阿斯匹林精氨酸对兔缺血心肌不应期和室颤阈变化的影响

实验观察了阿斯匹林精氨酸(AAs)对兔缺血心室肌不应期(ERP)和室颤阈(VFT)的影响。结果表明,阻断冠脉50min时,血小板聚集率(PAgR)增大11±5%,VFT降低24±3mA;缺血边缘区ERP较缺血10 min时缩短20±10 ms,缺血中心区延长35±12 ms,两区间不应期离散性(Di)增加52±17ms,各数值均与对照值差异显著(p<0.01)。阻断冠脉前0.5 hⅳAAs,上述参数变化明显减轻,与单纯阻断组缺血50 min时各数值变化相比,均p<0.01。结果提示,AAs具有抑制PAgR、减小Di和提高VFT的作用。     

西洋参茎叶总皂甙的药理、毒理研究

西洋参茎叶中提取的总皂甙,ip25和50mg/kg,可使小鼠自发活动次数由对照组的64.4±18.4减少为16.8±4.4和4.3±2.5(p<0.01);ig425和850mg/kg由73.3±19.7减少为30.8±14.6和18.4±4.8(p<0.01);ig850mg/kg能使阈下剂量的戊巴比妥钠催眠时间持续30.0±0.0min(p<0.01);ip20mg/kg和ig850mg/kg小鼠耐缺氧平均存活时间由对照组的37.6±8.2和37.5±7.7min延长为48.6±8.6和68.3±21.8min(p<0.01);ig30和60mg/kg,可对抗环磷酰胺引起的WBC减少。ip和ig给药,LD_(50)分别为204±SE2.6mg/kg和8511±SE1061mg/kg;长期毒性实验表明,动物体重、脏器重量、WBC、Hcmo各组间无显著差异,GPT、ZTT及TTT均在正常值范围,动物脏器经病理组织学检查属基本正常。     

蝙蝠葛碱犬体内药代动力学研究

目的研究不同给药途径及剂量的蝙蝠葛碱 (Dau)在犬体内药代动力学特征。方法采用拉丁方设计对5只犬进行静注、灌胃2种给药途径及5个剂量的实验 ,用HPLC_UV法测定血药浓度 ,计算药代动力学参数。结果犬静注Dau6mg·kg-1后 ,药物符合二室开放模型线性动力学消除过程 ,t1/2(α)6～12min ,K12>K21,t1/2 (β)(2.7±0.4)h ,Vd11.18L·kg-1。Dau灌胃给药后各犬C_T曲线呈显著双峰现象 ,各剂量组tpeak(1) 为 (0.8±0.6)～ (1.2±0.5)h ,tpeak(2)为(5.2±3.2)～ (6.5±1.9)h ,Cmax(2)一般小于相应的Cmax(1)。在12.5～25mg·kg-1范围Dau呈线性消除 ,两者t1/2(el)、CL、AUC/X0 等重要药代动力学参数均无显著性差异 (P>0.05) ,AUC随给药剂量成比例上升 ;在50mg·kg-1 以上剂量时 ,药物消除呈非线性 ,t1/2(el)、CL、AUC/X0等重要参数显著改变 (P<0.05) ,AUC超比例增加。结论灌胃给药后 ,Dau在犬体内广泛分布并从血液中迅速清除。在50mg·kg-1以下剂量时 ,最大血药浓度、AUC剂量依赖性增加 ,药物消除呈线性特征 ,超过此剂量 ,药物t1/2(el)、CL明显延长 ,提示大剂量下药物消除存在饱和动力学特征。     

蝙蝠葛碱对在体家兔左心室单相动作电位和有效不应期的影响

目的:研究蝙蝠葛碱(Dau)和索他洛尔对在体家兔左心室单相动作电位和有效不应期的作用.方法:采用单相动作电位测定技术记录家兔在体心脏单相动作电位,用程序电刺激法测定左心室有效不应期.结果:Dau 0.5mg·kg~(-1)·min~(-1)恒速静脉灌注明显降低单相动作电位幅度,由用药前的(17±6)mV降至给药后24min的(7.1±1.5)mV.Dan显著延长单相动作电位复极50％和90％时程及有效不应期,给药前分别为(130±26),(167±25),(128±12)ms,给药后24min分别延长至(198±33),(235±34),(185±25)ms.但对有效不应期与单相动作电位时程(MAPD_(90))之比值无明显影响.索他洛尔对上述各指标的作用与Dau相似.结论:研究结果表明,Dau和索他洛尔降低单相动作电位幅度,延长单相动作电位时程和有效不应期.     

