楸毒素对豚鼠离体心脏QT间期延长的作用研究

目的观察楸毒素(MTX)豚鼠离体心脏QT间期的影响,探究楸毒素对豚鼠离体心脏的作用。方法采用Langendorff逆行主动脉灌流法灌流6只豚鼠离体心脏。分别记录正常和给予楸毒素后的豚鼠心电图,测量心肌电生理指标。结果灌流结果显示,给予0.4μmol/L的楸毒素能显著缩短QT间期,从171.92±6.91ms缩短至142.96±5.89ms,缩短近16.85%,差异有统计学意义(P0.01);Tp-e有显著缩短,缩短约25.68%,差异有统计学意义(P0.05)。多非利特显著延长豚鼠心电图的QT间期;给予多非利特(Dofetilide,Do)后,再分别给予低中高三个浓度(0.2μmol/L、0.4μmol/L和0.6μmol/L)MTX,相比Do组,低浓度MTX对QT和Tp-e差异无统计学意义(P0.05);0.4μmol/L和0.6μmol/LMTX能够逆转多非利特的延长作用。结论楸毒素能缩短心脏的QT间期,对抗多非利特诱导的豚鼠离体心脏LQT2,对心律失常起治疗作用。     

四硫化四砷对急性早幼粒细胞白血病患者心电图QTc间期的影响

目的　探讨四硫化四砷 (As4S4)对急性早幼粒细胞白血病 (APL)患者心电图校正后QT(QTc)间期的影响。方法　复方柏子仁 (主要成分As4S4)治疗的 90例患者分为诱导缓解组和巩固维持治疗组。诱导缓解组测定并记录患者服药前及缓解后的血砷浓度及同步 12导联心电图 ;巩固维持治疗组测定并记录患者服药前及第 2 ,4 ,6 ,8,10疗程后的血砷浓度及心电图。测量每份心电图的QT间期值 ,以Bazett公式校正 ,计算出QTc,观察血砷浓度与QTc间期的关系。结果　无论诱导缓解组还是巩固维持治疗组 ,口服As4S4均能引起QTc间期的延长 ,QTc与As4S4的剂量及血砷浓度有关 ,随着As4S4的累积剂量或血砷浓度增大 ,QTc值及其延长的幅度也增大。在巩固维持治疗组服药的 10个疗程中 ,QTc值异常 (≥ 4 4 0ms)率平均为 37.7% ,随服用As4S4累积剂量的增加 ,各疗程血砷浓度缓慢上升 ,但各疗程之间的变化差异无显著性 (P >0 .0 5 )。各疗程中QTc间期虽逐步延长 ,但QTc值异常率在各疗程中无显著性差异 (P >0 .0 5 )。QTc异常的患者均无临床症状 ,未出现室性心动过速或尖端扭转型室性心动过速等病变 ,无一例患者因QTc间期延长而终止治疗。结论　As4S4治疗APL虽可引起QTc间期延长 ,且QTc间期的变化与血砷浓度呈正相关 ,但As4S4仍为一种安全的治疗     

急性心肌梗塞时心前导联QTc离散度对心室颤动的预测作用

目的　探讨急性心肌梗塞时 (AMI) QT间期离散度增加和心室颤动易感性之间的关系。方法　比较分析2 0例 AMI发病后 2 4h内并发心室颤动的患者 (心室颤动组 )和 2 0例未发生心室颤动的 AMI患者 (对照组 )在急诊入院时体表同步 12导心电图的心前 QT间期离散度和 QTc间期离散度。结果　心室颤动组 QTc间期离散度和 QT间期离散度均显著高于对照组 (分别为 70 ms± 30 ms与 32 ms± 15 ms和 6 7ms± 30 ms与 31ms± 17ms,P<0 .0 0 1)。结论　AMI时心前 QT间期离散度增加产生心室颤动的危险性增加     

