Prevention of myocardial reperfusion injury in experimental coronary revascularization following ischemic arrest by a novel antiinflammatory drug, ONO-3144.

The cardioprotective effects of a novel antiinflammatory drug, ONO-3144 (ONO), on ischemic-reperfused myocardium were investigated using an in situ pig heart model. Heart was subjected to 2 h of regional ischemia, with the final 1 h having superimposed global cardioplegic arrest followed by 1 h of reperfusion. ONO (20 microM) was administered after the arrest at the onset of reperfusion. Left ventricular developed pressure (LVDP), maximum rate of rise of left ventricular pressure (LV dp/dt), and left ventricular end-diastolic pressure (LVEDP) were measured under isovolumic conditions to assess cardiac contractility and compliance. ONO improved LVDP and LV dp/dt, and reduced LVEDP after 60 min of reperfusion compared to control. This drug also improved segment shortening and end-diastolic length significantly after 15 and 60 min of reperfusion. Slight improvements in oxygen consumption and creatine kinase (CK) release were also noted. In addition, ONO reduced lipid peroxidation and thromboxane formation but enhanced the production of prostaglandins. In vitro studied demonstrated ONO to be effective scavengers for both hydroxyl (OH.) and hypohalite (OCL.) radicals. The results suggest that myocardial reperfusion injury that developed after ischemic arrest was reduced significantly by ONO. This drug inhibited such injury, probably by directly scavenging potentially harmful radicals such as OH. and OCI., which are generated in ischemic-reperfused myocardium.     

巯基化合物对离体大鼠心脏缺血再灌所致心律失常的保护作用

本文研究了半胱氨酸(Cys)及其结构类似物半胱胺(MEA),N-乙酰半胱氨酸(NAC)、胱胺(CSSC),γ-氨丙基甲基异硫脲(APMT),对离体大鼠Langendortff心脏缺血再灌所致心律失常的保护作用.给药(0.1,0.6,3,6μmol/min)10min,结扎LAD 10 min再灌5 min。结果表明含游离巯基的Cys,NAC,MEA在0.6和3.6 μmol/min时,与生理盐水对照组相比可显著降低室颤发生率(P<0.01～0.001),缩短室颤时程(P<0.01～0.001).CSSC和APMT未见明显保护作用。此外,Cys,NAC和MEA还可明显增加冠脉流量(P<0.01),CSSC和APMT则反而使冠脉流量降低。     

Effects of pretreatment with 2-O-octadecylascorbic acid, a novel free radical scavenger, on reperfusion-induced arrhythmias in isolated perfused rat hearts.

The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.     

Chrysanthemum morifolium attenuated the reduction of contraction of isolated rat heart and cardiomyocytes induced by ischemia/reperfusion

The present study was aimed to investigate the effect of Chrysanthemum morifolium Ramat. (CM) on isolated rat heart and ventricular myocytes during ischemia/anoxia and reperfusion/reoxygenation. The ischemia/reperfusion injury was induced by ligation the left artery descending coronary of isolated rat heart for 30 min followed by 30 min reperfusion with Langendorff equipment. Cell contraction in enzymatically isolated ventricular myocytes was determined by a video tracking system. The results showed CM (0.25 g/L to 1.0 g/L) increased left ventricular developed pressure (LVDP), +/- dp/dt(max), LVDP x HR and coronary flow (CF) and decreased heart rate (HR) in dose dependent manner. CM (0.5 g/L) attenuated the reduction of LVDP, +/- dp/dt(max) and CF caused by ischemia/reperfusion. CM (0.25 g/L to 1.0 g/L) increased peak velocity of cell shortening/relengthening (+/- dL/dt(max)) and contraction amplitude (dL) of isolated ventricular myocytes in a dose-dependent way under control condition, but without significant effect on end-diastolic cell length (L0). Under anoxia 5 min followed by 10 min reoxygenation, CM attenuated the reduction in contractile parameters. The results suggest that CM processes cardioprotective effect during ischemia/anoxia and reperfusion/reoxygenation in the isolated rat heart and the ventricular myocytes.     

峨眉唐松草碱对离体大鼠心肌缺血再灌注损伤的保护作用

峨眉唐松草碱(methoxyadiantifoline 5μmol/L)显著降低大白鼠离体灌流心脏缺血再灌注损伤所致心室纤颤的发生率、延长窦性心律时间、减少心肌细胞中乳酸脱氢酶的释放及丙二醛的生成,显示其具有保护心肌及抑制脂质过氧化作用,效果与维拉帕米近似。     

Cicletanine improves myocardial function deteriorated by ischemia/reperfusion in isolated working rat hearts.

