预缺血对皮瓣缺血再灌注损伤的保护作用

目的　研究预缺血 (IPC)对大鼠腹部皮瓣缺血再灌注损伤的保护作用 ,并探讨其机制。方法　SD大鼠 2 0只 ,随机分成实验组和对照组 ,每组 10只 ;实验组在缺血前 ,先做预缺血处理 ;对照组皮瓣形成后 ,不做预缺血处理 ;然后两组均以血管夹持续阻断血流 8h ,松夹后恢复血流。术后第7d判断皮瓣成活情况。另外 ,两组在缺血前、缺血 8h及再灌注 3 0min ,分别抽取股静脉血 0 5ml,检测血清中超氧化物歧化酶 (SOD)活性和丙二醛 (MDA)含量。结果　 ( 1)实验组皮瓣平均存活率80 2 1%± 15 73 % ,明显高于对照组 5 2 80 %± 18 91% (P <0 0 1)。 ( 2 )实验组和对照组血清SOD活性及MDA含量在缺血前和缺血 8h ,差异无显著性意义。但在再灌注 3 0min ,实验组SOD活性平均为 ( 91 84± 7 85 )NU/ml,对照组为 ( 83 4 5± 9 71)NU/ml,差异有显著性意义 (P <0 0 5 ) ;实验组MDA含量平均为 ( 8 76± 1 0 4 )nmol/ml,对照组为 ( 9 71± 0 99)nmol/ml,差异也有显著性意义 (P <0 0 5 )。结论　IPC能提高大鼠腹部皮瓣的存活率 ,其机制与IPC能减轻氧自由基介导的缺血再灌注损伤有关。     

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。     

米诺环素对大鼠脑缺血-再灌注损伤模型的保护作用

目的探讨米诺环素对大鼠脑缺血-再灌注损伤模型的保护作用及其机制。方法选择健康成年雄性SD大鼠40只,随机分为假手术组、缺血-再灌注模型组、米诺环素组和0.9%氯化钠溶液组,每组10只,除假手术组外,其他3组均采用线栓法制备大脑中动脉栓塞短暂局灶性脑缺血模型。米诺环素组和0.9%氯化钠溶液组于缺血-再灌注损伤开始后分别腹腔注射给予米诺环素注射液(45 mg.kg-1)和等体积0.9%氯化钠溶液。观察各组大鼠脑神经功能缺损程度及缺血脑皮质乳酸脱氢酶(LDH)的活力,采用RT-PCR方法检测各组大鼠脑皮质神经生长因子受体TrkA mRNA的表达。结果米诺环素组大鼠缺血-再灌注损伤神经功能缺损体征明显改善,神经功能缺损程度评分[平均(0.95±0.46)分]明显低于模型组[平均(2.28±0.73)分](P<0.05),米诺环素组大鼠大脑皮质LDH活力[平均(7.91±0.32)×103U.g-1]和TrKA mRNA[平均(1.28±0.04)]亦均明显高于模型组[分别平均为(5.12±0.36)×103U.g-1和(0.71±0.06)](均P<0.01)。结论米诺环素可通过调节神经生长因子受体TrkA mRNA的表达保护缺血-再灌注性脑损伤大鼠。     

