心肌缺血预适应在急性心肌梗死中的临床意义

目的　探讨心肌缺血预适应在 AMI中的临床意义。方法　 12 0例初发 AMI患者 ,按 AMI发作前 48小时内有无心绞痛分为缺血预适应组 (IP组 n=6 6 )与对照组 (n=5 4) ,测定左心室射血分数 (L VEF)和左心室室壁运动情况、心肌酶 (CPK、CPK- Mb)峰值、心电图 QRS记分 ,观察住院期间心律失常、心功能不全、心源性休克和室壁瘤发生率并进行比较。结果　 IP组 CPK、CPK- Mb峰值、心电图 QRS记分和心功能不全、频发室性期前收缩、VT/VF和 II- III°房室传导阻滞 (AVB)的发生率以及住院期病死率明显低于对照组 (P<0 .0 5 ) ,而 L VEF值明显高于对照组 (P<0 .0 5 )。结论　心肌缺血预适应在 AMI病人中发挥了心脏保护作用 ,有利于减少心肌梗死面积和左心室收缩功能的恢复 ,并减少恶性心律失常的发生率及住院期病死率     

多普勒导丝对腺苷预处理保护冠状动脉微循环功能的评价

目的 :观察腺苷预处理 (APC)对缺血心肌相关冠状动脉 (冠脉 )微循环功能的保护作用。方法 :将建立心肌缺血模型的 12只中国小型家猪随机分为两组 :对照组 6只 ,仅制备心肌缺血模型 ;APC组 6只 ,制备模型前经冠脉注入腺苷 6mg。应用冠脉内多普勒导丝观察模型相关冠脉平均峰值流速 (APV)、舒张收缩流速比值(DSVR)、冠脉血流储备 (CFR)的变化。结果 :两组模型冠脉狭窄后 10min时APV、DSVR、CFR均较基础状态时明显下降 (P <0 .0 5或 <0 .0 1) ,APV、DSVR在随后实验过程中无明显变化 ;30min时两组CFR均有进一步降低趋势 (P >0 .0 5 ) ;6 0min时对照组CFR较 30min时明显降低〔(0 .96± 0 .2 7)∶(1.74± 0 .4 9) ,P <0 .0 5〕 ,而APC组CFR与 30min时相比差异无统计学意义〔(1.6 4± 0 .30 )∶(1.79± 0 .38) ,P >0 .0 5〕 ;但 12 0min时APC组CFR较前明显下降〔(0 .94± 0 .31)∶(1.6 4± 0 .30 ) ,P <0 .0 1〕 ,与同时间点对照组相比差异无统计学意义。结论 :心肌缺血模型相关冠脉在急性重度狭窄 6 0min时发生微循环功能障碍 ,APC对冠脉微循环功能具有保护作用 ,但持续时间较短。     

Evidence that the acute phase of ischemic preconditioning does not require signaling by the A2B adenosine receptor

Ischemic preconditioning (IPC) is a protective phenomenon in which brief ischemia renders the myocardium resistant to subsequent ischemic insults. Here, we used A_2BAR gene knock-out (A_2BKO)/β-galactosidase reporter gene knock-in mice and the A_2BAR antagonist ATL-801 to investigate the potential involvement of the A_2BAR in IPC, focusing on the acute phase of protection. Cardioprotection provided by acute IPC elicited by two 3-min occlusion/3-min reperfusion cycles was readily apparent in an isolated, Langendorff-perfused mouse heart model in studies using hearts from A_2BKO mice. IPC equivalently improved the recovery of contractile function following 20 min of global ischemia and 45 min of reperfusion in both WT and A_2BKO hearts by ~ 30-40%, and equivalently decreased the release of cardiac troponin I during the reperfusion period (from 5969 ± 925 to 1595 ± 674 ng/g and 4376 ± 739 to 2278 ± 462 ng/g using WT and A_2BKO hearts, respectively). Similarly, the infarct size-reducing capacity of acute IPC in an in vivo model of infarction was fully manifested in experiments using A_2BKO mice, as well as in experiments using rats pretreated with ATL-801. We did observe, however, a marked reduction in infarct size in rats following administration of the selective A_2BAR agonist BAY 60-6583 (~ 25% reduction at a dose of 1.0 mg/kg). While supportive of its concept as a cardioprotective receptor, these experiments indicate that the mechanism of the early phase of IPC is not dependent on signaling by the A_2BAR. We present the idea that the A_2BAR may contribute to the later stages of IPC dependent on the induction of stress-responsive genes.     

