阿魏酸钠与胺碘酮对家兔心室肌电生理作用的频率依赖性影响

与典型的Ⅲ类抗心律失常药物胺碘酮对比 ,研究在整体条件下阿魏酸钠对家兔心室肌电生理特性频率依赖性的影响。 16只家兔随机分为阿魏酸钠组与胺碘酮组 ,应用单相动作电位 (MAP)技术和心脏电刺激方法测定电生理参数 ,比较用药前后、窦性心律及不同起搏频率下心室肌有效不应期 (ERP)、MAP复极 90 %时程 (MAPD90 )的变化。胺碘酮用药后 15min ,在窦律及 180 ,2 0 0 ,2 2 0次 /分起搏频率下 ,MAPD90 的变化率分别为 5 1.5 2± 13.99,5 2 .35±14.5 0 ,5 6 .19± 14.6 3,5 7.15± 16 .6 6 (% ) ,ERP的变化率分别为 5 6 .34± 15 .6 6 ,6 0 .32± 17.0 1,6 1.2 4± 15 .5 4,6 1.0 2±14.0 3(% ) ;阿魏酸钠用药后 2 5min ,在窦律及 2 5 0 ,2 70 ,2 90次 /分起搏频率下 ,MAPD90 的变化率分别为 18.5 3± 3.78,15 .71± 4.41,18.0 0± 6 .12 ,2 0 .48± 5 .6 2 (% ) ,ERP的变化率分别为 18.2 5± 4.6 7,19.76± 3.6 4,2 1.31± 4.18,19.2 5±4.38(% )。结果表明 :阿魏酸钠与胺碘酮作用相似 ,用药后不同起搏频率与窦律时的ERP、MAPD90 变化率及ERP/MAPD90 比值的变化差异无显著性 ,P >0 .0 5。结论 :在整体条件下 ,阿魏酸钠延长心肌复极无逆频率依赖性     

门冬氨酸钾镁及其联合普罗帕酮对家兔心室肌电生理的影响

探讨门冬氨酸钾镁 (KMA)及其与普罗帕酮 (Pr)联合应用对心脏电生理的影响。将动物随机分组 ,分别静脉注射KMA、Pr以及KMA +Pr,采用心外膜单相动作电位 (MAP)记录技术于家兔左心室记录MAP。结果 :KMA、Pr、KMA +Pr各组均延长窦性心动周期 (SCL)、MAP复极达 5 0 %时程并增加心室有效不应期 (VERP) ;Pr、KMA +Pr还增加MAP复极达 90 %时程 (MAPD90 )及VERP/MAPD90 。较大剂量Pr有致心律失常作用 ,KMA与Pr联合使用心律失常发生率增加。结论 :KMA具有抗心律失常药物的电生理特性 ,单独应用推荐剂量的KMA是安全的 ;KMA与Pr联合应用的心脏电生理效应是两药各自作用程度的叠加。为避免致心律失常风险 ,KMA与Pr联合应用时应相应减小Pr剂量     

阿魏酸钠与胺碘酮对家兔心室肌细胞L型钙通道电流的影响

目的探讨阿魏酸钠对家兔心室肌细胞膜L型钙通道电流(ICa-L)的影响。方法酶解法急性分离兔单个心室肌细胞,以经典的Ⅲ类抗心律失常药物胺碘酮为对照,应用膜片钳全细胞记录技术观察3,10,30,100μmol/L的阿魏酸钠对心室肌细胞膜ICa-L的作用。结果阿魏酸钠及胺碘酮均呈浓度依赖性抑制L型钙电流。3,10,30,100μmol/L的阿魏酸钠对ICa-L的抑制率分别为11.1%±2.4%,26.9%±6.2%,40.5%±5.0%,61.9%±5.5%(P<0.05);1,3,10,30μmol/L的胺碘酮对ICa-L的抑制率分别为21.1%±3.8%,32.6%±2.6%,52.6%±4.6%,71.4%±7%(P<0.05);半数抑制浓度分别为32.6及9.5μmol/L,阿魏酸钠的抑制作用弱于胺碘酮(P<0.05)。阿魏酸钠及胺碘酮均能使ICa-L电流-电压曲线上移,稳态激活曲线右移,失活曲线左移,并可减慢钙通道灭活后的恢复过程。结论阿魏酸钠对ICa-L具有浓度依赖性阻滞作用,使ICa-L的激活减慢,失活加快,并且失活后的恢复时间延长,可能是其抗心律失常作用的电生理机制之一。     