无创性肢体缺血预适应的早期及延迟效应对中年大鼠心肌缺血再灌注损伤的保护作用和差异

目的研究无创性肢体缺血预适应的早期及延迟效应对中年大鼠心肌缺血再灌注(I/R)损伤的保护作用和差异。方法对预适应组中年大鼠实施1d或连续3d无创性后肢缺血预适应后,分别对其立即实施心脏I/R处理,或24h后再实施心脏I/R处理,与对照组(单纯实施心脏I/R)相比较,观察无创性肢体缺血预适应的早期和延迟效应对中年大鼠心脏I/R后心脏生理学指标[心率(HR)、平均动脉压(MAP)、ST段]、血清学指标、心律失常Lambeth评分、各组I/R后的心肌梗死面积的影响。结果无创性后肢缺血预适应的早期效应组保护效应作用明显。1E,3E组心脏梗死面积(IS/AAR)减小,与对照组IS/AAR[(50±9)%]比较,1E[(15±5)%]和3E[(35±10)%]组IS/AAR显著降低(P<0.05);心律失常Lambeth评分降低,1E[(2.6±0.9)分]、3E[(2.6±1.1)]分组与对照组[(4.2±0.8)分]比较,差异有统计学意义(P<0.05);血清中丙二醛(MDA)的含量减少,血浆中MDA的含量在1E[(7.4±1.2)nmol/ml]、3E[(6.8±0.9)nmol/ml]组中较对照组大鼠[(9.4±1.0)]nmol/ml均显著降低(P<0.05);超氧化物歧化酶(SOD)酶活性增加,血浆中SOD酶活性在1E[(295±30)U/ml]、3E[(345±22)U/ml]组中较对照组大鼠[(257.4±21.0)U/ml]均显著升高(P<0.05,P<0.01);谷胱甘肽过氧化物酶(GSH-PX)酶活性增加,与对照组[(1196±127)U/L]相比,早期预适应组1E[(1547±193)U/L],3E[(1624±69)U/L]组血清中GSH-PX的活性均显著增高(P<0.05)。结论无创性后肢缺血预适应的早期效应对中年大鼠心脏I/R损伤具有保护作用,且其作用大于其延迟效应。     

灯盏生脉胶囊对大鼠脑缺血及再灌注损伤的影响

目的:观察灯盏生脉胶囊对大鼠脑缺血及再灌注损伤的作用并探讨其作用机制。方法:将80只大鼠随机分为假手术1组、假手术2组、生理盐水对照组、灯盏生脉胶囊低剂量组、灯盏生脉胶囊高剂量组,每组16只。采用改良的ZeaLonga线栓法制作大鼠大脑中动脉阻塞模型,缺血前后口服灯盏生脉胶囊,进行神经病学评分,检测凝血酶原时间(PT)、纤维蛋白原(Fg)、血小板最大聚集率等血液学指标以及血浆内皮素(ET)、血清一氧化氮(NO)水平,并测量脑梗死体积、脑水肿体积、脑组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果:灯盏生脉胶囊低剂量组和高剂量组大鼠脑缺血再灌注2h及24h,神经病学评分均低于生理盐水对照组(1.75±0.68、1.71±0.77对2.35±0.86;1.88±0.81、1.71±0.69对2.65±1.17,P<0.05);灯盏生脉胶囊高剂量组大鼠PT较生理盐水对照组延长(18.0±0.8s对17.0±0.6s,P<0.05),ET含量则低于生理盐水对照组(13.9±4.9pg/ml对26.3±13.2pg/ml,P<0.05);灯盏生脉胶囊低剂量组和高剂量组大鼠脑梗死体积比及脑水肿体积比均低于生理盐水对照组(10.3±3.8%、9.7±5.7%对11.9±3.0%,7.7±3.0%、6.9±3.9%对18.3±7.0%,P<0.05);灯盏生脉胶囊低剂量组和高剂量组大鼠脑组织SOD活性均高于生理盐水对照组(291±78U/mg、301±92U/mg对213±40U/mg,P<0.05),MDA含量则明显低于生理盐水对照组(1.41±0.47nmol/mg、1.36±0.61nmol/mg对2.09±0.32nmol/mg,P<0.05,P<0.01);其余指标的差异无统计学意义(P>0.05)。结论:灯盏生脉胶囊具有防治大鼠脑缺血及缺血再灌注损伤的作用,其作用机制可能为提高抗氧化酶活性,抑制脂质过氧化反应、减少自由基对脑组织的损害,以及抑制凝血、降低血管阻力等。     

