碘杂环化合物IHC—72对心肌部分除极和触发活动的影响

用常规玻璃微电极技术，观察３，６－（二甲氨基）－二苯骈碘杂环依地酸盐对豚鼠右室乳头肌细胞膜部分除极引发的慢反应动作电位、哇巴因引发的延迟后除极及触发活动的影响。２．５μＭＩＨＣ－７２对ＳＡＰ各参数均无影响；２５．４，１０１．６μＭＩＨＣ－７２分别使动作电位时程缩短７．１％和４１％。     

普罗帕酮、维拉帕米对豚鼠乳头肌延迟后除极和触发电活动的影响

应用标准玻璃微电极技术，研究哇巴因诱发豚鼠心室乳头肌的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的变化规律及特点；探讨普罗帕酮和维拉帕米对ＤＡＤ和ＴＡ的影响。结果表明：①心室肌细胞在高浓度Ｃａ２＋条件下加哇巴因灌流时可以出现ＤＡＤ及ＴＡ，ＴＡ的诱发率为７７．８％（７／９）。②心室肌细胞诱发的ＤＡＤ幅度（ＤＡＤ－Ａｍｐ）、ＤＡＤ偶联间期（ＤＡＤ－Ｃ）和ＤＡＤ升支上升速率（ＤＡＤ－ｄｖ／ｄｔ）呈明显的频率依赖性，即刺激频率愈快，ＤＡＤ－Ａｍｐ愈高、ＤＡＤ－ｄｖ／ｄｔ愈快，ＤＡＤ－Ｃ则愈短。③上述两种抗心律失常药物均通过降低ＤＡＤ－Ａｍｐ、减慢ＤＡＤ－ｄｖ／ｄｔ和延长ＤＡＤ－Ｃ而发挥其抗触发性心律失常作用；两者对哇巴因诱发的ＤＡＤ和ＴＡ的抑制作用无显著性差异，在普罗帕酮或维拉帕米的作用下，哇巴因对ＴＡ的诱发率分别为３３．３％（３／９）和２２．２％（２／９），与哇巴因的诱发率（高钙条件下，７７．８％）比较Ｐ＜０．０１。     

环孢素A治疗Ⅰ型糖尿病临床研究

将３３例新发病的Ⅰ型糖尿病（ＩＤＤＭ）随机分为两组。治疗组接受环孢素Ａ（ＣｓＡ）和胰岛素治疗３～６个月，对照组单纯以胰岛素治疗。治疗第３、６和９个月时，治疗组完全缓解率分别为５２．９％、４６．７％和４０．０％；对照组为１２．５％、６．３％和６．３％（Ｐ＜０．０１、０．２５和０．０５）。缓解率与病程有关。治疗第６个月时，治疗组糖刺激状态的Ｃ肽水平明显高于对照组（Ｐ＜０．０５）。ＣｓＡ治疗后，外周血ＯＫＴ＿４／ＯＫＴ＿８细胞比值降至正常水平。平均最高血肌酐水平上升１１．９％，未发现严重副作用。ＣｓＡ治疗可保护和改善胰岛功能，促进发病早期ＩＤＤＭ缓解。     

武汉地区Ⅱ型糖尿病患者冠心病与载脂蛋白E基因型的关系

应用聚合酶链反应（ＰＣＲ）技术，对随机选择的１２５例ＮＩＤＤＭ患者和５０例非ＤＭ患者进行ＡｐｏＥ基因型检测，以研究ＮＩＤＤＭ患者ＣＨＤ与ＡｐｏＥ基因型间的关系。结果表明，ＮＩＤＤＭ患者心肌梗塞和缺血性心电图改变在Ａｐｏε４／４和ε４／３型组中发生率分别为２１％和４１％，但不同基因型组间差异无显著性。心绞痛在Ａｐｏε４／４和ε４／３型组中为５２％，显著高于ε３／３型组（３１％，Ｐ＜０．０５）。Ａｐｏε４／４和ε４／３型ＮＩＤＤＭ患者，任何证据的ＣＨＤ发生率为７２％，显著高于ε３／３型组（３７％）及ε２／２、ε３／２型组（３３％，Ｐ＜０．０１）。ＮＩＤＤＭ患者中ＣＨＤ组Ａｐｏε３／３和ε４／３基因型频率分别为５２％和３４％，分别低于（ε３／３）、高于（ε４／３）非ＣＨＤ组（７１％，Ｐ＜０．０５；１０％，Ｐ＜０．０１）；ＣＨＤ组ε４等位基因频率为２１％，明显高于非ＣＨＤ组（７％，Ｐ＜０．０１）。提示Ａｐｏε４／４和ε４／３为ＮＩＤＤＭ患者ＣＨＤ的重要危险指标。     

