槐定碱和氧化槐定碱的抗心律失常作用(英文)

研究氧化槐定碱（Ｏｘｙ）和槐定碱（Ｓｏｐ）对试验性心律失常的作用以及对心肌生理特性的影响．方法：应用各种心律失常模型观察药物对实验性心律失常的作用;离你心肌实验法观察药物对心房生理特性的影响．结果：Ｏｘｙ　５００　ｍｇ·ｋｇ－１　ｉｖ对抗乌头碱,哇巴因和结扎冠状动脉左前降支诱发的室性心率失常,使室性异位搏动数减少（Ｐ＜０．０５）,室速持续时间缩短（Ｐ＜０．０１）,室颤的发生率由 ７５％减少到１２．５％．其作用与 Ｓｏｐ １０ｍｇ· ｋｇ－１产生的结果相似． Ｏｘｙ ２５０ ｍｇ·ｋｇ－１ ｉｖ对抗氯化钡和氯仿－肾上腺素诱发的心率失常,此作用与 Ｓｏｐ １０ ｍｇ·ｋｇ－１产生的作用相似． Ｏｘｙ, Ｓｏｐ均有提高自律性,降低兴奋性及延长功能不应期的作用．结论：Ｏｘｙ与Ｓｏｐ在等效剂量时,有相似的抗心律失常作用。     

超声应变和应变率显像技术对肥厚型心肌病患者左室收缩功能的评价

应用超声应变及应变率显像技术评价肥厚型心肌病（HCM）患者左室局部心肌收缩功能。方法选取38例HCM患者作为观察组,选取健康志愿者36例作为对照组,分别进行组织多普勒超声检查,应用应变和应变率显像技术对局部心肌进行定量分析和评价。结果观察组患者左房内径、左室内径、左室收缩期末内径、室间隔厚度、左室后壁厚度均明显增加,左室射血分数明显减少（均P〈0．05）。观察组患者左室下壁、侧壁、后壁、前壁及室问隔心肌收缩期峰值应变、应变率均明显低于对照组（均P〈0．05）。结论应变和应变率显像技术能准确反映HCM患者左心室局部心肌收缩功能减退及特性的改变。     

臭氧对小鼠开阔行为、被动回避反应、脑区M受体和LPO的影响

幼年小鼠吸入臭氧（０．９ＰＰｍ）１２ｈ·ｄ－１连续３０ｄ后体重减轻。并减弱了东莨菪碱（Ｓｃｏｐ）对行为的作用，但增加了小鼠对Ｓｃｏｐ致记忆障碍的敏感性。受体结合实验显示、吸臭氧小鼠的额叶皮层和海马Ｍ受体数增加，纹状体Ｍ受体数减少。全脑过氧化脂质（ＬＰＯ）减少４７％，皮层ＬＰＯ减少４６％。     

舒张功能异常的高血压病患者左室心肌纵向收缩功能的研究

左室纵形肌纤维是导致长轴缩短和心室扭转的重要力量，因此反映左室纵轴收缩功能的中层缩短率是更符合生理状态的左室收缩功能参数。高血压病患者左室舒张功能降低时，是否也伴随着轻微的收缩功能的降低，以及二者的相互影响能否使我们在动力学和能量储备方面区分它们很难确定，因此本文测量了反映心内膜水平的左室腔收缩功能指标射血分数（EF）、短轴缩短率（FS）、相对室壁厚度（RWT）、左室质量指数（LVMI）、左室舒张末容积（LVEIM），左室心肌中层缩短率（mFS），包括实测中层缩短率（o-mFS）、收缩末环壁应力（cESS）、     