The effect of cicletanine, a novel furopyridine antihypertensive drug was compared with that of nitrendipine, a dihydropyridine slow calcium channel blocker, on cardiac function and reperfusion-induced ventricular arrhythmias in isolated working rat hearts subjected to 10-min ischemia induced by ligation of the left main coronary artery followed by 10-min reperfusion. Before ischemia, cicletanine and nitrendipine, perfused at concentrations of 3 x 10(-5), 6 x 10(-5), 10(-4), and 2 x 10(-4) or 10(-8) M, respectively, did not influence heart rate (HR), LV developed pressure (LVDP), its first derivative (LVdP/dtmax), and LV end-diastolic pressure (LVEDP), whereas aortic flow (AF) was decreased by 2 x 10(-4) M cicletanine only. Coronary flow (CF) remained unchanged by various cicletanine concentrations but was slightly increased by nitrendipine. In the concentration range of 3 x 10(-5)-10(-4) M, cicletanine improved AF either in ischemia or during reperfusion, whereas 2 x 10(-4) M had no such effect. Nitrendipine slightly attenuated ischemia/reperfusion-induced decrease in AF. Cicletanine and nitrendipine enhanced LVDP during ischemia. Ischemia-induced deterioration of LVdP/dtmax was reduced by cicletanine, during reperfusion, but this parameter was reduced by nitrendipine and the highest cicletanine concentration. Cicletanine decreased LVEDP significantly during ischemia and reperfusion, but nitrendipine had no such effect. All cicletanine concentrations reduced the incidence of irreversible ventricular fibrillation (VF) during reperfusion, an effect roughly concentration dependent in the range of 3 x 10(-5)-10(-4) M, whereas nitrendipine had no influence on arrhythmias.     

异甜菊醇对大鼠在体心肌缺血再灌注损伤的保护作用

目的在大鼠在体心肌缺血再灌注模型上进一步证实异甜菊醇对缺血再灌损伤心肌的保护作用。方法麻醉大鼠结扎左冠状动脉30min后再灌注90min。结扎前10min静脉注射异甜菊醇。心电图连续观察大鼠心室纤颤(VF)和室性心动过速(VT)的发生率;全自动生化分析仪测定血清乳酸脱氢酶(LDH)和肌酸激酶(CK)活性;测定心肌梗死范围;光学显微镜和电镜观察心肌组织学和超微结构改变。结果异甜菊醇0.5～2.0mg·kg-1有效减少大鼠心肌缺血再灌期VF和VT发生率,减少心肌梗死范围,降低血清LDH和CK活性。光镜及电镜观察可见异甜菊醇处理组心肌组织形态学及超微结构损伤明显轻于缺血再灌对照组。结论异甜菊醇对大鼠缺血再灌注损伤心肌有保护作用。     

慢性间歇性低压低氧对成年和幼年大鼠缺血/再灌注心脏保护作用的比较

目的观察慢性间歇性低压低氧(CIHH)对成年和幼年大鼠心脏缺血/再灌注损伤的保护作用的异同点。方法♂成年和新生Sprague-Dawlay(SD)大鼠随机分为4组:对照28d组(CON28)、对照42d组(CON42)、CIHH处理28d组(CIHH28)和CIHH处理42d组(CIHH42)。间歇性低氧处理组动物于低压氧舱分别接受28d、42d模拟3000米海拔高度(PB=525mmHg,PO2=108.8mmHg)的低压低氧处理,每天5h。对照组动物除了不接受低氧处理外,其它处理均与间歇性低氧组动物相同。应用Langendorff离体心脏灌流技术,给予心脏缺血(停灌30min)/再灌注(复灌60min)处理,记录离体大鼠心脏在不同时期的心功能变化。心功能参数包括左室发展压(left ventricular developing pressure,LVDP)、左室压力最大变化速率(maximum changerate of LVDP,±LVdp/dtmax)、左室舒张末压(left ventricularend di-astolic pressure,LVEDP)、冠脉流量(coronary flow,CF)和心率(heartrate,HR)。结果①对成年大鼠,基础状态和缺血/再灌注状态下CIHH28d组各心功能参数与CON28d组相比差异均无统计学意义。CIHH42d组各心功能参数均好于CON42d组,表现为LVDP、LVEDP、±LVdp/dtmax和CF恢复均增加(P<0.05)。②对幼年大鼠,基础状态下,CIHH大鼠CF较对照大鼠明显增多,其余心功能参数与对照大鼠无差异。CIHH大鼠缺血/再灌注后心脏功能的恢复明显好于对照动物,表现为LVDP、LVEDP、±LVdp/dtmax和CF恢复均增加(P<0.05),且CIHH42d组比CIHH28d组心功能改善更明显。结论CIHH可增强成年和幼年大鼠抗心肌缺血/再灌注损伤的能力,具有明显的心脏保护作用,CIHH42d组保护作用更为明显;CIHH的心脏保护作用有明显的年龄差异,在幼年大鼠更易产生保护作用。     

