD (APD70max-min: 11 ± 1 vs. 4 ± 1 ms, APD90max-min: 12 ± 1 vs. 5 ± 1 ms, p < 0.05). If combined with hypokalemia, afterdepolarizations induced polymorphic ventricular tachycardias in 1 of 8 hearts at K⁺ =3.0 mM and in 10 of 12 hearts at K⁺ = 2.0 mM. Prior to polymorphic ventricular tachycardia, dispersion of APD further increased (APD70max-min: 17 ± 3 ms; APD90max-min: 25 ± 3 ms; p < 0.05). Conclusions: This isolated beating mouse heart model can be used to study drug-induced action potential prolongation and repolarization-related ventricular arrhythmias provoked by bradycardia and hypokalemia. It may be suitable to identify a genetic predisposition to ventricular arrhythmias that may only become apparent under such proarrhythmic conditions.     

The influence of acute myocardial ischaemia on the class III antiarrhythmic action of sotalol

The effects of acute myocardial ischaemia on the Class III antiarrhythmic properties of dl-sotalol 10(-4) mol . litre-1 were studied in the isolated arterially perfused interventricular septum of the rabbit heart. Before ischaemia, sotalol increased mean action potential duration (APD90) from 267 +/- 6 to 406 +/- 19 ms (p less than 0.001 mean +/- SEM, n = 7 septa), and mean effective refractory period (ERP) from 222 +/- 7 to 291 +/- 10 ms. During 30 min zero flow global ischaemia, mean APD90 in the control group fell from 264 +/- 7 to 128 +/- 13 ms (n = 7). APD90 fell more rapidly in the sotalol group, so that the initial difference between the sotalol and control groups was abolished after 24 min ischaemia. In the sotalol group, ERP shortened rapidly during ischaemia, and was significantly less than in the control group after 30 min. These changes were associated with the development of substantial post-repolarisation refractoriness in the control but not in the sotalol group. There was a greater fall in action potential upstroke velocity in the controls than in the sotalol group. The results indicate that the Class III effect of sotalol gradually disappears during ischaemia. The effects on post-repolarisation refractoriness and upstroke velocity are compatible with the hypothesis that sotalol slows the rate of rise of extracellular potassium concentration in acute ischaemia. This is a potentially antiarrhythmic property.     

卡托普利对豚鼠心室肌细胞动作电位及外向延迟整流钾电流的作用

目的 探讨卡托普利对豚鼠心室肌细胞动作电位及外向延迟整流钾电流的作用。方法 采用内充3M KCL的标准微电极记录心肌动作电位。采用膜片钳全细胞技术，钳制电位-50mV，持续时间100ms，指令电位 40mV，记录外向延迟整流钾电流(Ik)最大峰电流。结果 与缺血组比较，卡托普利组APD30、APD50及ERP显著延长，APD50无显著变化。缺血组Ik幅度显著增高，而卡托普利组及卡托普利 缺血组显著降低。各组电流—电压关系曲线形态虽无显著变化，但缺血组显著上移，而卡托普利组、卡托普利 缺血组比缺血组下移。结论卡托普利降低外向钾电流及延长APD30、APD50和ERP。     

四氢巴马汀对在体犬跨室壁复极离散度的影响

从跨室壁复极离散度(TDR)的角度研究左旋四氢巴马汀(L-THP)的电生理作用。采用自制电极同步记录在体犬左室三层心肌细胞的单向动作电位(MAP),观察静脉注射L-THP前后动作电位时程(APD)、振幅(APA)、TDR及各层心肌有效不应期(ERP)的变化。结果:应用L-THP后三层心肌的动作电位复极90%的时程均延长(内、中、外层心肌分别为189.67±23.29msvs182.83±23.70ms、194.67±24.12msvs192.17±24.49ms和185.08±24.53msvs173.42±22.06ms,P均<0.01),内、外层心肌ERP显著增加(分别为164.54±20.53msvs159.08±20.08ms、161.60±21.28msvs150.99±18.93ms,P<0.01)、TDR降低(9.58±2.94msvs18.75±3.77ms,P<0.01),对APA无明显影响。结论:L-THP降低心室肌的TDR,延长心室内、外膜心肌细胞的ERP。     

缺血后处理对大鼠心室肌细胞内向整流钾电流和动作电位的影响

目的探讨缺血后处理(IPC)对大鼠心室肌细胞内向整流钾电流(IK1)和动作电位的影响及机制。方法实验分IPC组、缺血/再灌注(I/R)组、单纯灌流(SP)组,利用大鼠心脏建立离体灌注模型,采用胶原酶酶解法分离得到大鼠单心室肌细胞,采用膜片钳全细胞技术分别记录三组心室肌细胞电流和动作电位的变化。结果在-120mV和-30mV刺激电压水平,IK1电流密度:IPC组低于I/R组,I/R组高于SP组(P均<0.05),IPC组同SP组无差异(P>0.05)。与SP组和IPC组比较,I/R组静息电位明显升高(P<0.05);而动作电位幅度、20%动作电位时程、50%动作电位时程、90%动作电位时程均明显下降(P<0.05)。而IPC组各值与SP组无差异(P>0.05)。结论IPC可以降低大鼠缺血/再灌注心肌细胞IK1,延长缺血/再灌注心肌细胞APD。     

Class III antiarrhythmic action by potassium channel blockade: dofetilide attenuates hypoxia induced electromechanical changes.

OBJECTIVE: The aim was to examine the electromechanical effects of dofetilide, a new class III antiarrhythmic agent, in isolated guinea pig ventricular muscle during hypoxia. METHODS: Hypoxia was induced by superfusing guinea pig right ventricular papillary, muscles with Tyrode's solution gassed with 95% N2 + 5% CO2 [PO2 = 5.3(SEM 1.3) kPa]. Prior to hypoxia, the preparations were either pretreated for 30 min with 0.1 microM dofetilide (n = 6) or with 100 microM glibenclamide (a blocker of ATP sensitive K+ channels, n = 6), or not pretreated (n = 6). Sixteen additional preparations were exposed to 1 mM nicorandil (an activator of ATP sensitive K+ channels) in the absence (n = 6) and presence of dofetilide (n = 6) or glibenclamide (n = 4). Transmembrane action potentials and developed force were recorded using conventional microelectrode techniques and a force transducer. RESULTS: During normoxia, dofetilide markedly increased APD90 from 236(SEM 6) ms to 298(7) ms (p < 0.05) and the effective refractory period (ERP) from 248(5) ms to 315(6) ms (p < 0.05). In the drug free group, 60 min hypoxia decreased APD90 by 47(5)% (p < 0.05), ERP by 48(4)% (p < 0.05) and developed force by 71(6)% (p < 0.05) of baseline, respectively. These hypoxia induced effects were significantly attenuated after pretreatment with dofetilide or glibenclamide. Nicorandil decreased APD90 by 45(5)% (p < 0.05), ERP by 44(6)% (p < 0.05), and developed force by 69(10)% (p < 0.05) of baseline, respectively. Pretreatment with dofetilide or glibenclamide also significantly attenuated the nicorandil induced decreases in APD90, ERP, and developed force. CONCLUSIONS: Dofetilide, like glibenclamide, effectively attenuates hypoxia and nicorandil induced action potential shortening and the associated reduction in contractile force. Thus dofetidile would be expected to retain its antiarrhythmic efficacy during myocardial hypoxia or ischaemia.