7一氯苄基四氢巴马汀对大鼠α肾上腺素受体及心电图的影响

在大鼠肛尾肌标本，７－氯苄基四氢巴马汀（７－ｃｈｌｏｒ－ＢＴＨＰ）１０μｍｏｌ·Ｌ－１能竞争性地抑制苯福林致肛尾肌收缩的量效曲线，使量效曲线右移，最大效应不变，其ｐＡ２值为５．９，但对可乐定抑制电场刺激所致的大鼠输精管收缩的量效曲线无影。在毁脊髓大鼠，７－ｃｈｌｏｒ－ＢＴＨＰ５ｍｇ·ｋｇ－１在不同刺激频率下可使心率减慢，但对电刺激所致的血压升高无影响。７－ｃｈｌｏｒ－ＢＴＨＰ恒速灌注，能剂量依赖性地延长心电图Ｐ－Ｒ间期及减慢心率，直至动物死亡也未见过速性心律失常发生。     

双乙酰香茶菜甲素抗离体大鼠工作心脏缺血再灌注损伤的作用

目的：观察双乙酰香茶菜甲素（ＤＡＡ－Ａ）对心肌缺血再灌注损伤的作用，方法：离体大鼠心脏停灌４０ｍｉｎ，再灌２５ｍｉｎ，造成心肌缺血再灌注损伤模型，结果：ＤＡＡ－Ａ０．１３，０．２５，０．５０ｍｍｏｌ．Ｌ＾－１对再灌注所致心功能低下有心脏保护作用，降低室颤发生率及乳酸脱氢酶（ＬＤＨ），丙二醛（ＭＤＡ）的生成量，ＤＡＡ－Ａ０．２５ｍｍｏｌ．Ｌ＾－１改善心肌超微结构，结论：ＤＡＡ－Ａ抗心肌缺血再灌注损伤     

1－肉桂基－4－（2，3，4－三甲氧基苄基）－四氢吡嗪盐酸盐对大鼠心肌缺血再灌性心律失常的保护作用

采用整体大鼠心肌缺血再灌注模型，观察１－肉桂基－４－（２，３，４－三甲氧基苄基）－四氢吡嗪盐酸盐（ＣＴＴＰ）对缺血再灌性心律失常的保护作用．于结扎前３ｍｉｎ，ＣＴＴＰ２．５或５ｍｇ·ｋｇ－１ｉｖ，可显著降低缺血再灌损伤引起的室性心律失常发生率，缩短持续时间；能明显减少心肌谷草转氨酶，肌酸激酶和乳酸脱氢酶释放量；升高超氧化物歧化酶活性，减少脂质过氧化反应代谢产物丙二醛含量．提示ＣＴＴＰ抗心肌缺血再灌注心律失常的作用，可能与降低心肌脂质过氧化和增强氧自由基清除酶的活性有关．     

双乙酰香茶菜甲素抗离体大鼠工作心脏缺血再灌注损伤的作用

目的：观察双乙酰香茶菜甲素（ＤＡＡＡ）对心肌缺血再灌注损伤的作用．方法：离体大鼠心脏停灌４０ｍｉｎ，再灌２５ｍｉｎ，造成心肌缺血再灌注损伤模型．结果：ＤＡＡＡ０１３，０２５，０５０ｍｍｏｌ·Ｌ－１对再灌注所致心功能低下有心脏保护作用，降低室颤发生率及乳酸脱氢酶（ＬＤＨ），丙二醛（ＭＤＡ）的生成量．ＤＡＡＡ０２５ｍｍｏｌ·Ｌ－１改善心肌超微结构．结论：ＤＡＡＡ抗心肌缺血再灌注损伤的作用与其抗脂质过氧化损伤有关．     