Actions of flecainide on susceptibility to phase-2 ventricular arrhythmias during infarct evolution in rat isolated perfused hearts

The mechanism of flecainide-induced unexpected death remains uncertain. Phase-2 ventricular arrhythmias occur during infarct evolution. We examined whether flecainide (0.74 and 1.48 microM, representing the peak unbound plasma and total blood concentrations, respectively, at 'therapeutic' dosage) has proarrhythmic activity on phase-2 arrhythmia susceptibility during infarct evolution.To achieve this, we used the Langendorff-perfused rat heart preparation (n=8 per group) in which baseline phase-2 arrhythmia susceptibility is low. Left main coronary occlusion evoked phase-1 (acute ischaemia-induced) ventricular arrhythmias including fibrillation (VF) in all hearts. By 90 min, hearts were relatively arrhythmia-free.Randomized and blinded switch of perfusion to flecainide at 90 min caused no increase over baseline in the incidence of VF, tachycardia (VT) or premature beats (VPB) during the following 150 min of ischaemia, or during reperfusion (begun 240 min after the onset of ischaemia).In separate hearts, catecholamines (313 nM norepinephrine and 75 nM epinephrine) were co-perfused with flecainide from 90 min of ischaemia. Catecholamine perfusion increased heart rate, coronary flow and QT interval, and shortened PR interval (all P<0.05), actions that were not altered by flecainide. Catecholamine perfusion caused a weak nonsignificant increase in phase-2 VPB, VT and VF incidence, but there was no proarrhythmic interaction with flecainide.In conclusion, the present findings suggest that the increased risk of death associated with clinical use of flecainide is not due to facilitation of phase-2 ventricular arrhythmias.     

前列地尔与川芎嗪、黄芪合用对大鼠心肌缺血再灌注损伤的保护作用

目的 :观察前列地尔与川芎嗪 (LT )、黄芪(AM ) 3药合用对大鼠心肌缺血再灌注损伤的保护作用。方法 :采用在体大鼠开胸结扎冠状动脉左室支 30min后 ,松扎再灌注 60min造成心肌缺血再灌注模型并以 0 .9%氯化钠注射液为模型对照 ,观察 3药 :前列地尔 31.2 5μg·kg- 1,川芎嗪 2 5mg·kg- 1,黄芪 4 15mg·kg- 1合用对再灌注心肌组织中超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶(GSH PX)活力 ,丙二醛 (MAD)、Ca2 +含量及血清肌酸磷酸激酶同功酶 (CK MB)含量的变化 ,并同时心电图监测心律失常情况。结果 :与模型对照组相比3药合用可提高再灌注心肌组织中SOD ,GSH PX活力 ,差异有非常显著意义 (P <0 .0 1) ;并能降低再灌注心肌组织中MDA ,Ca2 +含量及血清CK MB含量 ,差异有非常显著意义 (P <0 .0 1) ;防止再灌注室性心律失常的发生 ,缩短心律失常的维持时间 ,降低ST段抬高的程度 ,差异有非常显著意义 (P <0 .0 1)。结论 :前列地尔与LT ,AM合用在保护心肌缺血再灌注损伤中有显著的作用 ,其保护作用主要与清除自由基有关     

ATP敏感性钾通道和线粒体通透转换孔参与白藜芦醇苷的心肌保护作用(英文)