纳络酮对猫体感诱发电位的影响

观察吗啡受体拮抗剂纳络酮(Naloxone)对氯胺酮麻醉状态下猫SEP的影响。采用刺激腕部正中神经记录对侧相应大脑皮层体感区诱发电位,观察到两组用药前CCT_p,CCT_(MN)及AMP分别为:生理盐水组6.3±1.1,10.9±1.8ms,15.2±6.0μV。纳络酮组6.5±0.6,10.5±0.6ms,19.2±6.4μV.用药后(纳络酮5mg/kg iv)AMP明显上升达用药前的2倍以上,而CCT_P或CCT_(MN)改变不明显。生理盐水组SEP也大致上有所增加,但两组间差异无显著性。说明大剂量纳络酮主要影响中枢神经元细胞的电活动而对神经纤维传导功能影响较小,从而表现出纳络酮对神经系统作用的选择性。     

盐酸尼非卡兰人体药代动力学研究

目的研究注射用盐酸尼非卡兰在中国健康人体的药代动力学。方法健康志愿者24名(男女各半),按体重配对,随机分组。以奥硝唑为内标,采用HPLC-紫外法测定尼非卡兰0.3mg/kg、0.4mg/kg单次静脉推注和0.4mg/kg静脉推注后以0.4mg·kg-·1h-1速度连续静脉输注6小时给药尼非卡兰时血浓度,采用《DAS2.0》程序计算其主要药代动力学参数。结果24名健康志愿者0.3mg/kg、0.4mg/kg静脉推注及注射用盐酸尼非卡兰0.4mg/kg的负荷剂量后,再给予注射用尼非卡兰0.4mg·g-1·h-1连续静脉输注,血清中尼非卡兰Cmax分别为(230.946±54.023)、(358.615±73.984)和(444.303±88.122)ng/ml;t1/2分别为(1.545±0.382)、(1.344±0.188)和(1.348±0.227)h;AUC0-t分别为(193.526±45.194)、(285.608±46.569)和(2609.02±498.200)ng·h·ml-1。结论HPLC法测定尼非卡兰血浓度血浆中内源性物质不干扰测定,方法简单,操作方便;尼非卡兰静脉注射给药人体内呈线性药代动力学过程;整个试验过程顺利,静脉推注和静脉输注给药志愿者无不良反应发生。     

甲基莲心碱对豚鼠心肌电—机械活动的影响

甲基莲心碱(Nef)0.1mM使豚鼠右心室乳头状肌的收缩力降低68. 3％,使动作电位APA和Vmax分别从112±5mV,240±37V/s降低到97±9 mV和86±25V/s;APD_(50),APD_(90)和ERP分别从173±23ms,205±17ms和201±16ms延长到201±26ms,239±28ms和249±23ms。Nef 1-200μM浓度依赖性地延长APD_(50),APD_(90)和ERP,降低Vmax和收缩力。30μM Nef能明显对抗10μM乙酰胆碱缩短豚鼠左心房APD的作用。结果提示,Nef对心肌Na~+,K~+,Ca~(2+)的跨膜转运均有抑制作用。     

环孢菌素对麻醉药作用的影响

本文报道小鼠肌注单剂量环孢菌素对戊巴比妥引起的睡眠作用和芬太尼的镇痛作用的影晌.给小鼠肌注环孢菌素60mg/kg,2h后,腹腔注射戊巴比妥钠50mg/kg,测定小鼠翻正反射消失到恢复的时间,测得小鼠睡眠时间为70.4±4.2min(n=6),与给予相同剂量戊巴比妥钠对照组(睡眠时间为30.4±3.2min)相比较,其睡眠时间延长2.3倍.小鼠分组肌注     

