水杉总黄酮对豚鼠工作心脏缺血再灌注损伤的影响

目的　观察水杉总黄酮对缺血再灌注损伤心肌的保护作用。方法　采用豚鼠工作心脏缺血再灌注损伤模型 ,观察水杉总黄酮对缺血再灌注损伤心肌心功能以及生化指标的影响。结果　水杉总黄酮能明显改善缺血再灌注损伤心肌的舒缩功能 ,剂量依赖性地降低冠脉流出液中肌酸磷酸激酶以及乳酸脱氢酶的活性 ,减少缺血心肌组织中丙二醛的含量。结论　水杉总黄酮对缺血再灌注损伤心肌具有保护作用 ,其机制与其抗脂质过氧化有关     

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3 min, CTTP 2.5或5 mg·kg^-1 iv，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.     

肝缺血再灌注脂质过氧化损伤及维生素C的保护作用

目的探讨维生素C(VitC)预防及治疗肝缺血再灌注脂质过氧化损伤的作用。方法制备家兔肝缺血再灌注模型 ,检测血浆及肝组织脂质过氧化产物丙二醛(MDA)和维生素E(VitE) ,动态观察肝形态学变化 ,并应用0.25g·kg-1VitC防治脂质过氧化损伤。结果肝缺血再灌注期间 ,MDA明显增高 ,VitE显著下降 ,肝形态学发生异常变化 ;缺血前及再灌注时应用VitC ,血、肝MDA均显著低于对照组 (P<0.01) ,VitE均明显高于对照组(P<0.01) ,肝形态学异常改变明显减轻。结论0.25g·kg-1VitC能抑制或减轻肝缺血再灌注脂质过氧化损伤。     

3，6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血再灌注心肌与抗脂质过氧化的关系

在大鼠在体心肌缺血再灌注模型上，观察了３、６（二甲氨基）二笨并碘杂六环柠檬酸盐（１６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用结果表明１－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧化酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成提示Ｉ６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性．防止膜脂质过氧化有关     

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．     

3,6—（二甲氨基）—二苯并碘杂六环柠檬酸盐保护大鼠缺血…

在大鼠在体心肌缺血再灌注模型上，观察了３，６－（二甲氨基）－二苯并碘杂六环柠檬酸盐（Ｉ－６５）的抗心肌缺血再灌注损伤及抗脂质过氧化作用。结果表明Ｉ－６５能明显改善缺血再灌注所致的心肌光镜及电镜下细胞结构损伤，升高心肌超氧化物歧人酶和谷胱甘肽过氧化物酶活性，减少丙二醛生成，提示Ｉ－６５对心肌缺血再灌注损伤的保护作用与保护氧自由基清除酶的活性，防止膜脂质过氧化有关。     

纳络酮对缺血再灌注心肌脂质过氧化物和钙含量的影响

利用大心肌缺血、再灌注模型，观察了纳络酮对缺血再藻注心肌脂质过氧化物（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）和钙含量的影响。结果表明：缺血、再灌注心肌ＬＰＯ和钙含量明显增加（Ｐ＜０．０５，Ｐ＜０．０１），再灌注心肌ＬＰＯ含量和钙含量明显高于缺血心肌（Ｐ＜０．０５，Ｐ＜０．０１），而缺血、再灌注心肌ＳＯＤ明显降低（Ｐ＜０．０１）；纳络用明显降低缺血、再灌注心肌ＬＰＯ和钙含量（Ｐ＜０．０５，Ｐ＜００１），但对ＳＯＤ的影响不明显（Ｐ＞０．０５）。提示：纳络酮抑制心肌缺血、再灌注时的脂质过氧化物反应，部份阻止细胞外钙跨膜内流，对心肌只响保护作用。     

赤土茯苓苷对离体大鼠心脏缺血再灌注损伤的保护作用

采用 Langendorff离体大鼠非循环灌流模型测定赤土茯苓苷对离体大鼠缺血再灌注损伤时心肌收缩力、冠脉阻力、心率的影响及其抗脂质过氧化作用。结果 2 mg/L,1 0 mg/L,50 mg/L赤土茯苓苷可保护缺血再灌注心肌超氧化物歧化酶与硒谷胱甘肽过氧化物酶 ,降低脂质过氧化产物丙二醛的含量 ,能增加再灌后冠脉流量、冠脉阻力 ,促进心肌收缩幅度的恢复 ,减轻心脏水肿 ,但对心率的影响未见统计学差异     

