血管紧张素Ⅱ及缬沙坦对犬心房肌细胞外向钾通道电流的作用

目的观察血管紧张素Ⅱ及缬沙坦对犬心房肌细胞外向钾通道电流的作用,探讨其参与房性心律失常的细胞电生理机制。方法急性分离单个犬心房肌细胞,采用全细胞膜片钳方法记录细胞膜快速延迟整流钾电流（Ikr）、缓慢延迟整流钾电流（Iks）、超快速延迟整流钾电流（Ikur）及短暂外向钾电流（Ito）。结果0.5μmol/L AngⅡ可增加Ikr、Iks,抑制Ito,对Ikur无明显影响;5μmol/L缬沙坦对Ikr、Iks、Ikur及Ito均有抑制作用。结论AngⅡ可能通过对外向钾电流的影响促进AF时的AER,缬沙坦作为AT1受体阻滞剂,可改善AF时的AER,对AF有防治作用。     

铅抑制大鼠背根神经元外向延迟整流钾通道

目的观察铅对电压依赖性外向延迟整流钾通道的作用。方法运用膜片钳技术，在急性分离的成年大鼠背根神经节细胞（DRGs）上进行。结果记录到DRG神经元外向延迟整流K+电流（IK），并观察到铅对IK的明显影响，1.0、2.0、4.0、8.0μmol/LPb2+作用后，IK平均分别减少（8.6±0.8）％、（38.6±6.2）％、（63.0±5.1）％和（89.0±8.8）％。Pb2+作用起效甚快，在Pb2+充分作用后，以普通外液冲洗，IK可得到不同程度的恢复。结论铅在较高浓度可阻断成年大鼠背根神经元电压依赖性外向延迟整流钾通道，这种阻断作用是剂量依赖性的、可逆的。     

钾离子外流在小鼠精子获能中作用

目的观察钾离子外流在小鼠精子体外获能的作用及机制。方法以金霉素（chlortetracycline，CTC）荧光染色后涂片观察小鼠精子体外获能率，进一步应用膜片钳技术在小鼠生精细胞膜上记录延迟整流钾离子电流（IDRK）。结果终浓度为50nmol／L的钾离子通道载体缬氨霉素处理小鼠精子，其B型精子发生率（％）与对照组相比显著增加（n=10，P〈0．05）；50nmol／L缬氨霉素显著增大小鼠粗线期精母细胞延迟整流钾离子电流，上调其Ⅰ-Ⅴ曲线。结论缬氨霉素通过激活延迟整流钾通道，增加胞内钾离子的外流，促发小鼠精子体外获能。关键词：精子细胞：体外获能：延迟整流钾通道：缬氧雹素     

半夏泻心汤含药血清对豚鼠胃窦平滑肌细胞影响

半夏泻心汤由半夏、黄芩、干姜、人参、炙甘草、黄连、大枣七味中药组成.以往研究表明,半夏泻心汤具有明显的调节胃肠运动作用[1-2].但对其作用机制方面的研究相对不足,特别是半夏泻心汤作用与胃平滑肌离子通道电流的关系报道较少,为探讨半夏泻心汤调节胃肠运动作用靶点,深入研究其作用机制,本实验用急性分离的豚鼠胃窦环行肌细胞和膜片钳等技术,观察半夏泻心汤含药血清对豚鼠胃窦环行肌细胞膜电位与毒蕈碱受体门控电流的影响.现将结果报告如下.     