血管紧张素Ⅱ及其受体拮抗剂对豚鼠心肌细胞电生理及L-型钙电流的作用

目的 探讨血管紧张素Ⅱ及其受体拮抗剂对豚鼠心肌细胞动作电位间期及L-型钙电流的作用。方法 分离豚鼠乳头肌的单个心室肌细胞，采用内充3mol／LKCl的玻璃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-40mV，保持时间200ms，指令电位为0，并记录L-型钙电流的最大峰电流。结果 灌注血管紧张素Ⅱ可致多种机制的心律失常。灌注1min，动作电位振幅、动作电位复极90％的间期（APD90）、静息膜电位（RMP）较对照状态显著降低或缩短；灌注3min，动作电位复极30％和50％的间期（APD30和APD50）及有效不应期均较对照状态显著缩短。膜片钳研究示血管紧张素Ⅱ灌注5min，L-型钙电流较对照状态显著增加，氯沙坦灌注1min L-型钙电流显著降低，灌注3min较1min进一步降低，电压-电流关系曲线形状均无显著变化。结论 血管紧张素Ⅱ降低动作电位幅度，缩短动作电位时程及有效不应期，电压依赖性增加L-型钙电流最大峰电流，具有致心律失常作用，氯沙坦电压依赖性地降低L-型钙电流。     

四硫化四砷对急性早幼粒细胞白血病患者心电图QTc问期的影响

目的探讨四硫化四砷(As4S4)对急性早幼粒细胞白血病(APL)患者心电图校正后QT(QTc)间期的影响.方法复方柏子仁(主要成分As4S4)治疗的90例患者分为诱导缓解组和巩固维持治疗组.诱导缓解组测定并记录患者服药前及缓解后的血砷浓度及同步12导联心电图;巩固维持治疗组测定并记录患者服药前及第2,4,6,8,10疗程后的血砷浓度及心电图.测量每份心电图的QT间期值,以Bazett公式校正,计算出QTc,观察血砷浓度与QTc间期的关系.结果无论诱导缓解组还是巩固维持治疗组,口服As4S4均能引起QTc间期的延长,QTc与As4S4的剂量及血砷浓度有关,随着As4S4的累积剂量或血砷浓度增大,QTc值及其延长的幅度也增大.在巩固维持治疗组服药的10个疗程中,QTc值异常(≥440 ms)率平均为 37.7%,随服用As4S4累积剂量的增加,各疗程血砷浓度缓慢上升,但各疗程之间的变化差异无显著性(P>0.05).各疗程中QTc间期虽逐步延长,但QTc值异常率在各疗程中无显著性差异(P>0.05).QTc异常的患者均无临床症状,未出现室性心动过速或尖端扭转型室性心动过速等病变,无一例患者因QTc间期延长而终止治疗.结论 As4S4治疗APL虽可引起QTc间期延长,且QTc间期的变化与血砷浓度呈正相关,但As4S4仍为一种安全的治疗APL的药物.     

早期康复治疗对无合并症急性心肌梗死患者QT间期离散度的影响

目的 :探讨早期康复治疗对无合并症急性心肌梗死 (AMI )患者QT间期离散度 (QTd)的影响。方法 :113例研究对象前瞻性随机分为早期康复治疗组 (5 4例 )及对照组 (5 9例 )。两组主要基线资料具可比性。早期康复组采用期康复治疗方案 ,对照组采用传统方案。所有研究对象分别在入院当时 (平均 9.3h± 1.9h)、第 1周末、第 2周末、第 3周末记录标准 12导联心电图。QT间期的测量从QRS波起点至T波终点 ,同一导联测量 3个心动周期 ,取其平均值。不同导联最大QT值减去最小为QTd值。结果 :早期康复组入院当时、第 1周末、第 2周末、第 3周末QTd(分别为 6 4± 14ms,4 6± 15ms ,4 3± 12ms,39± 13ms )与对照组 (分别为 6 7± 12ms,4 8± 16ms ,4 1± 13ms,4 0± 15ms)比较统计学上无显著性差异 (P >0 .0 5 )。结论 :无合并症AMI患者实行早期康复治疗不影响QTd值 ,因而不影响心肌电稳定性 ,提示该组患者早期康复治疗安全可行     

