卡维地洛对心脏缺血再灌注心律失常发生率的影响

目的 :评价第三代肾上腺素 β受体拮抗剂———卡维地洛 (Carvedilol,CVD)对大鼠在体心脏缺血再灌注心律失常发生率的影响。方法 :通过左前降支冠状动脉结扎 ,建立大鼠在体心脏缺血再灌注损伤模型。术前 7d连续胃管给CVD(1mg/kg) ,结扎左前降支冠状动脉 30min后松开进行再灌注 36 0min ,处死动物。观察室性心律失常和肌酸激酶 同工酶、乳酸脱氢酶、一氧化氮及丙二醛变化 ,并进行苏木精 伊红染色及电镜检查。结果 :CVD使再灌注期间室性心律失常发生率减少 5 3.85 % (P <0 .0 1) ,死亡率减少 5 7.15 % (P <0 .0 1)。CVD减少肌酸激酶 同工酶、低密度脂蛋白及丙二醛的释放 ,稳定一氧化氮的分泌。心肌苏木精 伊红染色及电镜检查对照组细胞明显呈片状或局灶性坏死 ,闰盘结构紊乱 ,大量反应性的中性粒细胞浸润于坏死细胞之间。CVD组心肌细胞损伤程度明显减轻 ,闰盘结构基本完整 ,粒细胞浸润也明显减少。结论 :CVD明显降低心脏缺血再灌注心律失常的发生率和死亡率 ,对大鼠在体缺血再灌注心脏具有强烈保护作用     

左旋精氨酸对兔右冠状动脉缺血再灌注心律失常的影响

目的研究左旋精氨酸（L-Arg）对兔右冠脉缺血再灌注（IR）致心律失常的影响。方法建立兔右冠脉IR模型,将48只兔随机分为IRa组（缺血30min再灌120min）、IRb组（缺血90min再灌120min）、IRa＋L-Arg组、IRb＋L-Arg组,记录心电图,计算心律失常评分与时间依赖关系,分析L-Arg干预的效果。结果①缺血期：随缺血时间延长,各组心律失常分数逐渐增加,出现不同程度的房室传导阻滞（AVB）、窦性及房性心律失常。②再灌注期：AVB发生次数减少,窦性及房性心律失常逐渐恢复窦性心律;不同时段心律失常评分IRa组显著低于IRb组、IRa＋L-Arg组和IRb＋L-Arg组明显低于IRa和IRb组、IRa＋L-Arg组显著低于IRb十L-Arg组。结论补充L-Arg具有抗右冠脉缺血所致的心律失常作用,缺血时间越长,L-Arg抗再灌注心律失常作用越差。     

缺血后适应对兔楔形心肌块缺血再灌注模型室性心律失常的影响

目的:观察缺血后适应对家兔左室楔形心肌块缺血再灌注模型室性心律失常诱发率的影响,并探讨其维持电生理稳定的机制。方法:将30只家兔随机分为对照组、缺血再灌注组和缺血后适应组,每组10只。缺血再灌注组和缺血后适应组在建立好楔形心肌块模型稳定1h后,停止台氏液灌注45min,缺血再灌注组继续灌注台氏液2h;缺血后适应组复灌初期采用复灌10s、停灌10s方案,重复6次后,恢复台氏液灌注2h。记录心肌块内、外膜心肌细胞跨壁动作电位、跨壁心电图、有效不应期(ERP)等电生理参数以及室性心律失常诱发率。实验结束后利用免疫荧光方法检测去磷酸化缝隙连接蛋白43(NP-Cx43)。结果:①对照组、缺血再灌注组、缺血后适应组的室性心动过速(VT)诱发率分别为0、80%(8/10)、10%(1/10),两两比较均差异有统计学意义(均P<0.05)。②与缺血再灌注组比较,缺血后适应组的跨室壁离散度、ERP等电生理参数得到改善,均差异有统计学意义(均P<0.05)。③免疫荧光显示对照组心肌NP-Cx43分布量极少;缺血再灌注组NP-Cx43含量增加且多分布在心肌细胞端端连接处;缺血后适应组NP-Cx43与缺血再灌注组相比含量要明显减少,差异有统计学意义(P<0.05)。结论:缺血后适应可显著降低室性心律失常诱发率,改善缝隙连接蛋白重构可能是其维持心脏电生理稳定的机制之一。     

