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。     

高乌甲素贴片释放度测定的研究

本文通过体内及体外实验观察了纳络酮对正常、缺血和再灌注心肌腺苷酸环化酶（AC）活性的影响。其结果表明：静脉注射纳络因（1mg．kg-1）可以明显降低缺血、再灌注心肌AC活性（P＜0．01，P＜0．05）；但纳络酮在体外对正常、缺血和再灌注心肌组织匀浆AC活性无明显抑制作用（P＞0．05）。提示：纳络酮本身对AC活性无直接抑制作用，它降低缺血、再灌注心肌AC活性可能与酶前调节有关。     

纳络酮对缺血再灌注心肌脂质过氧化物和钙含量的影响

利用犬心肌缺血，再灌注模型，观察了纳络酮对缺血再灌注心肌脂质过氧化物（ＬＰＯ），超氧化物岐化酶（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）；纳络酮明显降低缺血，再灌注心肌ＬＰＯ和钙含量（Ｐ〈０．０５，Ｐ〈０．０１）     

舒芬太尼对家兔心肌缺血再灌注后心功能的影响

目的观察舒芬太尼对家兔心肌缺血再灌注后心功能的影响并探讨其作用机制,为临床合理用药提供实验依据。方法 24只家兔随机分为3组:对照组、舒芬太尼组、纳络酮-舒芬太尼组,于缺血再灌注各个时期测定心功能指标。结果左室收缩峰压(LVSP)、左室发展压(LVDP)和心室收缩的最大速率(±dp/dt)缺血期明显降低,左室舒张末压(LVEDP)明显升高。而LVSP、LVDP和±dp/dt于心肌再灌注后未再进一步下降。而是随时间延长逐渐恢复并明显好转。结论心肌缺血再灌注对兔心功能有明显抑制,舒芬太尼能明显改善心脏功能,纳络酮可部分取消舒芬太尼的心肌保护作用。     

丹参酮对脊髓缺血再灌注损伤大鼠模型脊髓、血清谷氨酸含量的影响

目的观察丹参酮对脊髓缺血再灌注大鼠脊髓、血清谷氨酸水平探讨丹参酮保护脊髓的作用机制。方法选用SD大鼠88只,采用结扎腹主动脉的方法制作脊髓缺血再灌注模型。按随机数字表法将动物分为假手术组（n=8）、模型组（n=40）和丹参酮组（n=40）。A组在全麻下充分暴露脊髓,B组及C组采用Zivin法改进方法复制模型,随机在脊髓缺血再灌注30min、1h、4h、8h、12h的相应时间点切取脊髓,抽取下腔静脉血,检测缺血再灌注后脊髓谷氨酸、血清谷氨酸含量及对缺血再灌注4h、8h、12h,采用改良Tarlov评分标准进行神经功能评分。结果丹参酮组及模型组大鼠脊髓、血清谷氨酸含量均于脊髓缺血再灌注损伤后30min开始上升,缺血再灌注损伤4h后含量达到高峰,其后含量逐渐下降,12h后基本恢复正常。丹参酮组各观测点脊髓、血清谷氨酸含量均低于模型组。结论丹参酮能降低脊髓缺血再灌注大鼠脊髓谷氨酸含量,对大鼠脊髓缺血再灌注损伤具有保护作用。     

生长激素预处理对大鼠心肌缺血再灌注后细胞凋亡与能量代谢的影响

目的研究生长激素预处理对大鼠心肌缺血再灌注后心肌细胞凋亡及能量代谢的影响。方法42只大鼠采用完全随机设计方法分为3组，假手术组14只（假手术24h）、心肌缺血再灌注组14只、生长激素组14只，后2组均缺血30min，再灌注24h，其中生长激素组的每只大鼠术前皮下肌肉注射生长激素1 U／kg，连续7d，其中第7次皮下注射于手术前进行。前2组每只大鼠相应皮下肌肉注射生理盐水0．5ml／d。每组中均抽取8只大鼠，以TUNEL法检测缺血区心肌细胞凋亡情况，每组中剩余的抽取5只大鼠，以高效液相色谱法测定缺血区心肌三磷酸腺苷（ATP）并进行心肌组织病理、电镜超微结构观察。结果与假手术组比较，心肌缺血再灌注组再灌注24h后缺血区心肌细胞凋亡率和ATP消耗程度均明显上升（P〈0．05），心肌组织病理和超微结构改变明显；与心肌缺血再灌注组比较，生长激素组再灌注24h后缺血区心肌细胞凋亡率和ATP消耗程度均明显改善（P〈0．05），心肌组织病理和超微结构改变明显减轻。结论生长激素能减少心肌缺血再灌注后心肌细胞凋亡和ATP的消耗，说明生长激素对心肌缺血再灌注后的心肌具有保护作用。     