注射用丹参多酚酸盐对豚鼠心脏电生理和hERG电流的影响

目的：研究注射用丹参多酚酸盐（ZDDY）对豚鼠心脏电生理的影响,并对注射用丹参多酚酸盐的心脏安全性做出评价。方法：采用常规豚鼠在体心电图技术,改进的Langendoff灌流系统,常规细胞内动作电位记录法和膜片钳全细胞记录方法,观察药物对整体和离体心电图,动作电位时程（Action Potential Durations,APDs）以及人ether-a-go-go-related gene(hERG)通道电流的影响。结果： ZDDY 460.0 mg?kg-1使在体心电图PR间期从（61.0±2.8）ms延长到（70.9±0.9）ms;QRS间期从（15.3±1.8）ms延长到（17.0±2.1）ms,比较差异均具有统计学意义。ZDDY 0.51 mg?mL-1使离体心脏的心率(Heart Rate,HR)从（177.3±11.1）bpm减慢到（152.0±1.7）bpm,差异具有统计学意义。ZDDY 各浓度组对APDs和动作电位振幅(Amplitudes of Action Potential,APA)无影响。ZDDY 抑制50%hERG电流的浓度(Half Maximal Inhibitory Concentration,IC50)为（10.8±0.6）mg?mL-1。结论： 注射用丹参多酚酸盐在临床剂量下对豚鼠在体心脏作用安全;高剂量下对离体豚鼠心脏有减慢心率作用。     

O-甲基蝙蝠葛碱对麻醉犬ECG和血流动力学的影响

OMD系Dau的衍生物。本实验研究OMD 2.5mg/kg iv对14只麻醉犬的ECG和血流动力学的影响。实验发现,OMD具有明显降低SBP和DBP的作用,随剂量增大作用加强。同时表现出TPR降低,SV增加和PEP/LVET轻度增大。这些与Dau的作用相似。还观察到HR减慢,MPAP和PCWP无明显改变。本品2.5mg/kg对ECG无明显影响,5mg/kg使PR轻度延长,QRS和QTc均无明显改变。该结果与Dau对ECG的影响有明显差异,已有报道后者在同等剂量时明显延长PR和QRS。     

阿魏酸钠对家兔心室肌单相动作电位的影响

目的　探讨阿魏酸钠对心肌细胞单相动作电位的影响。方法　健康家兔 2 0只 ,随机平均分为两组 :对照组 (苄基四氢巴马汀组 )和实验组。按传统心内膜MAP记录方法经右颈外静脉插入四极接触电极导管至家兔右心室内膜记录MAP信号并同时记录Ⅱ导联心电图。对照组经耳缘静脉给予苄基四氢巴马汀 ( 5mg·kg-1) ,实验组给予阿魏酸钠( 0 6g·kg-1) ,给药前、后观察MAPA、MAPD5 0、MAPD90及ERP。结果　对照组用药前MAPA及MAPD2 0分别为( 2 7 0 1± 0 67)mV及 ( 79 0 5± 7 0 4 )ms,用药后分别为( 2 6 87± 0 73 )mV及 ( 77 5± 7 170 )mV(P >0 0 5 ) ;用药2 0 0 1 0 2 15收稿 ,2 0 0 1 0 4 13修回1 贵州省人民医院心内科 ,贵阳　 5 5 0 0 0 22 包头钢铁职工医院 ,包头　 0 14 0 0 0作者简介 :李　屏 ,女 ,36岁 ,医学硕士 ,副主任医师。Tel:0 85 1 5 934 319,E mail:lipingb @hotmail.com ;曾秋棠 ,男 ,36岁 ,医学博士 ,副教授 ,硕士生导师前MAPD5 0、MAPD90、ERP分别为 ( 97 5± 6 770 )ms、( 12 3 5± 5 80 )ms、( 111± 13 5 0 )ms,用药后分别为 ( 12 4 5± 8 96)ms、( 15 3± 7 5 3 )ms、( 14 2± 13 3 7)ms (P <0 0 1) ;实验组用药前MAPA及MAPD2 0分别为 ( 2 6 5 8±1 0 3 )mV及 ( 75± 5 77)ms,用     

新肌松药溴化双托品铵的药理学研究

溴化双托品铵是以阿托品为原料,合成而得的一种双季铵化合物。实验表明,家兔垂头量为0.134±0.016mg/kg;麻醉猫坐骨神经胫前肌阻断量为0.16±0.029mg/kg,作用持续21±3.9min。经典与电生理方法研究表明,它是一种非去极化型肌松药。家兔连续多次给药时有一定蓄积作用。麻醉猫快速静注给药,可使血压下降。若以缓慢静滴给药,降压作用显著减轻。对ECG则无明显影响。     

Relevance of inter- and intraventricular electrical dispersion to arrhythmogenesis in normal and ischaemic rabbit myocardium: a study with cromakalim, 5-hydroxydecanoate and glibenclamide

