心肌缺血预处理糖尿病大鼠细胞相关因子的变化

目的通过观察大鼠心肌梗塞面积和细胞相关因子的变化,探讨缺血预适应(IP)对缺血-再灌注(I/R)糖尿病大鼠心肌的保护作用.方法向健康SD大鼠腹腔内注射链脲佐菌素(60mg/kg)制造糖尿病大鼠模型.2天后,随机测定血糖,将血糖≥11.1 mmol/L定为糖尿病大鼠39只.2周后,麻醉大鼠,开胸结扎冠状动脉(冠脉)左前降支(LADCA)复制IP和I/R模型.将39只糖尿病大鼠分为IP糖尿病大鼠组(IP组)、非IP糖尿病大鼠组(NIP组)、糖尿病大鼠对照组(C组)各13只.记录Ⅱ导联心电图.测定心腔血清肌酸激酶MB同工酶(CK-MB)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α).心肌组织丙二醛(MDA)、Cu-Zn超氧化物岐化酶(Cu-ZnSOD)含量.取心脏切片大体染色,计算心肌缺血范围和心肌坏死范围.结果IP组和NIP组间心肌缺血范围无显著性差异(P>0.05).IP组心肌坏死范围较NIP组减少49.7%(P<0.01).再灌注期IP组室性心律失常减少,尤其是心室颤动(室颤)较NIP组显著减少52.9%(P<0.01).IP组CK-MB、IL-8和TNF-α及MDA显著低于NIP组(均P<0.05),IP组Cu-Zn SOD高于NIP组(P<0.05).结论IP可能通过抗氧化作用和减少TNF-α,减少心肌坏死范围和降低糖尿病大鼠室颤的发生率,从而减轻糖尿病大鼠心肌缺血-再灌注的损害.     

苯那普利后处理对离体大鼠心肌缺血再灌注损伤的保护作用

目的观察苯那普利后处理对离体大鼠心肌缺血再灌注（I／R）损伤的保护作用，初步探讨其可能的作用机制。方法应用Langendroff离体灌流装置，采用完全停灌复灌方法制作离体大鼠心肌缺血再灌注模型。32只SD大鼠随机等分为4组：对照组、I／R组、缺血预处理组和苯那普利后处理组。测定各组稳灌20min和再灌60min时的冠脉流量，改良亮绿变色酸法（GCA）观察心肌损害程度，免疫组化法检测心肌组织中核因子-κB（NF—κB）和肿瘤坏死因子（TNF—α）的表达。结果与对照组比，I／R组，再灌注60min时的冠脉流量减少（P〈0．01），心肌损害程度增加（P〈0．01），免疫组织化学染色可见NF—κB蛋白表达显著增强且主要表达在心肌细胞核（P〈0．01），TNF—α主要表达在心肌细胞胞质，呈强阳性。与I／R组相比，苯那普利后处理组再灌注60min时的冠脉流量增多[（4．3±0．4）ml／min和（3．5±0．5）ml／min，P〈0．05]，GCA染色心肌变性减轻，阳性率减低（14％±7％和40％±7％，P〈0．01），NF—κB表达减少（34．8％±4．7％和49．3％±9．7％，P〈0．05），TNF—α表达为弱阳性。苯那普利后处理组和预处理组相比较，差异无统计学意义（P〉0．05）。结论苯那普利后处理对缺血再灌注心肌具有保护作用，其机制可能与苯那普利后处理抑制NF—κB活性，减少TNF—α的表达有关。     

心肌缺血预适应对急性心肌梗死临床和近期预后价值的探讨

目的观察心肌缺血预适应对急性心肌梗死病人心肌损伤程度、恶性心律失常的发生和近期预后的影响。方法选择286例急性心肌梗死病人，分为缺血预适应组（IP组）158例，无缺血预适应组（NIP组）132例。均于入院后及入院24h内多次测定心肌肌酸激酶（CK）、肌酸磷酸激酶同工酶（CK－MB）、乳酸脱氢酶（LDH）及肌钙蛋白I（cTnI），取其峰值；比较两组恶性心律失常及心血管事件的发生率。结果1P组cK、cK－MB、LDH、cTnI峰值浓度显著低于NIP组（P〈0．01）。IP组病人心功能不全、心衰、梗死后心绞痛、恶性心律失常的发生率明显低于NIP组（P％0．01）。结论缺血预适应可减少其后发生急性心肌梗死病人心肌损伤面积，减少恶性心律失常及近期心脏事件的发生。     