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．     

普鲁卡因对离体豚鼠右心室缺血再灌注心肌电活动的影响

目的：研究普鲁卡因对离体豚鼠心室肌心律失常及跨壁传导等电生理特性的影响。方法：模拟在体正常和缺血再灌注条件，用玻璃微电极同时记录离体豚鼠心室肌内、外膜下心肌细胞跨膜电位。结果：普鲁卡因可明显地降低心律失常发生率、增加缺血再灌注过程的心内膜传导时间和跨壁传导时间、延长心肌动作电位时程和有效不应期，并可命名心肌兴奋性降低。结论：降低心肌兴奋性、消除折返激动和触发活动可能是普鲁卡因拮抗缺血再灌注心律失常的重要途径。     

氯氨酮对大鼠心肌缺血再灌注心肌细胞凋亡和Fas蛋白、Bcl-2蛋白表达的影响

目的:探讨氯胺酮作用下大鼠实验性心肌缺血再灌注时心肌细胞凋亡与Fas及Bcl-2蛋白表达的变化及与心肌组织损伤的关系,并分析心肌组织病理学损伤程度。方法:以穿线结扎或松扎左冠状动脉制备大鼠心肌缺血再灌注模型。32只大鼠随机分成假手术组(假手术4.5 h)、缺血再灌注组(缺血30min、再灌注4 h)、低剂量氯胺酮+缺血再灌注组(缺血30min、再灌注4h)及高剂量氯胺酮+缺血再灌注组(缺血30min、再灌注个4 h)。以缺口末端标记法检测心肌细胞凋亡的变化,S-P免疫组化法分别检测Fas与Bcl-2蛋白水平变化,做病理组织切片检查心肌损伤情况。结果:心肌缺血再灌注后心肌细胞凋亡指数及Fas蛋白阳性染色指数与Bcl-2蛋白阳性染色指数均增加,氯氨酮可减少心肌凋亡,减少Fas和Bcl-2蛋白阳性细胞表达;心肌缺血再灌注后心肌组织呈大小不一的灶性坏死,坏死周围有炎性细胞浸润,氯胺酮作用后坏死减轻,低剂量氯胺酮作用更明显。结论:心肌缺血再灌注时心肌细胞凋亡、Fas基因的蛋白与Bcl-2蛋白表达量均增加,氯氨酮可减少心肌凋亡,减少细胞Fas和Bcl-2蛋白阳性表达,从而减轻心肌损伤,且低剂量氯氨酮作用更明显。     

山楂叶总黄酮对大鼠心肌缺血再灌注损伤的心电图、一氧化氮及丙二醛变化的影响

目的：观察山楂叶总黄酮（hawthorn leaves flavonoids，HLF）对大鼠心肌缺血再灌注损伤的心电图、NO及丙二醛（MDA）变化的影响。方法：结扎大鼠冠状动脉左前降支，使心肌缺血30min，再灌注60min，制备急性心肌缺血再灌注损伤模型，缺血前10min，腹腔注射HLF（12．5、25．0、50．0mg／kg）。动态观察心电图，同时监测心电图ST段的变化，用硝酸还原酶法测定血清中NO浓度，采用硫代巴比妥钠（TAB）比色法测定组织内MDA含量。结果：HLF（12．5、25．0、50．0mg／kg）能减轻缺血再灌注损伤心肌心电图ST段变化，提高血清NO的浓度，降低心肌缺血再灌注时心肌组织MDA含量。结论：HLF能改善心肌缺血再灌注损伤心电图变化，对损伤心肌有保护作用，其机制与增加NO浓度、抗脂质过氧化的作用有关。     

The role of beta-adrenoceptors in coronary blood flow distribution in normal and ischemic canine myocardium.