长QT综合征的遗传学研究进展

长QT综合征(LQTS)是一组编码心肌细胞离子通道及相关蛋白基因突变,与恶性心律失常及心脏性猝死密切相关的遗传性心脏离子通道病。目前发现LQTS有17个亚型,共15个致病基因。LQTS主要遗传方式为常染色体显性遗传,以及常染色体隐性遗传,即伴有耳聋的Jervell和Lange-Nielsen综合征。最常见的LQT1、LQT2和LQT3亚型,约占LQTS的80%。LQT1和LQT2致病基因分别为编码心脏缓慢延迟整流钾电流(IKs)通道和快速延迟整流钾电流(IKr)通道α亚基的KCNQ1和KCNH2基因,LQT3致病基因为编码心脏电压门控钠通道(Nav1.5)钠通道α亚基的SCN5A基因。随着高通量测序在临床的广泛应用,LQTS基因诊断阳性率越来越高,对其致病基因和发病机制研究不断深入,有望实现对患者个性化精准诊治。     

模拟缺血时兔心室肌细胞快钠通道跨壁异质性的变化

目的探讨缺血时心肌细胞钠通道的异质性变化。方法以酶解法分离兔心室肌三层细胞,先后用正常和缺血液灌流模拟正常和缺血状态,并采用膜片钳全细胞记录法观察三层心室肌细胞快钠通道的活性和异质性变化。结果缺血后三层细胞失活曲线均左移,失活加速,三层细胞间INa失活半电压差异发生变化;缺血30 m in时INa灭活后恢复曲线与原来的三层细胞间由差异无统计学意义(P>0.05)变为差异有统计学意义(P<0.05)。各层细胞自身INa灭活后恢复随着缺血时间延长而减慢,但无统计学意义;缺血后三层细胞的钠电流(INa)电压依赖性、I-V曲线的形态轨迹未变,INa峰电流密度减小,三层细胞间峰电流密度差异发生变化。结论缺血时心肌钠通道的活性发生变化,从而影响心室肌三层细胞间INa的异质性及与通道电流平衡,与缺血性心律失常的发生有关,并可部分解释抗心律失常药物在正常和缺血心肌的不同作用。     

22例快速室上性心律失常静注胺碘酮复律疗效分析

胺碘酮原作为冠状动脉扩张药,后发现其抗心律失常作用而作为抗心律失常药广泛应用于临床,按Vaughan Williams分类法,归为Ⅲ类抗心律失常药.主要通过抑制电压依赖性钾通道,使外向钾电流受抑,动作电位(APD)和有效不应期(ERP)延长,而起抗心律失常作用,多用于室上性和室性快速心律失常的治疗[1].     

乐果对豚鼠心血管功能影响的实验研究

目的 探讨乐果对豚鼠心血管功能的影响。方法 用多导生理记录仪，分别在染毒前、染毒后立即(0min)、15、30、45、60min记录颈动脉血压和心室为压变化微分值峰值(dp/dt max)。按标准II导联记录心电图，测量心率、QT间期，PR间期、ST段变化，记录心律失常等。结果 豚鼠在给予大剂量乐果后，心率下降明显，QT间期以及PR间期延长，ST段压低，并出现多种心律失常；在染毒后5min血压即开始下降，心室内压变化微分值峰值也降低。预先给予阿托品可以明显延长动物存活时间，改善心律失常，但不能缓解QT延长等心电图改变，血压下降和心功能减弱也不能被缓解。结论 有机磷农药乐果可引起心血管功能紊乱。     

