急性缺血对犬在体左心室内膜整体复极的影响

目的探讨急性缺血对左心室内膜整体复极的影响。方法健康犬8只,应用非接触球囊标测技术,同步记录在体阻断左前降支30min前后心内膜各区域单极电图,计算心肌激动时间(AT)、激动恢复间期(ARI)和复极时间(RT),分析相关参数的变化。结果正常供血状态下心肌内膜存在复极梯度,但由于AT与ARI呈负相关,使复极离散性很小;急性缺血后缺血区AT延迟,ARI显著缩短,AT与ARI的负向相关性消失,复极离散性明显增加(P<0·01)。结论急性缺血后,传导减慢和激动恢复时间缩短共同导致心内膜复极离散性明显增加,有利于心律失常的发生。     

普鲁卡因胺对绵羊心室跨壁复极时间的影响

目的研究普鲁卡因胺对心室跨壁复极时间的影响。方法对6只绵羊用苯巴比妥麻醉后,开胸,用4个针状(p lunge need les)电极分别插入到左心室的基底部和心尖部,测量室壁激动-恢复间期(AR I)。静脉注射普鲁卡因胺20mg.m in-1后观察AR I的变化。结果窦性心律时,心外膜、中层心肌和心内膜的AR I差异无显著性,[分别为(266.0±30.5)m s、(265.0±28.9)m s和(265.7±28.1)m s,P>0.05]。普鲁卡因胺对各层心肌的AR I均有延长作用,心外膜、中层心肌和心内膜的AR I分别延长了(66.8±18.3)m s、(70.3±14.7)m s和(65.3±15.7)m s(P>0.05)。结论钠通道阻滞剂普鲁卡因胺对左室的心外膜、中层心肌和心内膜复极的延长程度相似。     

急性缺血后心室肌波长的整复性变化对心室纤颤发生的影响

目的了解急性缺血后心室肌波长的整复性变化对心室纤颤(室颤)发生的影响。方法选取健康成年杂种犬15只,采用心脏外科的方式开胸,切开并悬吊心包,暴露心脏。将64导心外膜标测电极置于左心室游离壁,将双极刺激电极(大头导管)置于64导心外膜标测电极旁,靠近室间隔侧。分别对正常的和急性缺血的心室肌以25mV为输出功率的程序化刺激(S1、S2),分别测量15条实验犬正常和急性缺血后心室肌的动作电位时程(APD)、传导速度(CV)及波长(WL)的整复性曲线的斜率及室颤阈值。分析正常和急性缺血后室颤阈值和3个斜率值的变化特点及差异。结果对正常和急性缺血心室肌诱发室颤的最长周期值(PI)进行比较,发现室颤阈值的差异具有统计学意义。同样对两组APD、CV及WL整复性曲线的斜率进行比较,WL整复性曲线表现差异有统计学意义。结论①急性缺血发生后,室性心动过速的发生更加容易诱发室颤;②WL的整复性对于预测室速转变为室颤的可能性优于APD和CV各自单独的整复性,可作为评估患者室颤发作可能性大小的有效指标。     

超声斑点追踪应变显像技术检测比格犬心肌急性缺血参数选择

目的探讨超声斑点追踪应变显像技术中不同参数在检测比格犬心肌急性缺血方面的敏感性。方法 10只比格犬,开胸结扎左冠状动脉前降支心尖部和心尖部末梢对角支60min,建立左心室前壁急性心肌缺血模型,按两级剂量5μg·kg-1·min-1和10μg·kg-1·min-1持续静脉滴注多巴酚丁胺;分别于基础状态、急性心肌缺血模型建立后、多巴酚丁胺小剂量负荷和大剂量负荷时采集标准左心室长轴二腔心、短轴乳头肌水平3个心动周期灰阶动态图像,斑点追踪应变软件分析记录左心室前壁中间段心内膜下长轴4个参数,即纵向应变(LS)、纵向应变率(LSr)、纵向速度(LV)、纵向位移(LD);短轴8个参数,即径向位移(RD)、径向速度(RV)、周向应变(CS)、周向应变率(CSr)、径向应变(RS)、径向应变率(RSr)、旋转角度(R)、旋转角度率(RR),分别进行各参数间的比较和相关分析。结果与基础状态相比,缺血状态的12个参数均显著下降,且R和RR参数下降更明显;多巴酚丁胺小剂量、大剂量负荷状态下12个参数中均仅有R和RR参数未能显著升高至基础状态,其他参数大致与基础状态参数一致。结论斑点追踪应变显像技术12个参数均能检测出比格犬心肌急性缺血,其中R与RR为斑点追踪应变显像技术检测比格犬心肌急性缺血最敏感参数。     