静脉联合应用美托洛尔和胺碘酮对缺血再灌注大鼠心律失常和心肌梗死范围的影响

目的观察静脉联合应用美托洛尔、胺碘酮对缺血/再灌注大鼠快速室性心律失常和心肌梗死范围的影响。方法Sprague-Dawley(SD)大鼠40只麻醉后,依缺血前所用药物不同,随机分为对照组、美托洛尔组、胺碘酮组、胺碘酮+美托洛尔组,复制缺血/再灌注模型,给药20min后,行缺血7min后,再灌注10min,观察再灌注期间室性心动过速和心室颤动的发生;然后再缺血30min,再灌注120min,观察心肌梗死/缺血区域面积比值,并经颈内动脉监测血压和心率。结果在观察过程中,各用药组血压、心率改变没有显著性差异。大鼠缺血/再灌注前静脉注射美托洛尔、胺碘酮显著减少缺血再灌注的室性心动过速,而胺碘酮+美托洛尔组进一步减少(P<0.01);同样,胺碘酮+美托洛尔组显著减少了再灌注诱发的总的心室颤动的发生(P<0.05),美托洛尔组、胺碘酮组没有统计学差异;不可逆心室颤动的发生,与胺碘酮组比较,美托洛尔组显著下降,胺碘酮+美托洛尔组较美托洛尔组进一步降低,但没有显著差异。美托洛尔组、胺碘酮组均减少了心肌梗死/缺血区域面积比率(P<0.05),胺碘酮+美托洛尔组则进一步降低(P<0.01)。结论联合应用美托洛尔和胺碘酮静脉注射可以进一步减少缺血/再灌注快速室性心律失常发生率,减少心肌梗死范围。     

氯沙坦和卡维地洛对缺血再灌注心肌细胞凋亡的影响

目的 :研究氯沙坦和卡维地洛对缺血再灌注心肌细胞凋亡的影响 ,比较氯沙坦和卡维地洛对缺血再灌注心肌损伤的保护作用。方法 :结扎Wistar大鼠左冠状动脉前降支 ,建立大鼠缺血再灌注动物模型 ,采用原位末端标记细胞凋亡法检测心肌细胞凋亡 ,并利用光学显微镜进行细胞计数。结果 :单纯缺血 再灌注组心肌细胞凋亡数较假手术组明显增多 (37.5 3± 9.2 2 /视野∶0 .18± 0 .0 9/视野 ,P <0 .0 5 ) ,氯沙坦和卡维地洛组心肌细胞凋亡数分别为 8.74± 3.5 1/视野和 7.6 3± 4 .0 5 /视野 ,较单纯缺血 再灌注组明显减少 (P <0 .0 5 ) ,氯沙坦和卡维地洛两组间无明显区别 (P >0 .0 5 )。结论 :氯沙坦和卡维地洛对缺血再灌注心肌细胞损伤具有相似的保护作用 ,可明显减少缺血再灌注心肌细胞凋亡     

再灌注心律失常的研究进展

再灌注心率失常在缺血心脏再灌注中发生很普遍,它与多种因素有关：氧自由基、钙离子、细胞间偶联、缺血预处理动作电位离子流,本文就目前的研究作一综述。     

腺苷预处理及后处理对兔窦房结缺血再灌注损伤致心律失常的影响

目的通过建立兔右冠状动脉缺血再灌注损伤模型,研究腺苷预处理和后处理对窦房结缺血再灌注所致心律失常的影响,探讨腺苷抗心律失常的心肌保护机理。方法家兔60只,随机分为:假手术组、缺血再灌注组、腺苷预处理组、腺苷后处理组,每组15只。通过结扎及放松右冠状动脉起始部建立在体兔窦房结缺血再灌注损伤模型,同步记录体表心电图,全程心电监护并分析心律演变情况,行心律失常评分。结果无论在缺血期还是再灌注期,腺苷预处理和后处理组心律失常评分较缺血再灌注组心律失常评分明显下降,但是预处理和后处理之间比较无显著差异。同时组织学检测亦观察到腺苷预处理及后处理后窦房结细胞损伤较缺血再灌注组轻。结论腺苷预处理及后处理皆可以降低缺血再灌注心律失常的发生,是减少心肌缺血再灌注损伤的机理之一。     