噻庚啶的抗心律失常作用和对心肌代谢的影响

在结扎大鼠左冠状动脉主支５ｍｉｎ．再灌注１５ｍｉｎ造成的再灌心律失常模型中．噻庚啶（Ｃｙｐ．４ｍｇ·ｋｇ－１，ｉｖ）明显降低再灌心律失常发生率，消除再灌引起的心室纤颤和室性心动过速．显著减少室性早搏个数．明显减慢心率．显著降低Ⅱ导ＥＣＧ的Ｐ波和Ｔ波电压．防止缺血所致ＳＴ段抬高。在离体灌流大鼠心脏心肌缺血再灌损伤模型中．Ｃｙｐ显著降低再灌心肌Ｃａ２＋聚积，有效防止Ｋ＋丢失．显著提高能量负荷（ＥＣ）．轻度提高腺苷三磷酸（ＡＴＰ）水平．显著降低腺苷一磷酸（ＡＭＰ）及次黄嘌呤核苷（ＩＮＯ）含量。表明：Ｃｙｐ有显著抗缺血再灌心律失常作用。并有拮抗钙．减轻Ｋ＋丢失和改善缺血再灌注心肌能量代谢作用。     

苯海索对大鼠急性前脑缺血再灌注损伤的保护

目的：研究苯海索（ｔｒｉｈｅｘｙｐｈｅｎｉｄｙｌ，ＴＨＰ）对大鼠急性前脑缺血再灌注损伤的保护作用。方法：用阻断四血管法造成急性前脑缺血再灌注损伤。ＴＨＰ１．５ｍｇ·ｋｇ－１或３ｍｇ·ｋｇ－１在缺血前５ｍｉｎ，再灌前和再灌注３０ｍｉｎ分３次静脉注射。结果：ＴＨＰ可剂量依赖性阻止脑组织和红细胞中超氧化物歧化酶活力下降及脑组织中乳酸脱氢酶（ＬＤＨ）活力下降，阻止外周血中ＬＤＨ活力增加和过氧化脂质含量增加，并促进脑电活动恢复和抑制脑水肿形成。结论：ＴＨＰ对大鼠急性前脑缺血再灌注损伤具有保护作用，其机制与抗脂质过氧化有关。     

核黄素对离体大鼠心脏再灌注心律失常的影响

在离体大鼠心脏缺血再灌注损伤模型上，研究核黄素（２．６×１０－５ｍｏｌ·Ｌ－１）对再灌注心律失常影响。结果发现：再灌早期再灌注组均发生心律失常，持续１３±３．８ｍｉｎ；核黄素组心律失常发生率仅为０．０８（１／１３），持续２．５ｍｉｎ，两项指标组间比较均有显著差异（Ｐ＜０．０１）。核黄素对再灌注心律失常的抑制作用，可能与其抗心肌细胞脂质过氧化和稳定膜相结构有关。     

7-氯苄基四氢帕马丁及奎尼丁对豚鼠离体心房及大鼠血管环的作用比较

７－氯苄基四氢帕马丁（７－Ｃｌ－ＢＴＨＰ）及奎尼丁（Ｑｕｉ）均能明显延长豚鼠离体左心房的功能性不应期,显著抑制肾上腺素诱发的自律性,但７－Ｃｌ－ＢＴＨＰ能明显增强豚鼠离体左心房的收缩力,而Ｑｕｉ则对其无影响．在心脏肥厚大鼠及正常大鼠的离体主动脉环,７－Ｃｌ－ＢＴＨＰ及Ｑｕｉ对去甲肾上腺素所致的收缩均有抑制作用．７－Ｃｌ－ＢＴＨＰ的ＩＣ５０分别为７６及３９μｍｏｌ·Ｌ－１,而Ｑｕｉ的ＩＣ５０则分别为４．６及８μｍｏｌ·Ｌ－１．Ｑｕｉ对氯化钾所致心脏肥厚及正常大鼠主动脉环的收缩有明显的抑制作用,其ｐＤ２′分别为４．３及４．０,而７－Ｃｌ－ＢＴＨＰ则对其无影响．结果提示７－Ｃｌ－ＢＴＨＰ的抗心律失常作用可能与延长不应期,降低自律性和抗α受体作用有关．     

乙酰香茶菜甲素抗心肌缺血再灌注损伤作用

用麻醉大鼠缺血４０ｍｉｎ，再灌注３０ｍｉｎ所致的心肌缺血再灌注损伤模型，观察了乙酰香茶莱甲素（ＤＡＡ－Ａ）对心肌缺血再灌注损伤的保护作用。ＤＡＡ－Ａ能提高缺血及再灌期左室收缩压（ＬｖＳＰ）及±ｄｐ／ｄｔｍａｘ，降低再灌注所致心律失常发生率，降低血浆中磷酸肌酸激酶（ＣＰＫ）、丙二醛（ＭＤＡ）、血栓素Ｂ２（ＴＸＢ２）的水平，缩小心肌梗塞面积。结果提示：ＤＡＡ－Ａ对心肌缺血再灌注损伤有明显保护作用，其机制与抗脂质过氧化损伤有关．     