肥厚型非梗阻心肌病患者Tp-Te间期和Tp-Te/QT比率的临床分析

目的:肥厚型非梗阻心肌病患者Tp-Te间期和Tp-Te/QT比率的临床意义.方法:收集肥厚型非梗阻心肌病患者60例,其中室间隔和左室后壁比值1.3～1.5组(组1)27例、比值≥1.5组(组2)33例,并与相匹配的健康人60例作为对照,分别测量并计算Tp-Te间期和Tp-Te/QT比率.结果:肥厚型非梗阻心肌病患者Tp-Te间期和Tp-Te/QT比率分别为(132.67±12.74)ms,0.34±0.04,时照组(80.67±12.74)ms,0.22±0.03,两组比较有显著统计学意义(均P<0.05).Tp-Te间期在组1为(117.41±11.23)ms、组2为(145.15±14.82)ms,两组比较有统计学意义(P<0.05),两组间Tp-Te/QT比率比较有统计学意义(0.38±0.02vs 0.31±0.02)(P<0.05).结论:肥厚型非梗阻心肌病患者Tp-Te间期和Tp-Te/QT比率显著延长,Tp-Te间期与左室厚度相关.     

校正QT间期在Shy-Drager综合征中的变化

目的:比较Shy-Drager综合征(SDS)患者的校正QT间期与正常人间的差异,并探讨其意义。方法:回顾比较20例SDS患者和20名年龄与性别相匹配的正常人的校正QT间期。结果:SDS患者的校正QT间期较正常人显著延长[(0.409±0.029)ms比(0.385±0.024)ms,P<0.05]。结论:SDS患者的校正QT间期延长,该指标对其临床诊断有一定帮助。     

乌鲁木齐"7·5事件"伤者临床心电图变化分析

目的 探讨乌鲁木齐"7·5事件"伤者在严重心理应激状态下的临床心电图的变化.方法 随机挑选60例入院患者作为事件组及正常健康人群60例作为对照组进行心电图常规检查,分析心电图的各项指标.结果 事件组患者心率(82.88±13.96)与对照组 (71.19±8.45) 相比较差异有统计学意义(P＜0.01).事件组患者在QT间期(370.03±37.95) ms、QTc(404.46±34.62) ms低于对照组(381.50±21.99) ms、(410.24±12.78) ms,与对照组比较差异有统计学意义(P＜0.05).结论 事件组患者心率、QT间期、QTc间期指标显著异常,表明在急性心理应激状态下心脏调节功能存在障碍,导致心律失常.     

用QT间期预测乙胺碘呋酮在血浆和在心肌的浓度

2例阵发性室速和7例心绞痛患者在进行心脏手术前,用Am(乙胺碘呋酮)口服治疗(每日200～400毫克)至少九个月。根据药物治疗前和进行手术之前当时所记录的心电图Ⅱ导联测量QT间期。手术开始时采集血浆和心肌标本,利用高性能液体层析法测量Cp(血浆浓度)和Cm(心肌浓度)。Am可致校正QT间期显着延长。在Cp和Cm之间存在着良好关联,而且两者均与校正QT间期的增长百分率有关。Cp和Cm与给药剂量(按每公斤每日的毫克计)也高度相关,校正QT间期的增长百分率也与给药剂量相关良好。因此校正QT间期延长的程度可在临床上用来估量Am的Cm。     

Pentamidine-induced long QT syndrome and block of hERG trafficking

The diamidine pentamidine is used to treat leishmaniasis, trypanosomiasis, and Pneumocystis carinii pneumonia. Treatment may be accompanied by prolongation of the QT interval of the electrocardiogram and torsades de pointes tachycardias. Up to now, it has been thought that therapeutic compounds causing QT prolongation are associated with direct block of the cardiac potassium channel human ether a-go-go-related gene (hERG), which encodes the alpha subunit of cardiac I(Kr) currents. We show that pentamidine has no acute effects on currents produced by hERG, KvLQT1/mink, Kv4.3, or SCNA5. Cardiac calcium currents and the guinea pig cardiac action potential were also not affected. After overnight exposure, however, pentamidine reduced hERG currents and inhibited trafficking and maturation of hERG with IC(50) values of 5 to 8 microM similar to therapeutic concentrations. Surface expression determined in a chemiluminescence assay was reduced on exposure to 10, 30, and 100 microM pentamidine by about 30, 40, and 70%, respectively. These effects were specific for hERG since expression of hKv1.5, KvLQT1/minK, and Kv4.3 was not altered. In isolated guinea pig ventricular myocytes, 10 microM pentamidine prolonged action potential duration APD(90) from 374.3 +/- 57.1 to 893.9 +/- 86.2 ms on overnight incubation. I(Kr) tail current density was reduced from 0.61 +/- 0.09 to 0.39 +/- 0.04 pA/pF. We conclude that pentamidine prolongs the cardiac action potential by block of hERG trafficking and reduction of the number of functional hERG channels at the cell surface. We propose that pentamidine, like arsenic trioxide, produces QT prolongation and torsades de pointes in patients by inhibition of hERG trafficking.     

