The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes

1. The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K⁺ channels, including the human ether-a-go-go related gene (HERG) channels, in Xenopus oocytes and tested them for their haloperidol sensitivity.
2. Haloperidol had only little effects on the delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 and I_sK, the A-type channel Kv1.4 and the inward rectifier channel Kir2.1 (inhibition <6% at 3 μM haloperidol).
3. In contrast, haloperidol blocked HERG channels potently with an IC₅₀ value of approximately 1 μM. Reduced haloperidol, the primary metabolite of haloperidol, produced a block with an IC₅₀ value of 2.6 μM.
4. Haloperidol block was use- and voltage-dependent, suggesting that it binds preferentially to either open or inactivated HERG channels. As haloperidol increased the degree and rate of HERG inactivation, binding to inactivated HERG channels is suggested.
5. The channel mutant HERG S631A has been shown to exhibit greatly reduced C-type inactivation which occurs only at potentials greater than 0 mV. Haloperidol block of HERG S631A at 0 mV was four fold weaker than for HERG wild-type channels. Haloperidol affinity for HERG S631A was increased four fold at +40 mV compared to 0 mV.
6. In summary, the data suggest that HERG channel blockade is involved in the arrhythmogenic side effects of haloperidol. The mechanism of haloperidol block involves binding to inactivated HERG channels.

     

氨酰心安治疗急性心肌梗塞早期室性心律失常的疗效观察

目的：观察氨酰心安治疗急性心肌梗塞早期心律失常的疗效;方法：将５９例急性心肌梗塞早期出现室性心律失常者随机分组,３０例给予小剂量氨酰心安治疗,并与２９例应用利多卡因者进行对照研究;结果：氨酰心安治疗组总有效率为８０．００％,利多卡因组为８６．２１％,两组对比无明显差异（Ｐ〉０．０５）;结论：小剂量氨酰心安治疗急性心肌梗塞早期室性心律失常疗效显著,安全可行。     

双腔起搏器对缓慢性心律失常并心力衰竭病人血流动力学的影响

目的评估双腔起搏器对缓慢性心律失常并心力衰竭病人血流动力学的影响。方法对20例缓慢性心律失常心衰病人经锁骨下静脉植人DDD型起搏器,对比分析术前及术后1～2周X线胸片、放射性核素门控心室显影和超声心动图检查结果。结果所有患者临床症状及心功能明显改善,术后心胸比例、射血分数（EF）、心排血量（CO）、心脏指数（CI）均明显好转［分别为0．70±0．13vs0．61±0．12、0．29±0．09vs0．38±0．10、2．30±0．81vs3．34±0．75（L／min）、1.31±0．71vs1．98±0．49（L／min·m2）,P＜0.05或P＜0．01］。结论DDD起搏器治疗能显著改善缓慢性心律失常心力衰竭病人的血流动力学,可作为治疗缓慢性心律失常并心力衰竭的有效方法之一。     

Ventricular arrhythmia revealing mitochondrial myopathy in a 69-year-old woman

We report a case of mitochondrial myopathy (MM), assessed byhistological and biochemical studies. This illness was diagnosedin a 69-year-old patient with myocardiopathy revealed by ventriculararrhythmias. The originality of this case lies in the patient'sage, the mode of onset and the biochemical features (i.e. normalmitochondrial enzymatic complexes but very low respiration whenusing glutamate as a substrate).     

心律平治疗室性及室上性心律失常疗效分析

目的 观察心律平治疗室性及室上性心律失常的疗效及副作用。方法 对于107例经心电图及临床确诊的室性及室上性心律失常患者，按口服心律平剂量不同分为：300mg／d组(33例)、450mg/d组(66例)、600mg/d组(8例)三组，10d为1个疗程；分析心律失常类型、心律平剂量与疗效的关系、副作用及原因。结果 心律平对室性及室上性心律失常总有效率分别为89．6％与79．7％(P＞0．05)；3种剂量与疗效关系不大(P＞0．05)；发生副反应19例，占17．8％，无效17例，占15.9％。结论 心律平对室性及室上性心律失常均；有良好治疗作用，较为安全。     

大豆苷元抗心律失常作用的研究

目的 :研究大豆苷元抗心律失常作用。方法 :常规抗心律失常方法。结果 :大豆苷元 (3.0,5.0mg·kg^-1)对氯仿诱发的小鼠室颤有明显的预防作用 ,大豆苷元 (0.8,1.0mg·kg^-1)对乌头碱诱发的大鼠心律失常有明显的治疗效果。大豆苷元 (0.2,0.3mg·kg^-1)还能对抗肾上腺素诱发的家兔心律失常 ,大豆苷元 (0.03% ,0.05%)能明显降低蟾蜍离体坐骨神经动作电位振幅。大豆苷元 (0.8,1.0mg·kg^-1)对氯化钙诱发的大鼠室颤具有预防作用 ,且能明显的降低大鼠的死亡率。以上作用具有明显的剂量依赖性。结论 :大豆苷元有明显的抗心律失常作用。其抗心律失常作用可能与其抑制Na⁺内流或Ca²⁺ 内流及与阻断-β 肾上腺素受体有关。     