目的探讨白藜芦醇苷(Poly)对大鼠缺血再灌注(I-R)心肌损伤的保护作用及其机制。方法应用Langendorff室技术制备离体大鼠心脏I-R损伤模型。雄性SD大鼠随机分为对照组、模型组、Poly(25, 50和75μmol.L-1)组、格列本脲(Gli) +Poly组、5-羟基癸酸(5-HD) +Poly组和苍术苷(Atr) +Poly组。对照组心脏由K-H液灌流110 min;模型组由K-H液灌流20 min后,停灌30 min,复灌60min;Poly组在I-R处理前用含不同浓度Poly的K-H液灌流10 min;Gli +Poly和5-HD+Poly组在I-R前分别用含Gli (10μmol.L-1)和5-HD(100μmol.L-1)的K-H液灌流5 min,再加入Poly (50μmol.L-1)灌流10 min;Atr +Poly组用含Poly(50μmol.L-1)K-H液灌流10 min及停灌30 min后,先用含Atr(20μmol.L-1)的K-H液灌流15 min,然后改用K-H液灌流。分别记录各组停灌前、停灌30 min和复灌60 min内的左心室舒张末压(LVEDP)、左心室舒张压(LVDP)、左心室等容期压力最大变化速率(±dp/dtmax)和冠脉流量(CF)等心功能指标。心脏复灌60 min后,用氯化三苯基四氮唑染色法测定心肌梗死面积,透射电镜下检测心肌超微结构变化。结果缺血前各组心功能参数无明显变化。与模型组相比,Poly可浓度依赖性地促进大鼠I-R后心功能的恢复,预防I-R损伤。复灌60 min后,Poly组大鼠心脏LVDP,±dp/dtmax和CF明显高于模型组;LVEDP则低于模型组;缺血前给予Poly(50μmol.L-1)10 min可明显减小I-R后心肌梗死面积,并改善心肌超微结构。Gli, 5-HD和Atr可阻断Poly对I-R心脏心功能参数和心肌梗死面积等的保护作用。结论 Poly具有明显的抗心肌I-R损伤作用,其心脏保护作用可能与其增加细胞膜和线粒体膜ATP敏感性钾通道开放和抑制线粒体通透转换孔开放有关。     

R56865, a potent new antiarrhythmic agent, effective during ischemia and reperfusion in the rat heart.

The antiarrhythmic effects of R56865 were characterized both in vivo and in vitro. Four groups (n = 12 per group) of anesthetized rats, subjected to 5- or 30-min coronary artery ligation and reperfusion, were studied: saline, dimethyl sulfoxide (DMSO) carrier, and R56865 (0.5 or 2 mg/kg) were administered as an intravenous (i.v.) bolus before ligation. After 5 min of ischemia, the incidences of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF), which were high in the saline (100 and 75%, respectively) and DMSO (100 and 82%, respectively) control groups, were abolished with both doses of R56865. With 30 min of ischemia, R56865 (2 mg/kg) significantly reduced the incidences of ischemia-induced VT and VF (from 100 and greater than 50% to 25 and 8%, respectively). For in vitro studies, five groups (n = 12 per group) of isolated rat hearts subjected to 10- or 30-min coronary ligation and reperfusion were studied: unmodified buffer and buffer containing DMSO or R56865 (10(-7), 10(-8), 10(-9) M). After 10 min of ischemia, R56865 (10(-7) M) decreased reperfusion-induced VT and VF (from 100 and 75% in buffer controls to 42 and 8%, respectively) when administered throughout the experiment. With 30 min of ischemia, R5685 (10(-7) M) reduced the incidences of ischemia-induced VT and VF (from 75 and 67% in the buffer controls to 25 and 25%, respectively). Although reperfusion after 30 min of ischemia did not induce VF in any of the groups studied, VT and other arrhythmias did occur and their incidences were reduced significantly by R56865. To investigate whether calcium overload might mediate the effects of R56865, hearts were perfused aerobically with a high-calcium/low-sodium medium. VT and VF occurred in 80% of control hearts; R56865 (10(-7) M) did not prevent these arrhythmias. In conclusion, R56865 exerts a potent effect against ischemia- and reperfusion-induced arrhythmias through a mechanism which appears to operate during ischemia.     

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Langendorff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. TPGFA 6-12 mg·L^-1显著降低30 min缺血+30 min复灌和吡那地尔(1.25 μmol·L^-1)+12 min缺氧+40 min再给氧两种模型的室性心动过速和心室纤颤发生率；TPGFA 3-12 mg·L^-1可显著减慢心率， 延长心电图的QT_c，减少K⁺从心肌细胞内丢失；12 mg·L^-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.     