beta-Adrenoceptor agonists increase myocardial ischemic injury, mainly by elevating myocardial oxygen consumption. Moreover, it has been shown that isoprenaline may "steal" regional myocardial blood flow (RMBF) from ischemic to non ischemic areas and from epicardium to endocardium. The mechanisms of these two isoprenaline-induced redistributions of RMBF have been investigated by the use of radioactive microspheres in an experimental model of canine myocardial ischemia with simultaneous measurement of ST-segment elevation. Isoprenaline increased RMBF in both epi- and endocardial non ischemic areas and in epicardial ischemic areas, leading to a significant decrease in the endo/epi ratio. After atenolol, isoprenaline still increased RMBF but to a lesser extent and the endo/epi ratio was still decreased. Salbutamol, in doses inducing no significant changes in cardiac parameters or myocardial oxygen consumption, produced effects similar to those of isoprenaline. These results indicate a non-homogeneous beta2-stimulation-induced vasodilation in endo- and epicardium, which might be due either to the higher epicardial coronary vasocilatory reserve or to a heterogeneous distribution of transmural beta2-adrenoceptors. Isoprenaline also decreased the ischemic/non ischemic total blood flow ratio (I/NI) and caused further increases in ST-segment elevation. These effects were abolished by atenolol pretreatment, indicating the deleterious effects of isoprenaline-induced tachycardia in this I/NI decrease and in the ischemic injury.     

Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs

This study was designed to examine whether physiologically tolerable insulin, which maintains lower blood glucose, can protect the myocardium against ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary blood flow) followed by 4 hours of reperfusion and treated with vehicle, glucose-insulin-potassium (GIK; glucose, 250 g/L; insulin, 60 U/L; potassium, 80 mmol/L), GK, or low-dose insulin (30 U/L) 10 minutes before reperfusion. Treatment with GIK exerted significant cardioprotective effects as evidenced by improved cardiac function, improved coronary blood flow, reduced infarct size, and myocardial apoptosis. In contrast, treatment with GK increased blood glucose level and aggravated myocardial I/R injury. It is interesting that treatment with insulin alone at the dose that reduced blood glucose to a clinically tolerable level exerted significant cardioprotective effects that were comparable to that seen in the GIK-treated group. This low-dose insulin had no effect on coronary blood flow after reperfusion but markedly reduced coronary reactive hyperemia and switched myocardial substrate uptake from fat to carbohydrate. Our results suggest that lower glucose supply to the ischemic myocardium at early reperfusion may create a "metabolic postconditioning" and thus reduce myocardial ischemia/reperfusion injury after prolonged reperfusion.     

Effect of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs

The calcium antagonist, diltiazem, was evaluated for its ability to reduce the extent of myocardial injury resulting from 90 min of left circumflex (LCX) coronary artery occlusion in anesthetized dogs. Administration of diltiazem (0.75 mg/kg over 10 min, followed by 600 microgram/kg/h for 4 h) was initiated 30 min prior to LCX occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres 30 min after LCX occlusion, and at 45 min and 24 h after reperfusion. At 24 h, after obtaining hemodynamic and RMBF measurements, excised hearts were processed by perfusion staining to determine the percent of left ventricle (LV) perfused by LCX (area at risk) and infarct size, with triphenyltetrazolium chloride. Infarct size, expressed as a percentage of the area at risk, was significantly lower in the diltiazem-treated group compared to the control group (27 +/- 4 vs. 42 +/- 5%, respectively). The area at risk, expressed as a percentage of left ventricular mass, was similar in both groups [41 +/- 2 and 44 +/- 3% (area at risk-LV)]. In addition, the marked elevation of tissue Ca2+ content in noninfarcted and infarcted myocardium within the area at risk (18 +/- 2 and 42 +/- 8 mumol Ca2+/g) in control animals was attenuated by diltiazem (6 +/- 3 and 18 +/- 8 mumol Ca2+/g). Diltiazem did not increase blood flow to ischemic myocardium during LCX occlusion. However, reflow to the inner layers of formerly ischemic myocardium during reperfusion was significantly greater in diltiazem-treated dogs. Both arterial blood pressure and heart rate were significantly lower in the diltiazem -treated group. In addition, mortality (1 vs. 4) and occurrence of ventricular arrhythmias during reperfusion were lower in diltiazem-treated dogs. The data suggest that diltiazem reduces myocardial ischemic injury by lowering myocardial oxygen demands indirectly via favorable hemodynamic alterations, and directly by limiting transmembrane Ca2+ fluxes during ischemia and reperfusion.     

Electrophysiologic and blood-flow responses in the endocardium and epicardium to disopyramide and MS-551 during myocardial ischemia in the dog.