经静脉安置埋藏式心脏复律除颤器的临床应用

目的　评价埋藏式心脏复律除颤器 (ICD)的治疗作用。方法　反复发作室性心动过速 (VT)患者安装 ICD,并随访 18个月。结果　术中测得除颤阻抗为 5 9欧 ,除颤阈值 <10 J。术后复发室性心动过速 ,均经 ICD治疗成功转复室性心律 ,有效率 10 0 %。结论　 ICD能有效转复恶性心律失常     

西藏高原移居内地人群心律失常分布特点分析

目的 :探讨西藏高原移居内地人群与世居内地人群心律失常分布的异同特征。方法 :选择从西藏高原移居成都市的汉族成人 5 0 0例为观察组 ,世居成都市的汉族成人 5 0 0例为对照组 ,就两组抽样调查人群数、性别、年龄及居住社区点进行配对 ,通过问诊查体及心电图和 /或动态心电图作出相应心律失常诊断。计数资料以病例数及百分比表示 ,两组数据采用卡方检验 ,P≤ 0 0 5有显著意义。结果 :观察组与对照组心律失常总检出率无明显差异(P >0 0 5 ) ,且与性别无关 (P值均 >0 0 5 ) ;但从检出的心律失常亚组人群中观察组窦性心动过缓高于对照组 (P <0 0 5 ) ,而窦性心动过速又不如对照组高 (P <0 0 5 )。心律失常与病种关系中 ,风心病致心律失常以对照组多见 (P <0 0 5 ) ,且主要为心房颤动。结论 :西藏高原移居内地人群心律失常总发生率与世居内地人群机遇相当 ,然而高原低氧环境致窦性心动过缓者显示部分人群并不因移居内地而逆转 ,但预后较好 ;世居内地人群窦性心动过速者因病种不同而发生率相对较高 ,但预后相对要差 ;心律失常与病种关系两组分布并不完全一致 ,风心病所致心律失常结果提示成都地区风心病患病率高于西藏地区     

温阳益气养阴活血法治疗缓慢性心律失常52例

目的:观察温阳益气养阴活血法治疗缓慢性心律失常的疗效.方法:治疗组52例采用自拟升率汤口服,对照组26例口服阿托品片,治疗1个月.结果:治疗组总有效率92%,对照组总有效率72%,两组有显著性差异,P＜0.05.结论:保元汤化裁方口服对缓慢性心律失常的疗效相对较好.     

Outcome of fetuses with heart disease diagnosed in utero

OBJECTIVE—To review the outcomes of 193 fetuses with cardiac abnormalities detected by echocardiography.METHODS—A total of 422 fetuses between 16 and 41 gestational weeks, referred to paediatric cardiologists for detailed echocardiography, were included in this study.RESULTS—Structural heart defects were found in 55 (28%), isolated arrhythmia in 105 (54%), and other non-structural abnormalities (dilated cardiomyopathy, hypertrophic cardiomyopathy, aneurysm of the foramen ovale, isolated pericardial effusion or echogenic foci) in 33 (17%) of 193 fetuses. Total mortality was 26%. The prognosis was poor in fetuses with structural heart defects; 37 of 55 cases (67%) died in utero or postnatally. Chromosomal abnormality was associated with structural heart defect in 38% of fetuses, of whom 38% died. Among fetuses with isolated arrhythmia survival was 95%. Poor outcome was associated with complete heart block (n=14) in 2 (14%) fetuses with hydrops and heart rate of less than 55 per minute, and with supraventricular tachycardia (n=21) in three (14%) neonates delivered prematurely at a mean gestational age of 33 weeks. Furthermore, nine of 12 fetuses (75%) with structural heart defects and arrhythmia died. Among fetuses with non-structural cardiac abnormalities, survival was 73%. Poor outcome was evident in fetuses with dilated cardiomyopathy in eight of 13 (62%) and with hypertrophic cardiomyopathy in one of eight (13%) of cases.CONCLUSIONS—Factors associated with a poor prognosis were: structural heart defect associated with chromosomal abnormality or arrhythmia, congestive heart failure associated with supraventricular tachycardia or complete heart block, especially if delivery occurs preterm; and fetal hydrops with congestive heart failure and atrioventricular valve regurgitation.