胺碘酮抗心律失常的新认识

胺碘酮为一有效的抗心律失常药，但因有多种不良作用而使其应用受到限制。近看来 的深入研究证明，小剂发碘酮疗法有高效且耐受良好。胺磺酮治疗能降低病死亡，尤其对心肌梗塞病例。当心肌梗塞病例忌用阻滞剂时，改用胺碘酮治疗能与β阻滞剂一样降低病死率。     

胺碘酮肺中毒

胺碘酮肺中毒是胺碘酮治疗最严重的并发症之一,是胺碘酮心外副作用中最危险者。1962年胺碘酮问世至1980年间国际文献中尚无胺碘酮肺部合并症的报道,1980年Rotmensch等首次报道胺碘酮引     

四氢巴马汀对家犬心室肌单相动作电位时程使用依赖性的研究

目的 :利用单相动作电位 ( MAP)技术研究在整体条件下四氢巴马汀对家犬心室肌 MAP时程的使用依赖性。方法 :同时记录家犬 ( 12只 )右室心尖部的 MAP和体表标准 II导联心电图 ,比较给药前后和在窦性心律以及 2 3 0、2 60、2 90、3 2 0次 /min起搏频率下心室肌有效不应期 ( ERP)、MAP复极 5 0 % ( MAPD50 )和复极 90 %( MAPD90 )的变化。结果 :给药 3 0 min( 2 0 m g/kg)后 ,在同一起搏频率下 ,ERP、MAPD50 、和 MAPD90 均明显延长 ,与给药前相比差异有极显著性意义 ( P <0 .0 1) ;随起搏频率增加 ,ERP、MAPD50 和 MAPD90 逐渐缩短 ,但比较给药后不同起搏频率与窦性心律时的 ERP、MAPD50 和 MAPD90 变化率以及 ERP/MAPD90 比值的变化 ,则差异无显著性意义 ( P >0 .0 5 )。结论 :在整体条件下 ,四氢巴马汀无逆向使用依赖性。     

胺碘酮的临床应用

历时二年余由本刊与赛诺菲 圣德拉堡 民生制药有限公司合作开展的可达龙 (盐酸胺碘酮 )临床应用征文活动已圆满结束 ,共收到论文 12 9篇 ,内容涉及心律失常各个方面 ,其中关于心房颤动的论文最多为 49篇 ,室性心动过速的论文次之为 43篇。此外 ,还涉及到胺碘酮对细胞因子、心肌存活的影响。副作用主要涉及到肺、甲状腺的影响以及与其他心律失常药合用时对致心律失常的影响。全国除广西、内蒙、宁夏、青海、江西没有获得征文外 ,其他省市自治区包括西藏均参加了此次征文活动。投稿以北京最多为 16篇 ,广东次之为 13篇。评选出优秀论文10篇 ,获奖论文 8篇。本刊此期组织专家述评、专题讲座及征文选登 ,旨在交流经验 ,在胺碘酮应用中求得一些共识 ,推动我国心律失常药物研究及治疗工作。     

美托洛尔对家兔在体心脏早期后除极的电生理作用

目的研究美托洛尔对家兔在体心脏早期后除极(EAD)的影响,以探讨美托洛尔治疗室性心律失常的机制。方法应用接触电极记录心内膜单相动作电位(MAP)技术,观察氯化绝诱发EAD时使用美托洛尔对心脏的电生理作用。结果美托洛尔可以减低EAD的振幅[其EAD％达(26.25±1.84)％],与对照组比较[其EAD％达(33.8±4.36)％]差异有显著性意义(P＜0.05)。结论后除极是心律失常发生的机制之一,美托洛尔对EAD有抑制作用,为美托洛尔治疗某些心律失常提供了理论依据。     

胺碘酮抗心律失常临床应用的评价

胺碘酮具有广泛、多种而独特的电生理效应和药理学作用,对各种快速心律失常均有明显疗效。其成功率和毒副反应的发生率,临床报道差别很大,与患者年龄、有无基础心脏病及其心功能状态、心律失常的特殊机理及药物的累积剂量等密切相关。     