This study aimed to investigate the role of electrical dispersion in arrhythmogenesis by using K(ATP) channel modulating agents. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated working rabbit hearts. Cromakalim (10 microM), glibenclamide (3 microM), or 5-hydroxydecanoate (100 microM) were administered before and throughout 30 min of regional ischaemia and 15 min of reperfusion. Before ischaemia, cromakalim reduced MAPD90 and ERP in all areas and facilitated induction of ventricular fibrillation in five of 12 hearts. In these hearts, cromakalim increased interventricular ERP dispersion from 17 +/- 5 to 38 +/- 5 ms. During ischaemia, cromakalim decreased MAPD90 dispersion within the left ventricle from 84 +/- 5 to 44 +/- 4 ms, but did not affect ERP dispersion and arrhythmogenesis. 5-Hydroxydecanoate had no effect on MAPD90 and ERP shortening or dispersion during ischaemia and reperfusion and was not antiarrhythmic. Glibenclamide reduced forward flow to zero, preventing further electrophysiologic studies. In conclusion, in this model, an increase in interventricular ERP dispersion predisposes to ventricular fibrillation in normoxic conditions after cromakalim administration. However, a decrease in ischaemia-induced MAPD90 dispersion by cromakalim does not affect arrhythmogenesis. A lack of effect of 5-hydroxydecanoate on electrical dispersion during ischaemia is accompanied by a lack of antiarrhythmic activity.     

Iloperidone (Fanapt?), a novel atypical antipsychotic, is a potent HERG blocker and delays cardiac ventricular repolarization at clinically relevant concentration

QT interval prolongation on the electrocardiogram (ECG) has extensively been reported with iloperidone, a novel antipsychotic drug. The objective of the present study was to evaluate the effects of iloperidone on cardiac ventricular repolarization at three different levels; in vitro, ex vivo and in vivo. (1) In vitro level: whole-cell patch-clamp experiments were performed on HERG-transfected HEK293 cells exposed to iloperidone 0.01-1 μmol/L (n = 35 cells, total) to assess drug effect on HERG current. (2) Ex vivo level: Langendorff retroperfusion experiments were performed on isolated hearts from male Hartley guinea pigs (n = 7) exposed to iloperidone 100 nmol/L with/without chromanol 293B 10 μmol/L to assess drug-induced prolongation of monophasic action potential duration measured at 90% repolarization (MAPD(90)). (3) In vivo level: ECG recordings using wireless cardiac telemetry were performed in guinea pigs (n = 5) implanted with radio transmitters and treated with a single oral gavage dose of iloperidone 3 mg/kg. (1) Patch-clamp experiments revealed an estimated IC50 for iloperidone on HERG current of 161 ± 20 nmol/L. (2) While pacing the hearts at stimulation cycle lengths of 200 or 250 ms, or during natural sinus rhythm (no external pacing), iloperidone 100 nmol/L prolonged MAPD(90) by respectively 9.2 ± 0.9, 11.2 ± 1.6 and 21.4 ± 2.3 ms. After adding chromanol 293B, MAPD(90) was further prolonged by 7.3 ± 3.3, 11.5 ± 2.3 and 29.2 ± 6.7 ms, respectively. (3) Iloperidone 3mg/kg p.o. caused a maximal 42.7 ± 10.2 ms prolongation of corrected QT interval (QTc(F)), 40 min after administration. Iloperidone prolongs the QT interval, the cardiac action potentials and is a potent HERG blocker. Patients are at increased risk of cardiac proarrhythmia during iloperidone treatment, as this drug possesses significant cardiac repolarization-delaying properties at clinically relevant concentration.     

Ischemia-induced action potential shortening is blunted by d-sotalol in a pig model of reversible myocardial ischemia