黄蜀葵花总黄酮预处理对家兔心肌缺血再灌注损伤的影响

目的研究黄蜀葵花总黄酮(Total F lavone of Abelmos-chusM an ihot(L)M ed ic,TFA)药理性预适应对家兔心肌缺血再灌注损伤的保护作用及机制。方法采用持续静脉推注TFA模拟预适应的实验方法,观察家兔冠状动脉左旋支经结扎、再灌后,其心肌组织病理损伤情况、血浆中MDA含量和SOD、GSH-PX活力的变化以及心肌组织中细胞间粘附分子ICAM-1的表达情况。结果TFA不同程度减轻缺血再灌注损伤家兔心肌病理损伤的严重程度;明显降低血浆中MDA的含量,同时增强SOD及GSH-PX的活力;下调缺血心肌组织中ICAM-1 mRNA的表达。结论TFA药理性预适应可通过抑制心肌脂质过氧化、抑制心肌炎症反应,对缺血再灌注损伤的心肌具有保护作用。     

1-（2，6-二甲基苯氧基）-2-（3，4-二甲氧基苯乙氨基）丙烷盐酸盐对大鼠离体心脏缺血再灌注损伤的保护作用

研究1-（2,6-二甲基苯氧基）-2-（3,4-二甲氧基苯乙氨基）丙烷盐酸盐（DDPH）对大鼠离体心脏缺血再灌注损伤的保护作用。方法：采用Langendorff大鼠离体心脏灌流技术,结扎冠状动脉前降支（LAD）40min,复灌120min后复制出大鼠离体心脏缺血再灌注损伤模型,观察DDPH对大鼠离体心脏左心室功能、心肌梗死范围、脂质过氧化及超微结构损伤的影响。结果：DDPH能显著改善大鼠离体心脏左心室功能,明显缩小心肌梗死范围,能显著提高大鼠心肌组织中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—Px）活性,降低心肌脂质过氧化代谢产物丙二醛（MDA）含量,减少心肌超微结构损伤。结论：DDPH对大鼠离体心脏缺血再灌注损伤有保护作用,其作用机制可能与抑制氧自由基的生成和脂质过氧化作用有关。     

Effects of sasanquasaponin on ischemia and reperfusion injury in mouse hearts

We investigated effects of sasanquasaponin (SQS), a traditional Chinese herb's effective component, on ischemia and reperfusion injury in mouse hearts and the possible role of intracellular Cl- homeostasis on SQS's protective effects during ischemia and reperfusion. An in vivo experimental ischemia model was made in mice (weight 27-45 g) using ligation of left anterior descending coronary artery, and in vitro models were made in perfused hearts by stopping flow or in isolated ventricular myocytes by hypoxia. The in vivo results showed that SQS inhibited cardiac arrhythmias during ischemia and reperfusion. Incidence of arrhythmias during ischemia and reperfusion, including ventricular premature beats and ventricular fibrillation, was significantly decreased in the SQS-pretreated group (P<0.05). Results in perfused hearts showed that SQS suppressed the arrhythmias, prevented against ischemia-induced decrease in contract force and promoted the force recovery from reperfusion. Furthermore, intracellular Cl- concentrations ([Cl-]i) were measured using a MQAE fluorescence method in isolated ventricular myocytes in vitro. SQS slightly decreased [Cl-]i in non-hypoxic myocytes and delayed the hypoxia/reoxygenation-induced increase in [Cl-]i during ischemia and reperfusion (P<0.05). Our results showed that SQS protected against ischemia/reperfusion-induced cardiac injury in mouse hearts and that modulation of intracellular Cl- homeostasis by SQS would play a role in its anti-arrhythmia effects during ischemia and reperfusion.     

Increased glycogen stores due to gamma-AMPK overexpression protects against ischemia and reperfusion damage

During ischemia, endogenous glycogen becomes the principal substrate for energy through glycolysis. Cardiac-specific manipulation of AMP-activated protein kinase (AMPK) by over-expression of its regulatory gamma-subunit induces glycogen storage. The aim of this study was to examine whether heart glycogen in transgenic mice overexpressing PRKAG2 may protect from ischemia and reperfusion injury. Isolated hearts were mounted on Langendorff apparatus and subjected to 30 min 'no-flow' or 'low-flow' ischemia and 60 min reperfusion. Hemodynamic measurements, tetrazolium staining, glycogen and lactate were used to monitor ischemia reperfusion damage. After low-flow ischemia, left ventricular pressure, coronary flow (CF) and the area of viable myocardium were 20-30% higher in PRKAG2 mice compared to controls. The basal levels of glycogen in PRKAG2 were 9.2 microg/g, markedly higher than in controls, but after low-flow ischemia they declined concomitantly with increased lactate washout in the coronary effluent. During no-flow ischemia there was neither protection nor consumption of glycogen in PRKAG2 hearts. Cardioprotection was also eliminated when PRKAG2 hearts were depleted of glycogen prior to low-flow ischemia. AMPK alpha Thr172 phosphorylation did not differ between PRKAG2 hearts and controls either during low-flow ischemia or reperfusion. We conclude that PRKAG2 hearts resist low-flow ischemia injury better than controls. Improved recovery was associated with increased consumption of glycogen, and was unrelated to AMPK activation. These findings demonstrate the potential of heart protection from ischemia and reperfusion injury through metabolic manipulation increasing the level and utilization of myocardial glycogen.     