用犬心程控刺激电药理学模型评价甲基莲心碱的抗心律失常作用

用冠脉Harris二期结扎并部分再灌注及吻合支缝扎法造成犬急性前壁心肌梗塞 ,5 - 8天后辅以心室程控刺激技术 (PES)进行心电生理检查及复制快速室性心律失常 ,观察甲基莲心碱 (Neferine)抗心律失常的电生理作用并与普鲁卡因胺(PA)对比。结果表明 ,Neferine可显著延长QTc间期 (P <0 0 1)及正常心肌和缺血心肌的有效不应期 (NERP及IERP) (P <0 0 1) ,提高正常心肌和缺血心肌舒张期兴奋阈值 (NET及IET) (P <0 0 1) ,缩小缺血心肌和左室心肌ERP离散度 (IDR和VDR) (P <0 0 1) ,抑制心室PES诱发的持续性室速 (SVT)或室颤 (VF) (P <0 0 1) ,并能有效地预防犬慢性心肌梗塞后再次缺血所致的自发性VF (P <0 0 5 ) ,表明Neferine有抗缺血性快速室性心律失常的作用 ,并具有与PA相似的心电生理和抗心律失常作用     

迷走神经刺激预处理对急性心肌缺血大鼠心肌P物质和降钙素基因相关肽的影响

目的观察迷走神经刺激预处理对急性心肌缺血大鼠心肌组织缺血区和非缺血区P物质(SP)和降钙素基因相关肽(CGRP)表达的影响。方法健康成年雄性SD大鼠24只,体质量270~300g,随机分为3组,每组8只,假手术组(S组)、单纯冠状动脉结扎组(I组)和迷走神经刺激预处理冠状动脉结扎组(VS组)。S组大鼠开胸后在冠状动脉左前降支下穿线不结扎;Ⅰ组大鼠开胸后结扎冠状动脉左前降支;VS组大鼠实施迷走神经刺激30min后结扎冠状动脉左前降支。各组在手术后计时3h。采用免疫组织化学、酶免疫法和反转录-聚合酶链反应法从蛋白和基因水平观察各组大鼠缺血区和非缺血区心肌SP和CGRP的表达。结果Ⅰ组大鼠缺血区心肌SP/SP mRNA和CGRP/β-CGRP mRNA的水平较S组升高(P<0.05),VS组低于Ⅰ组(P<0.05),但仍高于S组(P<0.05)。非缺血区各组的变化趋势类同缺血区,但各扎闭冠状动脉组SP/SP mRNA和CGRP/β-CGRP mRNA的水平均低于相应组缺血区的水平(P<0.05)。结论迷走神经刺激预处理可降低急性心肌缺血大鼠心肌组织SP和CGRP的表达,提示迷走神经刺激预处理可能参与缺血心肌的保护。     

Sono Vue声学造影评价急性缺血和梗死心肌的实验研究

目的采用氟硫微泡声学造影剂SonoVue及间歇二次谐波技术,探讨经静脉心肌声学造影(MCE)评价急性缺血及心梗心肌微循环灌注的价值。方法建立猪急性心肌梗死动物模型。分别于左冠前降支(LAD)结扎前、结扎后3h经静脉注射SonoVue进行MCE。于左室短轴乳头肌水平测定LAD结扎后正常灌注区与缺血灌注区心肌视频密度峰值强度(PI)、曲线下面积(AUC)及无灌注区心肌范围。实验结束对心肌行组织学染色,比较MCE及组织染色两方法所测得的左室梗死心肌面积占左室心肌总面积百分比。结果正常灌注区与缺血灌注区PI、AUC差异有显著性(88.27±8.57vs48.26±4.36;1392.80±198.01vs646.68±55.86,P<0.001)。MCE与组织染色两方法所测得的左室梗死心肌面积占左室心肌总面积百分比呈明显正相关(r=0.85,P<0.05)结论经静脉注射SonoVue,运用间歇二次谐波MCE可定量心肌微循环血流灌注,诊断心肌缺血,准确确定心肌梗死范围。     

钌红与三磷酸腺苷前体对再灌注损伤大鼠心脏的快速恢复作用(英文)