缺血预适应及侧支循环对缺血再灌注心肌的保护作用

目的 探讨急性心肌梗死前心绞痛产生的缺血预适应独立于或协同冠状动脉侧支循环对缺血-再灌注心肌的保护作用。方法 44例发病6 h内接受直接冠状动脉介入治疗(PCI)的急性心肌梗死患者,按梗死前48 h内有无心绞痛分成2组,有梗死前48 h内心绞痛(PA)组24例、无梗死前48 h内心绞痛(NPA)组20例,每组再按有无冠状动脉侧支循环血管分成两亚组,PCI完成后对梗死相关血管(IRA)血流进行TIMI分级评价,同时左心室造影,记录室壁运动记分(WMS)及左心室舒张末期压力(LVEDP),监测心肌酶48 h,PCI完成后1周、4周末分别行99mTc-MIBI心肌灌注显像(SPECT),比较前后显像缺损程度记分(SS)的变化,计算并比较两组及亚组间心肌挽救指数(MSI),第2周时行平衡法核素心室造影(ERNA),比较两组及亚组间左心室收缩功能参数、左心室舒张功能参数、心室收缩同步性(LVSS)的差异。结果 PA组心肌损伤标记物肌酸激酶(CK)及其同工酶(CK-MB)峰值水平显著低于NPA组[(1172±985)U/L比(2291±1267)U/L,P<0.05;(197±102)U/L比(316±144)U/L,P<0.05],冠状动脉造影(CAG)结果显示两组侧支循环Rentrop分级无差异,PCI完成时PA组IRA无再流(no-reflow)发生率显著低于NPA组(8.3％比20％,P<0.05),WMS和INEDP也显著低于NPA组[分别为(5.39±0.91比7.11±1.27),P<0.0     

不同时期无创肢体缺血预适应对急性心肌梗死大鼠的保护作用

目的:探讨急性心肌梗死前、再灌注前及再灌注时等不同时期,无创性肢体缺血预适应在减轻大鼠缺血/再灌注损伤中的作用。方法:所有大鼠随机分为4组(每组10只):心肌缺血/再灌注损伤组(A组)、急性心肌梗死前肢体缺血预适应组(B组)、再灌注前肢体缺血预适应组(C组)和再灌注初期肢体缺血预适应组(D组)。观察各组心电、心肌缺血范围(AAR)、心肌梗死范围(IA)、心肌梗死部位质量与左心室质量(LV)的比值(IA/LV)、梗死范围与缺血范围的比值(IA/AAR)、CK-MB值。结果:与A组相比,B、C、D 3组ST段抬高幅度、CK-MB值、IA/LV和IA/AAR比值均显著降低(P<0.01)。结论:无创性肢体缺血预适应在急性心肌梗死前、再灌注前及再灌注时的各个时期应用,都能明显降低大鼠心肌缺血/再灌注时的ST段抬高幅度,明显降低心肌酶水平,明显缩小心肌坏死面积。     

核素心脏显像评估心肌缺血预适应对老年人心肌梗死面积和心功能的影响

目的通过核素心脏显像评估心肌缺血预适应对老年人首发急性心肌梗死（急性心梗，ＡＭＩ）面积和心功能的影响。方法５３例首发急性心梗患者，根据心梗前２４小时有无心绞痛发作分为心绞痛组及无心绞痛组，均在急性心梗后２～４周行核素心脏显像。对比研究心梗的面积和心功能状况。结果心绞痛组和无心绞痛组心梗节段数分别是（３．２±２．６）段和（５．６±２．６）段，两组比较，差异有显著性（Ｐ＜０．０１）；左室扩大和反向运动的发生率分别为１２．０％（３例）和３９．３％（１１例）（Ｐ＜０．０５）；左室射血分数分别是（４９．３±８．６）％和（４１．８±１１．４）％（Ｐ＜０．０１）；高峰充盈率分别是（２．１±０．４）ｅｄｃ／ｓ和（１．６±０．６）ｅｄｃ／ｓ（Ｐ＜０．０１）。结论老年人ＡＭＩ前短期内心绞痛发作能缩小梗死面积，对左室功能有积极保护作用。     

