血管紧张素Ⅱ对豚鼠乳头肌电生理的作用

目的探讨血管紧张素Ⅱ(AngⅡ)是否具有直接的心脏毒性作用及致心律失常作用.方法采用标准微电极技术记录心肌细胞的单相动作电位,评价AngⅡ对豚鼠乳头肌心肌细胞的电生理作用及其致心律失常作用.结果AngⅡ可以致多种机制的心律失常,AngⅡ(10-5mol/L)灌注1min,动作电位Vmax,APA,APD90,RMP与对照状态比较分别为10.8±4.2∶16.3±7.2V/s,76.8±24.9∶106.7±17.7mV,235.4±58.3∶303.0±73.8ms,61.5±18.2∶92.0±14.8mV,P均<0.05,灌注3分钟APD30及APD50、ERP显著缩短,与对照状态比较分别为98.1±42.2∶124.9±44.0ms,145.5±25.4∶168.7±43.2ms,174.0±22.0∶252.0±24.0ms,P<0.05.结论AngⅡ可以降低动作电位幅度,静息膜电位及Vmax,缩短动作电位时程及有效不应期,具有致心律失常的作用.     

维拉帕米对缺血再灌注损伤心肌保护机制的探讨

目的 :探讨维拉帕米对缺血再灌注损伤心肌的保护作用及其机制。方法 :①建立家兔心肌缺血再灌注模型。将 2 4只家兔按再灌注时限的不同及是否给予维拉帕米 (0 .2mg/kg静脉注射 )干预分为 4组 (A1、A2、B1、B2 ) ,测定各组的心肌梗死范围 ,并在电镜下对缺血再灌注心肌进行超微结构观察。②根据心肌缺血再灌注不同时限对 33只家兔进行分组 ,采用免疫组化法检测同一剂量维拉帕米 (0 .2mg/kg静脉注射 )对缺血再灌注不同时限心肌组织bcl 2蛋白的表达情况。结果 :①与 0 .85 %氯化钠组比较 ,维拉帕米组可明显减小心肌梗死范围(P <0 .0 1) ,改善其超微结构的变化。②与假手术对照组和 0 .85 %氯化钠组比较 ,维拉帕米组能显著上调缺血再灌注心肌bcl 2蛋白的表达 (P <0 .0 1)。结论 :维拉帕米可明显减轻心肌缺血再灌注损伤 ,其心肌保护机制可能是通过其促进缺血再灌注心肌组织bcl 2蛋白的表达来实现的     

单相动作电位与兔心室肌缺血-再灌注的实验研究

目的:观察兔缺血再灌注心室肌心外膜单相动作电位(MAP)形态变化及触发活动与缺血再灌注心律失常的关系。方法:应用心外膜接触电极记录单相动作电位,观察在体兔心室肌缺血／再灌注期不同时段MAP各参数的变化。结果:(1)在缺血区,MAP振幅(MAPA)随着缺血时间的延长而缩短,在再灌注期仍未恢复正常,MAP的90％复极化间期(MAPD90)、MAPD50随着时间延长而缩短,而MAPD90改变尤其显著;(2)急性心肌缺血后5minMAP的心室复极离散度(MAPDd)显著增大(P<0.01),缺血30min时达到最大值。再灌注早期MAPDd也明显增大(P<0.01);(3)30％的缺血性心律失常及70％的再灌注心律失常与早期后去极化(EAD)有关,EAD振幅与室性早搏(VPB)的启动电位呈正相关。结论:急性心肌缺血时MAP的特征性形态变化是判断心肌缺血的一种简易、快速、可靠的方法;MAPDd增大是形成缺血性心律失常的重要电生理指标之一;EAD可能是缺血再灌注心律失常的发生机制之一。     

缺血后适应对急性缺血-再灌注犬心脏保护作用

目的:探讨缺血后适应对急性缺血-再灌注犬心脏保护作用及其与氧自由基关系。方法:21只杂种犬随机平均分为三组:对照组(Con组),结扎左前降支(LAD)1h,再灌注3h;缺血预适应组(Pre-C组),结扎LAD1h前行缺血预适应(5min结扎/5min再灌注,4次循环);缺血后适应组(Post-C组),结扎LAD1h后,再灌注前行缺血后适应(30s再灌注/30s再关闭,3次循环)。实验犬分别于缺血前、缺血1h、再灌注1、2、3h抽血检测丙二醛(MDA)及超氧化物歧化酶(SOD)。实验前、结束时抽血测定血清肌酸激酶(CK);结束时测定心肌梗死范围。结果:再灌注3h后,Pre-C组及Post-C组血清MDA含量低于Con组,P0.05,而SOD活性高于Con组,P0.05。再灌注3h后各组血清CK水平均升高,Pre-C及Post-C组低于Con组,P0.05。心肌梗死范围在Pre-C和Post-C组小于Con组,P0.05。结论:缺血后适应与缺血预适应相似,对缺血-再灌注心脏有保护作用;氧自由基的减少在其保护机制中可能发挥部分作用。     