联合检测循环抗原和抗体在血吸虫病基本控制地区应用价值的研究

血吸虫病基本控制地区７岁以上的人群共８４７名为检测对象，应用抗日本血吸虫ＣＣＡ单克隆抗体ⅢＤ１０建立的Ｄｅｔ－ＥＬＩＳＡ检测血吸虫循环抗原（ＣＡｇ），ＥＬＩＳＡ和ＩＨＡ检测循环抗体（ＣＡｂ）。结果ＣＡｇ的阳性检出率为３．１９％，ＥＬＩＳＡ和ＩＨＡ检测ＣＡｂ的阳性检出率分别为６．２６％和９．４５％，两者的检出车间差异有显著性（Ｐ＜０．０１），ＣＡｇ与ＣＡｂ（ＥＬＩＳＡ和ＩＨＡ检测）的联合检出率分别为６．８５％和１０．５１％，两者联合检测能提高检出率。     

家兔十二指肠粘膜碳酸氢盐分泌机理的研究

本实验旨在探讨ＨＣＯ３－分泌的调节及其转运的离子通道。取大白兔近端十二指肠，置于尤氏小室间（ＵｓｓｉｎｇＣｈａｍｂｅｒ），测定血管活血肠肽（ＶＩＰ）、前列腺素Ｅ２（ＰＧＥ２），二丁酰环磷腺甙（ｄｂ－ｃＡＭＰ）及电刺激（ＥＦＳ）对碳酸氢盐（ＨＣＯ３－）分泌量、电流（Ｉｓｃ）和电位差（ＰＤ）的影响，以及缺氧、缺氯、缺钠和加入ＤＩＤＳ（４，４－ｄｉｉｓｏｔｈｉｏｃｙａｎｏｓｔｉｌｂｅｎｅ－２，２’－ｄｉｓｕｌｆｏｎｉｃａｃｉｄ）、哇巴因（Ｏｕａｂａｉｎ）和神经毒素（Ｔｅｔｒｏｄｏｔｏｘｉｎ，ＴＴｘ）后对上述指标的影响。结果示，ＶＩＰ、ＰＧＥ２、ｄｂ－ｃＡＭＰ和ＥＦＳ均刺激ＨＣＯ３－分泌和Ｉｓｃ、ＰＤ的升高，而缺氧、缺钠和哇巴因呈抑制作用。ＤＩＤＳ和缺氯则完全抑制由ＰＧＥ２引起的刺激作用，部分抑制（５０％）由ＶＩＰ的刺激作用，而对ｄｂ－ｃＡＭＰ则无抑制作用。ＴＴＸ抑制由ＥＦＳ引起的作用。ＨＣＯ３－分泌与ＶＩＰ、ＰＧＥ２及ｄｂ－ｃＡＭＰ引起的细胞内ｃＡＭＰ水平不成正相关。     

强烈化疗治疗小儿急性淋巴细胞白血病临床研究

目的：观察强烈化疗治疗小儿急性淋巴细胞白血病（ＡＬＬ）的疗效。方法：８３ 例ＡＬＬ患儿用ＣＯＤＰＬ方案诱导治疗,缓解后用ＣＡＴ、ＨＤＭＴＸ、ＥＡ、ＶＰＤＬ方案早期巩固强化治疗,用ＭＴＸ、６－ＭＰ、ＶＰ、ＣＯＰ、Ａｒａ－Ｃ维持治疗,用ＣＯＡＰ、ＥＡ、ＶＰＤＬ方案定期加强治疗,用ＨＤＭＴＸ联合三联鞘注对庇护所白血病进行预防。结果：完全缓解（ＣＲ）率９６．４％ （８０／８３）;３ 例在诱导期死于败血症。６８例坚持治疗的患儿,中位随访３７（１８～１０８）个月,５ 年持续完全缓解（ＣＣＲ）率７６．２％ 。标危ＡＬＬ和高危ＡＬＬ的５ 年ＣＣＲ率分别为７９．６％ 和７２．９％ 。结论：强烈化疗及坚持治疗是提高小儿ＡＬＬ５年ＣＣＲ率的关键;严重感染仍是治疗失败的主要原因。     