Effect of nebivolol on QT dispersion in hypertensive patients with left ventricular hypertrophy.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased QT dispersion, which is considered an early indicator of end-organ damage and a non-invasive marker of risk for clinically important ventricular arrhythmias and cardiac mortality. The purpose of this study was to examine the effect of nebivolol antihypertensive therapy on QT dispersion in hypertensive subjects. Twenty-five subjects (15 men and 10 women, mean age 53.6 +/- 4.5 years) with essential arterial hypertension and mild-to-moderate LVH (blood pressure: 147.2 +/- 6.2/90.6 +/- 3.8 mmHg; left ventricular mass indexed: 149.1 +/- 10.7 g/m(2)) were compared with 25 age-matched healthy control subjects. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements. The QT dispersion was defined as the difference between the longest and the shortest QT interval occurring in the 12-lead electrocardiogram. The QT dispersion was corrected (QTc) with Bazett's formula. Hypertensive subjects were treated with 5 mg daily of nebivolol. The ECG and echocardiogram were repeated after four weeks of treatment. At baseline, hypertensive patients showed QT dispersion (56.9 +/- 6.4 vs. 31.7 +/- 8.4 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 33.2 +/- 7.8 ms, P < 0.001) significantly higher than control subjects. Four-week nebivolol treatment reduced blood pressure from 147.2 +/- 6.2/90.6 +/- 3.6 mmHg to 136.3 +/- 3.1/83.3 +/- 2.5 mmHg (P < 0.0001), and resting heart rate from 75.3 +/- 4.7 to 64.2 +/- 3.0 bpm (P < 0.001), without significant change in left ventricular mass (LVMi: 149.1 +/- 10.7 vs. 151.4 +/- 9.8 g/m(2), ns). Nebivolol-based treatment improved QT dispersion (56.9 +/- 6.4 vs. 40.5 +/- 5.8 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 42.2 +/- 5.6 ms, P < 0.001), which remained higher than in control subjects (P < 0.001 in both cases). The reduction of QT dispersion did not correlate with arterial BP reduction. In conclusion, nebivolol reduced increased QT dispersion in hypertensive subjects after four weeks. This effect, occurred without any change in LVM, did not seem to be related to the blood pressure lowering and could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.     

红花黄素对氧自由基所致的心肌细胞电生理异常的保护作用

背景氧自由基诱导的功能异常可能使心脏、肝脏、肾脏及脑等组织缺血性疾病的主要致病因素,对损伤有保护作用的药物研究成为当前的热点.目的研究红花黄素(Safflower yellow pigment,SYP)对氧自由基引起的豚鼠单个心室肌细胞损伤的保护作用.设计非随机对照的实验研究.地点、材料和干预本实验在哈尔滨医科大学药学院药理教研室完成.实验选用豚鼠30只,性别不限.以处置前单个心室肌细胞为正常对照,预先应用红花黄素(3.3μg/L)后,给予单个豚鼠心室肌细胞外源性氧自由基(1 mmol/L的H2O2).主要观察指标采用全细胞膜片钳技术,观察单个豚鼠心室肌细胞动作电位时程(action potential duration APD)和L-型钙电流、内向整流钾电流.结果1 nnnol/L的H2O2导致豚鼠心室肌细胞损伤,表现为动作电位时程缩短,APD50和APD90分别由正常对照组的(331.2±31.9)ms和(380.8±28.2)ms缩短至(169.5±76.0)ms和(238.4±21.3)ms(n=8,t=3.834,P＜0.01),红花黄素(3.3μg/L)能明显改善H2O2诱发的动作电位时程缩短;同时氧自由基H2O2抑制L-型钙电流,+10mV时,L-型钙电流峰值由对照的(-1023.45±74.34)pA减少到(-275.21±38.67)pA(n=6,P＜0.001);H2O2(1 mmol/L)也明显抑制内向整流钾电流(IK1),指令电位为-120 mV时,IK1由对照组的(-2 133.5±570.4)pA降低到(-567.0±218.0)pA.预先应用红花黄素10 min后,外源性氧自由基引起单个豚鼠心室肌细胞L-型钙电流的抑制作用得以改善,但不能改变H2O2对Ik1的抑制作用.结论预先应用红花黄素对H2O2损伤有一定的拮抗作用,说明其能够清除氧自由基,为临床应用治疗缺血性心脏病和康复措施的介入提供理论依据.     