巯基化合物对缺血再灌流所致大鼠离体心脏功能低下的保护作用

比较观察了半胱氨酸(Cys),N-乙酰半胱氨酸(NAC)及胱胺(CSSC)对Langendorff灌流大鼠心脏缺血再灌所致心功能低下的保护作用。心脏平衡后开始给药(3.6μmol/min)直至实验结束。Cys和NAC可使心脏缺血再灌后的LVP、±dP/dt和RPP迅速恢复至结扎前的水平,并显著高于生理盐水对照组,CSSC则未见有这些保护作用。三药均可使结扎期的冠脉流量明显高于对照。所试药物对Fenton反应生成的OH均有不同程度的清除,Cys的效果最强。     

Cardioprotective effects of a non-alcoholic extract of red wine during ischaemia and reperfusion in spontaneously hypertensive rats

1. We reported recently the cardioprotection conferred by a non-alcoholic extract of Cabernet-Sauvignon red wine (RWE) against alterations derived from ischaemia and reperfusion in normotensive rats. The aim of the present study was to assess the effects of RWE on ischaemia/reperfusion injury in hearts isolated from spontaneously hypertensive rats (SHR). 2. After stabilization, rat isovolumic perfused hearts were exposed to a 20 min global ischaemic period followed by 30 min reperfusion in the absence (ischaemic control (IC) hearts) or presence of RWE infused prior to ischaemia and early in reperfusion. In other hearts, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, was administered prior to RWE infusion (L-NAME + RWE). 3. Left ventricular developed pressure (LVDP), dP/dt(max) and left ventricular end-diastolic pressure (LVEDP) were used to assess myocardial function. 4. At the end of reperfusion, LVDP and dP/dt(max) decreased to 47 +/- 9 and 46 +/- 9% of baseline values, respectively, in IC. Treatment with the RWE significantly improved systolic postischaemic recovery (LVDP = 85 +/- 8%; dP/dt(max) = 83 +/- 5%) and attenuated the increase in LVEDP (23 +/- 6 and 53 +/- 8 mmHg in RWE and IC, respectively; P < 0.05). 5. In the L-NAME + RWE group, L-NAME completely abolished the systolic and diastolic protection induced by RWE (LVDP = 44 +/- 13%; dP/dt(max) = 43 +/- 13%; LVEDP = 60 +/- 10 mmHg). 6. These data are the first demonstration that a non-alcoholic extract of Cabernet-Sauvignon red wine protects SHR hearts from systolic and diastolic alterations induced by ischaemia and reperfusion through a nitric oxide-dependent mechanism.     

内源性硫化氢参与缺血后处理减轻离体大鼠心脏缺血/再灌注损伤

目的探讨内源性硫化氢是否参与缺血后处理减轻大鼠心肌缺血/再灌注损伤。方法Sprague Dawley(SD)大鼠离体心脏Langendorff灌流,平衡20min,全心缺血30min,复氧灌注60min,在复灌即刻给与短暂停灌15s/复灌15 s循环4次造成心肌缺血后处理模型。预先给予胱硫醚-γ-裂解酶(cystanthionine-γ-lysase,CSE)抑制剂炔丙基甘氨酸(L-propargylglycine,PAG),以及给予PAG后加用外源性硫化氢供体NaHS后处理,观察它们对缺血后处理的影响。记录心率(HR)、左室发展压(LVDP)、冠脉流出量(CF);检测灌流液中乳酸脱氢酶(LDH)活性、心肌组织CSE活性、硫化氢的含量以及心肌梗死面积。结果缺血/再灌注组LVDP下降、冠脉灌流液中LDH活性明显增加、心肌梗死面积增加(vsControl组,P<0.05)。缺血后处理组LVDP升高、冠脉灌流液中LDH活性下降、心肌梗死面积缩小(vsIR组,P<0.05)。PAG加缺血后处理组心肌CSE活性及H2S生成下降、并且逆转了缺血后处理的作用,而外源性硫化氢供体NaHS后处理组H2S生成回升、LVDP升高、心肌梗死面积缩小(vsIR组,P<0.05)。结论内源性硫化氢参与大鼠心肌缺血后处理减轻缺血/再灌注损伤。     

中叶素抑制大鼠心脏缺血/再灌注损伤

目的研究中叶素(Intermedin,IMD)对大鼠心脏缺血/再灌注(ischemia/reperfusion,I/R)损伤的保护作用及其可能机制。方法Langendorff方法灌流离体心脏,并造成I/R模型,以Power Lab多导生理记录仪记录灌流心脏心功能的变化,收集灌流后心肌组织及灌流液进行生化检测。结果IMD再灌注明显改善I/R造成的心功能抑制和组织损伤,可升高△LVP、LV±dp/dtmax,降低LVDP,增加心率及冠脉流量,同时使心肌LDH、总蛋白和肌红蛋白的漏出及心肌组织MDA生成明显减少,而心肌组织cAMP含量明显增加。且IMD的上述效应与同浓度ADM的效果相近。此外,I/R后心肌IMD受体Bmax和Kd值均增加。结论IMD有明显的抑制心脏I/R损伤的作用,该作用可能通过cAMP途径介导,且IMD抗I/R损伤的作用与强内源性心血管保护肽肾上腺髓质素相仿。     