Forefront of Na+/Ca2+ exchanger studies: role of Na+/Ca2+ exchanger--lessons from knockout mice

We used Na+/Ca2+ exchanger (NCX) knockout mice to evaluate the effects of NCX in cardiac function and the infarct size after ischemia/reperfusion injury. The contractile function in NCX KO mice hearts was significantly better than that in wild type (WT) mouse hearts after ischemia/reperfusion and the infracted size was significantly smaller in NCX KO mice hearts compared with that in WT mice hearts. NCX is critically involved in the development of ischemia/reperfusion-induced myocardial injury, and therefore the inhibition of NCX function may contribute to cardioprotection against ischemia/reperfusion injury.     

高渗灌注减轻正常及高血压大鼠心脏缺血再灌注损伤

目的：观察体外高渗灌注对正常及高血压大鼠心肌缺血及再灌注损伤的影响．方法：利用体外心脏逆行灌注装置将大鼠心脏在予以正常灌注液或高渗透压灌注液灌注后进行缺血及再灌注．监测缺血前后心肌功能、缺血后心肌肌酸激酶释放量,用高效液相加电化学法测定心肌儿茶酚胺释放量,用原子吸收光谱法测定再灌注后心肌钙离子含量．结果：高渗灌注可显著减轻正常及高血压大鼠心肌缺血损害,改善高血压大鼠缺血后心功能,减少心肌儿茶酚胺释放,但未能减少再灌注后心肌钙含量．结论：高渗灌注减轻心肌缺血与再灌注损害,其作用可能与减少心肌儿茶酚胺释放有关．     

Protective effects of FK409, a novel nitric oxide donor, against postischemic myocardial dysfunction in guinea-pig hearts

Effects of FK409 were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Nitric oxide electrode, fluorometry, and 31P nuclear magnetic resonance imaging were used to monitor changes in cellular high-phosphorous energy and nitric oxide and Ca2+ content in the heart together with simultaneous recordings of left ventricular developed pressure. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 40 min, and hearts were reperfused for 40 min. FK409 at 10(-8) M, which has a minimum inotropic effect on nonischemic hearts, was added to the cardioplegic solution. Treatment with FK409 reduced left ventricular developed pressure during and after ischemia and improved postischemic recovery of left ventricular developed pressure from 55.4% at 40 min of reperfusion in FK409-free hearts up to 80.4% in hearts treated with FK409 (p < 0.01). Flow rate at 1.5 min after treatment with the cardioplegic solution was 27.7 ml/min in hearts treated with FK409 compared with 21.2 ml/min in drug-free hearts (p < 0.01). Treatment with FK409 significantly effected preservation of tissue level of beta-adenosine triphosphate at the end of ischemia or reperfusion. During ischemia, arrested with the cardioplegic solution, intracellular Ca2+ accumulation and nitric oxide release were reduced. At the end of ischemia in FK409-treated hearts, nitric oxide release was 86% greater than in drug-free hearts without reference to the Ca2+ concentration. In cardiac surgery, normothermic arrested hearts are subject to damage by oxygen free radicals in reperfusion injury. Therefore, nitric oxide exogenously supplied by FK409 was responsible for the cardioprotective action, presumably by acting directly as an oxygen radical scavenger during reperfusion. A specific nitric oxide donor, like FK409, may have therapeutic use as a nitric oxide-mediated vasorelaxant and additional protective action for reperfusion-injury hearts.     

Effects of ET(A) and ET(B) receptor blockade on post-ischemic cardiac dysfunction and norepinephrine overflow in isolated rat hearts

We investigated the role of endothelin-A (ETA) and endothelin-B (ETB) receptors in ischemia/reperfusion-induced cardiac dysfunction and norepinephrine overflow using isolated rat hearts. According to the Langendorff technique, isolated hearts were subjected to 40 minutes of global ischemia followed by 30 minutes of reperfusion. Ischemia/reperfusion led to decreases in left ventricular developed pressure and coronary flow, and an increase in left ventricular end-diastolic pressure compared with pre-ischemic basal levels. An ETB receptor antagonist A-192621 at 1 microM worsened ischemia/reperfusion-induced cardiac dysfunction. In contrast, an ETA receptor antagonist ABT-627 at 5 microM with or without A-192621 improved the aforementioned cardiac dysfunction, to the same extent. Norepinephrine was massively released in coronary effluent from the hearts exposed to ischemia/ reperfusion. Treatment with ABT-627 significantly suppressed the norepinephrine overflow induced by the ischemia/reperfusion whereas A-192621 further enhanced it, which was completely abolished by the concomitant treatment with ABT-627. These results suggest that the detrimental effect of ETB receptor blockade on post-ischemic cardiac function is mediated by the ETA receptor-related action and that norepinephrine overflow from sympathetic nerve endings is closely related to the antagonist-induced functional changes of post-ischemic hearts.     