联合检测循环抗原和抗体在血吸虫病基本控制地区应用价值…

血吸虫病基本控制地区７岁以上的人群共８４７名为检测对象，应用抗日本血吸虫ＣＣＡ单克隆抗体Ⅲ Ｄ１０建立的Ｄｏｔ－ＥＬＩＳＡ检测血虫循环抗原（ＣＡｇ），以ＥＬＩＳＡ和ＩＨＡ检测循环抗体（ＣＡｂ）。结果ＣＡｇ的阳性检出率为３．１９％，ＥＬＩＳＡ和ＩＨＡ检测ＣＡｂ的阳性检出率分别为６．２６％和９．４５％，两者的检出率间差异有显著性（Ｐ〈０．０１），ＣＡｇ与ＣＡｂ（ＥＬＩＳＡ和ＩＨＡ检测）的联合检出率分别     

净化及非净化自体骨髓移植治疗白血病39例临床研究

报告自体骨髓移植治疗白血病３９例，其中非净化自体骨髓移植（ＡＢＭＴ）１４例，净化自体骨髓移植（ＰＡＢＭＴ）２５例。中位年龄２８岁（１０～４３岁）。ＡＭＬ２７例，ＡＬＬ１０例，ＣＭＬ２例。ＣＲ１３１例，ＣＲ２７例，ＮＲ１例。ＣＲ至移植时间中位数６．７个月（２～１９个月）。预处理方案：ＴＢＩ加Ａｒａ－ｃ、ＤＮＲ或ＶＰ１６。ＡＢＭＴ组及ＰＡＢＭＴ组３年无病生存（ＤＦＳ）率分别为６８．３２％及６７．５７％，复发率为３０．７６％及２６．８０％。但ＰＡＢＭＴ组ＡＭＬ患者３年ＤＦＳ率为８２．３５％及ＣＲ２期移７５％３年ＤＦＳ率为７５％，明显高于ＣＲ。期移植未净化者５０％。化疗组３年ＤＦＳ率为７．３８％及复发率７６．４％，两移植组疗效优于化疗组。     

老年NIDDM患者apoE等位基因频率变化的研究

为研究老年ＮＩＤＤＭ患者ＡｐｏＥ等位基因频率的变化，采用ＰＣＲ技术检测了４０￣８０岁ＮＩＤＤＭ患者１４０例的ａｐｏＥ基因型。结果表明，老年组ε４等位基因率为８．６％，明显低于非老年组的１７．９％（Ｐ〈０．０５）。当调整年龄和性别的影响后，ＮＩＤＤＭ患ε４和ε３与ＴＣ呈正相关（Ｐ分别〈０．０１及〈０．０５），ε４与ＬＤＬ－Ｃ呈正相关（Ｐ〈０．０１）。故我们推测，携ε４的ＮＩＤＤＭ患者ＴＣ和ＬＤＬ－Ｃ     

Study of the effects and mechanisms of berberine on slow-response action potentials

The effects of berberine on slow-response action potentials (SAP) of guinea pig papillary muscles were studied. SAP was elicited by histamine in a high concentration of potassium solution (27 mmol). The results showed that berberine (24.5 mumol) was able to increase action potential amplitude, maximum rate of depolarization, action potential duration 50, action potential duration 100 (n = 16, p less than 0.01) and effective refractory period (n = 10, p less than 0.01) of SAP by 6.2%, 21.1%, 50.1%, 47.2% and 92.2%, respectively, but did not affect the resting membrane potential (RMP). To the above parameters, except APD 100, berberine was no longer to induce any significant change by pretreating with propranolol. The results suggested that the effects of berberine on slow-response action potentials were mainly related to the facilitating of slow calcium inward current, which might result from stimulating the beta-adrenoceptor.     

黄芩甙对大鼠心室肌细胞触发性心律失常的影响及其机制

目的研究黄芩甙对触发性心律失常的影响,探讨黄芩甙抗心律失常的机制。方法酶解法分离大鼠心室肌细胞,全细胞膜片钳技术记录黄芩甙作用前后的L型钙电流(ICa-L)的变化,外科手术得到心室乳头肌,标准玻璃微电极技术记录黄芩甙作用前后跨膜动作电位(TAP)的变化以及哇巴因诱发的延迟后除极(DAD)和触发活动(TA)的影响。结果①在电压钳制下,黄芩甙对ICa-L均有明显抑制作用,随浓度的增加,对ICa-L的抑制作用逐渐增强。10,20和40μmol/L的黄芩甙对ICa-L的最大电流密度抑制作用分别由15.8±1.2pA/pF减小到11.3±0.9,8.2±0.8,4.9±0.6pA/pF(P均<0.05)。黄芩甙对ICa-L的抑制作用具有非常好的量效性,半效抑制浓度为27.7±1.9μmol/L。显著上抬I-V曲线。②20μmol/L黄芩甙明显缩短动作电位时程,抑制哇巴因诱导的DAD和TA。结论黄芩甙能抑制触发性心律失常,这可能与黄芩甙抑制心肌细胞ICa-L内流,减少细胞内Ca2+超载有一定关系。     