通脉灵对实验犬缺血再灌注心律失常的影响

再灌注心律失常是心源性猝死的重要原因之一。通脉灵注射液是复方中药制剂 ,有扩张冠脉血管、抗血小板聚集、降低血液粘度等作用〔1〕。本实验采用犬在体心脏缺血再灌注模型 ,观察通脉灵对缺血再灌注心律失常的影响 ,并对其作用机制进行初步探讨。1　材料与方法1.1　 动物及分组　健康杂种犬 ,雌雄兼用 ,体重 14 .6± 1.6 9kg,随机分为生理盐水对照 (NS)组、通脉灵临床剂量 (TM1 )组 ;通脉灵 2倍临床剂量 (TM2 )组和丹参对照 (DS)组每组 6只。1.2 　主要药品、仪器　通脉灵注射液 2 0 0 % ,批号 94 94 8,由沈阳医药集团公司药研所提供 ;…     

小鼠心肌缺血再灌注损伤模型制备及心肌梗死面积评价方法学比较

目的对小鼠心肌缺血再灌注损伤模型制备及心肌梗死面积评价方法进行比较。方法40只雄性BAB/c小鼠按完全随机设计方法分为传统方法组和改良方法组,传统方法组的心肌再灌注操作采用再次开胸、松开结扎线的方法,改良方法组的心肌再灌注操作为在体外松开结扎线,无需再次开胸。采用伊文思蓝-TTC双染色方法区分缺血再灌注损伤后心肌的梗死区(IA)、缺血危险区(AAR)和左心室总面积(LV)。同时采用传统算法和质量权重法计算心肌梗死面积,质量权重法即在传统算法的基础上,用切片中各区域面积乘以该片心肌质量的百分比,累加各切片的相应区域面积,再计算百分比。结果无论采用哪种算法,传统方法组与改良方法组心肌梗死面积(IA/AAR)差异无统计学意义(传统算法:传统方法组44.43%±2.28%,改良方法组44.24%±1.68%,P=0.96;质量权重法:传统方法组51.74%±2.26%,改良方法组54.51%±1.14%,P=0.23)。与传统方法组相比,改良方法组术后存活率高、麻醉剂使用剂量小、苏醒时间短(均为P<0.05)。此外,采用质量权重法计算AAR/LV、IA/AAR数据的标准差显著小于传统算法(AAR/LV:传统算法标准差2.90,质量权重法标准差1.24;IA/AAR:传统算法标准差2.22,质量权重法标准差:1.00)。结论与传统方法相比,改良方法能够更加稳定、有效地制备小鼠心肌缺血再灌注模型。此外,采用质量权重法计算的心肌梗死面积数据比传统方法准确性更高。     

陈旧性心肌梗死兔心室组织重塑及卡维地洛的影响

目的:模拟临床陈旧性心肌梗死(OMI),研究长期口服卡维地洛(CVD)对OMI后心室组织重塑的影响。方法:24只家兔按体重随机分为3组,OMI组(8只),结扎冠状动脉左回旋支,喂养3个月;CVD组(8只),手术同OMI组,并于手术当日开始服用CVD 0.33 mg.kg-1.d-1,持续给药至术后共3个月;假手术(Sham)组(8只),手术同OMI组,但不结扎冠状动脉、不服用CVD。3个月后应用全细胞膜片钳技术检测单个心肌细胞膜电容大小。结果:①和Sham组相比,OMI组的全心重、左室重、全心重/体重比值、左心室腔最大内径均显著增加(均P<0.05);CVD组与OMI组相比上述指标、远离梗死区室壁厚度及梗死面积均显著减小(均P<0.05)。②光镜下CVD组与OMI组比较,梗死周边区心肌细胞肿胀、变性程度减轻,淋巴组织浸润减少,心肌间质水肿减轻。仍可见梗死区纤维结缔组织增生,瘢痕形成,肉芽组织增多与存活的肌组织交错分布,脂肪组织浸润。③OMI组心肌细胞的膜电容与Sham组相比明显增大(P<0.05);CVD组心肌细胞的膜电容较OMI组降低(P<0.01)。结论:长期口服CVD可以逆转OMI兔的心室组织重塑。     

微小RNA在心肌缺血再灌注损伤中的作用及机制

微小RNA（microRNA,miRNA）是一类在进化上高度保守的小分子非编码RNA,大约南19～25个核苷酸组成,具有转录后渊控蛋白质编码基因表达的功能,     

A dynamic model forecasting myocardial infarct size before, during, and after reperfusion therapy: an ASSENT-2 ECG/VCG substudy.