肿瘤坏死因子在心肌缺血再灌注中的变化和意义

为探讨肿瘤坏死因子-α（TNF－α）在心肌缺血再灌注治疗中的变化及其意义，观察了急性心肌梗塞（AMI）溶栓治疗后血管再通与未通患者血浆TNF－α含量的动态变化，同时在兔心肌缺血再灌注（MI／R）模型上观察了血浆TNF－α、心肌组织中中性粒细胞的浸润、髓过氧化物酶（MPO）活性和丙二醛（MDA）含量。结果显示：（1）AMI发病早期（6h）血浆TNF－α含量高于正常对照31％（P＞0．05）；溶栓血管未通患者在发病24小时内较正常升高33．2％～38．6％（P＞0．05）；溶栓血管开通后在再灌注1小时较正常对照和溶栓前分别升高达76．7％和44．6％（P＜0．01，P＜0．05），再灌注4．5小时仍高于正常对照（P＜0．05），10小时后下降接近溶栓前水平。动物实验与临床结果相似，并发现，缺血与坏死心肌中有大量中性粒细胞浸润；MI1．5h／R1h或R4h组较MI1．5h组缺血心肌中MPO活性与MDA含量均明显升高（P＜0．05，P＜0．01），TNF－α释放与MPO活性呈正相关（γ＝0．72，P＜0．01）。结果提示，TNF－α参与了心肌缺血再灌注损伤的发病，TNF－α可能促进了中性粒细胞对心肌的浸润并与中性粒细胞共同导致了心肌损伤。     

缺血预适应对糖尿病大鼠再灌注心肌的保护作用

目的　通过建立大鼠缺血预适应 (IP)模型 ,探讨IP对缺血 再灌注 (I/P)糖尿病大鼠心肌的保护作用。方法　在SD大鼠腹腔内注射链佐星 (6 0mg/kg)制造糖尿病大鼠模型。 2d后 ,随机时刻测定血糖 ,将血糖≥ 11.1mmol/L定为糖尿病大鼠 2 2只 ,另外 2 2只血糖正常鼠为非糖尿病鼠。 2周后 ,麻醉大鼠 ,结扎和放松冠状动脉左前降支(LAD)复制IP和I/P模型。将 44只大鼠分为IP糖尿病大鼠组 (DIP组 )、IP非糖尿病大鼠组 (NDIP组 )、非IP糖尿病大鼠组 (DNIP组 )和非IP非糖尿病大鼠组 (NDNIP组 )各 11只。记录II导联心电图。取心脏切片染色 ,计算心肌缺血范围和心肌坏死范围。结果　各组间心肌缺血范围无显著差异 (P >0 .0 5 )。DIP组心肌坏死范围较DNIP组明显减小 (P <0 .0 1)。DNIP组室性心律失常增多 ,尤其心室颤动较其他各组显著增多 (P <0 .0 1)。结论　缺血预适应可以减轻糖尿病大鼠随后较长时间缺血 再灌注对心肌的严重损害 ,能减少心肌坏死范围和降低心室颤动的发生率。     