急性缺血后心力衰竭可能与高能化合物的合成障碍有关.用?Wistar大鼠进行离体心脏实验,30min全心缺血和30 min再灌注导致心肌收缩力显著下降,三磷酸腺苷含量不足和线粒体内钙含量升高 用钌红(1μmol·L~(-1))进行再灌注,线粒体内钙超负荷减轻,同时心肌收缩力增加,但三磷酸腺苷含量不变 用钌红,核糖(1mmol·L~(-1))和腺嘌吟(1mmol·L~(-1))同时进行再灌注,不但心肌收缩力显著升高,而且三磷酸腺苷含量显著恢复。实验表明,急性缺血后的心肌受线粒体内钙含量升高的影响,合成高能化合物的能力减低.钌红,核糖和腺嘌吟可协同性地提高心肌肉三磷酸腺苷含量和恢复心肌收缩力。     

急性心肌梗死溶栓成功者QT离散度分析

目的 为了解急性心肌梗死(AMI)患者的QT离散度(QTd).方法 观察首次AMI患者发病后6 h内接受静脉溶栓成功者30例的QTd,取其溶栓治疗前的心电图(ECG)对比观察其QTd的变化,所有ECG均用同一台12导ECG机,同一人测量.结果 溶栓前为(43.6±13.2)ms,溶栓成功后为(37.1±10.2)ms,两组经配对t检验,P<0.05.由于AMI部位与正常心肌之间存在缺血区域,缺血区心肌细胞膜动作电位复极化延缓,ECG表现为各导联的QT间期差值增大,即QTd延长,所以心肌复极不均性显著的增加为折返激动的形成提供了条件,易于发生室速等心律失常.心室复极越不一致,电不稳定性就越大.成功的溶栓治疗后,随着冠状动脉的血流的恢复和维持左心室射血功能得到改善,QTd明显比治疗前下降,表明AMI后再灌流区与非梗塞区心肌的复极趋于一致,增加了心电的稳定性.AMI时QT间期变化的可能机制与局部低温、局部传导延迟、神经性作用及局部细胞处低钙等有关.结论 因此,QTd可以用来评价心肌电活动状态和预测室性心律失常的发生.成功地容栓后,反映心室复极离散度的QTd下降可能是成功的溶栓治疗改善预后的一个重要机制.另一方面也可以用QTd作为溶栓成功与否的一个指标.作为一种预测心律失常的检查手段,QTd结合心率变异、晚点位检查,可提高AMI远期心律失常的预测准确性.     

普罗帕酮和普鲁卡因胺抗犬缺血性快速室性心律失常的对比研究(英文)

目的　观察普罗帕酮对犬在体心脏缺血性快速室性心律失常的心电生理影响并与普鲁卡因胺对比 ,以探讨其抗缺血性快速室性心律失常的效果及作用机制。方法　用冠状动脉左前降支结扎并部分再灌注法造成犬急性前壁心肌梗死 ,5～ 8d后 ,辅以心室程控电刺激 (PES)技术及冠状动脉内恒定微量直流电刺激技术 ,并诱发与终止持续性室性心动过速和心室纤颤 ,制备成犬急性心肌缺血再灌注后可控性快速室性心律失常的在体心脏心电模型 ,心电图对比观察普罗帕酮及普鲁卡因胺的抗心律失常作用。结果　普罗帕酮及普鲁卡因胺均能显著地延长心肌梗死犬的心电图QTc间期 (P <0 .0 1 )及正常和缺血心肌的有效不应期 (P <0 .0 1 ) ,降低缺血心肌和左室心肌的有效不应期离散度 (P <0 .0 1 ) ,提高正常心肌和缺血心肌的舒张期兴奋阈值 (P <0 .0 1 ) ,抑制PES诱发的持续性室性心动过速和心室纤颤 (P <0 .0 1 ) ,并能预防犬急性心肌梗死后再次缺血所致的自发性室性心动过速和心室纤颤 (P <0 .0 5)。结论　①该犬在体心脏心电药理学实验模型具有较好的重复性、可靠性及临床相关性 ,是一种有价值的心电药理学实验研究模型。②普罗帕酮及普鲁卡因胺均具有抗缺血性快速室性心律失常的心电生理作用 ,是有效的抗颤药物 ,两药效果相似     

Raloxifene improves coronary perfusion, cardiac contractility, and myocardial metabolism in the ischemic heart: role of phosphatidylinositol 3-kinase/Akt pathway