AIMS: Serial forecasts of final myocardial infarct (MI) size during fibrinolytic treatment (Rx) of ST-elevation MI would allow the identification of high-risk patients with a predicted major loss of viable myocardium, at a point when treatment may still be modified. We investigated a model for such forecasting, using time and the ECG. METHODS AND RESULTS: We collected 234 patients with ST-elevation MI, without signs of previous MI, bundle branch block, or hypertrophy. MI size was determined by the Selvester score and was "forecasted" at: admission with patients stratified by delay time and an ECG acuteness score into three groups (EARLY, DISCORDANT, and LATE); 90 min after Rx by > or =70% ST-recovery or not and occurrence of "reperfusion peaks"; 4 h after Rx by ST re-elevations. EARLY patients had smaller final infarct sizes than LATE (9.4 vs. 20%, P=0.01). EARLY patients with > or =70% ST-recovery without a reperfusion peak had smaller infarct sizes than those with (3.1 vs. 12.5%, P=0.001). EARLY patients without ST re-elevations had smaller infarct sizes (1.5%) than those with some (9%) or many re-elevations (12%), P<0.001. CONCLUSION: Final infarct size can be forecasted using delay time and serial ECGs. Serially updated forecasts seem especially important when both clock-time and initial ECG- signs indicate earliness.     

心肌缺血后处理对急性ST段抬高型心肌梗死再灌注损伤的保护作用

目的 探讨缺血后处理对ST段抬高型心肌梗死(STEMI)再灌注损伤的保护作用.方法 2006年10月至2009年1月在北华大学附属医院心内科住院并在12 h内行直接冠状动脉介入治疗(PCI)的STEMI患者64例,分为对照组(34例)及缺血后处理组(30例).对照组给予单纯再灌注治疗,缺血后处理组采用再灌注30 s/再缺血30 s,交替3次后再持续灌注的方法.比较两组再灌注心律失常的发生率、发病72 h的CK和CK-MB峰值及72 h的CK值动态变化、冠状动脉血流速度(CTFC)、室壁运动计分(WMSI)、左心室射血分数(LVEF)、QRS计分法测定心肌梗死面积(QRS-MIS)、心肌呈色分级(MBG)的变化.结果 对照组和缺血后处理组再灌注心律失常频发室性早搏发生率分别为52.9%(18/34)和26.7%(8/30,P＜0.05),短阵室性心动过速的发生率分别为58.8%(20/34)和23.3%(7/30,P＜0.05),CK峰值分别为(1732±480)U/L和(1162±548)U/L(P＜0.01),CK-MB峰值分别为(280±99)U/L和(165±70)U/L(P＜0.01),CTFC分别为(26.97±3.42)帧和(22.23±3.81)帧(P＜0.05),WMSI分别为1.82±0.83和1.27±0.52(P＜0.05),LVEF分别为0.47 ±0.10和0.55±0.08(P＜0.05),心肌梗死面积分别为(14.65±6.88)%和(10.60±4.97)%(P＜0.05),MBG分别为1.47±0.61和2.27±0.64(P＜0.05).结论 心肌缺血后处理能显著减轻STEMI患者心肌再灌注损伤,有显著的心肌保护作用.

Abstract：

Objective To observe the effect of ischemia postconditioning during the first minutes of reperfusion for the myocardial reperfusion injury in ST-segment elevation acute myocardial infarction (STEMI)patients undergoing emergency percutaneeus coronary intervention(PCI). Methods STEMI patients undergoing emergency PCI in affiliated hospital of Beihua University between October 2006 and January 2009 were randomly divided into two groups: the control group(n = 34)without any intervention after PTCA, and the postconditioning group(n = 30)with ischemia postconditioning within first minutes of reflow by 3 episodes of 30-second inflation and 30-second deflation with the angioplasty balloon. Reperfusion arrhythmias, CK and CKMB, corrected TIMI frame count(CTFC), wall motion score index(WMSI)and left ventricular ejection fraction(LVEF)by echocardiography were compared between the two groups. MI areas were evaluated with the ECG-54 criteria/32 system and myocardial blush grade(MBG)was measured. Results The incidence of reperfusion arrhythmias-frequent ventricular premature(26. 7% vs.52. 9%)and short array ventricular tachycardia beat(23.3% vs. 58. 8%)as well as values of peaks CK [(l162±548)U/L vs.(1732±480)U/L, P＜0. 01], CKMB[(165±70)U/L vs.(280±99)U/L,P＜0. 01],CTFC(22.23 ±3.81 vs. 26.97 ±3.42), WMSI(1.27 ±0.52 vs. 1.82 ±0.83),and infarction areas determined by ECG methods(10. 60% ±4. 97% vs. 14. 65% ±6. 88%, all P ＜0. 05)were all significantly lower in the postconditioning group than in control group while LVEF(0. 55 ± 0. 08 vs.0. 47 ±0. 10)and MBG(2. 27 ± 0. 64 vs. 1.47 ± 0. 61, all P ＜ 0. 05)were signiticantly higher in the postconditioning group than in control group. Conclusions Ischemia postconditioning can significantly reduce myocardial reperfusion injury in patients with STEMI.     