梗死前心绞痛对急性心肌梗死患者直接PCI术后的影响

目的　探讨梗死前心绞痛对首次急性心肌梗死 (AMI)患者直接经皮冠状动脉介入治疗 (PCI)术后的近期影响。方法　 10 0例首次 AMI患者 ,按梗死前有无心绞痛史分为 A(有心绞痛史 ,5 5例 )、B(无心绞痛史 ,4 5例 ) 2组 ,所有患者均在发病 12 h内行直接 PCI术。术前术后监测心肌酶变化 ;术后 2周行心血池显像测定左心室射血分数。并观察住院期间心律失常、心力衰竭或心源性休克的发生率及再梗死率、病死率。结果　 (1) A组肌酸激酶同工酶峰值低于 B组 (P<0 .0 5 )。 (2 ) A组自溶现象发生率高于 B组 (P<0 .0 5 ) ;A组无再流现象发生率低于 B组 (P<0 .0 5 )。 (3) A组左心室射血分数高于 B组 (P<0 .0 5 )。 (4 ) A组心力衰竭或心源性休克的发生率和再梗死率均低于B组 (P<0 .0 5 )。结论　梗死前心绞痛可促进 AMI患者梗死相关动脉自溶现象的产生 ,并可减少直接 PCI术后无再流现象的发生 ,从而改善心室功能和近期预后     

缺血预适应对高血脂动脉硬化兔心肌的影响

目的研究缺血预适应(IP)对高血脂动脉硬化兔心肌的影响。方法用高胆固醇饲料喂养家兔,血总胆固醇≥15mmol/L,29只高血脂兔分为三组,采用结扎/开放左冠状动脉前降支(LDADC)的方法,给予不同时间和强度的缺血预处理:无缺血预处理组(HR1);缺血预处理组(HR2);多次及延长缺血预处理组(HR3),24只正常血脂兔也分为三组(NR1,NR2,NR3),实验方法与上述各组相同。缺血预处理后阻断冠状动脉30min,再灌注30min,给予程序电刺激,测定心室颤动阈(VFT)。心肌切片氯化硝基四氮唑蓝染色(NBT),判断心肌梗死面积(IS)。结果IP对正常兔心肌有保护作用:NR2、NR3组与NR1组相比,IS缩小,(P<0.01);VFT增高(P<0.05);对高血脂兔无作用(P>0.05)。增加缺血次数,延长缺血时间,对正常血脂兔,保护作用无改变(P>0.05);但加重高血脂兔后续缺血的损害:IS增加(P<0.01);VFT降低(P<0.05)。结论缺血预处理的保护作用与心肌的状态有关。对高血脂、动脉硬化兔心肌,缺血预处理的保护作用可能消失。     

心肌缺血预适应对急性心肌梗死静脉溶栓冠脉再通的影响

目的探讨心肌缺血预适应对急性心肌梗死静脉溶栓治疗冠脉再通的影响。方法84例急性心肌梗死患者接受尿激酶静脉溶栓治疗,分梗死前有心绞痛组和梗死前无心绞痛组,依据临床间接血管再通标准观察两组再通情况,部分病例进行冠脉造影检查。结果两组再通率分别为74%和29.4%,差异有统计学意义(P<0.01)。结论心肌缺血预适应可提高急性心肌梗死静脉溶栓的冠脉再通。     

缺血预处理时心肌细胞三磷酸腺苷含量和超微结构变化

采用生物发光技术，分别测定缺血预处理和对照组再灌注60min时心肌细胞三磷酸腺苷（ATP）含量，同时留取心肌标本行光镜和电镜观察，探讨缺血预处理保护心肌的作用机理。结果表明：①缺血预处理组心肌细胞ATP含量明显高于对照组，差异显著（P＜0．05）；②缺血预处理组光镜、电镜所见心肌损伤均明显比对照组轻。提示：缺血预处理可以减少心肌细胞能量消耗，保护线粒体的结构和功能，从而对缺血心肌具有一定保护作用。     

