苯那普利对离体大鼠缺血再灌注心肌的保护作用

目的观察苯那普利对离体大鼠缺血再灌注心肌的保护作用,初步探讨其作用机制。方法应用Langendorff装置,采用完全停灌复灌的方法制作离体大鼠心肌缺血再灌注模型。将24只SD大鼠随机等分3组:对照组(KH液持续灌注110 min),缺血再灌注组(KH液灌流20 min,停灌30 min,再灌注60 min),苯那普利组(缺血30 min,再灌注60 min,灌注液加入苯那普利10-6mol/L)。观察再灌注心律失常发生情况、血流动力学、光镜下心肌结构改变、心肌肿瘤坏死因子-α(TNF-α)免疫组织化学染色。结果与缺血再灌注组比,苯那普利组再灌注60 min内室性心动过速、心室颤动发生率降低;血流动力学指标明显改善;光镜可见炎症损伤减轻。免疫组织化学染色可见TNF-α蛋白阳性表达主要在心肌细胞胞浆苯那普利组呈弱阳性;对照组阴性;缺血再灌注组强阳性。结论苯那普利对缺血再灌注心肌具有保护作用,其机制可能与抑制TNF-α表达、减轻炎症有关。     

苯那普利后处理减轻离体心脏缺血再灌注损伤的观察

目的探讨苯那普利后处理对大鼠离体心脏缺血再灌注损伤的影响及其机制。方法应用Landendorff装置建立大鼠离体心脏缺血再灌注模型。将24只SD大鼠随机等分为3组：缺血再灌注组（I／R）、缺血后处理组和苯那普利后处理组。生化法检测各组稳灌20min和再灌60min肌酸激酶（CK）的水平,改良亮绿变色酸法观察心肌损害程度,硝基还原酶法测定各组再灌注末一氧化氮（NO）含量,测定心肌组织丙二醛（MDA）含量。结果与缺血再灌注组相比,苯那普利后处理组心肌梗死面积缩小[（14±7）％比（40±7）％,P〈0．01];再灌注流出液中CK含量减少[（100．8±31．8）U／ml比（188．5±49．1）U／ml,P〈0．01];心肌MDA含量降低[（2．5±0．7）nmol／mg prot比（4．4±0．6）nmol／mg prot,P〈0．01）;苯那普利后处理组再灌注流出液中NO含量明显高于缺血再灌注组[（101．7±8．7）μmol／L比（27．8±5．9）μmol／L,P〈0．01]。结论苯那普利后处理具有显著的心肌保护作用,这种心脏保护作用可能与增加NO浓度和抗脂质过氧化有关。     

缬沙坦抗大鼠心肌缺血再灌注心律失常的作用

缺血再灌注 (ischemia reperfusion ,I/R)心律失常是心肌I/R损伤中一种最常见的表现 ,特别是快速恢复冠状动脉血流可诱发致命性心律失常室性心动过速 (室速 )和心室颤动(室颤 )。动物实验已证实 ,血管紧张素转换酶抑制剂(ACEI)具有抗I/R心律失常作用。但血管紧张素Ⅱ受体(AT1受体 )拮抗剂缬沙坦在心肌I/R心律失常中的作用尚未见报道。本研究利用大鼠心肌I/R模型 ,观察缬沙坦对大鼠心肌I/R心律失常的作用。1.材料与方法 :4 8只雄性Sprague dawley大鼠 ,体重(2 98± 2 2 )g ,随机均分三组 ,灌喂给药。缬沙坦组 30mg·kg-1·d-1,苯那普…     

