腺苷对大鼠心肌缺血再灌注心律失常的影响

目的 :研究腺苷对大鼠心肌缺血再灌注 （I/ R）致心律失常的影响以及与 ATP敏感性钾通道 （KATP）的关系。方法 :采用结扎大鼠左冠状动脉前降支造成缺血 10 min,然后再灌注 15 m in,诱发室性心律失常。在心肌缺血前分别给予腺苷 （2 ,6 mg/ kg）及 KATP阻断剂格列本脲 （Glib,7.5 mg/ kg）。结果 :1与对照组相比 ,腺苷 2 ,6 m g/ kg两剂量组可明显减少 I/ R室颤的发生率 （P<0 .0 1） ,降低心律失常评分分值 （P<0 .0 1） ,能明显降低磷酸肌酸激酶 （CPK ）和乳酸脱氢酶 （L DH）活性 （P<0 .0 1）。 2 Glib阻断 KATP后 ,诱发出严重的室性心律失常 ,且 CPK,L DH值均显著高于对照组 （P<0 .0 1）。 3腺苷 6 mg/ kg在 Glib阻断 KATP后 ,亦可降低室性心律失常分值 ,降低 CPK,L DH水平 ,同Glib组相比较 ,P<0 .0 1或 P<0 .0 5。结论 :腺苷对大鼠 I/ R心肌损伤有明显的保护作用 ,而 KATP的开放可能是其保护作用的部分机制     

维拉帕米拮抗内皮素-1的心血管效应

内皮素 (endothelin,ET)系具有强列缩血管作用的活性多肽 ,ET家族中 ET- 1在心血管系统含量最高 ,其生物学效应由 ETA 和 ETB受体介导。 ET可增高心肌细胞 [Ca2 +]i,造成钙超载及心肌细胞早后去极化 ,在整体动物可引起心律失常。已有报道钙拮抗剂维拉帕米 (verapamil,vera)能保护ET- 1所致的组织损伤。本研究旨在观察麻醉大鼠 vera预处理对 ET- 1所致心律失常及血压变化等心血管效应的影响。SD大鼠 42只 ,随机分为 5组 ,对照组静脉注射生理盐水 2 0 0μl,4个 vera预处理组分别注射 Vera 0 .5 ,1.0 ,2 .0和 8.0mg/ kg,2 0 m in注毕 …     

冠状动脉内磁化支架置入术后冠状静脉窦血中NO与ET-1水平的变化

目的 :观察冠心病患者冠状动脉内置入磁化支架后冠状静脉窦血中一氧化氮 （NO）与内皮素 - 1（ET- 1）水平的变化 ,探讨磁化支架防治冠状动脉再狭窄的机制。方法 :经皮腔内冠状动脉成形术及冠状动脉内支架置入术的冠心病患者随机分为磁化支架组 （2 3例 ）及非磁化支架对照组 （16例 ）。经股静脉将 6 F右冠状动脉造影导管置入冠状静脉窦采血 ,采用 Griess法及非平衡法分别测定冠状动脉内支架置入术前及术后 6 h内冠状静脉窦血中 NO及ET- 1的水平。结果 :磁化支架组术后 6 h冠状静脉窦血中 NO含量较对照组相比显著升高 （P<0 .0 1） ;磁化支架组ET- 1水平的改变 ,包括术后即刻降低 P<0 .0 1)与 6 h回升 （P<0 .0 1）都不如对照组明显 ,两组 ET- 1水平在 3h有显著性差异 （P<0 .0 5 ）。结论 :冠状动脉内磁化支架置入术后 NO升高与 ET- 1水平变化趋缓反映了靶区血管局部内皮细胞功能改善 ,磁化支架置入术后急性冠脉痉挛及远期冠脉再狭窄的发生率降低可能与此有关     