四丙酰关附醇胺对大鼠离体心脏再灌性心律失常及心肌离子含量的影响

在大鼠离体Ｌａｎｇｅｎｄｏｒｆ灌流心脏观察四丙酰关附醇胺（ＴＰＧＦＡ）对再灌性心律失常及心肌Ｎａ＋，Ｋ＋，Ｃａ２＋水平的影响．ＴＰＧＦＡ６－１２ｍｇＬ－１显著降低３０ｍｉｎ缺血＋３０ｍｉｎ复灌和吡那地尔（１．２５μｍｏｌＬ－１）＋１２ｍｉｎ缺氧＋４０ｍｉｎ再给氧两种模型的室性心动过速和心室纤颤发生率；ＴＰＧＦＡ３－１２ｍｇＬ－１可显著减慢心率，延长心电图的ＱＴｃ，减少Ｋ＋从心肌细胞内丢失；１２ｍｇＬ－１时还减少细胞内Ｃａ２＋堆积．结果表明ＴＰＧＦＡ可保护大鼠离体心脏的再灌性心律失常，其作用机理可能与抑制外向Ｋ＋电流有关．     

葛根注射液抗心肌缺血作用药理研究

目的 考察葛根注射液的抗心肌缺血作用。方法 考察葛根注射液高中低剂量组对大鼠离体心脏左室峰压(LVSP)、冠脉流量(CF)及大鼠离体心脏缺血再灌注后的LVSP、左室舒张期末压(LVEDP)、心率(HR)、CF的影响。结果 葛根注射液可升高大鼠离体心脏心肌收缩力及冠脉流量;对离体心脏缺血再灌注导致的LVSP和LVEDP的升高、心率及冠脉流量的降低均有对抗作用。结论 葛根注射液具有抗心肌缺血的作用。     

莲房原花青素对大鼠心肌缺血再灌注损伤的保护作用

目的探讨莲房原花青素(LSPC)对大鼠心肌缺血再灌注损伤的作用。方法用麻醉大鼠冠脉结扎30 min后，再灌注45 min造成心肌损伤模型。离体大鼠心脏经停灌30 min后，用正常K-H液复灌30 min，造成心肌损伤模型。均于实验前给予药物或生理盐水。结果LSPC可降低复灌后血清ET和Ang II的浓度，抑制MDA含量升高，并保持SOD活性及NO的水平。心脏复灌以后冠脉流量和心率明显恢复，心肌细胞酶CK和LDH漏出减少，心肌组织黄嘌呤氧化酶(XO)的活性降低，心肌超微结构的病理变化改善等。结论LSPC对整体及离体大鼠心肌缺血再灌注损伤具有保护作用。     

葛根注射液抗心肌缺血的药理作用研究

目的 考察葛根注射液的抗心肌缺血作用.方法 考察葛根注射液高中低剂量组对大鼠离体心脏左室峰压(LVSP)、冠脉流量(CF)及大鼠离体心脏缺血再灌注后的LVSP、左室舒张期末压(LVEDP)、心率(HR)、CF的影响.结果 葛根注射液可升高大鼠离体心脏心肌收缩力及冠脉流量;对离体心脏缺血再灌注导致的LVSP和LVEDP的升高、心率及冠脉流量的降低均有对抗作用.结论 葛根注射液具有抗心肌缺血的作用.     