胺碘酮对家兔急性心肌缺血左室跨壁复极离散度的影响

目的:探讨胺碘酮对家兔急性缺血左室心肌楔形组织块电生理特性和跨壁复极离散度（TDR）的影响及其抗缺血心律失常的机制。方法: 建立冠状小动脉灌注家兔左室心肌楔形组织块模型,应用浮置玻璃微电极和心电图同步记录技术,观察急性无灌流心肌缺血时,胺碘酮对内外层心肌细胞的动作电位时程（APD）、TDR和心律失常的影响。结果: ①左心室楔形组织块停止灌注后,胺碘酮组内、外膜心肌细胞的APD较对照组明显延长[(228±19) ms vs.(212±6) ms,P<0.05］,且外膜APD的延长更明显[(203±15) ms vs.(180±5) ms,P<0.05］。②急性缺血各时间段,APD较缺血前均缩短,以外膜APD缩短更明显,导致TDR增大。用药后TDR明显短于对照组。结论: 胺碘酮可延长内、外膜心肌细胞的APD,且外膜APD的延长明显,并可减小急性缺血心肌的TDR,这可能是其抗心律失常机制的细胞电生理基础。     

阿魏酸钠对早期糖尿病肾病的影响

目的 观察阿魏酸钠对早期糖尿病肾病（DN）的作用。方法 将90例伴有微量白蛋白尿的2型糖尿病患者随机分为常规治疗组（RTG组）和阿魏酸钠治疗组（SFG组）,进行治疗观察。结果 与治疗前比较,SFG组UAER及尿ET均显著降低（P＜0．01）,并且脂质代谢紊乱亦有改善;而RTG组UAER与尿ET治疗前后比较,差异无显著性（P＞0．05）。结论 阿魏酸钠具有降低DN患者肾脏尿微量白蛋白的排泄和改善脂代谢的作用,其机制可能与拮抗ET与其受体结合有关。     

Evidence for voltage-dependent block of cardiac sodium channels by tetrodotoxin

The effects of tetrodotoxin (TTX) on cardiac sodium channels in guinea-pig ventricular muscle were investigated. Membrane potential was controlled using a single sucrose gap voltage clamp method, and the maximum upstroke velocity of the ventricular action potential (Vmax) was used as an indicator of drug-free sodium channels. Reduction of Vmax by TTX was found to be both voltage- and time-dependent, similar to the effects of many local anesthetic drugs, with the exception that TTX concentrations high enough to produce significant use-dependent block (e.g. 2 microM), also produced significant tonic block, even at potentials negative to -85 mV. The mechanism underlying use-dependent block was determined by defining the time course of block development at potentials between -40 and +20 mV, and the time course of recovery at -85 mV. In 2 microM TTX, the time course of block development at +20 mV contained two phases, a fast phase (tau less than 3 ms) having a mean amplitude of 8.1 +/- 3.2% of control Vmax, and a slow phase (tau = 429 +/- 43 ms) having an amplitude of 35 +/- 2% of control Vmax (n = 5). Recovery from use-dependent block at -85 mV occurred with a time constant of 324 +/- 58 ms (n = 5). The effects of TTX could be well-described by a modulated receptor model with an estimated 12 mV drug-induced shift of inactivation, and state-dependent dissociation constants of 10, 4 and 0.3 microM for rested, activated and inactivated channels. These same drug rate constants could also be used to adequately simulate the reported effects of TTX on plateau sodium currents in a variant model with slow inactivation kinetics.     