胰岛素对缺血再灌注的保护作用

文章阐述了胰岛素在中枢神经系统的来源，胰岛素在全脑缺血和局灶性脑缺血中的应用及其神经保护机制，指出胰岛素的应用有望成为缺血性脑血管病的一种治疗方法。     

葛根素对缺血-再灌注损伤器官保护作用的研究进展

葛根素是从豆科葛属植物葛根中提取的一种异黄酮类化合物,具有扩张脑血管和抗脑缺血组织自由基生成等药理作用。随着对葛根素实验研究和临床研究的不断深入,发现葛根素对心、脑、肺、肝、肠等器官缺血-再灌注损伤具有保护作用,有望成为治疗缺血-再灌注损伤的有效药物。本文就近年来葛根素对缺血-再灌注损伤器官保护作用的进展进行综述。     

缺血后处理对再灌注大鼠胃黏膜细胞的保护作用

目的探讨缺血后处理对再灌注大鼠胃黏膜的保护作用及其抗氧化机制。方法制备胃缺血后处理模型;实验分为5组（n=6）：假手术组（S）、单纯缺血-再灌注组（I—R）、缺血预处理组（IPC）、缺血后处理组（I-post）、缺血后处理＋缺血预处理组（I-post＋IPC）。记录各组胃黏膜损伤指数并检测胃黏膜丙二醛（MDA）含量、超氧化物歧化酶（SOD）的活性变化;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测胃黏膜细胞的凋亡。结果 与S组相比,I—R组胃黏膜损伤指数和黏膜细胞凋亡率显著升高,胃黏膜MDA含量屁著增加,SOD活性明屁降低;在IPC组、I-post组和I-post＋IPC组,胃黏膜损伤指数与细胞凋亡率较I—R组显著降低,胃黏膜MDA含量也显著降低,而SOD活性明显升高;I-post＋IPC组对再灌注的胃黏膜损伤无叠加保护作用,分别与IPC组和I-post组相比,各项指标的差异无统计学意义。结论缺血后处理可显著减轻胃黏膜再灌注损伤,其效应与缺血预处理相似,其机制之一可能与其再灌注后氧自由基的生成减少,抑制胃黏膜细胞膜脂质过氧化、使冉灌注的胃黏膜细胞凋亡减轻有关。     

雷诺嗪对豚鼠离体心肌缺血-再灌注损伤心功能的保护作用

目的 探讨雷诺嗪对豚鼠离体缺血-再灌注模型的心功能保护及其作用机制.方法通过离体Langendorff模型灌流方法,观察雷诺嗪对血流动力学改变和心肌钙离子含量变化的作用.结果雷诺嗪可增加缺血再灌注心肌 LVDP、+dp/dtmax和-dp/dtmax水平,减少再灌注末心肌组织Ca2+含量;R1、R2与I/R组相比较,P＜0.05,P＜0.05,P＜0.05,R1与R2组比较P＜0.05.结论雷诺嗪可改善心脏收缩、舒张功能,防止心肌细胞钙超载,并且呈剂量依赖性.     

吡格列酮对大鼠缺血再灌注诱导的内质网应激相关的心肌保护作用

目的观察吡格列酮对大鼠心肌缺血再灌注损伤（MIRI）时JNK、p-JNK及caspasc-12蛋白表达的影响,探讨吡格列酮通过JNK通路对内质网应激途径的心肌保护作用。方法Wistar大鼠40只随机分为假手术组（sham组）、缺血再灌注组（I／R组）、I／R＋Pio（吡格列酮）组及I／R＋Pi0＋sP600125组各10只。制作大鼠MIRI模型;TUNEL检测心肌细胞凋亡,免疫组织化学检测各组caspase-12表达变化,westernBlot法检测各组JNK、P-JNK的表达。结果吡格列酮预处理组大鼠心肌细胞凋亡、JNK磷酸化率及caspase-12蛋白表达水平明显比I／R组降低（P〈0．05）,加用JNK抑制剂（SP600125）后上述指标进一步下降,与吡格列酮组比较差异有统计学意义（P〈0．05）。结论缺血再灌注损伤可激活JNK通路,诱导过度的ERS,增加ER凋亡信号介导的细胞凋亡。吡格列酮预处理可减少ER凋亡信号介导的细胞凋亡,JNK信号途径在吡格列酮预处理抑制ER凋亡信号分子活化的机制中发挥重要作用。     