The aim of this study was to determine whether a quantitative relation exists between changes in regional myocardial blood flow (RMBF) and those in electrophysiologic determinants recorded via left ventricular endocardial and epicardial bipolar electrograms after administration of disopyramide (DP) and a class III antiarrhythmic drug, MS-551 (MS), during myocardial ischemia in the dog. Dogs were given DP (1 mg/kg, i.v., n = 14), MS (1 mg/kg, i.v., and 0.1 mg/kg/min, d.i.v., n = 13), or saline (n = 12). The effective refractory period (ERP) was determined by an S1-S2 extrastimulus method, and RMBF by a nonradioactive microsphere technique. The duration of regional electrograms (DRE) was measured as an indicator of conduction time in the myocardium. DP blunted ischemia-induced shortening of ERPs and lengthened DREs at the endocardial and epicardial sites, with a greater effect seen epicardially (p < 0.01 each). DP reduced RMBF, especially at the endocardial surfaces of the ischemic zone (p < 0.05). MS prolonged ERPs at the endocardial and epicardial sites in the ischemic and normal zones (p < 0.05-0.01), but there were no significant differences between the two sites. MS prolonged DREs (p < 0.05), but the magnitude of the prolongation of the DREs was similar to the values in the control group. MS had no effects on RMBF. DP treatment prolonged DREs at both sites in the ischemic zone more markedly than MS or saline treatment (p < 0.01 each). DP reduced RMBF at the endocardial site of the ischemic zone more markedly than MS or saline (p < 0.05 in each). Accordingly, MS prolonged ERPs, but did not increase disparities between endocardial and epicardial sites in the ischemic myocardium, whereas DP had a greater ERP-prolonging effect at the epicardial site than at the endocardial site. DP reduced endocardial RMBF more markedly than epicardial RMBF. These observations suggest that differences in ERPs between endocardial and epicardial ischemic myocardium caused by DP treatment are not due to the difference in RMBF reduction between the two tissue layers, and that DP and MS do not affect the same population of ion channel(s) when ERPs are prolonged.     

Effects of resveratrol, a flavinoid found in red wine, on infarct size in an experimental model of ischemia/reperfusion

OBJECTIVE: Resveratrol is a potent anti-inflammatory and anti-oxidant flavinoid found in red wine. Resveratrol has been shown to improve ventricular function and decrease lactic dehydrogenase release after ischemia in rats. The aim of this study was to test whether resveratrol could provide direct cardioprotection to myocytes during acute myocardial infarction. METHOD: Anesthetized, open-chest rabbits (N= 24) were subjected to 30 minute coronary artery occlusion followed by 3 hr reperfusion. Before the onset of ischemia (15 minutes), the rabbits were randomly assigned (n = 8 in each group) to either high-dose (1.5 mg/kg) resveratrol, low-dose (0.15 mg/kg) resveratrol or ethanol vehicle, and the effects on infarct size and regional myocardial blood flow (RMBF) were tested. RESULTS: Hemodynamic parameters and size of ischemic risk region (29% to 35% of the left ventricle) were similar in all groups. Infarct size, expressed as a mean (SEM) percentage of the risk region, was 46% (5%) of the risk region in controls, 46% (7%) in the low-dose group and 54% (3%) in the high-dose group (p = .53). Thus, treatment with resveratrol had no effect on infarct size at either dose. There were no differences in RMBF in the risk zone or in nonischemic tissue, during either occlusion or reperfusion. CONCLUSIONS: In this intact model of ischemia and reperfusion, resveratrol fails to provide cardioprotection. The mechanism of other beneficial effects (e.g., improvement of function) that are observed with resveratrol probably do not result from increased RMBF or a reduction in myocardial necrosis.     