瑞芬太尼预处理对心力衰竭大鼠心肌的保护作用

目的探讨瑞芬太尼预处理对阿霉素心衰大鼠离体心肌缺血/再灌注损伤的作用。方法 60只成年♂SD大鼠(250±20)g,尾静脉注射阿霉素2μg·g-1,每周1次,共6周,制成阿霉素心衰大鼠模型。随机将阿霉素心衰大鼠分为6组:对照组(Sham组)、缺血/再灌注组(I/R组)、缺血预处理组(IPC组)、10μg·L-1瑞芬太尼预处理组(RPC 1组)、30μg·L-1瑞芬太尼预处理组(RPC 2组)、60μg·L-1瑞芬太尼预处理组(RPC 3组)。采用Langendorff离体大鼠心肌灌注模型。除Sham组为持续灌注165 min外,所有心脏予以30 min缺血,90 min再灌注。IPC组在缺血前结扎左冠状动脉5 min,松开5 min,共3个循环。RPC组在缺血前给予含浓度分别为10、30、60μg·L-1的瑞芬太尼的K-H液灌注5 min后改用不含瑞芬太尼的K-H液灌注5 min,共3个循环。记录各组心脏在平衡末、再灌5 min、再灌30 min、再灌90 min时的心率(HR)、左室发展压(LVDP)和左室压力升高或降低最大速率(±dp/dtmax)、冠脉流量(CF)并测定冠脉流出液中乳酸脱氢酶(LDH)的活性。再灌末TTC法计算心肌缺血梗死区(IS/AAR)。Western blot半定量检测p-Akt和总Akt的含量。结果平衡灌注末各组间心功能指标(基础值)差异未见统计学意义(P>0.05)。再灌5、30、90 min时,RPC 2组和RPC 3组的LVDP、±dp/dtmax、CF较I/R组高,LDH值较I/R组低(P<0.05)。灌注结束后,见RPC 2组、RPC 3组的IS/AAR较I/R小,p-Akt表达水平升高(P<0.05),而IPC组和RPC 1组的各项指标较I/R组无差异。结论 RPC在一定程度上减轻阿霉素心衰大鼠心肌缺血/再灌注损伤,而缺血预处理对阿霉素心衰大鼠心肌缺血/再灌注损伤无明显保护作用。     

CT灌注成像技术用于断肢再植骨骼肌再灌注损伤实验性研究

目的 评价在断肢再植骨骼肌再灌注损伤的评估中应用CT灌注成像技术的效果。方法 2017年7—8月,选择60只SD大鼠,采用随机数字表法分为假手术组和再植组(其中分为夹闭1 h、2 h、4 h和8 h等4个亚组),通过钳夹大鼠左侧股动静脉,建立大鼠左后肢的断肢模型,夹闭左侧股动静脉1 h、2 h、4 h、8 h后恢复血供。应用多排螺旋CT灌注扫描比较各组的血流量(BF)、相对血流量(rBF)、血容量(BV)和相对血容量(rBV)等灌注指标、乳酸脱氢酶(LDH)和肌酸激酶(CK)水平,探究rBF与LDH和CK水平的相关性,并应ROC曲线评价rBF、LDH和CK预测再灌注后肢体坏死的效能差异。结果 与假手术组BF (4.08±1.09) mL·(100 g)-1·min-1,rBF 1.03±0.07,BV (4.85±1.21)mL·(100 g)-1,rBV 1.03±0.07,造影剂通过总时间(TT)(38.06±10.11) s,造影剂达峰时间(TTP)(27.54±6.37) s相比,再植组术侧1 h,2 h,4 h,8 h的BF(3.55±1.06),(3.12±0.91),(2.76±0.82),(2.39±0.71) mL·(100 g)-1·min-1、rBF(0.92±0.12),(0.86±0.10),(0.81±0.11),(0.75±0.12)、BV(4.31±1.11),(3.80±0.96),3.31±0.87),(2.89±0.81) mL·(100 g)-1和rBV(0.91±0.11),(0.85±0.11),(0.80±0.10),(0.75±0.09)明显降低(P＜0.05),TT(43.21±10.31),(49.03±11.26),(55.23±12.13),(59.41±12.35) s和TTP(31.21±7.31),(35.36±8.26),(39.78±9.13),(44.16±9.35) s明显延长(P＜0.05)。与假手术组(160±50) U/L,(120±40) U/L相比,不同时间的再植组的LDH(300±120) U/L,(350±150) U/L,(380±160) U/L,(420±180) U/L和CK(320±140) U/L,(360±150) U/L,(420±160) U/L,(480±170) U/L水平明显升高(P＜0.05);其中,夹闭时间越长,LDH和CK的水平越高(P＜0.05)。线性相关性分析显示,术侧相对血流量rBF与LDH(r＝-0.710,P＜0.001)和CK(r＝-0.738,P＜0.001)水平呈明显的负相关。受试者工作特征曲线(ROC曲线)显示,应用rBF预测肢体坏死的诊断效能(AUC＝0.974)明显高于LDH(AUC＝0.724)和CK(AUC＝0.754)。结论 在断肢再植骨骼肌再灌注损伤的评估中应用CT灌注成像技术具有较高的应用价值。     