异丙肾上腺素对犬心房肌细胞动作电位及L型钙电流的影响

目的研究两种浓度的异丙肾上腺素(Isoproterenol,ISO)对犬心房肌细胞(AP)及L型钙电流(ICa,L)的作用。方法采用离体灌注和消化的方法获取心房肌细胞,用全细胞记录技术记录单个心房肌细胞AP以及ICa,L。结果低浓度ISO(10nmol/L)可延长APD,可使90%AP时程(APD90)延长34.4%,并降低AP平台期水平。高浓度ISO(1μmol/L)可减少APD,APD90减少32.1%。两种浓度的ISO均可诱发AP后除极及触发活动。10nmol/L和1μmol/LISO分别增加ICa,L36.7%和49.3%。结论两种浓度的ISO对心肌细胞ICa,L均有促进作用,Ca2+内流引起的肌浆网Ca2+释放可能是房性心律失常的发生机制之一。     

Arrhythmogenic Effects of Quinidine on Catecholamine-Induced Delayed Afterdepolarizations in Canine Atrial Fibers

Arrhythmogenic Effects of Quinidine on Catecholamine-induced Delayed Afterdepolarizations. We studied the effects of quinidine and tetrodotoxin (TTX), two drugs that block Na⁺ channels, on delayed afterdepolarizations (DAD) caused by norepinepbrine in atrial fibers of the canine coronary sinus. At long stimulus cycle lengths of 10 seconds, quinidine increased the amplitude of the afterdepolarizations and caused triggered activity within 1–2 minutes. Simultaneously, action potential duration (APD) was lengthened but upstroke velocity was not decreased. Prolonged exposure to quinidine eventually decreased upstroke velocity but DAD amplitude remained larger than control and triggered activity was still induced more easily. The effects of quinidine to increase afterdepolarizations was partially related to its prolongation of the APD since shortening APD with repolarizing current decreased DAD amplitude. However, DAD amplitude remained larger than control indicating that quinidine caused triggering by other mechanisms as well. TTX, on the other hand, which blocks Na⁺ channels but shortens APD, decreased DAD amplitude and triggered activity. Part but not all of these effects resulted from the shortening of APD by TTX since prolongation of APD with depolarizing current only partially restored DAD amplitude. Anti-arrhythmic drugs, therefore, may have effects on DADs that partly result from changes in the APD. Quinidine may cause cardiac arrhythmias by virtue of its effects to potentiate triggered activity.     

Histamine induced or enhanced delayed afterdepolarization and triggered activity in guinea-pig papillary muscles. A preliminary study

We used standard microelectrode techniques to study the histamine induced or enhanced delayed afterdepolarization (DAD) and triggered activity (TA) of guinea-pig papillary muscle superfused with low-potassium Tyrode's solution. Before histamine, a series of driven action potentials did not induce DAD and TA. Immediately after histamine (10(-5)M), DAD was induced and, finally, TA was induced after high rate pacing (150/min to 300/min). The effect of histamine was antagonized by cimetidine (5 X 10(-6) to 5 X 10(-5)M) but not by diphenhydramine. Also, the amplitude of DAD decreased after verapamil (10(-7) to 3 X 10(-6)M) and lidocaine (4 X 10(-5) to 8 X 10(-5)M). To investigate indirect evidence of increased cyclic AMP mediation in this histamine induced DAD, we studied the effects of a phosphodiesterase inhibitor (papaverine 10(-5)M) or activator (N-methylimidazole 20 mM) on the histamine induced or enhanced DAD. The former enhanced and the latter depressed the histamine-induced (or enhanced) DAD. Thus, histamine may induce or enhance the DAD and TA by increasing the slow inward current. This mechanism may be mediated by histamine H2-receptors and the adenylate cyclase system in the cardiac ventricular muscle.     