κ-阿片受体激动剂U50488H对内皮素-1所致大鼠室性心律失常的影响

目的:研究κ-阿片受体选择性激动剂U50488H是否可通过调节内皮素-1(ET-1)表达的水平,进而影响c-Src蛋白酪氨酸激酶(PTK)的表达以实现抗心律失常的作用。方法:将42只大鼠随机分为7组(每组6只):正常对照组、U50488H组、U50488H+nor-BNI组、nor-BNI组、ET-1组、ET-1+U50488H组及ET-1+U50488H+nor-BNI组。左心室及股动脉插管观测大鼠心率(HR)、动脉压(ABP)、左心室内压(LVP)及心脏收缩和舒张功能(±LVdp/dtmax)等血流动力学指标,并计算大鼠室性心律失常的发生情况和大鼠的死亡率。实时荧光定量PCR检测ET-1及ET-1受体(ETRA)mRNA表达;Western blot测定ETRA及下游分子c-Src PTK的表达水平。结果:U50488H可显著抑制ET-1所致大鼠ABP、LVP以及心脏收缩、舒张功能的升高,并可显著降低ET-1所致大鼠室性心律失常的发生率和死亡率(P<0.01),以及抑制心肌ET-1 mRNA的水平(P<0.01)。给予ET-1后,磷酸化(P)-c-Src PTK的表达水平升高,U50488H可显著降低c-Src PTK的水平以及ET-1引起的P-c-Src PTK表达的水平(P<0.05),此作用可被κ-阿片受体阻断剂nor-BNI所阻断。结论:κ-阿片受体选择性激动剂U50488H可抑制ET-1所致大鼠室性心律失常发生。该作用可能与抑制ET-1及其下游分子c-Src PTK的表达有关。     

冠状动脉粥样硬化患者影像表现与冠状动脉循环血浆内皮素-1和一氧化氮水平的关系

目的　观察冠状动脉粥样硬化影像表现与冠状动脉循环血浆内皮素 - 1( ET- 1)和一氧化氮 ( NO)水平的关系。方法　 5 1例行冠状动脉造影者 ,造影前取血测定冠状静脉窦 ( CS)和冠状动脉开口 ( AO)血浆 ET- 1和 NO水平。冠状动脉腔径狭窄≥ 5 0 %者为严重冠状动脉病变组 ,反之为对照组。分析记录严重冠状动脉病变组病变血管数、狭窄病变数、闭塞病变数和病变范围积分。结果　 1.严重冠状动脉病变组 CS血浆 ET- 1水平 ( ET- 1CS)和 CS与AO的差值 ( ET- 1CS- AO)明显高于对照组 ( P<0 .0 5 ) ;严重冠状动脉病变组 ET- 1CS明显高于 AO血浆 ET- 1水平( ET- 1AO) ( P<0 .0 5 )。 2 .严重冠状动脉病变组 NOCS和 NOCS- AO明显低于对照组 ( P<0 .0 5 ) ;严重冠状动脉病变组NOCS明显低于 NOAO( P<0 .0 5 )。 3 .严重冠状动脉病变组 ,ET- 1CS- AO与冠状动脉病变范围积分呈显著正相关 ( P<0 .0 5 ) ,NOCS- AO与冠状动脉病变范围积分呈显著负相关 ( P<0 .0 5 )。结论　冠状动脉粥样硬化影响冠状动脉循环血浆 ET- 1和 NO水平 ,粥样硬化病变范围与冠状动脉循环血浆 ET- 1和 NO水平有相关关系     

内皮素-1对新生大鼠心肌细胞的影响及机制

目的:研究内皮素-1（ET-1）诱导心肌肥大的机制及对抗的药物。方法:在培养新生大鼠心肌细胞中,采用L-型钙通道阻滞剂拉西地平（larc id ip ine）和MN9202、钙激活氯通道阻断剂尼氟灭酸（n iflum ic ac id,NFA）、蛋白激酶C（prote in k inase C,PKC）通路的阻断剂白屈菜季氨碱（chelerythrine,che）和ERK通路阻断剂PD98059（PD）观察内皮素-1在诱导心肌蛋白质合成中的影响。结果:对照组（DMEM）蛋白质含量为273±20μg/m l,ET-1组为312±30μg/m l,较对照组升高14%。ET-1+NFA组、ET-1+che组、ET-1+MN9202组、ET-1+larc id ip ine组、ET-1+PD98059组分别为280±10μg/m l、283±10μg/m l、285±27μg/m l、275±22μg/m l、293±33μg/m l;与ET-1组比较分别降低10%、9%、8.6%、13.1%、6.1%。结论:ET-1刺激引起的心肌细胞蛋白合成与钙激活氯通道和L-型钙通道有关,PKC和ERK通路在ET-1诱导心肌肥大的信号转导通路中起重要作用。     