Influence of rate-dependent cellular uncoupling on conduction change during simulated ischemia in guinea pig papillary muscles: effect of verapamil

This study was performed to determine if the changes in cellular coupling induced by simulated ischemia were rate-dependent and if they contributed to the rate-dependent conduction slowing that occurs in this setting. We also sought to determine if the known ability of verapamil to prevent ischemia-induced conduction changes might be related to the preservation of cellular coupling. We studied the effects of increasing stimulation frequency from 0.5 to 2.0 Hz on the simultaneous changes in the maximum rate of rise (Vmax) of the action potential upstroke, conduction velocity, and internal longitudinal resistance (ri) determined by the voltage ratio method in superfused guinea pig papillary muscles under conditions of simulated ischemia (SI). When stimulation frequency was 0.5 Hz, 30 minutes of SI caused a 16.5% decrease in Vmax, a 16% increase in ri, and a 12.9% decrease in conduction velocity. When stimulation frequency was increased to 2.0 Hz, 30 minutes of SI caused a 30% decrease in Vmax, a 72.9% increase in ri, and a 21.4% decrease in conduction velocity. Thus, the changes were rate-dependent. Verapamil (1 X 10(-6) M) did not influence the changes in these parameters during SI at 0.5 Hz nor the decrease in Vmax during SI at 2.0 Hz, but it did prevent the rate-dependent increase in ri. Verapamil also prevented the rate-dependent decrease in conduction velocity induced by SI. Our results suggest that during simulated ischemia the rate-dependent component of the increase in Ri contributes to the rate-dependence of the conduction slowing.(ABSTRACT TRUNCATED AT 250 WORDS)     

索他洛尔对豚鼠心室肌动作电位及延迟整流钾电流的作用特性

目的　研究索他洛尔对豚鼠乳头状肌动作电位 (AP)和单个心室肌细胞延迟整流钾电流的作用及索他洛尔致心律失常的可能机制。方法　用标准微电极技术和全细胞膜片钳技术 ,分别测定豚鼠乳头状肌AP和单个心室肌细胞离子电流。结果　在索他洛尔浓度为 10 0 μmol/L时可明显延长APD ,使APD2 0 和APD90 分别延长13.33%和 19.71%。且该作用随BCL增加而增加 ,呈现出逆频率依赖性特点。在单个心室肌细胞的实验中10 0 μmol/L索他洛尔仅对IKr有阻滞作用 ,使IKr及IKr,tail的幅值从 (0 .6 8± 0 .2 7) pA/pF和 (0 .94± 0 .30 ) pA/ pF降至(0 .4 7± 0 .18) pA/ pF和 (0 .6 0± 0 .32 )pA/ pF ;且此作用也呈逆频率依赖性。结论　索他洛尔对心肌电生理的逆频率依赖性的作用特性可能是其诱发尖端扭转性室速 (TdP)等心律失常的机制之一。     

The effect of magnesium versus verapamil on supraventricular arrhythmias

Magnesium has previously been used in the treatment of various arrhythmias, but few randomized and prospective studies are available. In a single-blind study, the efficacy and safety of intravenous magnesium sulfate (bolus doses of 5 + 5 mmol followed by infusion of 0.04 mmol/min) versus verapamil (5 + 5 mg followed by 0.1 mg/min) was evaluated in 57 patients with supraventricular arrhythmias (supraventricular tachycardia, atrial fibrillation, and atrial flutter) of recent onset (less than 1 week). Fifteen (58%) of the patients receiving magnesium (n = 26) converted to sinus rhythm within 4 h, and 16 (62%) within 24 h. Verapamil caused a lower ventricular rate, but only six (19%) of the patients (n = 31) converted to sinus rhythm within 4 h (p < 0.01) and 16 (52%) within 24 h (NS). No side effects were observed during magnesium infusion, whereas six patients receiving verapamil had to be withdrawn from further study medication due to symptomatic side effects (hypotension in three, cardiac failure in three). Magnesium appears to be an effective and safe drug for the treatment of supraventricular arrhythmias. The overall efficacy for conversion to sinus rhythm is at least as effective as with verapamil, and its action is more rapid.     