Delay of occurrence of reperfusion-induced ventricular fibrillation in the isolated rat heart with superoxide dismutase.

The effects of superoxide dismutase (SOD) on reperfusion-induced ventricular fibrillation (R-VF) were determined in isolated, perfused rat hearts with reperfusion after durations of regional myocardial ischemia ranging from 5 to 37.5 min. SOD (100 U/ml) was perfused during both ischemia and reperfusion periods. Regional myocardial ischemia was produced by acute occlusion of the left anterior descending coronary artery (LAD). Reperfusion after a brief period of ischemia (8 min) resulted in R-VF in 33% of SOD-perfused hearts as compared with 100% of control hearts that exhibited this arrhythmia (p less than 0.05). The incidence of R-VF was not affected by SOD with intermediate duration of ischemia of 10, 15, and 22.5 min. Reperfusion after a relatively long 30-min period of ischemia did not result in R-VF in control hearts, but 87% of SOD-treated hearts still exhibited this arrhythmia (p less than 0.05). No hearts exhibited R-VF with reperfusion after 37.5 min of ischemia. Thus, SOD shifted the occurrence of R-VF to longer durations of ischemia without affecting the peak incidence of this arrhythmia. In contrast to effects of SOD on incidence of R-VF, SOD had no effect on onset times of this arrhythmia. Nor did SOD affect reperfusion-induced ventricular tachycardia (VT), heart rate (HR), or coronary flow. These results suggest that SOD may have delayed onset of electrophysiologic derangements that were specifically responsible for R-VF. SOD may be classified as a modulator of R-VF.     

Protection of the reperfused ischemic isolated rat heart by phosphatidylcholine.

We examined phosphatidylcholine (PC) effects on the isolated rat heart subjected to low- or zero-flow ischemia followed by reperfusion. Untreated hearts subjected to 30 min of low-flow ischemia recovered 15% contractility following reperfusion compared to time-control hearts. Phosphatidylcholine (0.005%) addition either 10 or 20 min before ischemia significantly enhanced recovery to approximately 61% and reduced the incidence of arrhythmias during ischemia and reperfusion. Contracture during ischemia and reperfusion was significantly reduced when PC was added 20 min before ischemia. Phosphatidylcholine was ineffective when administered at the time of reperfusion except for a moderate reduction in arrhythmia development. Phosphatidylcholine also produced a salutary effect when added 20 min prior to zero-flow ischemia. Subsarcolemmal mitochondria (SLM) and, to a much lesser degree, interfibrillar mitochondria (IFM) of untreated hearts subjected to low-flow ischemia and reperfusion exhibited depressed oxidative phosphorylation which was prevented by PC. Both mitochondrial populations exhibited a marked depression in ADP/ATP translocase activity; however, this was generally unaffected by PC. Subsarcolemmal mitochondria but not IFM of zero-flow ischemic reperfused hearts also exhibited significantly depressed oxidative phosphorylation, which was unaffected by PC. Zero-flow ischemia produced a rapid and total cessation of contractility. Both populations exhibited a substantial PC-insensitive reduction in translocase activity. Our results demonstrate, for the first time, a protection by PC on the reperfused ischemic heart. The PC-induced protection following low-flow but not zero-flow ischemia is associated with improved SLM oxidative phosphorylation suggesting dissimilar contribution of mitochondria to reperfusion-associated myocardial injury.     

立西普利和卡托普利对离体缺血再灌大鼠心脏的保护作用

本文研究了血管紧张素转移酶抑制剂立西普利(Lis)和卡托普利(Cap)对离体大鼠心脏缺血再灌引起损伤的保护作用。实验证明Lis 100nmol/L和Cap 200μmol/L能明显降低心肌组织中丙二醛(MDA)的含量,保护超氧化物歧化酶(SOD)的活性。此外,这两种转移酶抑制剂均能升高心肌组织中前列环素(PGI_2)和谷胱甘肽(GSH)的含量。表明它们对心肌缺血再灌损伤均具明显的保护作用。