The purpose of this study was to investigate, in an anesthetized pig model of low-flow myocardial ischemia, the electrophysiologic effects of the class III drug d-sotalol during myocardial ischemia. Serial monophasic action potential (MAPD90) recordings and refractory period determinations from the anterior and posterior left ventricular wall were taken in 25 pigs during baseline, after low-flow posterior wall ischemia, after d-sotalol infusion under nonischemic conditions, and after repeated posterior wall ischemia while continuing the drug. Measurements were done at 60 and 150 beats/min after radiofrequency ablation of atrioventricular conduction. At baseline, MAPD90 and refractory periods were comparable in the anterior and posterior wall (323 +/- 15 vs. 318 +/- 10 ms, and 267 +/- 10 vs. 262 +/- 11 ms at 60 beats/min, respectively). In the absence of d-sotalol, low-flow regional ischemia was associated with a significant shortening of MAPD90 in the posterior versus the anterior wall (267 +/- 20 vs. 317 +/- 20 ms at 60 beats/min; p = 0.006). Similarly, ischemia-induced shortening of the refractory periods in the posterior wall was apparent (230 +/- 16 ms in the posterior wall vs. 274 +/- 14 ms in the anterior wall at 60 beats/min). In contrast, ischemia was no longer associated with shortening of MAPD90 (360 +/- 17 ms posterior wall and 360 +/- 20 ms anterior wall at 60 beats/min) and refractory periods (304 +/- 19 ms posterior wall vs. 316 +/- 15 ms anterior wall at 60 beats/min) during combined posterior wall ischemia and d-sotalol infusion. Similar findings were obtained during pacing at 150 beats/min. d-Sotalol attenuates ischemia-induced action potential shortening. This property should decrease dispersion of cardiac repolarization and be antiarrhythmic. On the other hand, longer APD under ischemic conditions may favor calcium overload, which may trigger new arrhythmias.     

Antiarrhythmic and electrophysiologic effects of sublingual ibutilide fumarate

Ibutilide fumarate is a class III antiarrhythmic agent in phase III clinical trials. Due to rapid hepatic metabolism, ibutilide has a low oral bioavailability (< 10%). To assess alternate routes of administration, we performed repeated studies of the electrophysiologic effects of sublingual ibutilide (0.03, 0.1, and 0.3 mg/kg; 0.07, 0.2, and 0.7 m?mol/kg) in pentobarbital anesthetized dogs. Peak significant increases in QTc interval, ventricular effective refractory period (VERP), and right ventricular monophasic action potential duration (MAPD90) were achieved 30 min following 0.1 or 0.3 mg/kg (0.2 and 0.7 m?mol/kg) ibutilide and were coincident with peak plasma ibutilide levels. The duration of significant effects ranged from 2 to 5 h. Peak effects were: QTc + 121 msec, MAPD90 + 71 msec, and VERP + 53 msec. The 0.3 mg/kg (0.7 m?mol) dose significantly decreased heart rate 10 min post dosage through 5 h. The 0.03 mg/kg (0.07 m?mol) dose increased MAPD90 at 1 to 2 h but was otherwise ineffective. The plasma half life of ibutilide was 2.8 h, with a 72% bioavailability relative to an equivalent intravenous dose. Based on the electrophysiologic results, we chose to test the 0.1 mg/kg (0.2 m?mol) sublingual ibutilide dose for termination of sustained atrial flutter in anesthetized dogs with y-shaped right atrial incisions. The administration of 0.1 mg/kg (0.2 m?mol) sublingual ibutilide during sustained atrial flutter resulted in termination of atrial flutter in all cases (n = 4) after a mean time interval of 11.4 ± 0.8 min. Termination of atrial flutter was associated with ibutilide plasma levels of 19.6 ± 6.3 ng/ml, and 30 and 18 msec increases in atrial and ventricular effective refractory periods. Atrial flutter could be reinduced in 2 dogs, on at 3 h and one at 4 h post ibutilide administration. The ability to reinduce atrial flutter was associated with a reduction in ibutilide plasma levels to 2.3 ± 0.7 ng/ml. We conclude that sublingual ibutilide is rapidly absorbed and produces significant electrophysiologic and antiarrhythmic effects, and is a potential alternative to intravenous and oral therapy. ©1995 Wiley-Liss, Inc.     

Effects of the type-1 Na+/H+-exchange inhibitor cariporide (Hoe 642) on cardiac tissue