大鼠压力超负荷性心肌肥厚与氧自由基的关系

实验采用腹主动脉缩窄法复制大鼠心肌肥厚模型，观察心肌过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）水平以及尼群地平（Ｎｉｔ）和卡托普利（Ｃａｐ）治疗的作用。结果表明：大鼠腹主动脉缩窄后，左室重量增加，同时心肌匀浆中ＬＰＯ含量增高，ＳＯＤ活性下降，经相关关系分析，ＬＶＷ／ＢＷ与心肌组织ＬＰＯ含量显著正相关，ｒ为０．７６９，而与总ＳＯＤ活性呈显著性负相关，其ｒ为０．７８５。应用Ｎｉｔ、Ｃａｐ治疗能降低心肌组织中ＬＰＯ含量，升高ＳＯＤ活性，明显阻止心肌肥厚的形成。研究结果表明，氧自由基可能参与了心肌肥厚的发生和发展     

前胡丙素对肾性高血压左室肥厚大鼠心功能、左室顺应性及心肌胶原含量的影响

观察前胡丙素对肾性高血压左室肥厚（ＬＶＨ）大鼠心功能、左室顺应性及心肌胶原含量的影响。用两肾一夹肾性高血压动物模型，ｉｇ前胡丙素（ＰｒａＣ）９周。结果，与ＬＶＨ组相比，ＰｒａＣ组的ＣＦ／ＨＷＷ及ＣＯ／ＨＷＷ分别增加３１３％和２８９％；ＬＶＳＰ和－ｄｐ／ｄｔｍａｘ负值分别增加１６７％和２７８％；ＬＶＥＤＰ和Ｔ值分别降低３４９％和３６５％；ＰＶ曲线接近正常组水平；左室肌羟脯氨酸降低２３８％。提示ＰｒａＣ可提高ＬＶＨ大鼠心脏收缩及舒张功能，改善心肌顺应性     

应用多普勒组织成像技术观察曲美他嗪对冠心病局部心肌缩功能的影响

目的：观察曲美他嗪（TMZ）对冠心病左室局部收缩功能的影响，并评价多普勒组织成像技术（DTI）在研究药物改善局部心肌功能的中的价值。方法：44例冠心病患者，随机分为两组，对照组服用消心痛＋钱 道阻滞剂，TMZ组在上述药物基础上加用TMZ。应用DTI技术测量两组服药前后左室壁12节段收缩运动速度（Vs），平均左室收缩运动速度（↑-Vs）。结果：（1）TMZ组用药后室壁12例段局部收缩运动速度（Vs）参数中有7节段存在显著性差异（P＜0．05或P＜0．01），对照组前后比较Vs无显著差异，（2）平均左室收缩运动速度（↑－Vs）在TMZ组治疗后明显提高，差异有显著性（P＜0．05）。结论：（1）TMZ对冠心病患者在休息状态下能够改善左室局部收缩功能。（2）DTI能够定量分析冠心病缺血性心肌对药物治疗前后左室局部收缩运动的变化的变化，对指导临床用药有一定参考价值。     

三维超声心动图技术对频发室性早搏患者左室心肌同步性评价

目的　分析频发室性早搏患者左室心肌收缩同步性。方法　应用心脏三维定量高级插件测量５０例频发室性早搏 患者与４５例正常对照组左室１６节段心肌达到最小收缩体积的时间的最大差值结果，即达到最小收缩体积的时间的最大差值结果 （Ｔｍｓｖ１６ Ｄｉｆ）；计算标准差，即最小收缩体积的时间的标准差结果。结果　与正常对照组比较，其达到收缩末最小容积值所在曲线 上的位置较为离散，左室１６节段心肌Ｔｍｓｖ１６ Ｄｉｆ显著增大。结论　三维超声心动图技术能够客观准确的评价此类患者左室心肌 收缩同步性。     