柯萨奇病毒B3感染大鼠心室肌钙通道基因表达及其功能变化

目的探讨柯萨奇病毒B3(CoxsackieviruB3,CVB3)感染大鼠心室肌钙通道的基因表达特点及其功能改变。方法取1~3日龄新生SD大鼠15只行心室肌细胞原代培养,将培养48 h且已形成规律搏动的心室肌细胞随机分为病毒感染组(CVB3株感染培养,n=8)与正常对照组(n=7),比较两组大鼠的细胞形态、结构变化特点等;采用半定量逆转录聚合酶链反应(RT-PCR)检测两组大鼠L型钙通道亚单位mRNA的表达;应用全细胞膜片钳技术对CVB3感染前后心室肌细胞L型钙电流(ICa-L)变化进行测定,记录细胞膜电容(Cm)、电流密度、电压依赖性激活与失活等动力学参数。结果正常心室肌细胞主要表现为三角形、梭形、多边形等形态,搏动规律有力,搏动细胞百分比>95%;接种CVB3培养3 d后细胞搏动开始减慢且呈不规律搏动,细胞变圆、扁梭,折光性增强,最终停止搏动、脱落、死亡;CVB3感染3 d后,溶酶体增多,线粒体空泡变形,细胞核肿胀,核膜破裂。病毒感染组心室肌细胞L型钙通道α1和β亚单位mRNA表达水平分别为(4.02±0.07)、(2.08±0.06)均高于正常对照组(P<0.05);而两组α2/δ亚单位mRNA表达水平差异无统计学意义。在-20~+10 mV测试电压下,病毒感染组ICa-L密度为(-8.65±0.99),较正常对照组明显增加(P<0.05);但CVB3感染培养对大鼠心室肌细胞Cm、电压依赖性激活与失活特性无显著影响。病毒接种后第4天,病毒感染组CVB3特异蛋白基因片段RNA均为阳性,正常对照组CVB3特异蛋白基因片段RNA均为阴性,差异有统计学意义(P<0.05),病毒感染组病毒接种1~4 d CK-MB浓度均高于正常对照组(P<0.05)。结论 CVB3感染大鼠心室肌细胞L型钙通道α1和β亚单位mRNA表达上调,ICa-L密度增大,可能是CVB3感染对心室肌细胞产生损伤作用的病理机制。     

洋地黄中毒的治疗进展(下)

毒性心律失常治疗进展一、快速型心律失常的治疗;包括室性早搏,快速型房性,交界性和室性心律失常 1.钾治疗:临床上如无窦缓,Ⅱ—Ⅲ度房室传导阻滞,肾功能衰竭,高血钾症,即使血清钾正常也应使用。因为钾能与洋地黄竞争受体,延迟或减少洋地黄同心肌的结合;钾还可降低心肌的自律性和应激性,减慢舒张期除极速度,从     

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.     

Molecular genetics of the long QT syndrome: clinical aspects

The long QT syndrome (LQTS) is a heart disorder which is characterised by the prolongation of the QT interval of the surface electrocardiogram and is associated with malignant arrhythmias, syncopal episodes, torsade de pointes form ventricular tachycardias and an increased risk of sudden cardiac death. There are two familial forms of LQTS, the autosomal dominant Romano-Ward syndrome and the autosomal recessive Jervell-Lange-Nielsen syndrome which is associated with congenital senzorineural deaf-mutism. Recent advances in molecular genetics have allowed to identify mutations in four genes, KvLQT1 (11p15.5), HERG (7q35), SCN5A (3p21) and minK (21q22), which cause LQTS. There is a fifth genetic locus known on chromosome 4 (4q25-27), where the disease causing gene has not been identified yet. As LQTS genes code proteins which form sodium and potassium channels of the heart, LQTS can be regarded as the disease of cardiac ion channels. The KvLQT1 and minK genes code the slowly activating, delayed rectifier (Iks) potassium channel, the HERG gene code the rapidly activating, delayed rectifier (Ikr) potassium channel of the heart, while the SCN5A gene codes a cardiac sodium channel. Mutations in KvLQT1, minK and HERG genes affects repolarising, rectifier potassium currents, while SCN5A mutations cause delayed inactivation and reopening of the cardiac sodium channel, which initiates the depolarisation of cardiac cells. Both alterations result in a prolongation of cardiac repolarisation which is represented in the elongation of the QT interval. Elucidation of the genetic base of the disease provided new tools in the clinical management of LQTS. It has been shown that changes in the repolarisation parameters on the ECG may be predictive for the causative gene and different LQTS genes are associated with different clinical picture. More importantly, it is possible to use "gene-specific" therapy in LQTS which specifically targets ion channels affected by given gene mutations.     