褪黑素对缺血再灌注心律失常的作用

目的:探讨外源性褪黑素(M LT)对在体大鼠心脏缺血再灌注心律失常的作用。方法:34只大鼠随机分为对照组、缺血再灌注(I/R)组及缺血再灌注 褪黑素(I/R M LT)组,I/R组及I/R M LT组在体大鼠心脏左冠状动脉前降支完全阻断10 m in,再灌15 m in,监测记录室性心动过速、室颤的发生情况,并测定局部再灌注心肌中M DA(丙二醛)的含量和SOD(超氧化物歧化酶)的活性。结果:室性心动过速、室颤的发生率I/R M LT组明显低于I/R组(P<0.05);I/R组M DA的含量明显高于对照组及I/R M LT组(P<0.01),SOD活性明显低于对照组及I/R M LT组(P<0.01),I/R M LT组M DA含量及SOD活性与对照组无明显差异(P>0.05)。结论:褪黑素可抑制在体大鼠心脏缺血再灌注心律失常的发生,其作用机制可能与其作为自由基清除剂抗氧化作用有关。     

洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制的研究

目的:探究洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制。方法:将24只Sprague-Dawley(SD)大鼠随机分为3组(n均=8):模型对照组(C);洛伐他汀(Lovastatin)组(L),胃管直接灌注洛伐他汀15mg·kg-1·d-12周;洛伐他汀复合L-硝基精氨酸甲酯(L-NAME)组(N),洛伐他汀15mg·kg-1·d-1直接灌胃2周同时腹腔注射L-NAME30mg·kg-1·d-1;2周后建立在体急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)以及肌酸激酶(CK)的变化情况。结果:L组和N组较C组心率明显减慢(P<0·01),缺血再灌注心律失常消失和再灌注时左心室内压下降最大速率(-dp/dtmax)下降程度减轻(P<0·05);洛伐他汀明显减少再灌注时血浆中MDA生成和LDH及CK的释放(P<0·01),并且提高心肌组织SOD活性(P<0·05),各项血脂指标不变。结论:洛伐他汀对大鼠心脏急性缺血再灌注时具有延迟性心肌保护作用。这种保护作用除与其增加一氧化氮(NO)合成相关外,还可能通过直接或间接方式稳定心肌细胞膜表面的离子通道,减少再灌注心律失常的发生,具体机制需待进一步实验证明。     

ERK1/2在大鼠心肌缺血预处理中的作用

目的 探讨缺血预处理(IPC)对大鼠心肌缺血再灌注(I/R)心律失常的影响以及细胞外信号调节的蛋白激酶(ERK1/2)在IPC中的作用.方法 健康雄性Wistar大鼠16只,随机分为 (I/R)组和IPC组,观察标准肢体导联(Ⅱ)导的心电图,并用Western-blotting方法 测定心肌ERK1/2的磷酸化表达.结果 IPC组心律失常评分、ERK1/2磷酸化表达显著低于I/R组(P<0.01).结论 IPC可能通过增强心肌ERK1/2活性而保护心肌,减轻大鼠缺血再灌注心律失常的严重程度.     

福辛普利钠预处理结合缺血后适应对大鼠心肌缺血再灌注损伤的保护作用

目的 观察福辛普利钠预处理结合缺血后适应(IPoC)对大鼠心肌缺血再灌注(I/R)损伤后氧化应激和促炎性细胞因子的影响.方法 Spragn-Dawley大鼠60只,随机分为假手术组(心脏前降支下置线不结扎,n=15),I/R组(心脏前降支结扎30 min,再灌注1 h,n=15),IPoC组(心脏前降支结扎30 min,予以3次10 s的再灌注/缺血循环,再持续灌注1 h,n=15),福辛普利钠+IPoC组(福辛普利钠片0.9 mg/kg,连续灌胃14 d,于末次灌胃2 h后,施以IPoC组的干预过程,n=15).后三组大鼠再灌注1 h,所有实验大鼠腹主动脉取血并分离出心脏组织.比色法测定血清肌酸激酶同工酶(CK-MB)和肌钙蛋白T(cTnT)的含量,NBT染色测定大鼠左心室心肌梗死面积,比色法测定超氧化物歧化酶(SOD)含量,硫代巴比妥酸法测定丙二醛(MDA)含量,放射免疫法测定血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量,酶联免疫吸附测定法测定心肌组织IL-1β、IL-6和TNF-α水平.结果 IPoC组大鼠血清CK-MB和cTnT水平均显著低于I/R组(P均<0.01),大鼠心肌梗死面积明显小于I/R组(P<0.01),血清SOD含量高于I/R组(P<0.01),MDA含量低于I/R组(P<0.01),血清和心肌组织炎症因子IL.1β、IL-6和TNF-αt水平均显著低于I/R组(P值分别小于0.05、0.05和0.01).福辛普利钠+IPoC组大鼠心肌梗死面积和CK-MB含量均低于IPoC组(P均<0.05),血清SOD含量高于IPoC组(P<0.05),血清IL-6和心肌组织TNF-α水平均低于IPoC组(P值分别小于0.05和0.01).结论 福辛普利钠预处理可加强IPoC对I/R大鼠心肌的保护作用,其机制可能与抑制氧化应激和早期炎症反应有关.     