心脏缺血预处理对急性心肌梗死后QT间期离散度的影响

目的　采用动物实验方法 ,探讨心肌缺血预处理 (MIP)对急性心肌梗死 (AMI)后QT间期离散度 (QTd)变化的影响。方法　观察AMI组 (A组 )与MIP组 (B组 )新西兰兔在AMI后的QTd ,并行心内电生理检查诱发室性心动过速 (VT) ,对两组的指标进行比较 ,同时设置假手术组 (C组 )作对照。结果　 3组手术前QTd比较著差异无显著性 (P 0 0 5 ) ;C组手术前后比较差异亦无显著性 (P 0 0 5 ) ;B组MIP前QTd与A组比较差异无显著性(P >0 0 5 ) ,在AMI后 ,B组QTd明显小于A组 (P <0 0 0 1)。结论　在AMI的家兔模型 ,B组QTd及诱发VT的发生率显著低于A组 ,提示MIP可以少AMI的QTd变化及室性心律失常发生。     

细胞膜钠钙交换蛋白在大鼠心肌缺血预适应及腺苷诱导预适应中的作用及其信号转导

目的 探讨细胞膜钠钙交换蛋白（NCX）在心肌缺血预适应及药物诱导预适应中的作用及可能的信号转导途径.方法 培养乳鼠心肌细胞随机分为缺血/再灌注组、缺血预适应组、腺苷预处理组、钙调素依赖蛋白激酶Ⅱ（CaMKⅡ）抑制剂KN-93＋缺血预适应组、KN-93＋腺苷预处理组及对照组.各组乳酸脱氢酶（LDH）漏出量用生化法测定（n=5）,钠钙交换蛋白mRNA表达以半定量RT-PCR检测（n=5）,NCX活性以液闪仪测定Na^＋依赖的^45Ca^2＋摄取率表示（n=5）.结果 （1）缺血/再灌注组LDH漏出量显著增加（P＜0.05）,缺血预适应及腺苷预处理组LDH漏出量均显著降低 （P＜0.05）;KN-93预作用后,缺血预适应及腺苷预处理组LDH漏出量均显著增加（P＜0.05）. （2）缺血/再灌注组NCX ^45Ca^2＋摄取率比对照组高（P＜0.005）.缺血预适应及腺苷预处理组较缺血/再灌注时NCX ^45Ca^2＋摄取率显著低（P＜0.05）,且腺苷预处理组NCX ^45Ca^2＋摄取率较缺血预适应组更低（P＜0.05）. KN-93＋缺血预适应组与缺血/再灌注组NCX ^45Ca^2＋摄取率差异无统计学意义, KN-93＋腺苷预处理组较缺血/再灌注组NCX ^45Ca^2＋摄取率低（P＜0.05）.（3） 缺血/再灌注组NCX mRNA的表达比对照组显著高（P＜0.05）;缺血预适应及腺苷预处理组NCX mRNA的表达均显著低（P＜0.05）;KN-93处理后缺血预适应组及腺苷预处理组NCX mRNA的表达水平显著高（P＜0.05）,且腺苷预处理组NCX mRNA的表达较缺血预适应组更高（P＜0.05）.结论 缺血预适应及腺苷预处理对心肌的保护作用与细胞膜NCX有关,缺血预适应中NCX对心肌损伤保护作用经CaMKⅡ介导,而在腺苷预处理中NCX对心肌损伤保护作用仅部分经CaMKⅡ介导.     

Prevention of contrast induced nephropathy by ischemic preconditioning in patients undergoing percutaneous coronary angiography

Background

Contrast-induced nephropathy (CIN) is the acute deterioration of renal function after parenteral administration of radio contrast media in the absence of other causes. The true incidence of CIN varies because of differences among the published studies in the definition of CIN, the proportion of high-risk patients, the types of contrast media, and the use of preventive measures. Remote ischemic preconditioning (IPC) may offer a non-pharmacological prevention strategy for lowering CIN in patients undergoing coronary procedures. The assumption that IPC produces protective effects on tissues or organs by multiple brief cycles of ischemia and reperfusion applied to another remote tissue or organ.