Ischemia leads to intracellular acidification which can be counteracted by the Na⁺/H⁺-exchange mechanism. A blockade of this exchanger has been hypothesized to cause stronger intracellular acidification in the course of ischemia thereby protecting the heart from ischemic damage. The aim of our study was to find out (1) whether in the course of ischemia areas become electrically silent, (2) whether this is enhanced by the Na⁺/H⁺-exchange inhibitor cariporide (4-Isopropyl-3-methylsulfonylbenzoyl-guanidine; Hoe 642) and whether cariporide has protective effects. Therefore, we submitted isolated rabbit hearts, perfused according to the Langendorff technique to regional ischemia (LAD occlusion) for 30 min followed by 30 min reperfusion with (n=7) or without (n=7) pre-treatment with 1 μM cariporide. Under these conditions 256-channel epicardial potential mapping was carried out. Under non-ischemic conditions cariporide did not alter any of the parameters under observation. We found that ischemia led to marked alterations of the activation pattern, to action potential shortening and a marked increase in the dispersion of refractoriness. In the ischemic region there was a significant ST deviation from the isoelectrical line (control 32±10; 30 min ischemia: 290±35 arbitrary units [a.u.]). This was markedly reduced by cariporide (control 39±10; 30 min ischemia: 170±25 a.u.). The increase in dispersion by ischemia (by 50±5 ms) was significantly counteracted by cariporide (increased dispersion by 20±4 ms). In a similar way the alteration of the activation pattern was antagonized. Under the influence of cariporide we found a lower increase in the left ventricular enddiastolic pressure, and a significantly slower recovery of the action potential duration. After 30 min of ischemia 24±5 (control series) 24.5±5 mm² (cariporide) became electrically silent. In a second series of experiments the incidence of arrhythmia was assessed: we found ventricular fibrillation in 6/7 untreated control hearts and in 4/7 cariporide treated hearts. In a third series of experiments we determined the intracellular [ATP] after 30 min of LAD occlusion using a histochemical method. We observed a decrease in [ATP] in the ischemic region as compared to the non-ischemic right ventricular wall, which was less pronounced in cariporide-treated hearts. Thus, we conclude that (1) cariporide protects the heart from ischemic damage and (2) at least under these conditions an enlargement of the electrically silent area did not occur. Received: 8 August 1997 / Accepted: 23 March 1998     

甲基莲心碱对兔心内传导系统的影响

在麻醉兔观察了甲基莲心碱(Nef)对心内传导功能的影响。Nef 4 mg/kg iv明显延长兔SACT和CSNRT,增大SNRTI,表明对窦房结传导功能有显著抑制作用。Nef恒速iv 1～8 mg/kg,剂量依赖性地延长兔HBE A—H和H—V,增宽V波,使ECGP—R延长,这些作用与奎尼丁相似。结果表明Nef对心脏房—室、希氏束—浦肯野纤维—心室肌的传导有显著的抑制作用。     

Blockade of IKs by HMR 1556 increases the reverse rate-dependence of refractoriness prolongation by dofetilide in isolated rabbit ventricles

1. The rate-dependent contributions of the rapid and slow components of the cardiac delayed rectifier K+ current (IKr and IKs, respectively) to repolarization are not fully understood. It is unclear whether the addition of IKs block will attenuate reverse rate-dependence seen after IKr block. 2. The individual and combined electrophysiological effects of selective IKr and IKs blockers, dofetilide and HMR 1556, respectively, were evaluated using Langendorff-perfused rabbit hearts. Monophasic action potential duration at 90% repolarization (MAPD90) and ventricular effective refractory period (VERP) were determined at cycle lengths (CLs) of 200-500 ms (at 50 ms intervals). 3. Dofetilide (1-100 nM) prolonged MAPD90 in a concentration-dependent manner (P < 0.001, n = 6) with reverse rate-dependence (P < 0.0001). In contrast, HMR 1556 (10-240 nM) alone did not prolong MAPD90. However, in the presence of 7.5 nM dofetilide, HMR 1556 (100 nM) increased the extent of reverse rate-dependence by further prolonging MAPD90 at CLs of 400, 450 and 500 ms (P < 0.05, n = 9) and, to a lesser extent, at shorter CLs (e.g. by 17 +/- 4 ms at CL 500 vs 2 +/- 3 ms at CL 200 ms). 4. Effects of dofetilide and HMR 1556 on VERP were similar to those on MAPD90. The slope of the VERP vs CL relation was steeper after the combination (0.081 +/- 0.013) than after dofetilide alone (0.028 +/- 0.018, P < 0.01, n = 9). 5. Blockade of rabbit IKs increased reverse rate-dependence of IKr block.     

粉防己碱对麻醉兔心内传导系统的影响

在麻醉兔观察了粉防已碱对心内传导功能的影响,粉防已碱8mg/kg iv后10min,明显延长兔SACT、SNRT和SNRTc,使SNRTI增大,说明其对窦房结传导功能和自律功能有显著的抑制作用。粉防已碱恒速iv 3～15mg/kg,剂量依赖性地抑制房-室传导,使HBE A-H和ECG P-R延长,但对H-V和V波无明显影响,这与奎尼丁不同。结果表明粉防已碱只抑制室上性传导,对室内传导无影响。