Effects of Flunarizine on Impulse Initiation in Canine Purkinje Fibers

Effects of Flunarizine on Impulse Initiation. Introduction: The calcium channel blocker, flunarizine, selectively blocks accumulation of intracellular calcium during conditions of calcium overload. It has been reported to selectively terminate delayed after depolarization-induced arrhythmias in intact dogs. Methods and Results: Using standard microelectrode techniques, we studied the effects of flunarizine on the transmembrane action potential and various arrhythmogenic mechanisms in canine Purkinje fibers. Flunarizine significantly decreased the fast response action potential duration at 50% repolarization in a concentration-dependent manner (10-⁸ to 10-⁵M), but had no effect on maximum diastolic potential, overshoot, maximum upstroke velocity (V_max), or APD at 90% repolarization. For Ca²⁺-induced slow response action potentials, flunarizine decreased the overshoot, and prolonged action potential duration at both 50% and 90% repolarization. It had no effect on automaticity of Purkinje fibers exposed to solutions containing either low [K⁺] or barium chloride. Flunarizine, 10-⁵M, inhibited the development of both ouabain-induced and calcium- and catecholamine-induced delayed after depolarizations. It did not inhibit the development of cesium-induced early afterdepolarizations. Conclusions: Thus, in vitro, flunarizine selectively suppresses delayed after depolarizations and has no effects on early afterdepolarizations or normal or abnormal automaticity. Hence, its utility in intact animal models of triggered arrythmias is borne out mechanistically in these isolated tissue studies. (J Cardiovasc Electrophysiol, Vol. 3, pp. 306–314, August 1992)     

维拉帕米对缺血-再灌注豚鼠乳头肌电生理的保护作用

目的:研究再灌注心律失常发生机制及维拉帕米的保护作用.方法:采用标准微电极细胞电生理方法.结果:对照组RMP,APA,APD50,Vmax,ERP随缺血时间的延长而降低,随正常充氧台氏液的复灌而回复,20分钟后恢复对照状态.维拉帕米治疗组复灌20分钟除ERP,APD90外APA,APD50,Vmax未恢复至对照状态.对照组10例标本均发生了再灌注心律失常,6/10例为室早,5/6例于复灌4.5±2.6分钟时出现DAD或EAD,并发生触发性室早.4/10例发生持续性心动过速,持续10.4±5.0分钟.快速起搏可以超速抑制,但不能终止.治疗注组8/10例未出现心律失常,仅2/10例发生室早,均未记录到EAD或DAD.结论:触发活动及自律性增高是再灌注心律失常的主要发生机制,维拉帕米可有效地拮抗再灌注心律失常的发生.     

自发性高血压大鼠左心室流出道自发性电活动的特征

利用玻璃微电极细胞内记录方法 ,记录了自发性高血压大鼠 (SHR)和Wistar鼠左心室流出道自发性慢电位和自发性快电位的特征。结果发现 ,SHR自发性快电位的动作电位时程 (APD)、复极至 5 0 %时间 (APD50 )和复极至 90 %的时间 (APD90 )均明显长于Wistar鼠 (P <0 0 1) ;SHR的自发放电频率 (RPF)明显慢于Wistar鼠 (P <0 0 5 )。结果提示 :SHR左心室流出道自发性的快电位和慢电位均表现为APD、APD50 和APD90 的延长 ,RPF减慢     

乙酰胆碱对离体豚鼠心房肌动作电位及其脱敏的影响

目的 :研究迷走神经递质乙酰胆碱 （ACh）对离体豚鼠心房肌细胞动作电位 （AP）的影响及其对心房肌的脱敏 ,探讨脱敏可能发生的机制。方法 :采用标准玻璃微电极细胞内记录方法 ,观察不同浓度 （0 .0 1,0 .1,1μm ol/ L） ACh对心房肌细胞 AP的影响及对动作电位时程 （APD）和收缩力的脱敏现象 ,并观察了受体或通道水平的阻断剂阿托品、氯化铯 （Cs Cl）对 ACh所致的心房肌 APD脱敏的影响。结果 :10 .0 1,0 .1,1μm ol/ L ACh分别缩短 APD的变化率为 （6 .0 2± 1.0 4） % ,（14.2 0± 3.79） % ,（30 .2 0± 3.6 5 ） %。 2 0 .0 1μmol/ L ACh对心房肌细胞没有脱敏 ;0 .1μm ol/ L ACh对心房肌细胞 APD有轻微脱敏 ,脱敏持续时间为 1m in;而 1μmol/ L ACh对心房肌细胞 APD脱敏明显 ,脱敏持续时间为 5 m in。 31μmol/ L 阿托品与 2 0 m mol/ L Cs Cl并不能阻断 1μmol/ L ACh对心房肌细胞APD的脱敏。结论 :ACh缩短 APD的作用随浓度增大而增大 ;ACh对离体豚鼠心房肌细胞 APD的脱敏有浓度依赖性与时间依赖性 ;脱敏的发生可能与毒蕈碱型胆碱能受体及 Ik,ACh电流有关。