牛磺酸对急性局部脑缺血大鼠脑血流和脑梗死体积的影响

目的 :研究牛磺酸对脑缺血再灌注模型大鼠的局部脑血流和脑梗死体积的影响。方法 :用大脑中动脉栓塞 (MCAO)法制作大鼠急性局部脑缺血再灌注模型 ,分别用 10 ,4 0和 80mg·kg- 1牛磺酸经腹腔注射给药 ,检测缺血 1h和灌注 30min内脑血流 ,再灌注 2 4h后进行神经功能缺损评分并计算脑梗死体积的大小。结果 :MCAO引起大脑中动脉供血区脑血流显著下降 ,牛磺酸可减少脑血流量下降的幅度 ;缺血 1h再灌注 2 4h后 ,模型组脑梗死体积为 (33±s 9) % ,而牛磺酸治疗组脑梗死体积明显缩小 ,各组分别为 (17± 5 ) % ,(12± 5 ) %和 (11± 3) % ;牛磺酸治疗组神经缺损评分比模型组小。结论 :牛磺酸可以增加缺血局部的脑血流量 ,缩小脑梗死体积 ,对急性脑缺血具有脑保护作用。     

大鼠局灶性脑缺血再灌注后不同时间E-选择素、P-选择素和细胞间粘附分子-1的表达

目的观察大鼠脑缺血再灌注(I/R)后不同时间P-选择素(P-selectin)、E-选择素(E-selectin)和细胞间粘附分子-1(ICAM-1)的表达及中性粒细胞浸润脑组织的情况,探讨粘附分子在脑缺血再灌注损伤中的作用。方法采用Zea-Longa线栓法,建立大鼠局灶性脑缺血模型。缺血1 h后拔出栓线进行再灌注,假手术组除不插线外其余手术操作同模型组。分别于再灌注后4、8、12、24、48 h,将动物麻醉下处死,快速取出脑组织,采用HE染色的方法,观察缺血再灌注不同时间脑组织形态学变化;采用免疫组化方法观察再灌注不同时间脑组织中P-selectin、E-selectin和ICAM-1的阳性表达数及表达部位;采用免疫荧光双标法,观察P-selectin、E-selectin和ICAM-1的表达及其定位;采用流式细胞术定量检测P-selectin、E-selectin和ICAM-1的表达;采用生化法测定缺血侧脑组织中髓过氧化物酶(MPO)的活性,以反映白细胞浸润的情况。结果缺血再灌注后,缺血侧脑组织发生明显的病理学形态改变,并且随着再灌注时间的延长,病理学形态改变逐渐加重。缺血再灌注后P-selectin、E-selectin、ICAM-1共表达于血管内皮细胞,与假手术组〔P-selectin:(4.99±0.08)channel;E-selectin:(4.17±0.13)channel;ICAM-1:(4.17±0.13)channel〕相比,I/R 4 h〔(5.46±0.09)channel;(4.60±0.14)channel;(4.56±0.12)chan-nel〕、I/R 8 h〔(5.87±0.24)channel;(5.08±0.14)chan-nel;(5.41±0.22)channel〕、I/R 12 h〔(6.48±0.18)chan-nel;(5.72±0.18)channel;(5.66±0.16)channel〕、I/R 24 h〔(7.16±0.11)channel;(6.09±0.09)channel;(5.61±0.09)channel〕及I/R 48 h〔(5.82±0.28)channel;(5.37±0.25)channel;(5.27±0.16)channel〕各组均升高(P<0.01),且表达峰值出现在缺血再灌注后24 h左右。在缺血再灌注后4~24 h大鼠脑组织中P-selectin(r=0.975,P<0.01)、E-selectin(r=0.977,P<0.01)和ICAM-1(r=0.749,P<0.01)的表达增加具有时间依赖性。脑缺血再灌注后MPO活性明显升高,I/R 4 h组(0.107±0.015)U.g-1、I/R8 h组(0.202±0.010)U.g-1、I/R 12 h组(0.242±0.010)U.g-1、I/R 24 h组(0.273±0.006)U.g-1和I/R 48h组(0.294±0.006)U.g-1与假手术组(0.043±0.008)U.g-1相比,差异均具有显著性(P<0.01),其峰值出现在缺血再灌注后48 h左右。在缺血再灌注后4~48 h,MPO活性增高具有时间依赖性(r=0.982,P<0.01)。结论大鼠局灶性脑缺血再灌注后24 h粘附分子E-selectin、P-selectin和ICAM-1表达增加最明显,而MPO活性在脑缺血再灌注后48h增加最明显,E-selectin、P-selectin和ICAM-1上调共同参与炎症反应,介导白细胞浸润,引起缺血再灌注性脑损伤。     