缺血预处理对糖尿病在体大鼠心肌环磷酸腺苷及环磷酸腺苷依赖蛋白激酶表达的影响

目的 探讨糖尿病大鼠心肌缺血预处理（IPC）后环磷酸腺苷（cAMP）及环磷酸腺苷依赖蛋白激酶（PKA）表达的变化.方法 选取糖尿病与非糖尿病SD大鼠各30只,分为3组（n=10）：假手术（Sham）组,缺血再灌注（I/R）组及IPC组.比较各组血清肌酸激酶（CK）、肌酸激酶同工酶（CK MB）、乳酸脱氢酶（LDH）、心肌梗死面积（MI）及心肌cAMP、PKA含量的变化.电镜标本观察心肌线粒体.结果 非糖尿病大鼠中,IPC组与I/R组比较,CK减少[（2428.32±170.19）vs（6324.06±356.26） U/L,P＜0.05],LDH减少[（1698.98±129.65）vs（4660.15±115.84） U/L,P＜0.05],CK-MB减少[（1450.43±23.56）vs（3280.90±71.33）U/L,P＜0.05],MI减少[（5.63±9.32）％vs（17.75±7.36）％,P＜0.05].糖尿病大鼠中,IPC组与I/R组比较,CK、LDH、CK-MB、MI未见明显缩小[（5962.63±145.22）vs（6012.13±124.08） U/L,（5998.44±123.40）vs（6023.54±89.01）U/L,（4011.13±81.09）vs（4380.71±76.21）U/L,（18.54±2.39）％vs（15.25±4.33）％,P＞0.05].非糖尿病大鼠中,IPC组与I/R组比较,cAMP增加[（0.61±0.07）vs（0.32±0.06） pmol/g,P＜0.05],PKA含量增加[（17.05±1.75）vs（12.68±1.13） pmol/（mg·min）,P＜0.05],糖尿病大鼠IPC组cAMP、PKA含量无明显增加[（0.35±0.04）vs （0.37±0.08） pmol/g,（12.14±2.15）vs（11.79±1.16） pmol/（mg·min）,P＞0.05].非糖尿病大鼠IPC组线粒体的损伤减轻,而糖尿病大鼠IPC组线粒体损伤未见减轻.结论 非糖尿病大鼠IPC可保护心肌.糖尿病抑制IPC的心肌保护作用,其机制可能与糖尿病大鼠心肌cAMP信号系统表达受抑制有关.     

TNF—α在慢性实验性糖尿病大鼠MCAO中的观察

目的：观察STZ诱导下慢性实验性糖尿病大鼠,持续性MCAO后缺血区肿瘤坏死因子－α（TNF－α）含量变化。方法：以STZ诱导产生慢性实验性糖尿病大鼠模,用线栓法制备大脑中动脉梗塞模型（MCAO）,以ELISA法检测TNF－α。结果：持续性缺血2小时后,糖尿病组缺血侧TNF－α含量较对照组缺血侧显升高。结论TNF－α可能是糖尿病加重缺血性脑损的一个重要因素。     

尼可地尔对心肌缺血再灌注损害的作用

目的：观察KATP通道开放剂预处理对在体缺血再灌注（ischemia／reperfusion,I／R）心脏的影响。方法：建立在体大鼠心脏缺血再灌注模型。将60只大鼠随机分成4组：缺血再灌注（I／R）组,尼可地尔（NIC）组,KATP通道阻滞剂格列苯脲（GLI）＋NIC组,GLI组。测定各组心肌梗塞范围,血清肌酸激酶（CK）,乳酸脱氢酶（LDH）浓度,监测各组心电图,应用透射电镜观察超微结构的变化。结果：与I／R组比较,NIC组心肌梗塞范围显著减小[（52．9±14．2）％：（20．3±6．4）％。P〈0．005],血浆CK,LDH浓度显著减少（P〈0．05）,但并不能减少心律失常的发生;GLI＋NIC组和GLI组与I／R组相比,心肌梗塞范围、血清CK、LDH浓度无显著性差异。结论：非特异性KATP通道开放剂尼可地尔有部分心肌保护作用,推测在缺血再灌注中发挥作用的KATP通道可能是对心电生理影响较小的亚型。     