Effects of minoxidil on ischemia-induced mechanical and metabolic dysfunction in dog myocardium

Effects of minoxidil on ischemia-induced myocardial mechanical and metabolic dysfunction were examined in anesthetized open-chest dogs. A regional portion of the left ventricle was made ischemic for 20 min by ligating the left anterior descending coronary artery, and then reperfused for 120 min. Dimethylsulfoxide or minoxidil (0.3, or 1.0 mg/kg) was injected intravenously 10 min before ligation. Ischemia decreased regional myocardial contraction, and reperfusion recovered it but incompletely. Myocardial metabolic derangement was observed during ischemia, such as decreases in the myocardial levels of ATP and creatine phosphate. These metabolic changes caused by ischemia were restored by reperfusion. Minoxidil injection at 0.3 and 1.0 mg/kg significantly decreased blood pressures but increased coronary flow. Pretreatment with minoxidil significantly enhanced the recovery of myocardial contraction during reperfusion after ischemia. The levels of ATP and creatine phosphate in the ischemic myocardium were significantly preserved by minoxidil at 0.3 mg/kg. No significant effect of minoxidil on the metabolism was observed in the 120 min reperfused myocardium. In conclusion, minoxidil improved the mechanical dysfunction in the reperfused heart and the drug at low dose preserved high-energy phosphates during ischemia.     

Myocardial cytoprotective efficacy of azapropazone in a canine heart model of regional ischemia and reperfusion

The present study assessed the efficacy of azapropazone (AZA) in pentobarbital-anesthetized dogs subjected to 120 min of regional ischemia [left anterior descending coronary artery (LAD) ligation] followed by 5 h of reperfusion. Azapropazone was given 30 min prior to LAD occlusion (100 mg/kg i.v.), 35 min prior to LAD release (50 mg/kg, i.v.), and at 2.5 h postreperfusion (50 mg/kg i.v.). Regional myocardial blood flow (RMBF) and area at risk (AAR) were determined with radiolabeled microspheres. The degree and extent of ischemia (anaerobic metabolism) and necrosis were delineated with 14C-deoxy-2-D-glucose (14C-DG) and 111In-antimyosin, respectively, in control (n = 7) and AZA (n = 7)-treated groups. In mild (60-80% normal RMBF) and moderate (30-60% normal RMBF) flow-restricted areas, AZA resulted in a significant decrease in the degree and extent of ischemia (p less than 0.01) with the limitation of infarct size (p less than 0.01). However, AZA did not produce a significant infarct size limitation in the severe flow-restricted area (0-30% of normal RMBF). The effect of AZA is expressed primarily in moderate flow-restricted myocardium with the subsequent infarct size limitation.     

丹参酮ⅡA对异丙肾上腺素致心肌缺血损伤大鼠apelin及其受体的影响

目的:观察异丙肾上腺素(ISO)致心肌缺血损伤大鼠的心肌组织中apelin及其受体APJ的变化,探讨丹参酮ⅡA改善其心肌缺血损伤的作用机制.方法:雄性SD大鼠分为正常对照组、ISO组、不同剂量丹参酮ⅡA治疗组.皮下注射ISO建立大鼠心肌缺血损伤模型,ELISA分析检测血浆和心肌apelin和NO的含量,real-time PCR方法检测心肌中apelin及其受体APJmRNA表达,Western blot方法检测心肌组织中APJ、eNOS及其磷酸化蛋白水平.结果:与正常对照组比较,ISO组大鼠血浆和心肌组织apelin和NO含量均下降,心肌组织中apelin和APJ mRNA水平表达下调(P＜0.01),APJ、eNOS磷酸化蛋白水平降低;与ISO组相比,中、高浓度的丹参酮ⅡA可以明显增加大鼠血浆和心肌组织中apelin和NO含量,增加心肌组织中apelin和APJ mRNA表达水平,增加心肌组织中APJ和eNOS磷酸化蛋白水平.结论:丹参酮ⅡA抗大鼠心肌缺血损伤的机制可能与其上调心肌组织apelin/APJ mRNA的表达、提高apelin/APJ蛋白水平、增加eNOS磷酸化水平和NO生成有关.     

Effects of propranolol on regional myocardial blood flow and function during severe coronary stenosis in dogs

The effects of propranolol alone or associated with atrial pacing were studied on regional myocardial blood flows (RMBF) and regional contractility (sonocardiometry) in non-ischemic, moderately and severely ischemic areas of the canine myocardium. In non-ischemic areas, propranolol reduced both epicardial and endocardial flows, increased the endo/epi ratio and decreased regional contractility. The reductions in subendocardial flow and function were correlated. In moderately and severely ischemic areas, propranolol increased subendocardial flow, reduced subepicardial flow, increased the endo/epi ratio and preserved or even slightly improved regional contractility. There was a good correlation between the propranolol-induced protective effects on regional contractility and the drug-induced increase in subendocardial flow since under atrial pacing subendocardial flow no longer increased and regional function dropped dramatically.