伊贝沙坦对急性心肌梗死后左室容积和功能的影响

目的 本研究通过应用二维结合多普勒超声技术比较伊贝沙坦组与常规治疗组对急性心肌梗死后心室腔径、心肌重量指数及心功能的影响。方法 将85例AMI随机分为常规治疗组（对照组）42例、伊贝沙坦治疗组（治疗组）43例。采用二维结合多普勒超声分别在心肌梗死后1周、26周进行左室容积和功能测定。结果 心梗后26周伊贝沙坦组与对照组比较左室舒张末期容积减少，左室射血分数增加，左室心肌重量指数均明显降低。心肌梗死后26周，左室E峰最大血流速度与高峰充盈率升高。结论伊贝沙坦能明显减轻心肌梗死后心肌肥厚和左室的扩大，改善左室收缩及舒张功能。     

甲基黄酮醇胺对麻醉犬的心血管效应

本文观察了甲基黄酮醇胺（ＭＦＡ）对麻醉犬冠脉血流和心功能的影响。静脉注射５ｍｇ／ｋｇ可降低血压和心率，并增加主动脉流量和冠脉流量，但对左室收缩压（ＬＶＳＰ）、左室舒张末期压（ＬＶＥＤＰ）及左室收缩压、舒张压变化最大速率（±ｄｐ／ｄｔ＿ｍａｘ）无明显影响；ＭＦＡ降低心肌耗氧指数、总外周阻力和冠脉阻力，并增加心搏出量，作用时间超过３０ｍｉｎ。研究表明ＭＦＡ可望成为防治缺血性心脏病的有效药物。     

Inducible nitric oxide synthase depresses cardiac contractile function in Zucker diabetic fatty rats

Cardiac contractile dysfunction is a common occurrence in type 2 diabetes. The aim was to examine if inducible nitric oxide synthase (iNOS) causes cardiac dysfunction in Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. ZDF and Zucker lean control rats (20 week old) were studied at 6 h after recovery from halothane anaesthesia and surgery that involved insertions of catheters into the iliac arteries, iliac veins and the left ventricle via the right carotid artery. Protein expression and activity of iNOS in the hearts were measured by immunostaining and arginine-citrulline conversion assay, respectively. Both groups had similar baseline left ventricular developed pressure and maximum rate of rise of left ventricular pressure (+dP/dt), but heart rate and rate pressure product were lower in the ZDF than control rats. Dobutamine dose-dependently increased left ventricular developed pressure, +dP/dt, heart rate and rate pressure product in both groups, but the responses were less in the diabetic than control rats. The activity and protein expression of iNOS and nitrotyrosine were higher in the hearts of the diabetic than control rats. Selective inhibition of iNOS by 1400 W (N-3-aminomethyl-benzyl-acetamidine) did not alter responses to dobutamine in the control rats, but augmented the effects of dobutamine on left ventricular developed pressure and rate pressure product in the diabetic rats. The results indicate that activation of iNOS contributed to left ventricular contractile dysfunction in the ZDF rats, and this was partially reversed by selective inhibition of the activity of iNOS.     

可视化动缘探测系统同步检测慢性心衰对豚鼠心肌细胞舒、缩功能和钙瞬变的影响

目的建立豚鼠慢性充血性心力衰竭(CHF)模型,采用可视化动缘探测系统同步检测慢性心衰对豚鼠心肌细胞舒缩功能及钙瞬变的影响。方法采用有无呼吸困难、左心室质量与体质量比值、肺质量与体质量比值、室壁厚度及血流动力学指标判断,以降主动脉缩窄法建立豚鼠CHF模型成功后,以酶解法急性分离其左室心肌细胞,用可视化动缘探测系统同步检测慢性心衰豚鼠心肌细胞收缩力和钙瞬变的变化,并与正常豚鼠心肌细胞进行比较。结果降主动脉缩窄8 wk后,出现呼吸困难的豚鼠,其左室收缩压及舒张末压显著性增高,左室压上升和下降最大速率降低;左心室质量与体质量比值、肺质量与体质量比值及室壁厚度明显增高,呈现明显的心衰指征;心衰心肌细胞与正常细胞相比,其收缩幅度、收缩和舒张速度均明显减弱;舒张期细胞内钙升高,钙瞬变幅度减小,舒张期钙减少50%所需时间延长,但收缩期钙及细胞内钙达峰时间无明显改变。结论降主动脉缩窄8 wk后,豚鼠呼吸困难是判断CHF模型形成的指标;慢性心衰可使心肌细胞收缩力下降,钙瞬变幅度减小,这为探讨慢性心衰的发生机制提供了实验依据。     

The effects of nitroglycerin on exercise-induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine.