Effect of spontaneous reperfusion on myocardial infarct size

The effect of perfusion of the infarct artery on myocardial infarct size was studied in 39 patients who had not received interventive therapy. At predischarge coronary angiography, 19 patients had subtotal and 20 total occlusion of the infarct artery. The early ST-segment elevation recorded on a 12-lead electrocardiogram was used as an index of the amount of initially jeopardized myocardium. Infarct size was estimated by peak serum creatine kinase and, at discharge, by a QRS score, sigma Q and sigma R on a 12-lead electrocardiogram, and by radionuclide global and infarct segment left ventricular ejection fraction. Despite a similar degree of initial ischemia (sigma ST), infarct size was smaller in the 11 patients with anterior infarction and subtotal occlusion than in the 9 patients with anterior infarction and total occlusion when measured by peak serum creatine kinase (2114 +/- 1192 U/l vs. 3653 +/- 1059 U/l, p less than 0.02), QRS score (5.0 +/- 2.7 vs. 9.6 +/- 3.5, p less than 0.01), sigma Q (3.25 +/- 2.74 mV vs. 5.92 +/- 3.56 mV, p less than 0.10), sigma R (4.36 +/- 1.25 mV vs. 2.16 +/- 0.91 mV, p less than 0.001), global left ventricular ejection fraction (45.0 +/- 12.2% vs. 33.4 +/- 6.7%, p less than 0.05), and infarct segment ejection fraction (40.4 +/- 8.2% vs. 30.3 +/- 5.4%, p less than 0.05). In the inferior infarct patients, both the degree of initial ischemia and final infarct size were similar in the 8 patients with subtotal and in the 11 patients with total occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

促红细胞生成素与心肌缺血再灌注损伤

近年来促红细胞生成素(erythropoietin,EPO)的非造血生物作用逐渐引起关注。研究表明,EPO 可以减轻缺血缺氧时心肌细胞的损伤,减少心肌细胞的调亡,从而使其可能成为预防和治疗心肌缺血再灌注损伤的一条途径。     

A3 adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells

The goal of this study was to examine whether the A₃ adenosine receptor (A₃AR) agonist Cl-IB-MECA protects against myocardial ischemia/reperfusion injury when administered at the time of reperfusion in an in vivo mouse model of infarction induced by 30 min of coronary occlusion and 24 h of reperfusion. Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100 μg/kg i.v. bolus + 0.3 μg/kg/min subcutaneously via implantation of Alzet mini-osmotic pumps) reduced myocardial infarct size ∼ 37% from 50.1 ± 2.5% in vehicle-treated mice to 31.6 ± 2.8% in Cl-IB-MECA-treated mice, and significantly reduced the number of leukocytes that infiltrated into the ischemic-reperfused myocardium. Cl-IB-MECA did not reduce infarct size or limit leukocyte accumulation in studies using B6 congenic A₃AR gene “knock-out” mice or in chimeric mice lacking the expression of A₃ARs in bone marrow (BM)-derived cells. Subsequent mechanistic studies demonstrated that Cl-IB-MECA inhibited migration of mouse neutrophils isolated from BM towards the chemotactic substance c5a in trans-well migration assays, and inhibited leukocyte migration into the peritoneal cavity in a mouse model of thioglycollate-induced peritonitis. We conclude that treating with the A₃AR agonist Cl-IB-MECA at the time of reperfusion provides effective protection from ischemia/reperfusion injury in the heart through activation of the A₃AR expressed in BM-derived cells, potentially by suppressing the robust inflammatory reaction that occurs during reperfusion and neutrophil-mediated tissue injury.