Importance of sodium ions in the protective effects of high-potassium, high-glucose solution on electromechanical activities in the guinea-pig myocardium

The protective effects of high-K, high-glucose solution (GK solution) on electromechanical activity in the isolated guinea-pig ventricular muscle were studied. The basal test solution (basal GK solution) contained 30 mM KCl, 230 mM glucose and 4 mM NaHCO3, that is nominally Ca-free. Various types of GK solutions were also prepared by modifying the composition of this solution. When the muscle was exposed to the basal GK solution, the resting potential fell to about -40 mV, the muscle lost the excitability, and an irreversible contracture gradually developed. This contracture was prevented by elevating [Na]o above 60 mM. Reduction of [K]o to 20 mM, addition of EGTA (0.4 mM), or lowering the temperature (23 degrees C) also suppressed the above contracture. When the GK solution with high Na (106-115 mM NaCl added to basal GK solution in exchange for glucose) was applied, contractures frequently developed upon reintroduction of Tyrode solution (Ca-paradox-like phenomenon). Thus the Ca-free GK solution with 60 mM Na (56 mM NaCl added to basal GK solution in exchange for glucose) induced no contracture, either during or after the test period. Recovery of the action potential after this application was all but complete. On the other hand, addition of 0.9 to 1.8 mM Ca to this solution produced another type of contracture which was sensitive to verapamil. The cardioplegic effects of the Ca-free GK solution with 60 mM Na persisted under hypoxic conditions, and glucose appeared to play a significant role in preventing the hypoxia-related contracture. In contrast, the high-Na (110 mM Na) GK solution containing 0.2 to 0.5 mM Ca and Tyrode solution, both of which produced no contracture under normoxic conditions, did produce contractures under hypoxic conditions. Therefore, Ca-free GK solution containing an appropriate concentration (around 60 mM) of Na may protect the normoxic and hypoxic myocardium against intracellular Ca overload. The related mechanisms involved were discussed with special reference to membrane functions and intracellular Ca-regulating systems.     

胺碘酮和索他洛尔对家兔不同部位心室肌细胞电生理特性的影响

目的　观察胺碘酮和索他洛尔对家兔跨左心室壁不同部位心肌细胞电生理特性的影响 ,从组织水平探讨两种药物致尖端扭转性室性心动过速 (torsadedepointes,TdP)发生率不同的原因。方法　采用标准玻璃微电极记录技术 ,记录心外膜心肌、中层心肌和心内膜心肌的跨膜动作电位 (trans membranceactionpotential,TAP)。在不同基础周长 (basiccyclelength ,BCL)刺激下 (2 50～ 2 0 0 0ms) ,分别观察 0 3～ 3 0 μmol·L- 1 浓度的胺碘酮和 1 0～ 1 0 0 μmol·L- 1 浓度的索他洛尔对 3种心肌TAP的影响。结果　胺碘酮频率依赖性和浓度依赖性地延长 3种心肌的动作电位时限 (actionpotentialduration ,APD90 ) ,由于 3种心肌的APD90 延长程度近似 ,用药后跨心室壁复极离散度 (transmuraldispersionofre polarization ,TDR)无明显增加。索他洛尔呈逆频率依赖性和浓度依赖性地延长 3种心肌的APD90 ,与心外膜心肌和心内膜心肌相比 ,中层心肌的APD90 延长更明显 ,使TDR明显增加 ,且随着剂量的增加这种作用更为显著。在 2 0 0 0msBCL刺激时 ,1 0 0 μmol·L- 1 浓度的索他洛尔诱发早期后除极 (earlyafterde polarization ,EAD) ,胺碘酮无此作用。 结论　胺碘酮和索他洛尔对跨心室壁不同部位心肌细胞电生理特性产生不同的     

Electrophysiologic correlates of the inotropic effects of Isoproterenol in canine myocardium

The action of l-isoproterenol was studied in isolated canine papillary muscles. The simultaneous action potential and contraction traces were first recorded in digital form on magnetic tape and later measured and analyzed by a computer program. The data were controlled and grouped to permit a three-way analysis of variance in order to test significant effects and correlations. Complete dose-response curves were performed both before and after beta-adrenergic blockade with (±)propranolol. It was demonstrated that isoproterenol produced and increase in the peak potential, the height and duration of the plateau (phase 3), and the rate of repolarization of the action potential (phase 4). Corresponding increases in peak tension, time to peak tension, rate of tension development, and rate of relaxation of the contraction were noted. At the highest isoproterenol concentrations, occasional after-potentials and after-contractions occurred. The changes in the action potential were explained by changes in the inward calcium current, while the inotropic effect on the contraction was attributed to the resulting increase in intracellular calcium concentration. These effects were all blocked by the addition of propranolol, but the blockade could be overcome by increasing the isoproterenol concentration of the perfusate.