血管紧张素ⅡAT1受体拮抗剂对大鼠全心缺血-再灌注损伤的保护作用

目的 探讨血管紧张素Ⅱ AT1受体拮抗剂(Losartan)对大鼠全心缺血—再灌注损伤的保护作用及机制。方法 采用Langendorff离体全心灌流装置，研究Losartan对大鼠全心缺血—再灌注心律失常，CPK，LDH，MDA，SOD，Ang Ⅱ的影响。结果 Losartan减少再灌注期心律失常的发生，加快再灌注期高度房室传导阻滞的恢复，缺血期：CPK及LDH I/R组较对照组明显增加，Losartan组较I/R组显著降低。再灌注期：CPK及LDH I／R组较对照组明显增加，Losartan组较I／R组明显降低。心肌组织MDA，Ang Ⅱ的含量I／R组明显高于对照组，SOD的含量两组比较无显著性差异。心肌组织MDA含量，Losartan组明显低于I／R组而Ang Ⅱ增高，SOD含量两组比较亦无显著性差异。结论 Losartan具有拮抗离体大鼠全心缺血—再灌注损伤的作用，是通过抑制Ang Ⅱ与ATl受体结合，抑制氧自由基的产生而发挥拮抗I／R作用。     

辛伐他汀后适应对血脂正常大鼠缺血再灌注心肌保护作用

【】 目的：探讨辛伐他汀药物后适应对缺血再灌注损伤大鼠髓过氧化物酶(MPO)、丙二醛(MDA)的影响,探讨其减少心肌损害的可能机制。方法：将30只SD大鼠随机分为假手术组(SH)、缺血/再灌注组(I/R组)、辛伐他汀后适应组(SIM组)。通过结扎大鼠冠状动脉前降支制作心肌梗死模型。SH组、I/R组：再灌注前经颈静脉注射生理盐水1ml;SIM组：再灌注前经颈静脉给予辛伐他汀(1mg.100g-1)注射。再灌注2小时后抽静脉血测定CK-mb、MPO、MDA及心肌梗死面积。结果：①各组大鼠血脂测定均在正常值范围内;②与SH组比较,I/R组、SIM组CK-mb、MPO、MDA均有增高(P<0.05);与I/R组比较,SIM组CK-mb、MPO、MDA下降(P<0.05);③与SH组比较,I/R组、SIM组心肌梗死面积明显(P<0.05);SIM组心肌梗死面积小于I/R组 (P<0.05)。结论：辛伐他汀后适应治疗可以减轻大鼠心肌炎症反应及心肌梗死面积,保护心肌并减轻缺血再灌注损伤的作用。     