缺血后适应通过上调miRNA-21，miRNA-126发挥心脏保护效应

[摘要]：目的 探讨缺血后适应在大鼠心肌缺血再灌注时发挥保护作用的相关机制。方法将30只成年雄性SD大鼠每组10只,分为三组,假手术组：开胸后将6-0无损伤缝线穿过左冠状动脉前降支不阻断血管。缺血再灌注损伤组：使用6-0无损伤缝线阻断左冠状动脉30min后开放血管。缺血后适应组：缺血30min后,立即行缺血后适应(开放10s 阻断10s,反复3次）。采用伊文思蓝和氯化三苯基四氮唑染色法测定缺血面积和梗死面积;通过实时荧光定量PCR检测各组大鼠再灌注2 h体内miRNA-21,miRNA-126表达水平;通过ELISA法,硝酸还原酶法测定各组大鼠再灌注2 h体内TNF-α,Il-6、NO浓度。结果 Sham组未见明显心肌缺血和坏死面积,IPC组大鼠心肌AAR／LV与I/R组比较差异无统计学意义[(39.04±6.81)％比41.05± 8.04)％,P>0．05],IPO组大鼠心肌IS／AAR则低于IR组(25.64±5.76)％比(47.25±7.26)％, P<0.05]。I/R组、Ipost组术后miRNA-21,miRNA-126表达水平较Sham组升高,Ipost组升高更为明显。I/R组大鼠血清TNF-α,Il-6浓度明显高于Ipost组,I/R组血清NO浓度明显低于IPC组。miRNA-21与TNF-α,Il-6呈正相关（r=-0.934 、-0.925 ,p＜0.05,）,与NO无明显相关性（r=0.135,p＞0.05）。miRNA-126与TNF-α,IL-6呈负相关（r=-0.926、r=-0.935,p＜0.05）、与NO呈正相关性（r=0.553,p＜0.05）。结论 缺血后适应处理可减少大鼠心肌梗死面积,改善大鼠心肌缺血再灌注损伤。其心肌保护内在机制可能与调控miRNA-21,miRNA-126表达,抑制相关炎性因子释放有关。     

TNF—α值与糖尿病大鼠视网膜病变关系

目的：探讨不同病程糖尿病大鼠血浆肿瘤坏死因子－α（TNF－α）水平与糖尿病大鼠光,电镜上视网膜病理改变及病情相关指标的关系。方法：复制糖尿病视网膜病变＊（DR）大鼠模型,分别在其糖尿病持续3－6个月时,对其视网膜进行形态学观察,采用酶联免疫吸附法测定血浆TNF－α水平,同时测定血糖（BG）,糖化血红蛋白（GHbA1C),血浆胰岛素（Ins)及肽（CP）水平。结果：相同病程模型组与治疗组相比较,TNF－α,BG,GHbl1c显著升高（P＜0．01）,Ins,CP显著降低（P＜0．01）,病理形态学改变明显重重,不同病程间模型组比较,TNFα,BG,GHbAlcjo显著升高（P＜0．01）,Ins,CP显著降低（P＜0．01）,病理形态学改变明显加重,可见新生血管,不同病程治疗组间比较,TNFα,BG,GHbAlc,Ins,CP比较无显著差异。6个月组大鼠视网膜病理改变较3个月组无减轻。结论：TNFα水平随病情加重,病程延长,视网膜病变加重而增高,TNF－α可能是DR的一个重要危险因素,参与了DR的病理发展过程。α     

Value of the myocardial performance index in myocardial infarction

The myocardial performance index represents an easy and reproducible parameter of both systolic and diastolic left ventricular function for the risk stratification of patients following acute myocardial infarction.     

Effects of myocardial edema on the development of myocardial interstitial fibrosis

OBJECTIVE: The mechanism by which chronic myocardial edema causes cardiac dysfunction is poorly understood. We hypothesized that myocardial edema triggers cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is the most abundant constituent of the interstitial matrix, we examined the effects of edema development on cardiac collagen metabolism. METHODS: We utilized a chronic pulmonary artery banded rat model that produces right ventricular hypertrophy with myocardial edema and left ventricular edema without hypertrophy or hyperplasia. Wet to dry ratios (index of edema), collagen type I and III concentrations, prolyl 4-hydroxylase (P4-H) and collagen type I and III mRNA levels, collagenase activity and transforming growth factor-beta were measured in both ventricles. RESULTS: Right and left ventricular wet to dry ratios were significantly elevated from 1 to 28 days after pulmonary artery banding compared to sham rats. Right and left ventricular collagen types I and III and P4-H mRNA levels increased significantly at 3 days followed by significant increases in right and left ventricular collagen concentration 7 days after pulmonary artery banding. Right ventricular collagenase activity increased at 3 days while left ventricular collagenase activity decreased 7 days after PA banding. CONCLUSIONS: We conclude that myocardial edema preceded the observed increase in collagen deposition and that edema may have triggered increased collagen synthesis by fibroblasts. leading to fibrosis development.     