冠心病患者血浆降钙素基因相关肽和内皮素-1水平的临床研究

目的 :观察冠心病患者血浆降钙素基因相关肽 （CGRP）和内皮素 -1（ET-1）在发病时和治疗后含量的变化。方法 :以放射免疫法测定 12例急性心肌梗死 （AI）、3 3例心绞痛 （AP）患者发病第 1天和治疗后第 7天的 CGRP及ET-1含量 ,并与 2 0例正常人对照。结果 :AMI组和 AP组第 1天 CGRP较对照组增高 （P<0 .0 5 ） ,两组的 ET-1明显增高 ,有非常显著差异 （P<0 .0 1）。治疗后第 7天两组数据与对照组相比无明显差异 （P>0 .0 5 ）。结论 :CGRP与ET-1在冠心病发病早期均有不同程度地增高 ,两者之间显著正相关 ,并与冠心病的严重程度相关     

心肌内向整流钾通道（IK1）激动剂缺血预处理对再灌注性心律失常的影响

目的 在麻醉大鼠或离体灌流大鼠心脏建立缺血/再灌注（再灌注）性心律失常模型,应用心肌内向整流钾通道（IK1） 激动剂zacopride（扎考比利）中文 缺血预处理观察zacopride对再灌注性心律失常的效应并分析可能的机制。方法 在体实验：结扎SD大鼠心脏冠状动脉左前降支,局部缺血15 min,松扎后再灌15 min,建立再灌注性心律失常模型。在缺血前3 min（缺血预处理,pretreatment）分别给予1.5、15 或50 µg/kg zacopride。应用利多卡因（Lidocaine）做阳性对照药,IK1非特异性阻断剂氯喹拮抗zacopride的效应。全程连续记录心电图。离体实验：麻醉SD大鼠,开胸取出心脏,建立Tyrode液-Langendorff离体灌流系统,结扎SD大鼠心脏冠状动脉左前降支,局部缺血15 min,松扎后再灌15 min,建立离体再灌注性心律失常模型。缺血前3 min分别给予0.1、1或10 µmol/L zacopride观察预处理对离体再灌注性心律失常的影响,IK1非特异性阻断剂BaCl2 1 µmol/L拮抗zacopride的效应。结果 在体实验：应用1.5~50 zacopride缺血预处理可显著抑制再灌注诱发的心律失常,最适剂量为15 µg/kg（P<0.05）,与利多卡因效应相仿（P>0.05）;离体实验：Langendorff离体灌流心脏应用0.1~10 μmol/L zacopride缺血预处理可有效抑制再灌注心律失常的发生,1 μmol/L为zacopride作用最适浓度,其效应被1 μmol/L BaCl2明显逆转。结论 大鼠在体和离体实验证明,zacopride预处理可有效抑制再灌注性心律失常;应用低剂量的BaCl2可消除zacopride的抗心律失常作用,表明zacopride抗缺血-再灌注性心律失常作用是通过其激动IK1通道介导的。     

CT-1C-末端多肽对大鼠心肌缺血后再灌注心电图的影响

目的观察CT-1C-末端多肽不同干预方式对大鼠心肌缺血再灌注损伤心电图变化的影响。方法用结扎-松解SD大鼠冠状动脉左后降支的方法制作MI／R模型。27只SD大鼠随机分为4组：正常组（N，n=5）；疾病组（D，n=6），结扎30min后开始再灌注；MI／R后干预组（T，n=8），结扎30min后开始再灌注并腹腔注射CT-1C-末端多肽100μg/kg；MI／R前干预组（O，n=8），腹腔注射CT-1C-末端多肽100μg/kg后进行MI／R实验。实验过程中，动态监测心电图，观察ST段、心率、PR间期及心律失常的发生情况。结果①结扎前4组大鼠的心率和PR间期与正常组大鼠无差别（F=0．6633，p〉0．05）；②结扎冠状动脉左后降支30min内，三组大鼠的心率都明显减慢，PR间期也明显延长，与结扎前比较差异有显著性（p〈0．01）。再灌注2h内，疾病组（D）大鼠的心率进一步减慢，PR间期也进一步延长，与结扎后比较，差异不显著；MI／R前干预组大鼠的心率及PR间期与结扎后比较，差异有显著性（p〈0．01）。MI／R后干预组（T）大鼠心率无明显变化，与结扎后比较，无显著差异；③缺血30min内，仅疾病组（D）有1只大鼠发生心律失常（16．67％）；再灌注后，三组大鼠心律失常发生率均有增加，且各组间存在明显差别（x^2=4．419，p〈0．01），其中T组发生率最低（12．5％），O组发生率最高（62．5％），疾病组（50％）。结论①缺血及再灌注损伤均可导致SD大鼠心率减慢，PR间期延长，并易于再灌注后发生心律失常；②于缺血30min后开始再灌注的同时，施加CT-1C-末端多肽干预，可以防止SD大鼠MI／R后心率进一步减慢，减少心律失常的发生率；③SD大鼠接受CT-1C-末端多肽腹腔注射7天后，再遭受MI／R损伤，其再灌注后的心率进一步明显减慢，且心律失常的发生率增高。     