二氮嗪恢复缺血预处理对老年大鼠心肌的保护作用

目的 探讨二氮嗪(DZ)对经缺血预适应(IPC)后的老年大鼠缺血再灌注(I/R)心肌的影响及可能机制.方法 取老年和青年Wistar大鼠,建立离体心脏Langendorff灌注模型,分7组(每组8只):青年对照组、青年I/R组、青年IPC组、老年对照组、老年I/R组、老年IPC组、老年DZ组.对照组全心灌流90 min.I/R组心脏灌流30 min后,缺血30 min,再复灌30 min.IPC组灌流10 min,经2次缺血5 min再灌注5 min后,缺血30 min,再复灌30 min.DZ组灌流10 min,给予含DZ(100 μmol/L)的K-H液灌注20 min,余同IPC组.比较各组复灌30 min后心排血量(CO)、左室发展压 (LVDP)、左室内压最大上升和下降速率 (±dp/dtmax) 的恢复率;检测缺血前及复灌30min后冠脉流出液中肌酸激酶 (CK) 活性及一氧化氮(NO)含量和心肌中丙二醛 (MDA)、超氧化物歧化酶 (SOD) 的含量.结果 青年大鼠中,IPC组与I/R组比较,CK生成明显减少,NO含量明显增加,MDA含量明显降低,SOD含量明显增加,CO、LVDP、+dp/dtmax、-dp/dtmax恢复率明显增加(P＜0.01).而在老年大鼠中,IPC组与I/R组比较上述指标无明显统计学差异(P＞0.05),DZ组与I/R组比较有明显统计学差异 (P＜0.05或P＜0.01).结论 IPC对老年大鼠I/R心肌保护作用减弱,其机制可能与NO信号通路表达受抑制有关,DZ可恢复IPC对老年大鼠I/R心肌保护作用.     

Attenuation of reperfusion-induced ventricular fibrillation in the rat isolated hypertrophied heart by preischemic diltiazem treatment

Summary The ability of the calcium antagonist diltiazem to protect against reperfusion-induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4±32.3) compared with 27 seconds (mean 110.6±36.6; p<0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 µg reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 µg diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p<0.01), and sustained VF from 82% to 8% (p<0.01). Median VF duration in this group was reduced to 0 seconds (p<0.05; mean 24.7±22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups. We suggest that the attenuation by diltiazem of reperfusion-induced arrhythmias observed in this model was related to an energy-sparing effect during ischemia. This study shows that diltiazem administered acutely before the onset of ischemia attenuates reperfusion-induced arrhythmias in the hypertrophied myocardium, despite its greater susceptibility to reperfusion-induced arrhythmias.     

Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat

Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat. There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied. Rats (n = 16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle. PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001). On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p = 0.007). VT occurred in four (25%) of PC versus all (100%) of controls (p less than 0.001). PC reduced mean duration of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion. There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 +/- 4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

米诺环素预处理对大鼠缺血性室性心律失常的影响

目的观察米诺环素(MC)预处理对大鼠心肌缺血性室性心律失常的影响并探讨其可能机制。方法采用冠状动脉左前降支结扎法建立大鼠心肌梗死(MI)模型。将60只雄性SD大鼠随机分成6组:MI组,MI+MC组,MI+LY294002(LY)组,MI+5-羟基癸酸(5-HD)组,MI+MC+LY组及MI+MC+5-HD组。各组在制作MI模型前分别给予生理盐水、MC、LY、5-HD、MC+LY、MC+5-HD预处理。持续心电监护,观察缺血30 min内各组室性心动过速(VT)和心室颤动(VF)发生率、以及VT+VF持续时间、发生次数和室性心律失常的严重程度。缺血30min后迅速摘取心脏,用TTC法测心肌梗死面积。结果与MI组比较,MI+MC组的VT发生率无明显变化(P0.05),但VF发生率显著降低,VT+VF持续时间、发生次数和严重程度以及心肌梗死面积显著减少(P均0.05);而MI+MC+LY组及MI+MC+5-HD组上述指标与MI组无差异。结论 MC预处理可以减轻大鼠MI诱导的室性心律失常,这种作用可能与3-磷酸肌醇激酶/Akt信号通路和线粒体ATP敏感性钾离子通道的激活有关。     

Lack of significant effects of superoxide dismutase and catalase on development of reperfusion arrhythmias