IHC-72抗大鼠缺血再灌注心律失常及脂质过氧化作用

在大鼠整体模型上,观察了IHC-72对缺血再灌注心律失常及脂质过氧化作用的影响.缺血1h、再灌注30min,出现明显的心律失常,血浆谷草转氨酶(GOT)、乳酸脱氢酶(LDH)及游离脂肪酸(FFA)释放明显增加;心肌组织超氧化物歧化酶(SOD)活性显著降低、丙二醛(MDA)含量增加。IHC-725mg·kg~(-1)明显降低室早、室速及室颤发生率,缩短室速及室颤持续时间;显著减少GOT、LDH和FFA的释放,保护SOD活性、减少MDA生成。结果提示:IHC-72具有抗缺血再灌注心律失常及抗脂质过氧化作用。     

Cardioprotective effects of recombinant human extracellular-superoxide dismutase type C in rat isolated heart subjected to ischemia and reperfusion.

The cardioprotective effect of recombinant human extracellular-superoxide dismutase type C (rh-EC-SOD C) was studied in isolated perfused rat heart subjected to left coronary artery ligation for 30 or 60 min followed by 30-min reperfusion. A comparison was made with the effects of bovine CuZn-SOD. Reperfusion after 30-min coronary artery ligation was associated with a release of creatine kinase (CK) into the coronary effluent (71 +/- 5.2 IU/30 min), which was markedly reduced (39 +/- 5.5 IU/30 min) in hearts perfused with rh-EC-SOD C (28 mg/L). CuZn-SOD (4 or 20 mg/l) or a lower concentration of rh-EC-SOD C (5.6 mg/l) did not significantly attenuate CK outflow during reperfusion, however. In both vehicle- and SOD-treated hearts, the left ventricular developed pressure (LVDP) and the coronary flow recovered to 80-90% of baseline at the end of the reperfusion period. Increasing the ischemic period from 30 to 60 min caused a much more pronounced cardiac injury measured after 30-min reperfusion. In the hearts that received vehicle, recovery of LVDP (in percentage of baseline values) at the end of reperfusion was 58 +/- 2%, which was increased to 84 +/- 3 and 83 +/- 5% after treatment with rh-EC-SOD C (28 mg/L) and CuZn-SOD (20 mg/L), respectively. The corresponding values for recovery in coronary flow were 54 +/- 3% (vehicle), 69 +/- 4% (rh-EC-SOD C), and 74 +/- 3% (CuZn-SOD).(ABSTRACT TRUNCATED AT 250 WORDS)     

生脉注射液对离体家兔心脏缺血再灌注损伤保护作用的实验研究

目的观察生脉注射液对离体家兔心脏缺血再灌注损伤的保护作用。方法采用离体兔心Lan-gendorff灌注实验模型,离体兔心24只随机分成3组每组8只。正常对照组连续灌注Krebs-Henseleit(K-H)液60 min;缺血再灌注组关闭主动脉套管停止灌注,30 min后恢复37℃K-H液灌注60 min。生脉注射液组步骤同缺血再灌注组,但在复灌时先用生脉注射液的K-H液(浓度为每500 ml K-H液中加入生脉注射液40 mL)灌注30 min。记录血流动力学指标:冠状动脉流量、左心室舒张压(LVDP)、左心室压力时间变化率(±DP/DT);检测冠状动脉流出液中丙二醛(MDA)、超氧化物歧化酶(SOD)、肌酸激酶(CK)、乳酸脱氢酶(LDH)浓度和心肌组织中MDA、SOD含量。结果生脉注射液组可明显改善缺血再灌注后的血流动力学变化:±DP/DTmax和LVDP较缺血再灌注组显著升高,冠状动脉流量增大;冠状动脉流出液中MDA、LDH、CK以及心肌组织中MDA浓度降低,而冠状动脉流出液和心肌组织中SOD含量均升高(P<0.05),与缺血再灌注组比较,超微结构损伤较轻(P<0.05)。结论生脉注射液具有抗兔离体心脏缺血再灌注损伤的作用。