酪氨酸激酶和磷酸酶及蛋白激酶C在As2O3调控NB4细胞和皮层神经元凋亡中的作用

目的　研究蛋白酪氨酸激酶和蛋白酪氨酸磷酸酶及蛋白激酶C(PKC)在三氧化二砷 (As2O3 )调控白血病细胞和人脑皮层神经元凋亡中的作用 ,观察As2 O3 对人脑皮层神经元和白血病细胞的胞浆游离钙 ([Ca2 ]i)浓度的影响。方法　用Fluo 3/AM荧光探针标记人白血病细胞和人脑皮层神经元[Ca2 ]i,激光共聚焦显微镜实时测定不同浓度As2 O3 干预后 [Ca2 ]i的变化并观察蛋白酪氨酸激酶和磷酸酶抑制剂对 [Ca2 ]i变化的影响。磷基转移法测定细胞膜和胞浆的PKC活性。琼脂糖凝胶电泳法观察细胞DNA的片段化。结果　 1μmol /L的As2 O3 使NB4细胞的 [Ca2 ]i明显增高 ,而对人脑皮层神经元 [Ca2 ]i影响不明显。 2 μmol /L以上的As2 O3 引起两种细胞 [Ca2 ]i增高 ,此作用被磷酸酶抑制剂钒酸盐呈浓度依赖性促进 ,被蛋白酪氨酸激酶抑制剂金雀异黄素呈浓度依赖性抑制 ,2 ,5 ,10μmol/L钒酸盐作用 2 4 0s时NB4细胞的 [Ca2 ]i总增加率分别为 (6 .5± 2 .3) % ,(2 1.7± 2 .1) %和 (4 9.2± 2 .5 ) % ;人脑皮层神经元为 (6 .7± 2 .1) % ,(19.4± 2 .5 ) %和 (5 2 .3± 2 .7) % ;2 ,5 ,10 μmol/L金雀异黄素作用 2 4 0s时NB4细胞的总抑制率分别为 (6 .7± 2 .9) % ,(2 5 .6± 2 .5 ) %和 (5 2 .2± 3.5 ) % ;人脑皮层     

QT dispersion from body surface ECG does not reflect the spatial dispersion of ventricular repolarization in sheep

The correlation between the QT dispersion on body surface ECG and the dispersion in ventricular repolarization from the cardiac surface was studied in six sheep anesthetized with pentobarbital. The standard 12-lead body surface ECG and multiple ventricular epicardial ECGs were simultaneously recorded. The activation-recovery interval (ARI) was measured from the unipolar epicardial ECGs. The pooled QT dispersion from the six animals was significantly smaller than the pooled ARI dispersion (22.7 +/- 2.6 vs 33.0 +/- 6.9 ms, P < 0.01). There was no correlation between the QT and ARI dispersion. The unipolar epicardial ECGs were then converted into bipolar ECGs and epicardial QT intervals were subsequently acquired from these ECGs. The average value of epicardial QT dispersion from the six animals was similar to that of body surface ECG, but was less than the ARI dispersion (27.5 +/- 6.8 vs 33.0 +/- 6.9, P < 0.01). A good correlation between the epicardial QT dispersion and ARI dispersion was identified (r = 0.84, P < 0.05). In addition, a prolongation in ventricular repolarization, induced by an increase in coronary flow, elicited a pooled ARI dispersion of 62.3 +/- 6.2 ms (n = 6), which was larger than the simultaneously recorded body surface QT dispersion (28.3 +/- 9.8 ms, n = 6, P < 0.01). No correlation between the ARI and QT dispersion was found in the presence of the prolonged ventricular repolarization. In conclusion, QT dispersion from a 12-lead body surface ECG seems to underestimate the spatial dispersion of ventricular repolarization acquired from sheep epicardium.     