Summary It has been reported that agents having the ability to scavenge oxygen-derived free radicals reduce the severity of ventricular arrhythmias that occur after brief coronary occlusion and reperfusion. Superoxide dismutase plus catalase (SOD + CAT) or placebo was administered in a blinded randomized fashion prior to coronary occlusion in rats (n = 25 each group) undergoing a 5-min left coronary occlusion followed by 15 min of reperfusion. During reperfusion, ventricular tachycardia (VT) developed in 96 % of animals in both groups. Reperfusion ventricular fibrillation (VF) developed in 60 % of the placebo group vs 56 % in the SOD + CAT group (p =1.0). Irreversible VF occurred in 40 of the placebo group vs 20 % in the SOD + CAT group (p = 0.22). Atrioventricular block occurred in 12 % of placebo and 4 % of SOD + CAT animals (p = 0.61).There were no significant differences between groups in duration of VT (85 ± 15 s (mean ± SEM) placebo vs 81 ± 14 s SOD + CAT, p = 0.81), total duration of VT plus VF (391 ± 76 s placebo vs 256 ± 64 SOD + CAT, p = 0.45) or numbers of single ventricular ectopic beats (65 ± 15 placebo vs 97 ± 18 SOD + CAT, p = 0.18). Heart rate at reperfusion was slightly higher in control than SOD + CAT animals (340 ± 33 vs 319 ± 32, p = 0.02). Risk zone size, determined by Monastral blue injection, was equal in both groups (34 ± 2 % of ventricular mass). The occurrence of reperfusion VF in this model could not be predicted by heart rate at reperfusion (331 ± 33 VF animals vs 328 ± 36 no VF, p = 0.77), or by risk zone size (34 ± 2 %, VF and no VF groups).Treatment with SOD + CAT did not reduce the overall incidence or duration of reperfusion arrhythmias in this model, though such treatment was associated with a non-significant trend toward less irreversibility of VF.Supported in part by National Institutes of Health SCOR HL-26215, Bethesda, Maryland 660     

The effects of antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia in rats.

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.     

Noradrenaline reduces ischemia-induced arrhythmia in anesthetized rats: involvement of alpha1-adrenoceptors and mitochondrial K ATP channels

Introduction: We have evaluated the part played by the mitochondrial ATP‐sensitive potassium (mK_ATP) channels on effect of α₁‐adrenoceptor activation by noradrenaline in ischemia‐induced ventricular arrhythmia. Methods and Results: Anesthetized rats were subjected to 25 minutes of regional ischemia, and infarct size (IS) and ischemia‐induced ventricular arrhythmia were measured. Group I served as saline control with ischemia (n = 9). In group II (n = 9), the ischemic period was preceded by three short episodes of ischemia, followed by reperfusion. In group III, noradrenaline (2 μg/kg, IV, n = 9) was injected prior to ischemia. In group IV, an α₁‐adrenoceptor blocker (prazosin, 0.5 mg/kg, IV, n = 6) was administrated prior to noradrenaline injection. In Groups V and VI, rats received a specific mitochondrial K_ATP channel inhibitor [5‐hydroxydecanoic acid (5‐HD), 10 mg/kg, IV, n = 6] prior to or after noradrenaline injection. Ischemic preconditioning (IPC) and noradrenaline markedly reduced incidences of ventricular fibrillation (VF) (0%, 0% vs. 55.5% in control, P < 0.05) and ventricular tachycardia (VT) (11%, 44.5% vs. 100% in control, P < 0.001 and P < 0.05), duration of VF + VT (3 ± 1 seconds, 4.7 ± 2.1 seconds vs. 52.9 ± 6 seconds in control, P < 0.001), number of VF + VT episodes (1.7 ± 1.7, 5.75 ± 2.4 vs. 60.5 ± 8 in control, P < 0.001), severity of arrhythmias (0.3 ± 0.3, 1.7 ± 0.5 vs. 3.9 ± 0.3 in control rats, P < 0.001 and P < 0.01), and IS (13.6 ± 1.8%, 18.2 ± 1.5% vs. 49.6 ± 2.4% in control, P < 0.001). Administration of prazosin or 5‐HD prior to or after noradrenaline injection intensified incidences of VF (66.6%, 66.6% and 50%, P < 0.05) and VT (100%, 100%, and 100%, P < 0.05), duration of VF + VT episodes (70.2 ± 10.5 seconds, 69.8 ± 6.75 seconds, and 60.8 ± 14.9 seconds, P < 0.001), number of VF + VT episodes (56 ± 16.4, 67 ± 11, and 45 ± 3.5, P < 0.01, P < 0.001, and P < 0.05), severity of arrhythmias(3.8 ± 0.3, 4 ± 0.5, and 3.7 ± 0.2, P < 0.01, P < 0.05, and P < 0.01), and IS (45.5 ± 3%, 46.8 ± 3.4%, and 43 ± 2.5%, respectively, P < 0.001) compared with the noradrenaline‐treated group. Conclusion: Prazosin or 5‐HD treatment eliminated the beneficial effects of noradrenaline on arrhythmogenesis and infarct size.     