1 Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise-induced regional myocardial dysfunction in conscious dogs. 2 We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy. 3 Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end-diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4 DHE (5 micrograms kg-1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function. 5 After pretreatment with DHE, infusion of nitroglycerin (15 micrograms kg-1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end-diastolic pressure and an increase in left ventricular dp/dtmax. 6 These results suggest that DHE will not worsen exercise-induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE.     

Effects of isosorbide 5-mononitrate on cardiovascular function. (I). Effects on the left ventricular system

Effects of isosorbide 5-mononitrate (5-ISMN) on cardiovascular function were compared with those of isosorbide dinitrate (ISDN), verapamil and propranolol. In anesthetized open-chest dogs, intravenous injection of 5-ISMN (1 mg/kg, 3 mg/kg) scarcely decreased cardiac contractile force (CCF) and heart rate (HR). The systolic blood pressure (SBP) fell in a dose-dependent manner, and the degree of the change was greater than that in diastolic blood pressure (DBP). Especially, left ventricular pressure (LVP) and left ventricular dp/dt (LVdp/dt) were significantly decreased, and a considerable reduction in left ventricular end-diastolic pressure (LVEDP) was also observed. Intravenous injection of verapamil (0.3 mg/kg) considerably lowered DBP. While HR, CCF, LVP and LVdp/dt were markedly decreased, LVEDP showed a moderate increase. Propranolol (0.5 mg/kg, i.v.) greatly decreased LVdp/dt together with HR and CCF. Conversely, LVEDP showed a slight increase. There was no change in SBP, DBP and LVP. The vasodilating potency of 5-ISMN was 150 times smaller than that of ISDN on the contractile response in isolated rabbit thoracic aorta. On the other hand, in terms of decrease in pulse pressure, the potency exhibited by 5-ISMN was about 4 times (intravenous administration in anesthetized dogs) or 1.5 times (oral administration in conscious dogs) smaller than that of ISDN. The present results suggest that 5-ISMN shows a high bioavailability and a potency comparable to ISDN, especially in the case of peroral administration. Taking these results together with the fact that transient left ventricular failure occurs during myocardial ischemia into consideration, it is thought that peroral 5-ISMN preparation may be useful in the therapy of angina pectoris.     

Beta-blocking and hemodynamic effects of ASL-8052

The hemodynamic and cardiac beta-blocking effects of ASL-8052 (esmolol), an ultrashort-acting beta-blocker, were examined in pentobarbital-anesthetized dogs. The compound produced dose-dependent reductions in heart rate, left ventricular dP/dt, right ventricular contractile force, and diastolic arterial blood pressure in dogs with intact autonomic function. ASL-8052 was devoid of any hemodynamic effects in ganglion-blocked animals. Responses to isoproterenol (except for diastolic blood pressure) were blocked by ASL-8052 in qualitatively similar fashion in both groups of animals. The compound reduced the rate-pressure product and decreased diastolic coronary blood flow. The reactive hyperemic response to a 10-s occlusion of the left circumflex coronary artery was not modified by ASL-8052. Heart rate and contractile force dose-response curves to isoproterenol were equally shifted to the right in a dose-dependent, parallel fashion by constant infusion of ASL-8052. During infusion of large doses in reserpinized dogs, the compound decreased heart rate, contractility, and arterial blood pressure, while left ventricular end-diastolic pressure increased. No intrinsic sympathomimetic effect was observed. Tachycardia induced by either stimulation of the right ansa subclavia or intravenous injection of isoproterenol was blocked to an equivalent degree by ASL-8052. These data indicate that ASL-8052 produces hemodynamic effects that are characteristic of and explained by beta-adrenergic receptor blockade. However, direct cardiac depression is observed at extremely high doses.     