脂质体携载前列腺素E_1抗心肌缺血再灌注损伤

目的　研究脂质体携载前列腺素E1(Lipo PGE1)减轻心肌再灌注损伤的机理。方法　 2 4只家兔随机分成Lipo PGE1组 ,PGE1组及对照组 ,每组 8只。以家兔左冠脉前降支 (LAD)结扎 6 0min ,再灌注 12 0min为缺血再灌注模型 ,于再灌注前 10min分别自耳缘静脉静注Lipo PGE1(2 μg·kg-1PGE1) ,PGE1(2 μg·kg-1)及等容量的脂肪乳剂 (Lipo PGE1的溶剂 ) ,以Evans蓝及氯化三苯基四氮唑 (TTC)双重染色确定缺血心肌及梗塞心肌范围 ,通过测定心肌组织髓过氧化物酶 (MPO)活性反应缺血心肌中性粒细胞浸润程度。结果　Lipo PGE1组梗塞心肌占危险区心肌重量百分比(32 2 0 %± 4 70 % )比较对照组 (44 5 7%± 5 46 % )及PGE1(42 0 9%± 6 93% )降低 (P <0 0 1) ;Lipo PGE1治疗组缺血区心肌组织MPO活性〔(1 9± 1 2 )U·g-1〕较对照组〔(5 3± 2 4)U·g-1〕及PGE1组〔(4 2± 2 0 )U·g-1〕均降低 ,边缘区心肌组织MPO活性〔(1 4± 1 1)U·g-1〕较对照组〔(3 3± 1 5 )U·g-1〕也降低 (P <0 0 5 )。结论　Lipo PGE1能有效抑制再灌注心肌中性粒细胞的浸润 ,减轻心肌再灌注损伤。     

ACUTE ISCHEMIC PRECONDITIONING AND HIGH SUBCHRONIC CO EXPOSURE INDEPENDENTLY INCREASE MYOCARDIAL TOLERANCE TO ISCHEMIA

This study was designed to investigate whether exposure to carbon monoxide (CO) could alter or raise the ischemic tolerance induced by preconditioning. To this end, isolated rat hearts were aerobically perfused for 20 min. Hearts were then randomized to two groups: (1) a further 20-min aerobic perfusion, and (2) ischemic preconditioning (2 cycles of 5 min of ischemia followed by 5 min of reperfusion). Hearts were then subjected to 25 min of low-flow (0.3 ml/min.) global ischemia (37°C) and 30 min of reperfusion. In parallel studies, the same protocols were performed in hearts from rats previously exposed to subchronic CO (600 ppm for 2 wk). Ischemic preconditioning accelerated the development of ischemic contracture (onset = 6.0 ± 0.3 vs. 8.6 ± 0.9 min), increased the preischemic coronary flow (19.0 ± 1.0 vs. 11.6 ± 0.6 ml/min/ g), improved contractile recovery (73.7 ± 8.9 vs. 30.8 ± 7.5%), but was without effect on reactive hyperemia (151.2 ± 4.7 vs. 149.2 ± 5.1%) and incidence of ventricular arrhythmia during reperfusion (55.6 vs. 60.0%) compared to a control group. CO exposure alone increased the baseline coronary flow (20.1 ± 1.5 vs. 12.8 ± 0.6 ml/min/g) and the contracture magnitude (54.8 ± 6.8 vs. 37.1 ± 4.8%), improved both contractile recovery (66.1 ± 6.3 vs. 30.8 ± 7.5%) and ventricular arrhythmia incidence (22.2 vs. 60.0%), and increased the hyperemic coronary flow (26.7 ± 1.5 vs. 19.1 ± 0.7%). Preconditioning after CO exposure exacerbated ischemic contracture (shorter onset and higher magnitude), and increased the reactive hyperemia (29.8 ± 1.4%), but raised the beneficial effects on contractile recovery (85.4 ± 8.4%) without alteration of ventricular tachycardia prevention (22.2%). Thus, CO-exposed hearts could be preconditioned in the same way as normal myocardium.     