The purpose of this study is to examine whether raloxifene, one of the selective estrogen receptor modulators, could improve myocardial ischemia and to assess the mechanisms involved. In open-chest beagle dogs anesthetized by intravenous infusion of sodium pentobarbital, the left anterior descending coronary artery (LAD) was perfused from the left carotid artery through an extracorporeal bypass tube. Raloxifene was infused into the LAD through the bypass tube under either ischemic or non-ischemic conditions. In the non-ischemic heart, raloxifene had no effect on coronary blood flow, fractional shortening, and myocardial metabolism. However, raloxifene caused an acute increase in both coronary blood flow and fractional shortening, and also improved myocardial anaerobic metabolism in the ischemic heart. These effects were partially attenuated by pretreatment with either L-NAME or wortmannin and were completely abolished by ICI182780 (an estrogen receptor antagonist) or L-NAME plus charybdotoxin (a blocker of Ca-activated K channels). Raloxifene also increased both Akt activity and the NO level, with these changes being completely abrogated by pretreatment with wortmannin. These results demonstrated that raloxifene improves coronary perfusion, cardiac contractility, and myocardial metabolism by release of NO and opening of Ca-activated K channels in the ischemic heart, and that NO production is mediated by the phosphatidylinositol 3-kinase/Akt pathway.     

The effect of cibenzoline on myocardial damages in dogs

The antiarrhythmic and cardioprotective effects of cibenzoline (4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) were investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline (25 ml) was administered, and 20 min after, the left anterior descending coronary artery (LAD) was occluded for 2 h; in the cibenzoline group, cibenzoline (2 mg/kg), was administered 10 min before 2 h LAD occlusion. Blood pressure and appearance of arrhythmias were monitored throughout the experiment. Two h after occlusion, mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions were measured polarographically. Fractionation of myocardial tissue from both ischemic and non-ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. Administration of cibenzoline significantly reduced the appearance of ventricular arrhythmias in association with ischemia. Cibenzoline did not change significantly blood pressure and heart rate. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 h occlusion were observed. Administration of cibenzoline maintained significantly mitochondrial function and prevented significantly leakage of lysosomal enzymes. These results indicated that cibenzoline has a cardioprotective as well as an antiarrhythmic effect on ischemic myocardium.     

Reduction of acute myocardial ischemia in rabbit hearts by nafazatrom

The effects of oral nafazatrom pretreatment (10 mg/kg, twice a day, for 10 days) on myocardial ischemia were studied in the rabbit heart during 6-h occlusion of the left anterior descending coronary artery (LAD). The tension-time index (TTI), hemodynamics, and ischemia size were determined (Evan's blue-triphenyltetrazolium chloride staining with planimetry). In drug-vehicle controls, left ventricular (LV) and peripheral pressures and LV dP/dtmax decreased, while heart rate, end-diastolic pressure, the TTI, and electrocardiographic ST segments increased. Hemodynamics were nearly unaltered in the nafazatrom-pretreated animals, except for a heart rate elevation during the initial phase of LAD occlusion. In drug-treated hearts, 45 +/- 6% of the LAD perfusion region at risk was ischemic, showing a patchy distribution. In vehicle controls, 82 +/- 4% (p less than 0.02 vs. nafazatrom pretreatment) of the LAD-perfused myocardial regions was transmurally ischemic, showing a uniform pattern. Thus, nafazatrom pretreatment prevented most hemodynamic changes following LAD occlusion in the rabbit heart. Significant amounts of the muscle remained normoxic within the nonperfused arterial regions. These results indicate that the inhibition of lipoxygenase enzymes by nafazatrom may delay the development of ischemic damage to the heart following acute coronary artery occlusion.     

Differential electrophysiological effects of amiodarone on ventricular muscle and Purkinje fibers in canine one-day-old myocardial infarction

1. We examined the electrophysiological effects of acute exposure to amiodarone (AM) on ischemic myocardium. 2. Regional myocardial ischemia was performed by occlusion on left anterior descending coronary artery in dog heart. 3. Conventional glass microelectrode techniques were used for electrophysiological investigation of regional ischemia. 4. The effects of AM on action potentials of subendocardial Purkinje fibers and ventricular muscle excised from ischemic area were studied and compared the findings with those obtained from non-ischemic area. 5. Acute exposure to AM, 4.4 x 10(-5) M, prolonged the total duration of action potential in the ischemic ventricular muscle and decreased the maximum upstroke velocity of action potentials significantly. 6. On the other hand, in the ischemic Purkinje fibers, AM produced no significant actions. 7. These findings suggest that AM's antiarrhythmic activity is, at least in part, due to its differential effects on repolarization of ischemic Purkinje fibers and ventricular muscle.     