A comparison of the effects of adenosine and verapamil on the conduction and pacemaker system of isolated guinea pig hearts

Adenosine and verapamil are effective in the treatment of supraventricular arrhythmias. Also, both substances can provoke sinus node arrest or a third-degree atrioventricular (AV) block with a ventricular escape rhythm. The aim of this study was to compare the effects of adenosine and verapamil on sinus rate and on the rate of the ventricular escape rhythm while a third-degree AV block was induced by both drugs. Experiments were performed on isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. A third-degree AV block was induced by adenosine at a concentration of 30 μm and by verapamil at a concentration of 1 m?m. Adenosine (30μm) reduced sinus rate only moderately whereas it nearly halved the rate of the ventricular escape rhythm compared with that produced by cutting the AV node. In contrast, verapamil left the rate of the ventricular escape rhythm unchanged but nearly halved the spontaneous sinus rate compared with control conditions. In conclusion, adenosine and verapamil given at dosages with comparable effect on the AV node have markedly different effects on different pacemakers in the same heart. In the treatment of supraventricular arrhythmias, adenosine probably should be used with great caution since it can cause a very slow ventricular escape rhythm.     

Age-related differences in excitation-contraction coupling in rat papillary muscle

Summary To investigate the possible role of an alteration in excitation-contraction coupling during development, aging and senescence we compared simultaneously recorded mechanical and electrical activity of left ventricular papillary muscles from 3, 6, 12, and 24-month-old male rats. In addition, the effects of calcium and verapamil on excitation-contraction coupling were evaluated.We recorded transmembrane action potentials during both isometric and isotonic contractions. At an external bath calcium=2.4 mM, action potential duration at 75% complete repolarization (APD₇₅) was significantly prolonged as a function of age (3 mo=28.2±2.7; 6 mo=29.5±2.6; 12 mo=49.5±5.6; 24 mo=121±8.5 msec) while peak developed tension (DT) was not significantly altered (3 mo=5.13±0.53; 6 mo=4.75±0.53; 12 mo=7.26±0.51; 24 mo=6.01±0.67 g/mm²). The correlation coefficient (r value) for APD₇₅ and DT was strong for 3-month-old animals (r=0.99) but weakened as a function of age (6 mo=0.93; 12 mo=0.81; 24 mo=0.57). Similar results were observed when APD₇₅ was correlated with time-to-peak tension (TPT) (3 mo=0.95; 6 mo=0.98; 12 mo=0.85; 24 mo=0.68), time-to-one-half relaxation (T1/2R) (3 mo=0.91; 6 mo=0.97; 12 mo=0.85; 24 mo=0.81) and time to peak shortening (TPS) (3 mo=0.89; 6 mo=0.81; 12 mo=0.82; 24 mo=0.51). Correlations between action potential duration and contractile parameters became weak in all age groups upon the addition of verapamil (V). The correlation between APD₇₅ and DT for 3-month-old animals decreased by 34% upon the addition of V while a 70% decrease was seen in 24-month-old animals. Similar results were seen when APD₇₅ was correlated with TPT, T1/2R and TPS when V was added to the perfusate. Our results indicate that excitation-contraction coupling, as evidence by alterations in not only the contractile apparatus but also in the surface membrane, may be altered in ventricular muscle as in function of age.Support in part by NIH Grants # HL 21933-04, # 07071-06 and a Herman Raucher Investigatorship Award of the New York Heart Association to Dr. Joseph M. Capasso. Animals used in this study were generously awarded to Dr. Capasso by the Animal Acquisitions Branch of the National Institute of Aging.     

对－呋喃硝苯啶对豚鼠心脏乳头状肌动作电位参数的影响

对－呋喃硝苯啶（Ｐ－Ｎｉｆ）是新近合成的一种药物，为钙拮抗剂硝苯啶的呋喃衍生物。本文采用微电极技术，在离体豚鼠乳头肌上，就Ｐ－Ｎｉｆ对乳头肌细胞跨膜动作电位离子流的影响进行了观察。发现３０μｍｏｌ／Ｌ的Ｐ－Ｎｉｆ可缩短快反应细胞的ＡＰＤ５０、ＡＰＤ９０及ＡＰＤ，缩短ＥＲＰ，同时明显降低慢反应动作电位的幅度和ＡＰＤ５０、ＡＰＤ９０及Ｖｍａｘ，提示Ｐ－Ｎｉｆ的作用和Ｎｉｆ相似，主要是阻断钙通道。     