氯胺酮硬膜外超前镇痛的临床观察

目的观察术前硬膜外腔应用氯胺酮超前镇痛的临床效果。方法80例子宫肌瘤手术患者随机分为两组,每组40例。两组患者手术前硬膜外分别注射氯胺酮30mg(Ⅰ组)和+生理盐水0.6ml(Ⅱ组),手术结束前5分钟两组患者硬膜外腔均给予一次性加入吗啡2mg镇痛。观察术后视觉模拟(VAS)评分、止痛药应用情况及不良反应。结果Ⅰ组和Ⅱ组各时段VAS疼痛评分有显著性差异(p<0.05);Ⅰ组和Ⅱ组各时段使用止痛药人次也有显著性差异(p<0.05)。结论术前硬膜外应用注射氯胺酮具有超前镇痛作用,可以加强吗啡术后镇痛的作用。     

Ketamine as a party drug

Ketamine is a new party drug, which is easy to obtain. For this reason, it is possible that physicians will be increasingly confronted with users that have medical problems. Relatively few cases of ketamine intoxication with a fatal outcome have been reported thus far. Ketamine is very hallucinogenic; people can experience unpleasant flashbacks even weeks after the drug has been eliminated from the body. Ketamine has a short half-life; the elimination half-life is about 2.5 h. A serious intoxication can lead to aspiration, acidosis, rhabdomyolysis, epileptic seizures, respiratory depression, and cardiac arrest. Ketamine is frequently used as a party drug in combination with other substances. As a result, the chance of untoward effects is increased. Anaesthetists use ketamine for short surgical procedures, sedation and analgesia. It is also used more and more often as an analgesic in patients who do not respond well to opioids.     

腰硬联合加氯胺酮麻醉在小儿手术中的应用

目的：观察氯胺酮辅助腰- 硬联合麻醉用于小儿手术的临床疗效.方法：选择择期手术患儿93 例,随机分为观察组50 例（腰-硬联合加氯胺酮麻醉组） 和对照组43 例（氯胺酮静脉复合麻醉）.观察两组患儿麻醉前后平均动脉压（MAP）、心率（HR）、脉搏氧饱和度（SpO2）的变化及氯胺酮药物剂量、术后清醒时间及不良反应的发生情况.结果：两组MAP、HR、SpO2 比较差异无统计学意义,观察组氯胺酮用药剂量、术后清醒时间明显低于对照组（P〈0.05）,不良反应发生率为18.0%（9/50）,与对照组比较差异有统计学意义（P〈0.01）.结论：腰硬联合加氯胺酮麻醉用于小儿手术效果满意,安全性高,是小儿手术的理想麻醉方法.     

Ketamine-associated urological symptoms

Ketamine is used as an anaesthetic and in third-line pain management. Furthermore, recreational use of the drug is becoming increasingly popular due to its dissociative and hallucinogenic effects. Ketamine can affect the urothelium, possibly with long-term damage to the bladder and kidneys. An otherwise healthy, 22-year-old female smoker was referred to our clinic. Shortly after starting recreational ketamine she experienced gross haematuria, urgency, frequency and dysuria. There had been no febrile episodes or flank pain. Her urine cultures were sterile. Physical examination, blood tests, urinary cytology and abdominal ultrasound results were normal. A severely inflamed bladder was seen during cystoscopy. Biopsies showed denuded urothelium and inflammation of the submucosa without malignancy. The precise mechanism of ketamine-associated urological symptoms is currently unknown. Treatment, therefore, is symptom-targeted and cessation of ketamine is imperative. We recommend that ketamine use is considered in patients with otherwise unexplained urological symptoms.     

KETAMINE: THE FORGOTTEN ANAESTHETIC?

ABSTRACT: Ketamine has many properties that are advantageous to the practitioner in a rural setting, particularly if solo. The personal experience of the author is recounted, and a technique for using ketamine is outlined.