Protective effect of monoclonal antibodies against LFA-1 and ICAM-1 on myocardial reperfusion injury following global ischemia in rat hearts

The effects of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (MAbs) on the reperfusion injury of rat cardiac tissues after global ischemia were studied. Studies were performed using an isolated blood perfused heart preparation in which hearts were subjected to 30 min of global ischemia followed by 40 min of reperfusion. Isolated rat hearts were perfused with blood from an anesthetized support rat with or without anti-LFA-1 or anti-ICAM-1 monoclonal antibody administration (n = 10 in each group). Ventricular function, myocardial tissue water content and myocardial energy status were evaluated in this model. In the control group, ischemia and reperfusion of isolated hearts resulted in a 63.6 ± 2.7% recovery of left ventricular developed pressure (LVDP) and a 44 ± 7 % increase in coronary vascular resistance compared with pre-ischemic baseline values. Treatment with anti-LFA-1 MAb or anti-ICAM-1 MAb resulted in a 77.2 ± 1.5% and a 80.4 ± 3.0% recovery of LVDP, respectively. In addition, increase in coronary vascular resistance was only 23 ± 7% and 13 ± 6% in anti-LFA-1 and anti-ICAM-1-treated groups, respectively. Values are significantly different between the control group and MAb-treated groups. Ischemia and reperfusion resulted in a 16% increase of myocardial tissue water content (3.71 ± 0.03 in pre-ischemic baseline versus 4.29 ± 0.08 ml/g dry weight) in the control group, whereas that resulted in only 3.0 and 5.7 % increase in anti-LFA and anti-ICAM-1-treated groups, respectively. The difference between the control group and MAb-treated groups was significant. Cardiac energy status as assessed by adenosine triphosphate (ATP) concentration was markedly reduced in the control group at 40 min of reperfusion compared with pre-ischemic baseline values (5.70 ± 0.27 vs. 14.92 ± 0.48 μmol/g dry weight). In contrast, the reduction of myocardial ATP concentration at 40 min of reperfusion was significantly inhibited by anti-LFA-1 and anti-ICAM-1 monoclonal antibody treatment (5.70 ± 0.27 vs. 8.96 ± 0.52 and 8.10 ± 0.47 μmol/g dry weight, respectively). These results suggest that a LFA-1/ICAM-1 pathway plays a critical role in the pathogenesis of postischemic myocardial injury during early reperfusion period.     

蝙蝠葛碱对猫冠脉结扎和复灌性心律失常的影响及电生理作用

本文报道蝙蝠葛碱(Dau)对猫缺血和非缺血心脏MAP和FRP的影响及其抗心律失常作用。剂量依赖性延长猫左心室MAPD_(50)和MAPD_(90)及FRP,累积剂量9mg/kg时,分别由给药前的170±19ms,216±16ms和177±15ms延长至197±20ms,249±18ms和238±20ms。Dau5mg/kg iv,然后以0.1mg/kg·min~(-1)恒速灌注30min,可防止缺血边缘区MAPD_(50)缩短,使缺血边缘区,中心区和非缺血区FRP延长,并降低3个区域间FRP离散程度和LAD结扎和复灌引起的VF发生率和死亡率。     