Greater quinidine-induced QTc interval prolongation in women

BACKGROUND: Prolongation of the electrocardiographic QT interval by drugs is associated with the occurrence of a potentially lethal form of polymorphic ventricular tachycardia termed torsades de pointes. Women are at greater risk than men for development of this adverse event when taking drugs that prolong the QT interval. To determine whether this may be the result of gender-specific differences in the effect of quinidine on cardiac repolarization, we compared the degree of quinidine-induced QT interval lengthening in healthy young men and women. METHODS: Twelve women and 12 men received a single intravenous dose of quinidine (4 mg/kg) or placebo in a single-blind, randomized crossover trial. Total plasma and protein-free concentrations of quinidine and 3-hydroxyquinidine were measured in serum. QT intervals were determined and corrected for differences in heart rate with use of the method of Bazett (QTc = QT/RR1/2). RESULTS: As expected, the mean QTc interval at baseline was longer for women than for men (mean +/- SD; 407 +/- 7 versus 395 +/- 9 ms, P < .05). The slope of the relationship between change in the QTc interval (delta QTc) from baseline to the serum concentration of quinidine was 44% greater for women than for men (mean +/- SE; 42.2 +/- 3.4 versus 29.3 +/- 2.6 ms/microg per mL, P < .001). These results were not influenced by analysis of 3-hydroxyquinidine, free concentrations of quinidine and 3-hydroxyquinidine, or the JT interval. CONCLUSIONS: Quinidine causes greater QT prolongation in women than in men at equivalent serum concentrations. This difference may contribute to the greater incidence of drug-induced torsades de pointes observed in women taking quinidine and has implications for other cardiac and noncardiac drugs that prolong the QTc interval. Adjustment of dosages based on body size alone are unlikely to substantially reduce the increased risk of torsades de pointes in women.     

Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography

Increased QT dispersion (QT(d)) has been associated with increased risk for ventricular arrhythmias. Pathologic extracellular electrolyte concentrations may result in ventricular arrhythmias. The aim of this study was to evaluate the effect of electrolyte abnormalities on QT(d). Ten consecutive patients with isolated electrolyte abnormalities were selected for each of the following groups: hypokalemia, hyperkalemia, hypercalcemia, hypocalcemia, hypomagnesemia, and normal controls. Standard 12-lead electrocardiography was performed for each patient and average QT, JT, and RR intervals were calculated for each lead. Dispersion of QT, JT (JT(d)), and QTc (QTc(d)) intervals were calculated as the range between the longest and shortest measurements. Compared with controls, only patients with hypokalemia had a greater QT(d) (115 +/- 31 vs. 49 +/- 15 ms), JT(d) (116 +/- 34 vs. 52 +/- 12 ms), and QTc(d) (141 +/- 40 vs. 58 +/- 1 ms), (P < 0.05). In an experimental substudy, seven rats were maintained on K(+) and seven on Mg(2+)-free diet followed by normal diet. Experimental hypokalemia significantly increased QT(d) (10 +/- 4 to 37 +/- 7 ms), and QTc(d) (32 +/- 6 to 79 +/- 27 ms) (P < 0.05), whereas hypomagnesemia did not. Restoration of serum potassium resulted in normalization of dispersion (QT(d), 14 +/- 2; QTc(d), 34 +/- 6 ms). Hypokalemia increases the dispersion of ventricular repolarization that may be responsible for arrhythmias. Even though hyperkalemia, hypocalcemia, and hypercalcemia are known to affect ventricular repolarization, our study shows that they are not associated with increased dispersion.     

Temporary disturbances of the QT interval precede the onset of ventricular tachyarrhythmias in patients with structural heart diseases