Protective effect of Crataegus oxyacantha against reperfusion arrhythmias after global no-flow ischemia in the rat heart

The protective effect against reperfusion arrhythmias of a 3-month oral pretreatment with a dried extract of Crataegus oxyacantha (LI 132) (standardized to 2.2 % flavonoids) was studied with the Langendorff heart of the rat after global no-flow ischemia. The heart was perfused with a modified Krebs-Henseleit solution in which the K⁺ content was reduced to 3.4 mmol/l in order to lower the fibrillation threshold. According to pilot experiments which considered various durations of global no-flow ischemia ranging from 10 to 20 minutes, two durations were chosen for the present study: 20 minutes (group 20) in which ventricular fibrillation (VF) was the predominant form of arrhythmias, and 18 minutes (group 18) in which the prevalence of VF was markedly lower despite the small difference in the duration of ischemia. Crataegus pretreatment significantly (p = 0.02) reduced the average prevalence of malignant arrhythmias (VF + Flutter) as observed during the 20-min-period of reperfusion as follows: – group 20: from 89% (control, n = 9) to 51% (LI 132, n = 7), – group 18: from 48% (control, n = 8) to 8% (LI, 132, n = 8). In group 20, ventricular tachycardia (VT) could be observed only in the treated group, because of the predominance of VF in the control group. LI 132 pretreatment reduced the average prevalence of VT in group 18 in spite of the identical percentage of occurrence (6 out of 8 rats, with and without treatment) due to a shorter duration of the VT episodes. Thus, under the conditions of our experiments, effective prevention against reperfusion arrhythmias by Crataegus pretreatment was evident. Received: 13 July 1998, Returned for revision: 11 August 1998, Revision received: 15 September 1998, Accepted: 14 October 1998     

Reperfusion-induced arrhythmias are critically dependent upon occluded zone size: relevance to the mechanism of arrhythmogenesis

The relationship between reperfusion-induced arrhythmias and the size of the occluded zone was examined. The isolated perfuse rat heart was used because its negligible collateral flow maximizes susceptibility to arrhythmias and reduces variability. Ischemia lasting 10 min was followed by 10 min of reperfusion. A constant-pressure perfusion system (which precludes coronary steal) permitted measurement of the rapidity of restoration of coronary flow. Mean occluded zone sizes of 0, 7.2 +/- 1.1, 19.5 +/- 1.5, 45.8 +/- 1.7, 30.1 +/- 4, and 100% of the total ventricular weight were obtained by sham ligation, distal, medial and proximal ligation of the left main coronary artery, right arterial ligation and the induction of global ischemia, respectively. Occluded zone size correlated positively (r = 0.86, P less than 0.001) with a linearly-additive arrhythmia score irrespective of the site of ischemia (left versus right ventricle). In globally ischemic hearts, ventricular fibrillation (VF) depended upon ventricular beating rate during ischemia, occurring only if the rate exceeded 150 beats/min. If this factor were taken into consideration, VF incidence exhibited a sigmoidal relationship with occluded zone size. During the first min of reperfusion, the rapidity of restoration of coronary flow was inversely related to occluded zone size (P less than 0.001) and had a small but significant effect on the severity of arrhythmias; slow recovery of flow increased susceptibility. We conclude that when reperfusion is elicited at the moment of peak susceptibility to arrhythmias, VF incidence is determined principally by occluded zone size. Heart rate during ischemia becomes relevant at rates less than 150 beats/min, when a protective effect is seen. Since VF incidence was 100% in hearts reperfused after global ischemia, an interface between non-ischemic tissue and reperfused tissue is therefore unnecessary for arrhythmogenesis during reperfusion, and flow of injury current between non-ischemic and reperfused tissue can be ruled out as a mechanism of arrhythmogenesis. The initiation of reperfusion-induced arrhythmias must therefore take place within the reperfused tissue.     