Improvement of postischemic contractile dysfunction of dog heart by MCI-154, a novel cardiotonic agent

The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutamine, that have largely cyclic AMP-dependent mechanisms of action. Regional myocardial contractility (segment shortening) and tissue ATP levels were severely depressed in reperfused myocardium. MCI-154 (0.3 and 1 microgram/kg per min) improved the regional function of postischemic myocardium and decreased left ventricular end-diastolic pressure and systemic aortic pressure when infused i.v. from 30 min after reperfusion. The improvement of regional function caused by MCI-154 (1 microgram/kg per min) was more pronounced than that caused by milrinone (1 microgram/kg per min) or dobutamine (1 microgram/kg per min), although the drugs produced an equal increase in cardiac performance (peak positive left ventricular dP/dt). These results suggest that MCI-154 produces a more pronounced improvement of regional myocardial function than milrinone and dobutamine, presumably by increasing the responses of the contractile protein system to Ca2+. In this respect, MCI-154 would be of much benefit for the treatment of postischemic left ventricular dysfunction.     

The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs.

1. To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. 2. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15 micrograms kg-1 15 min-1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. 3. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end-diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4. Treadmill exercise led to an increase in systolic arterial and left ventricular end-diastolic pressure. In contrast, isoprenaline-induced stimulation led to a decrease in diastolic arterial and left ventricular end-diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress-induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. 5. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. 6. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.     

Relationship between myocardial cation content and injury in reperfused rat hearts treated with cation channel blockers.

A role for K+ and Ca2+ channel blockers in cardiac contractile dysfunction and myocardial ionic imbalance was examined in isolated rat hearts with 35-min ischemia and 60-min reperfusion. The K+ channel blockers glibenclamide (1-30 microM) and sematilide (1-30 microM), Ca2+ channel blockers diltiazem (0.1-3 microM) and nicardipine (0.03-1 microM) and fast Na+ channel blocker tetrodotoxin (0.01-0.3 microM) were delivered for the last 3-min pre-ischemia. Ischemia-induced increase in Na+ content was attenuated by diltiazem and tetrodotoxin at all concentrations employed and by nicardipine at 0.3 microM, whereas the ischemia-induced loss of K+ was suppressed partially by glibenclamide and sematilide and almost completely by the two drugs in combination. Left ventricular developed pressure of untreated hearts did not recover upon reperfusion, which was associated with increases in myocardial Na+ and Ca2+ contents and decreases in K+ and Mg2+ contents. Glibenclamide and sematilide neither enhanced the post-ischemic recovery of left ventricular developed pressure nor affected cation changes during reperfusion. Diltiazem enhanced the recovery of left ventricular developed pressure and attenuated imbalance of the myocardial Na+ during ischemia and of all myocardial cations examined during reperfusion. The effects of nicardipine on these parameters were small. Tetrodotoxin enhanced the recovery of left ventricular developed pressure and reversed the imbalance of all myocardial cations examined during reperfusion in a concentration-dependent manner. The results suggest that blockade of transmembrane flux of K+ during ischemia plays a minor role in the improvement of post-ischemic contractile recovery, rather blockade of transmembrane flux of Na+ attenuates the ischemia and reperfusion injury.     

槐胺碱的心血管作用

槐胺碱(Sa)对麻醉猫、兔和大鼠均有明显的降压作用,降压机理与交感神经节阻断作用和直接扩张外周血管有关。离体心脏实验表明,Sa有负性频率,增加冠脉流量和一定的正性肌力作用。Sa能推迟乌头碱诱发的大鼠心律失常发生时间,缩短心律失常的持续时间,并能降低氯仿诱发的小鼠室颤发生率。其对实验性血栓形成和ADP诱导的血小板聚集作用无影响。