An increase in sinus rate prior to ventricular tachyarrhythmias has been demonstrated in previous studies. There is no clear data available concerning changes in ventricular de- and repolarization prior to ventricular tachyarrhythmias, especially in patients with structural heart disease. Therefore, the aim of this study was to analyze the QT and QTc interval (Bazett's formula immediately before the onset of ventricular tachyarrhythmias in stored electrograms of patients with ICDs. The study analyzed 228 spontaneous ventricular tachyarrhythmia episodes in 52 patients (mean age 64 +/- 10 years, 49 men, 3 women) and compared them with 146 electrograms of baseline rhythm recorded during regular ICD follow-up. Mean ventricular cycle length (CL), QT interval, and QTc were measured before the onset of ventricular tachyarrhythmia and during baseline rhythm. Prior to ventricular tachyarrhythmias onset, CL was significantly shorter than during baseline rhythm (714 +/- 139 vs 828 +/- 149 ms, P < 0.0001). By contrast, the QT interval (430 +/- 67 ms) and QTc interval (518 +/- 67 ms) were significantly prolonged before the onset of ventricular tachyarrhythmias as compared to baseline rhythm (QT 406 +/- 67 ms, QTc 450 +/- 61 ms; P < 0.0001). CL, QT, and QTc changes were independent of concomitant treatment with antiarrhythmic drugs. Ventricular tachyarrhythmias are preceded by a significant prolongation of the QT and QTc intervals. This phenomenon may represent a greater than normal disparity of repolarization recovery times possibly facilitating the development of ventricular tachyarrhythmias.     

Electrophysiologic Effects of Beta-blocking Agent, Tilisolol, on Isolated Guinea Pig Ventricular Myocytes

BACKGROUND: Electrophysiologic effects of a beta-blocking agent, tilisolol, were studied with isolated guinea pig ventricular myocytes using the whole cell patch clamp technique. METHODS AND RESULTS: Tilisolol at 10 μM or higher concentrations prolonged action potential duration (APD) at 90% repolarization (APD(90)) and at 100 μM or higher concentrations shortened APD at 20% repolarization (APD(20)) without changes in resting membrane potential. At 10 μM concentration tilisolol prolonged APD(90) from 236.6 +/- 55.3 ms in the control to 253.4 +/- 52.4 ms (n = 16; P <.01), while APD(20) was unaffected. At 100 μM tilisolol, APD(20) was shortened from 143.6 +/- 15.7 ms in the control to 133.7 +/- 22.6 ms (n = 8; P <.05). Under voltage clamp, tilisolol decreased the delayed rectifier K(+) current (I(K1)). Applications of 10 μM and 100 μM tilisolol reduced the maximal conductance of I(K) by 35.7 +/- 3.5% and 47.4 +/- 3.5% of the control, respectively, without changes in voltage dependence (n = 10). Tilisolol at 100 μM decreased the L-type Ca(2+) current (I(Ca.L)) by 22.0 +/- 9.8% (n = 6) of the control, and the inactivation curve was shifted to a hyperpolarizing direction. CONCLUSIONS: Tilisolol has a direct membrane action to depress I(K) and I(Ca.L), in addition to its beta-receptor blocking action.     

Angiotensin II Receptor Regulates Ionic Currents in Guinea Pig Ventricular Myocytes

BACKGROUND: Previous studies have shown that angiotensin II (Ang II) receptors are preset in a wide variety of target tissues and that Ang II regulates the target tissue functions through Ang II receptors. However, the action of Ang II receptors on transsarcolemmal currents in ventricular myocytes has not been elucidated. METHODS AND RESULTS: We performed whole-cell voltage clamp and patch clamp experiments to determine the effects of Ang II-receptor agonists and antagonists on ionic currents in single isolated guinea pig ventricular myocytes. We found that extracellular perfusion of Ang II (30 nM) increased the L-type Ca(2+) current from 581 +/- 27 to 837 +/- 42 pA (n = 5, P <.01). Ang II also prolonged the Ca(2+) current activation and inactivation time constants. These were reversible by losartan (100 nM), a type 1 Ang II receptor (AT(1)) blockade. On the other hand, perfusion of 30 nM Ang II decreased K(+) current (I(K)) from 1543 +/- 28 to 1194 +/- 50 pA (n = 5, P <.05) and K(+) tail current (I(K-tail)) from 275 +/- 24 to 206 +/- 29 pA (n = 5, P <.05). These effects were also abolished by perfusion of losartan. However, perfusion of Ang II resulted in an increase of inward rectified K(+) current (I(K1)) in whole-cell recordings. Single channel recordings showed that the increase in I(K1) was attributed to a burst opening current with a larger unit of amplitude. These effects were reversed by saralasin but not losartan, indicating possible type 2 Ang II receptor (AT(2)) involvement. CONCLUSIONS: Our results provide evidence that Ang II receptors regulate the transsarcolemmal currents in single guinea pig ventricular myocytes. Therefore, Ang II regulation of ionic currents is mediated through the different subtypes of Ang II receptors.