Exogenous hydrogen sulfide postconditioning protects isolated rat hearts against ischemia-reperfusion injury

Hydrogen sul fi de (H2S) is an endogenous gaseous mediator, produced by cystanthionine-gamma-lysase (CSE) in the cardiovascular system. Hydrogen sulfide given before ischemia can decrease myocardial ischemia and reperfusion injury. The present study investigated: (1) if hydrogen sulfide given at early reperfusion could decrease myocardial ischemia and reperfusion injury; (2) if the protective effects of hydrogen sulfide were related to mitochondrial ATP-sensitive K+ (KATP) channels opening. In isolated rat heart model, treatment of heart with NaHS (H2S donor) at the onset of reperfusion resulted in a concentration-dependent limitation of infarct size and creatine kinase release. The optimal NaHS concentration for cardioprotection is 1 microM. The cardioprotective effects of NaHS (1, 10 microM) were comparable to those of ischemic postconditioning. The KATP channels blocker, Glibenclamide or 5-hydroxydecanoate, reversed the cardioprotective effects of NaHS. The datum provided further evidence that exogenous H2S postconditioning protected rat heart against ischemia and reperfusion injury. Mitochondrial KATP channel opening is implicated in the postconditioning of H2S.     

Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been reported to have beneficial effects on cardiac function. The authors used the Langendorff model of ischemia/reperfusion (I/R) injury in isolated rat heart to determine whether ghrelin exerts direct cardioprotective effects. Also, the capacity of ghrelin to bind to sarcolemmal membrane fractions before and after ischemia and reperfusion was examined. Compared with vehicle administration, administration of ghrelin (100-10,000 pM) during the reperfusion period resulted in improvement in coronary flow, heart rate, left ventricular systolic pressure, and left ventricular end-diastolic pressure. Ghrelin also enhanced the rates of left ventricular contraction and relaxation after ischemia following reperfusion. Administration of ghrelin during reperfusion reduced myocardial release of lactate dehydrogenase and myoglobin, indicating protection against cardiomyocyte injury. In addition, ghrelin attenuated the depletion of myocardial ATP resulting from ischemia and reperfusion. A receptor-binding assay demonstrated that maximum binding capacity of ghrelin to sarcolemmal membranes was significantly increased after ischemia and was further increased after I/R. However, Scatchard analysis showed that the affinity of ghrelin for its receptor was not altered. The authors have concluded that administration of ghrelin during reperfusion protects against myocardial I/R injury. The cardioprotective effects are independent of growth hormone release and likely involve binding to cardiovascular receptors, a process that is upregulated during I/R.     

Fenofibrate attenuates impaired ischemic preconditioning-mediated cardioprotection in the fructose-fed hypertriglyceridemic rat heart

We investigated in this study whether or not the ischemic preconditioning (IPC)-mediated cardioprotective effect against ischemia–reperfusion (I/R) injury exists in the fructose-fed hypertriglyceridemic (HTG) rat heart. Langendorff-perfused normal and fructose-fed (10 %?w/v in drinking water, 8 weeks) HTG rat hearts were subjected to 30-min global ischemia and 120-min reperfusion. IPC protocol included four brief episodes (5 min each) of ischemia and reperfusion. Myocardial infarct size using triphenyltetrazolium chloride staining, markers of cardiac injury such as lactate dehydrogenase (LDH) and creatine kinase (CK-MB) release, coronary flow rate (CFR), and myocardial oxidative stress were assessed. High degree of myocardial I/R injury, by means of significant myocardial infarct size, elevated coronary LDH and CK-MB release, reduced CFR, and high oxidative stress, was noted in the HTG rat heart as compared to the normal rat heart. The IPC-mediated cardioprotection against I/R injury was markedly impaired in the HTG rat heart as compared to the normal rat heart. Interestingly, pharmacological reduction of triglycerides using 8-week treatment protocol with fenofibrate (80 mg/kg/day, p.o.) restored the IPC effect in the HTG rat heart that was blunted by coinfusion, during the IPC reperfusion protocol, of a specific inhibitor of phosphoinositide-3-kinase (PI3-K), wortmannin (100 nM). The IPC failed to protect the HTG rat heart against I/R injury. Fenofibrate treatment reduced high triglycerides in the fructose-fed HTG rat and subsequently restored the cardioprotective effect of IPC.     