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     

半胱氨酰白三烯受体拮抗剂pranlukast对小鼠局灶性脑缺血的治疗作用

目的　观察半胱氨酰白三烯受体拮抗剂pranlukast(ONO 10 78)在小鼠局灶性脑缺血后的治疗作用。方法　采用大脑中动脉阻塞造成小鼠持续性局灶性脑缺血 ,缺血后1、6、2 4h分别给小鼠腹腔注射 pranlukast或依达拉奉 ,观察药物对缺血 2 4、4 8h后的神经功能缺损症状 ,4 8h后的脑梗死体积、两侧大脑半球比值、神经元密度的影响。结果　Pranlukast 0 1、0 2mg·kg-1及依达拉奉 3、10mg·kg-1均能减轻神经症状、减小脑梗死体积、降低缺血侧 /非缺血侧大脑半球比值、减轻海马CA1区、皮层和纹状体的神经元密度降低。结论　Pranlukast脑缺血后给药对脑损伤有治疗作用 ,提示有治疗缺血性脑卒中的临床前景。     

Local effects and mechanisms of antiarrhythmic peptide AAP10 in acute regional myocardial ischemia: electrophysiological and molecular findings

Previously, it was shown that antiarrhythmic peptides and our lead substance AAP10 enhance electrical intercellular communication via gap junctions. Now, we wanted to elucidate whether AAP10 acts preferably in the ischemic area and the molecular mechanism of this peptide. Seventeen rabbit hearts were isolated, perfused according to Langendorff, and submitted to 30-min local ischemia by LAD occlusion with/without AAP10 (50 nM). Electrophysiology was assessed by 256 channel epicardial mapping. Finally, the ischemic zone, border zone, and non-ischemic zone were excised, and the cardiac gap junction protein connexin43 (Cx43), its phosphorylation state, and the distribution at the polar and lateral membrane of cardiomyocytes were determined by Western blot and immunofluorescence. Ischemia led to a decrease in activation recovery interval (ARI) homogeneity, which could be completely prevented by AAP10. Moreover, ischemia-induced activation wave slowing in the ischemic border zone was antagonized by AAP10. In ischemic center and border zone, but not in the non-ischemic area, (phospho-Cx43/dephospho-Cx43)-ratio decreased. This was also significantly antagonized by AAP10. Serine 368 was identified as one phosphorylation site for the activity of AAP10. In the non-ischemic area, AAP10 had no influence on Cx43 phosphorylation state. Interestingly, ischemia led to a loss of Cx43 from the cell poles and lateral sides in the ischemic area and border zone. AAP10 completely prevented the ischemia-induced decrease in polar Cx43 presence. In the ischemic area, AAP10 prevents from ischemia-induced Cx43 dephosphorylation and loss of Cx43 from the gap junction at cell poles and in parallel prevents the decrease in ARI homogeneity and attenuates ischemia-induced slowing of activation wave propagation. The AAP10 action seems confined to the ischemic area. Supported by a grant from the Deutsche Forschungsgemeinschaft DFG.     

Specific effects of nitroprusside on myocardial O2 balance following coronary ligation in the dog heart

The effect of gradual infusion of nitroprusside was studied in healthy and in ischemic hearts. In two areas of the left ventricular surface (ischemic and non-ischemic) local coronary blood flow was measured by a thermistor technique. Isometric contractile tension was recorded with strain gauge arches, and nicotinamide-adenine-dinucleotide (NADH) redox state was measured simultaneously in both regions using a two-channel fluorometer. Aortic blood pressure was also recorded. It was found that at an infusion rate of 1.0 microgram/kg/min, nitroprusside increased regional coronary blood supply in the healthy heart as well as in the ischemic and nonischemic areas of left anterior descending artery (LAD)-ligated hearts. Flow elevation was similar in all regions (37.0 +/- 6.1, 42.5 +/- 13.5 and 45.36 +/- 14.8%, respectively). At higher doses, a decrease of 6-10% in blood pressure had a detrimental effect on the coronary flow to the ischemic region without reducing flow to the nonischemic region. The NADH redox level was not significantly improved by nitroprusside in spite of elevated coronary blood supply to all regions examined. Moreover, higher doses of nitroprusside resulted in a significant elevation in NADH levels that could be correlated to the decrease in blood pressure. It is concluded that the effect of nitroprusside on coronary blood supply and myocardial O2 balance may be strongly dependent on the magnitude of its effect on blood pressure.