心肌灌注断层显像对急性心肌梗死再灌注的研究

目的　通过心肌灌注断层显像研究急性心肌梗死 (AMI)患者经尿激酶或冠状动脉介入治疗前后心肌梗死面积的变化。方法　用99m锝甲氧基异丁基异腈心肌灌注断层显像测定 12 0例AMI患者心肌再灌注前后的心肌梗死面积。结果　再灌注组 (n =81)和无再灌注组 (n =36 )首次心肌显像心肌缺损面积无显著性差异 (P >0 0 5 ) :再灌注组再次显像心肌缺损面积明显小于首次显像 (2 2 3± 3 1%和 31 9± 5 6 % ,P <0 0 5 ) ;无再灌注组再次显像心肌缺损面积与首次显像无明显差异 (2 9 6± 2 8%和 32 4± 5 l% ,P >0 0 5 ) ;预后不良组心肌缺损面积明显高于预后较好组 (35 8± 6 1% ,n =32和2 0 6± 4 0 % ,n =88,P <0 0 5 )。结论　心肌灌注断层显像可作为AMI再灌注疗效评价较准确的手段     

Effect of nifedipine on the myocardial and vascular response to myocardial ischemia

Summary Nifedipine reduces reactive hyperemia following brief coronary artery occlusions. To determine whether this is related to improvement in collateral blood flow to ischemic myocardium or alterations in myocardial oxygen consumption, ten chloralose anesthetized dogs were instrumented with coronary sinus catheters, circumflex artery flowmeters, and ultrasonic microcrystals for measurement of myocardial segment shortening. Myocardial oxygen consumption and circumflex coronary artery flow were determined at rest and during incremental infusions of isoproterenol. Myocardial blood flow measured with microspheres and segmental function were assessed during and following 30- and 60-second coronary artery occlusions. Thirty minutes after the intravenous administration of nifedipine, 10 g/kg iv, all measurements were repeated. Nifedipine did not alter myocardial oxygen consumption or the relationship between oxygen consumption and circumflex coronary artery flow either at rest or during isoproterenol infusion. Following 60-second coronary occlusions, nifedipine reduced peak circumflex coronary artery flow (176±99 vs. 128±68 cc/min) and reactive hyperemia debt repayment (221±84 vs. 158±66%; p<0.01). Nifedipine did not alter flow to ischemic segments during coronary artery occlusions (0.16±0.10 vs. 0.19±0.13 ml/min/g mean transmural flow). Furthermore, nifedipine did not affect the severity of ischemic segment dysfunction, nor the rate of recovery of ischemic segment function following release of coronary artery occlusion. We conclude that the reduction in reactive hyperemia induced by nifedipine was not related to alterations in the severity of hypoperfusion in ischemic areas, or alterations in myocardial oxygen consumption. Reductions in reactive hyperemia produced by nifedipine did not impair recovery of mechanical function in postischemic myocardium.This study was supported in part by grants HL01162 and HL20598 from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, Maryland; and by a grant-in-aid from the American Heart Association, Minnesota Affiliate, Inc. Dr. Homans was a fellow of the American Heart Association, Minnesota Affiliate, and recipient of National Research Service Award (HL06575) from the National Heart, Lung and Blood Institute of the National Institute of Health at the time that this work was performed.     