异氟烷对离体大鼠心脏缺血后能量代谢的影响及其机制

目的研究异氟烷对心肌缺血/再灌注期间能量代谢和功能的影响及其可能机制。方法实验采用离体大鼠心脏Langendorff灌注模型,分为未处理组、异氟烷组、cheleryth-rine(蛋白激酶C抑制剂)+异氟烷组、chelerythrine组。药物处理(或未处理)后,所有心脏均缺血30min,复灌60min。以Maclab生理实验系统记录心脏的血流动力学指标,HPLC方法测定心肌能量物质含量,免疫印迹方法分析蛋白激酶C(proteinkinaseC,PKC)亚型在细胞内的分布和活性。结果异氟烷明显延缓心肌缺血15min时心肌ATP的耗竭,改善再灌注后的心肌收缩功能以及能量代谢障碍的恢复,增加PKC-δ和-ε亚型的膜转位。PKC抑制剂chelerythrine减少异氟烷诱导的PKC-δ和-ε亚型的膜转位以及心肌功能和ATP的恢复。结论异氟烷延缓心肌缺血期间ATP的耗竭及改善复灌后心肌功能和能量代谢,该保护作用是由PKC介导的。     

Acadesine attenuates ischemic cardiac dysfunction in the isolated blood-perfused rabbit heart

Acadesine (AICA-riboside) is a nucleoside analog with cardioprotective properties. Most previous studies demonstrating cardioprotection with acadesine have been conducted in buffer-perfused hearts, and no study has investigated the dose-response relationship to acadesine in a blood-perfused model. The objective of this study was to investigate the dose-related cardioprotective effects of acadesine in donor-perfused, isolated rabbit hearts subjected to 12 × 3 min episodes of global ischemia with intervening periods of reperfusion of 5 min duration. Five groups of hearts were studied: saline control and four treatment groups of acadesine, 0.1, 0.2, 0.5, 2.0 gm/kg/min (0.4, 0.8, 2.0, 8.0 μmol/kg/min) constant intravenous infusion to the support animal. Left ventricular (LV) pressure and coronary blood flow (CBF) in the isolated hearts were measured. In control hearts, baseline LV developed pressure averaged 129 ± 7 mmHg and declined to 43 ± 3% of baseline after 12 periods of ischemia and reperfusion. Acadesine significantly improved recovery of function at the lower doses tested, i.e., hearts treated with 0.1, 0.2, and 0.5 mg/kg/min (0.4, 0.8, 2.0 μmol/kg/min) recovered 61 ± 5%, 67 ± 7%, and 65 ± 7% of LV pressure, respectively (P < 0.05 vs. saline). This protective effect was not observed with the highest dose of acadesine, 2.0 mg/kg/min (8.0 μmol/kg/min) (52 ± 6%). The greatest recovery of function corresponded to plasma acadesine concentrations of 27 ± 6.0 μM, but the beneficial effect was lost when plasma concentrations reached 205 ± 28 μM. These results suggest that repetitive episodes of ischemia and reperfusion induced stunning in isolated blood-perfused rabbit hearts, and that the severity of this dysfunction is attenuated by treatment with acadesine. © 1994 Wiley-Liss, Inc.     

Janus激酶-信号转导子与转录激活子信号通路在硫化氢后处理离体缺血再灌注大鼠心肌中的作用

目的 探讨Janus激酶-信号转导子与转录激活子(JAK2/STAT3)信号通路在硫化氢后处理(H2S)减轻离体大鼠心脏缺血/再灌注(I/R)损伤的作用.方法 应用Langendorff离体心脏灌流装置、通过停灌30 min/复灌60 min的方法建立SD大鼠I/R模型.按照处理及再灌注成分分为持续灌注对照组,I/R组...     

Glimepiride Treatment Upon Reperfusion Limits Infarct Size via the phosphatidylinositol 3-Kinase/Akt Pathway in Rabbit Hearts