尿激酶对血管升压素诱发的大鼠梗死心肌的保护作用

目的 :探讨尿激酶对血管升压素 （Pit）诱发大鼠梗死心肌的保护作用。方法 :以 SD大鼠腹腔注射 Pit（3 0 U/kg）造成心肌梗死模型 ,观察腹腔注射尿激酶 （5万 U / kg）对血清心肌酶 （CK、CK-MB、L DH）释放量、心电图 ST段抬高程度以及心肌病理损伤程度的影响。结果 :Pit组较对照组心肌酶 （CK、CK-MB、L DH）释放量以及心肌病理损伤程度均显著增加 （P<0 .0 1） ,ST段显著抬高 （P<0 .0 1） ;Pit+ UK组则较 Pit组心肌损伤程度明显减轻 （P<0 .0 1） ,CK、CK-MB、L DH和 ST段分别降低 54.2 %、54.5%、48.4%和 56.5% （均为 P<0 .0 1）。结论 :尿激酶对 Pit性心肌梗死大鼠的心肌具有明显的保护作用     

Anti-arrhythmic effect of magnesium cations. Protection against ventricular excitability during cardiotonic therapy]

This study showed the effectiveness of magnesium sulphate during digitalis therapy complicated by ventricular hyperexcitability. 28 patients with cardiac disease and ventricular arrhythmias in heart failure were studied. Magnesium sulphate was given by slow intravenous infusion (30--50 mg/min) twice daily. The anti-arrhytmic action allowed treatment with digitalis until improvement in cardiac function was observed. The mechanism of the action of magnesium sulphate in digitalis--induced arrhythmias is discussed.     

镁对急性缺血及再灌注心肌易损期延长的拮抗作用

本实验发现，兔心急性缺血及再灌注早期心室肌易损期（ＶＰ）均明显延长，并伴有自发性心律失常发生率增高。静脉滴注硫酸镁可使这种延长的ＶＰ明显缩短甚或＂消失＂，并使自发性心律失常发生率降低。提示硫酸镁可通过缩短ＶＰ这一途径降低心肌的易损性。     

Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation

OBJECTIVE: To assess the role of electrolyte imbalance in cardiac arrhythmias associated with congestive heart failure. DESIGN: Serum magnesium and potassium levels, urine magnesium excretion and the incidence of ventricular arrhythmias were assessed throughout the study. The patients who displayed complex arrhythmias after the first week of hospital medication were randomized 2:1 to double-blind magnesium supplementation or placebo. SETTING: The study was carried out in one municipal hospital, providing primary care. SUBJECTS: A total of 588 consecutive patients were screened for eligibility (clinical heart failure >/=6 months; NYHA class II-IV; left ventricular ejection fraction 相似文献   

Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality

Two hundred patients with acute myocardial infarction were entered into a randomised double-blind trial where they received either intravenous magnesium sulphate or saline for 24 hours after admission to hospital. The incidence of ventricular arrhythmias necessitating treatment was reduced by more than half in the group receiving magnesium sulphate. There were two deaths in the group receiving magnesium sulphate and seven receiving saline placebo. Total cardiac events were significantly reduced in the magnesium treated group. These reductions cannot be attributed to differences in risk factors or therapy between the two groups, either before or during the period of study. These results suggest that magnesium administration reduces the incidence of serious tachyarrhythmias and death after acute myocardial infarction and that this simple regime warrants further study.     