Assessment of myocardial contractility by the sector scanning of myocardial infarct patients

A comparative assessment of left-ventricular myocardial contractility in patients with myocardial infarction was made using sector scanning and ventriculographic techniques. Eight patients were investigated within 2-4 hours of the infarction, and twenty patients, on days 20-25 of the disease. Ultimate diastolic, ultimate systolic and stroke volumes were calculated, as was the expulsion fraction, using the mono- and biplane method and modified formula 5/6 AL. Ventriculography was the testing method. Sector scanning is shown to be one of the most informative methods of myocardial contractility assessment in patients with myocardial infarction; the formula 5/6 AL appears to yield the best information when left-ventricular volumes are computed.     

新生儿窒息合并心肌损害血清心肌酶变化

目的了解新生儿窒息后心脏损害和血清心肌酶变化的关系。方法选择12例窒息新生儿和10例正常新生儿于生后24h内取静脉血检测谷草转氨酶(AST)、乳酸脱氢酶(LDH)、α-羟丁酸脱氢酶(-αHBDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB),并作心电图检查。结果窒息组生后血清AST、LDH、-αHBDH、CK、CK-MB明显高于对照组,两者差异有非常显著性(P<0.01);窒息组心电图均有各种异常改变。结论窒息新生儿通过早期监测血清心肌酶变化和心电图,可及早诊断和防治心肌损害。     

Relation between the kinetics of thallium-201 in myocardial scintigraphy and myocardial metabolism in patients with acute myocardial infarction

Objective—To investigate the relations between myocardial metabolism and the kinetics of thallium-201 in myocardial scintigraphy.
Methods—46 patients within six weeks after the onset of acute myocardial infarction underwent resting myocardial dual isotope, single acquisition, single photon emission computed tomography (SPECT) using radioiodinated 15-iodophenyl 3-methyl pentadecaenoic acid (BMIPP) and thallium-201, exercise thallium-201 SPECT, and positron emission tomography (PET) using nitrogen-13 ammonia (NH₃) and [F18]fluorodeoxyglucose (FDG) under fasting conditions. The left ventricle was divided into nine segments, and the severity of defects was assessed visually.
Results—In the resting SPECT, less BMIPP uptake than thallium-201 uptake was observed in all of 40 segments with reverse redistribution of thallium-201, and in 21 of 88 segments with a fixed defect of thallium-201 (p < 0.0001); and more FDG uptake than NH₃ uptake (NH₃-FDG mismatch) was observed in 35 of 40 segments with reverse redistribution and in 38 of 88 segments with fixed defect (p < 0.0001). Less BMIPP uptake in the resting SPECT was observed in 49 of 54 segments with slow stress redistribution in exercise SPECT, and in nine of 17 segments with rapid stress redistribution (p < 0.0005); NH₃-FDG mismatch was observed in 42 of 54 segments with slow stress redistribution and in five of 17 segments with rapid stress redistribution (p < 0.0005).
Conclusions—Thallium-201 myocardial scintigraphy provides information about not only myocardial perfusion and viability but also about myocardial metabolism in patients with acute myocardial infarction.

Keywords: thallium-201 SPECT;  BMIPP SPECT;  FDG PET;  myocardial infarction;  redistribution     

Stress factors in myocardial infarct patients before the appearance of myocardial infarct

Apart from somatic risk factors and the smoking of cigarettes more attention in the development of the myocardial infarction must be ascribed to the psychosocial and psychoemotional stress and its false processing. For the judgment of the stress in patients with myocardial infarction a questionnaire was constructed. It contains those questions the answer of which showed significant differences in comparison to the persons with healthy coronary vessels. The inquiries were answered by altogether 110 patients with myocardial infarction. In order to obtain references to definite characteristics concerning the structure of the personality of our patients with myocardial infarction, we used the INR-questionnaire after B?ttcher. In either sex moments of "self-stressing" dominate. Professional conflicts were mentioned more by men, familial problems more by women. Among others, definite characteristics concerning the structure of the personality (rigidity) of patients with myocardial infarction seem to be a reason for the deficient strain under stress or they increase the sensitiveness to stress. From the results of the examinations requirements to the psychic rehabilitation of patients with infarction are derived, which must be carried out parallel to the somatic rehabilitation.