The phenomenon termed postconditioning, that is, brief episodes of ischemia/reperfusion at the onset of reperfusion reduce infarct size, is thought to involve the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Treatment with a drug activating PI3K at the onset of reperfusion may confer a similar cardioprotection. The sulfonylurea glimepiride has been shown to activate PI3K in human endothelial cells. We therefore tested in rabbit hearts whether glimepiride can produce postconditioning-mimetic actions. Langendorff-perfused rabbit hearts were subjected to 30 min of global ischemia and 120 min of reperfusion, and infarct size was determined by triphenyltetrazolium staining. Phosphorylation of Akt was analyzed by Western blotting. Glimepiride (10 μM) treatment for the first 10 min of reperfusion significantly reduced infarct size from 67.2 ± 1.3% in controls to 35.8 ± 4.5% (P<0.01). This infarct size–limiting effect of glimepiride was abolished by a selective inhibitor of PI3K (5 μM LY294002, 65.4 ± 3.4%). Phosphorylation of the PI3K substrate Akt was significantly increased in glimepiride-treated hearts when compared to controls (P<0.05). Glimepiride-induced Akt phosphorylation was inhibited by LY294002. In conclusion, our study demonstrates that glimepiride treatment upon reperfusion reduces infarct size in rabbit hearts via a PI3K/Akt-mediated pathway. The postconditioning-mimetic action of glimepiride may be beneficial for the treatment of diabetic patients with ischemic heart disease.     

Protection of the right ventricle from ischemia and reperfusion by preceding hypoxia

We have previously shown that 2 weeks of hypoxia protect the right ventricle of the rat heart from subsequent ischemia and reperfusion (I/R). In the present study, we examined the following: (1) Do shorter periods of hypoxia protect from subsequent I/R? (2) Does intermittent normoxia increase the cardioprotective effect? (3) Is hypoxia-inducible factor-1α (HIF-1α), erythropoietin (EPO), or vascular endothelial growth factor (VEGF) involved in the protective effects? Preischemic cardiac work was followed by global ischemia, reperfusion, and postischemic cardiac work (15 min each). External heart work was determined at the end of both work phases. Four groups of hearts were investigated: hearts from normoxic rats (n?=?8), hearts from rats after 24 h of continuous hypoxia (10.5% inspired oxygen, n?=?7), hearts from rats after 24 h hypoxia with a single intermission of 30 min normoxia (n?=?9), and hearts from rats after 24 h hypoxia and multiple intermissions of 30 min normoxia (n?=?7). Protein levels of HIF-1α and mRNA levels of EPO and VEGF were determined in right ventricular tissue of normoxic and hypoxic hearts. Postischemic right heart recovery was better in all three hypoxic groups compared with normoxic hearts (61.8?±?5.9%, 65.6?±?3.0%, and 75.7?±?2.6% vs. 46.0?±?3.9%, p?p?p?=?0.02). No differences in EPO and VEGF mRNA levels were found between normoxic and hypoxic hearts. Twenty-four hours of continuous hypoxia protect the isolated working right heart from subsequent ischemia and reperfusion. When preceding hypoxia is interrupted by multiple reoxygenation periods, there is a further significant increase in cardiac functional recovery. HIF-1α may be involved in the protective effect.     

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.     

Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid Diet Supplement on Tolerance to the Cardiotoxicity of Epirubicin and to Ischaemia Reperfusion in the Isolated Rat Heart

Abstract: We compared the effects of 2 weeks dietary supplement of docosahexaenoic acid, eicosapentaenoic acid or olive oil on myocardial tolerance to the cardiotoxicity of the anthracycline epirubicin and to ischaemia reperfusion. Isolated rat hearts from the dietary groups were perfused at a constant flow rate of 12.5 ml/min. The hearts were subjected to a 20 min. period of epirubicin infusion by a side arm of the perfusion system at a rate of 0.2 mg/min. or a 20 min. period of global ischaemia. After 10 min. of epirubicin infusion a significantly (P<0.05) higher aortic pressure (an index of coronary resistance during constant flow perfusion) was observed in the olive oil group; 130±22% (mean±S.D.) compared to hearts in the docosahexaenoic acid; 108±9% (mean±S.D.), and eicosapentaenoic acid; 105±7% (mean±S.D.), group. Hearts from docosahexaenoic acid-fed rats showed a significantly increased left ventricular end-diastolic pressure (an index of contracture); of 66±30 mmHg (mean±S.D.) after 15 min. of global ischaemia compared to eicosapetaenoic acid fed rats; 37±18 mmHg (mean±S.D.), and significantly higher release of lactate dehydrogenase during the following 30 min. period of reperfusion compared to olive oil-fed rats. We conclude that eicosapentaenoic acid and docosahexaenoic acid could be useful during epirubicin infusion and that docosahexaenoic acid could be harmful during ischaemia reperfusion.