Antiarrhythmic effect of ischemic preconditioning during low-flow ischemia

Abstract. Short episodes of ischemia (ischemic preconditioning) protect the heart against ventricular arrhythmias during zero-flow ischemia and reperfusion. However, in clinics, many episodes of ischemia present a residual flow (low-flow ischemia). Here we examined whether ischemic preconditioning protects against ventricular arrhythmias during and after a low-flow ischemia and, if so, by what mechanism(s).Isolated rat hearts were subjected to 60 min of low-flow ischemia (12% residual coronary flow) followed by 60 min of reperfusion. Ischemic preconditioning was induced by two cycles of 5 min of zero-flow ischemia followed by 5 and 15 min of reperfusion, respectively. Arrhythmias were evaluated as numbers of ventricular premature beats (VPBs) as well as incidences of ventricular tachycardia (VT) and ventricular .brillation (VF) during low-flow ischemia and reperfusion. Ischemic preconditioning significantly reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. This antiarrhythmic effect of preconditioning was abolished by HOE 140 (100 nM), a bradykinin B₂ receptor blocker. Similar to preconditioning, exogenous bradykinin (10 nM) reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. Furthermore, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by glibenclamide (1 µM), a non-specific blocker of ATP-sensitive K⁺ (K_ATP) channels. Finally, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by HMR 1098 (10 µM), a sarcolemmal K_ATP channel blocker but not by 5-hydroxydecanoate (100 µM), a mitochondrial K_ATP channel blocker. In conclusion, ischemic preconditioning protects against ventricular arrhythmias induced by low-flow ischemia, and this protection involves activation of bradykinin B₂ receptors and subsequent opening of sarcolemmal but not of mitochondrial K_ATP channels.     

热休克对再灌注性心律失常的影响及其作用机制的研究

目的研究热休克预处理对SD大鼠再灌注性心律失常的影响及其作用机制。 方法将32只SD大鼠随机分为热休克组(n=16)和对照组(n=16)。热休克组大鼠给予热休克预处理而对照组则否。采用Langendorff离体心脏灌注法,先稳定灌注40分,再停灌20分,然后复灌60分。心电图记录再灌注时心律失常情况。并检测再灌注时心脏流出液肌酸激酶(CK)的活性。以Westernblot法检测两组心脏组织中70KD热休克蛋白(HSP70)的相对含量。另外还检测心肌组织中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)等抗氧化酶的活性,及脂质过氧化物丙二醛(MDA)的含量。 结果热休克组的再灌注性心律失常发生率明显较对照组为低,表现为心室颤动发生率在热休克组为0,而对照组为6/16。室性心动过速发生率热休克组为3/16,而对照组为7/16,以热休克组为低(P＜0.05)。再灌注过程中心肌CK的释放量热休克组31.4±6.8IU/L较对照组42.3±8.9IU/L显著减少(P＜0.001)。热休克组心脏组织HSP70表达量较对照组显著增多,信号条带积分吸光值热休克组为6.39±1.98,对照组为4.62±2.05(P＜0.01)。热休克组抗氧化酶活性较对照组明显增强,而脂质过氧化物则降低。 结论热休克预处理可以减轻SD大鼠心肌再灌注性损伤,减少再灌注性心律失常的发生,此作用与心脏组织中HSP70含量的增加和抗氧化酶活性的显著增强有关。