硫酸镁对家兔在体心脏跨室壁心肌复极不均一性的影响

目的：观察静脉注射索他洛尔后，硫酸镁对家兔跨室壁心肌复极不均一性的影响，探讨其治疗室性心律失常的机制。方法：采用单相动作电位（monophasic action potential,MAP)记录技术，同步记录12只开胸兔左室心外膜心肌、中层心肌和心内膜心肌的MAP，在静脉注射索他洛尔基础上，静脉滴注硫酸镁后观察其对心肌得极不均一性的影响。结果：（1）索他洛尔剂量依赖性地显延长中层心肌的MAP复极100％时程，增加跨室壁复极离散度（transmural dispersion of repolarization,TDR)；静脉滴注硫酸镁后TDR明显减少。（2）索他洛尔剂量依赖性地诱发早期后除极（early afterdepolarization,EAD)和尖端扭转型室性心动过速（torsade de pointes,TdP)的发生率；硫酸镁抑制索他洛尔诱导的EAD和TdP。结论：硫酸镁逆转索他洛尔所致的TDR增加，抑制索他洛尔诱导产生EAD，其治疗TdP的机制可能与此有关。     

Antiarrhythmic effects of intravenous magnesium sulfate in torsade de pointes. Apropos of 6 cases

The antiarrhythmic properties of magnesium salts, known for many years, are periodically recalled but rarely used in daily clinical practice. They are usually used in digitalis-induced arrhythmias and are rarely indicated in other conditions; they are often reserved for cases in which a magnesium deficiency is suspected. In 6 cases of torsades de pointes, magnesium sulphate was administered at a dose 1 to 3 g by direct intravenous injection. Although hypokalaemia was a common finding, a low magnesium concentration was only found in one case. The ventricular arrhythmia regressed completely at the end of the injection in 4 cases (one after two injections). One positive but incomplete response was observed in the only case of magnesium deficiency, probably due in retrospect to inadequate dosage. Finally, one patient with very poor ventricular function had recurrence after a good initial response. The diversity of the clinical and biological findings in this series suggests a specific antiarrhythmic action of the magnesium ion, apparently independant of the correction of magnesium deficiency; experimental studies suggest that the mode of action is a direct antagonism of Mg++-K+ and/or Mg++-Ca++. Compared to usual means of treatment of torsades de pointes (isoprenaline infusion or pacing) the advantages of intravenous magnesium sulphate are clear-cut: innocuity, simplicity and rapidity of administration, and almost immediate efficacy.     

Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations

Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.     

Electrophysiologic and antiarrhythmic effects of magnesium in patients with inducible ventricular tachyarrhythmia.

Intravenous magnesium is reported to be effective in the treatment of ventricular arrhythmias associated with hypomagnesemia, digitalis toxicity, or prolongation of the QT interval. In most previous reports, magnesium was added to conventional antiarrhythmic drugs that had failed. There are few data on the antiarrhythmic efficacy of magnesium as monotherapy in patients without these associated abnormalities. Ten patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia by programmed electrophysiologic testing were treated with intravenous magnesium. Following magnesium infusion, all patients still had inducible ventricular tachyarrhythmia. Moreover, magnesium therapy was not associated with significant changes in ventricular refractory period or in the morphology, cycle length, or hemodynamic response to induced ventricular tachycardia. These data suggest that intravenous magnesium has no significant electrophysiologic or antiarrhythmic effects in patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia.     

Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation

The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spironolactone reduced arrhythmia and maintained magnesium homeostasis in patients with congestive heart failure

BackgroundPatients with congestive heart failure (CHF) often have increased aldosterone activity that leads to hypomagnesemia. Hypomagnesemia can induce arrhythmias, an important cause of death in patients with CHF. We determined whether the aldosterone receptor antagonist spironolactone improved magnesium homeostasis and reduced arrhythmias in patients with CHF.Methods and ResultsWe randomized 116 consecutive patients with CHF into placebo control group (n = 58) and spironolactone group (20 mg daily, n = 58) in addition to conventional therapy. Plasma magnesium concentration (PMC), erythrocyte magnesium concentration (EMC), and erythrocyte magnesium efflux were not different between the 2 groups of patients before treatment. Compared with control patients, patients treated with spironolactone for 6 months had increased PMC and EMC and decreased erythrocyte magnesium efflux. Patients on spironolactone therapy also had a marked decrease of 24-hour mean heart rate, ventricular and atrial premature beats, and the risk of atrial fibrillation/flutter. Pooled data from the 116 patients showed that patients with a higher EMC or a lower sodium-dependent erythrocyte magnesium efflux had a slower heart rate, fewer ventricular premature beats, and a lower risk of atrial fibrillation/flutter.ConclusionsOur results suggest that reducing cellular magnesium efflux and loss may contribute to the spironolactone-reduced arrhythmias in patients with CHF.