硫化氢对离体大鼠心脏缺血/再灌注损伤的影响及机制初探

目的观察内源性CSE/H2S通路的改变以及给予H2S供体对缺血/再灌注心脏的影响,探讨该通路与心脏缺血/再灌注损伤的关系及作用机制。方法采用Langendorff离体灌流装置、通过停灌30min/复灌30min方式造成Wistar大鼠心肌缺血/再灌注损伤模型;采用外源性NaHS(40μmol.L-1)分别在停灌30min前(SIR)与停灌30min后处理(IRS)对缺血/再灌注心脏的影响。记录心脏收缩期左心室内压上升的最大变化速率(+dp/dtmax)、舒张期左心室内压下降的最大变化速率(-dp/dtmax)及左室内压差(LVP=左室收缩压-左室舒张压)。采用比色法检测灌流液中乳酸脱氢酶(LDH)、心肌MDA及SOD;采用比色法检测心肌胱硫醚-γ-裂解酶(CSE)活性;采用RT-PCR方法测定心肌组织CSEmRNA表达。结果与缺血/再灌注组(I/R)30min相比,SIR组及IRS组±dp/dtmax、LVP均增高,LDH降低;I/R组MDA水平高于对照组(CON)、SIR组及IRS组(P<0.05,P<0.01);IR组SOD活性低于SIR组及IRS组(P<0.05),但与CON组差别无显著性;I/R组大鼠心肌CSE活性低于CON组(P<0.05);而大鼠心肌CSEmRNA的表达与CON组差异无显著性。结论在缺血前后给予外源性NaHS均可改善因再灌注损伤引起的心肌收缩及舒张功能障碍;其作用机制可能是通过提高心肌SOD活性,增加氧自由基清除而拮抗缺血/再灌注引起的心功能及细胞膜损伤;心肌缺血/再灌注时内源性CSE活性抑制可能与心功能障碍及细胞损伤有关。     

丹金合剂对大鼠心肌缺血再灌注损伤的保护作用

目的:探讨丹金合剂对大鼠心肌缺血再灌注损伤的保护作用。方法:通过结扎大鼠冠状动脉左前降支(LAD)制成心肌缺血再灌注损伤模型,观察丹金合剂在心肌缺血再灌注状态下对心功能及心肌组织酶的影响。结果:丹金合剂能显著的升高大鼠心肌缺血再灌注引起的左室内压(LVSP)、左室内压最大上升与下降速率(dp/dtmax);降低心肌丙二醛(MDA)含量,增高超氧化物歧化酶(SOD)、Na 、K -ATPase,Ca2 、Mg2 -ATPase的活力。结论:丹金合剂对大鼠心肌缺血再灌注损伤具有保护作用。     

银杏内酯A对缺血/再灌注损伤的大鼠心功能的影响

目的探讨银杏内酯A(Ginkgolide A,GA)对离体大鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤的心功能的影响。方法 Langendorff灌注离体大鼠心脏,用停灌复灌的方式制备心肌缺血/再灌注损伤模型,记录左心室收缩峰压(LVSP)、左心室舒张末压(LVEDP)、收缩压和舒张压最大变化速率(±LVdp/dtmax)和心率(HR)的变化,并测定复灌后冠状动脉流出液中LDH和SOD的含量及心肌梗死面积。分离单个细胞进行GA预处理,模拟缺血/再灌注培养后检测心肌细胞存活率和单个心肌细胞的收缩幅度。结果 GA预处理以后,LVSP、-dp/dtmax和HR在复灌10 min时较缺血/再灌注组具有明显的改善(P<0.05),并增加心率,减少LDH的生成,增加SOD的活性,降低心肌梗死面积。经GA预处理的心肌细胞存活率明显提高,10μmol.L-1GA能够明显提高缺血后单个心肌细胞的收缩幅度。结论 GA对缺血/再灌注损伤的心肌具有一定的改善作用。     

Effects of increased heart work on release of norepinephrine and ventricular arrhythmias following reperfusion in the isolated rat heart.

The influence of increasing left atrial pressures (0.5, 1.0, and 2.0 kPa) on the incidence of ventricular arrhythmias and the liberation of prelabeled norepinephrine (3H-NE) was investigated in the isolated working rat heart. Acute regional myocardial ischemia (30 min) was produced by ligature of the left main coronary artery with subsequent release of the ligature to achieve reperfusion, which consistently provoked ventricular arrhythmias. The magnitude of regional ischemia was measured by microspheres, and the efflux of 3H-labeled NE compounds was measured in the coronary effluent. Our data show that an increase in atrial pressure enhanced reperfusion arrhythmias, but the magnitude of NE release was not directly related to the occurrence of arrhythmias. It is proposed that increased heart work has an arrhythmogenic effect by enhancing the severity of regional ischemia.