Prolonged protective effect of the calcium antagonist anipamil on the ischemic reperfused rabbit myocardium: Comparison with verapamil

Summary To assess whether pretreatment with the calcium antagonist anipamil protects the heart against ischemic and reperfusion damage and to establish how long the protection persists after cessation of the therapy, rabbits were injected subcutaneously twice daily for 5 days with 2 mg/kg body weight of this drug. The heart was then isolated 2, 6, or 12 hours after the last injection and was perfused by the Langendorff technique during a control period and 90 minutes of total ischemia (37°C), followed by 30 minutes ofreperfusion. Diastolic and developed pressure was monitored; coronary effluent was collected and assayed for creatine phosphokinase (CPK); mitochondria were harvested and assayed for respiratory activity, ATP production, and calcium content; and tissue concentration of adenosine triphosphate (ATP) and creatine phosphate were determined. The data obtained with anipamil were compared with those obtained with verapamil administered to the rabbit at the same dose and following the same procedure.Pretreatment with anipamil induced a negative inotropic effect under normoxic conditions; reduced the rate and extent of depletion of ATP and creatine phosphate during ischemia, with an incomplete restoration of the nucleotides after reperfusion; maintained mitochondrial function and calcium homeostasis during ischemia and reperfusion; reduced the rate of CPK release; and improved the recovery of ventricular function on reperfusion. The protective effects of anipamil persisted for as long as 12 hours after the last administration. In contrast, the protective and negative inotropic effects of verapamil were no longer apparent in heart isolated 6 or 12 hours after the last dose of the drug.It is concluded that anipamil pretreatment provides a protection against some of the deleterious effects of myocardial ischemia and reperfusion and that this effect is substantially longer than that of verapamil. The protective effect of anipamil (like that of verapamil) is probably secondary to a reduction of the rate of ATP hydrolysis during ischemia, although alternative mechanisms of action cannot be excluded.     

别隐品碱抗心律失常效应及其对动作电位的影响

目的研究别隐品碱(ALL)抗心律失常效应及其对心室肌动作电位的影响.方法选择大鼠和豚鼠以静脉给乌头碱、哇巴因和氯化钡造动物心律失常的模型,观察ALL对心律失常的效应,分离豚鼠乳头状肌观察ALL对动作电位的影响.结果ALL(30和100mg/kg)对乌头碱、哇巴因和氯化钡致动物实验性心律失常有良好的对抗作用,使各种试剂诱发的室早、室速、室颤及停搏的剂量增加.ALL可降低动作电位上升幅度(APA)和0相最大上升速率(Vmax).3.0～100.0 μmol/L的ALL以浓度依赖性方式使离体乳头状肌动作单位时程(APD)延长,其中30.0μmol/L的ALL使APD90延长67.5%.结论ALL具有抗实验性心律失常的效应,此效应可能与其影响心肌组织的电生理密切相关.     

机械牵张对缺血乳头肌动作电位的影响

目的 :研究机械牵张对模拟缺血状态下体外豚鼠乳头肌动作电位 (AP)的影响。方法 :建立模拟缺血条件下体外豚鼠乳头肌机械牵张模型 ,2 4只豚鼠随机分为正常对照组、单纯缺血组和缺血加链霉素组 ,每组 8只。利用细胞内标准玻璃微电极技术 ,记录并观察一定牵张力 ( 2 0 0mg强度 )作用下体外豚鼠乳头肌细胞AP各参数 [AP 0相最大升速率 (Vmax)、AP幅值 (APA)、AP复极达 2 0 %的时程 (APD2 0 )、AP复极达 5 0 %的时程(APD50 )和AP复极达 90 %的时程 (APD90 ) ]的变化。结果 :正常对照组牵张前后AP各参数无明显变化 (均P >0 .0 5 ) ;与正常对照组相比 ,单纯缺血组和缺血加链霉素组在牵张前上述参数均显著降低 (均P <0 .0 1) ;单纯缺血组 ,牵张使AP的Vmax和APA显著下降 ,APD2 0 、APD50 和APD90 明显缩短 (均P <0 .0 1) ;在缺血加链霉素组 ,牵张前后AP的上述指标无显著变化 (均P >0 .0 5 )。结论 :机械牵张易导致缺血心肌电生理参数变化 ,即缺血心肌对牵张反应的敏感性增加 ;而且牵张激活性离子通道阻滞剂———链霉素可以有效抑制该效应