冠脉痉挛与变异型心绞痛和急性心肌梗死的关系

目的 探讨冠脉痉挛与变异型心绞痛(VA)和急性心肌梗死(AMI)的关系。方法 对30例AMI和14例VA患者施行冠状动脉造影(CAG),以冠脉狭窄>50％为CAG阳性。结果 在30例AMI患者中有4例CAG正常,在14例VA中,CAG正常2例,狭窄程度在50％～90％的12例。结论 本文结果提示,冠脉痉挛在VA和AMI的发病中起着十分重要的作用。冠脉痉挛不仅可以发生在有严重狭窄的冠状动脉,亦可以发生于造影正常的冠状动脉。     

梗死前心绞痛对急性心肌梗死患者经皮冠状动脉介入治疗术后无再流现象的影响

目的探讨梗死前心绞痛(PIA)对急性心肌梗死(AMI)患者经皮冠状动脉介入治疗(PCI)后无再流现象的影响。方法100例首次AMI患者均在发病12h内行PCI术。所有患者按照有无无再流现象分为2组:无再流组(15例)和再流组(85例)。监测心肌酶谱和C反应蛋白(CRP)变化;放射性核素测定心功能;观察室壁瘤、心力衰竭发生率和住院病死率。结果无再流组PIA发生率显著低于再流组(P<0.01);而前壁梗死的发生率高于再流组(P<0.05);肌酸激酶同工酶峰值和CRP水平均显著高于再流组(P<0.01)。无再流组放射性缺损面积显著大于再流组(P<0.01);左室射血分数显著低于再流组(P<0.01);心力衰竭、室壁瘤发生率和死亡率均高于再流组(P<0.05)。多元Logistic回归分析结果显示,缺乏PIA是发生无再流现象的独立预测因素(OR=6.12,P=0.01)。结论缺乏PIA是发生无再流现象的独立预测因素,而无再流现象与心力衰竭和死亡率增高密切相关。     

Dilazep dihydrochloride prolongs the infarct size-limiting effect of ischemic preconditioning in rabbits

Recent studies have indicated the key role of adenosine receptor activation as a trigger for ischemic preconditioning (PC). Hence, the augmentation of endogenous adenosine may potentiate the cardioprotective effects of PC. In this study, we aimed to test the hypothesis that dilazep dihydrochloride, an adenosine transport inhibitor, potentiates the PC effect. Protocol 1: Infarcts were produced in open-chest anesthetized rabbits by 30-min occlusion of a coronary artery and 2 days' reperfusion. PC was elicited by a preceding 5-min occlusion and either 5, 40, or 120 min of reperfusion. PC with the 5-min reperfusion markedly limited the infarct size after the 30-min ischemia (infarct size to area at risk (IS): 10% ± 3% vs 41% ± 3%, P < 0.05). PC was not protective when the reperfusion periods were 40 or 120 min (IS: 47% ± 5% and 44% ± 3%, P = not significant (NS) vs control, respectively). However, concomitant treatment with dilazep (0.2 mg/kg) preserved the PC effect in the 40-min reperfusion group (18% ± 5%, P < 0.05 vs control) but not in the 120-min reperfusion group (43% ± 4%, P = NS vs control). Protocol 2: Infarct was produced in a similar rabbit model by either a 45- or 50-min occlusion of a coronary artery and 2 days of reperfusion. PC was elicited by a preceding 5-min occlusion and a 5-min reperfusion. PC was protective in the 45-min occlusion group (30% ± 7% vs 67% ± 3%, P < 0.05) but not in the 50-min occlusion group (74% ± 4% vs 79% ± 5%, P = NS). Treatment with dilazep (0.2 mg/kg) failed to retrieve protection in this preconditioned group (77% ± 6%, P = NS vs 50-min occlusion group without PC). Thus, dilazep prolonged the infarct size-limiting effect of PC, but failed to retrieve protection in the group with a longer sustained ischemia. Received: September 6, 2000 / Accepted: March 9, 2001     

Regional differences of myocardial infarct development and ischemic preconditioning

The spatial and temporal development of myocardial infarction depends on the area at risk (AAR), the severity and duration of blood flow reduction (energy supply) as well as on heart rate and regional wall function (energy demand). Both supply and demand can vary within the AAR of a given heart, potentially resulting in differences in infarct development. We therefore retrospectively analyzed infarct size (IS, %AAR, TTC) in 24 anesthetized pigs in vivo following 90 min hypoperfusion and 120 min reperfusion of the LAD coronary artery, which supplies parts of the LV septum (LVS) and anterior free wall (LVAFW). The total LAD perfusion territory averaged 49.8 +/- 14.2 (SD) g (49.2 +/- 8.4% of LV); 61.4 +/- 8.1% of the AAR was LVAFW. IS within the LVS was 25.3 +/- 15.1%, while IS within the LVAFW was 16.6 +/-10.1% (p<0.05). While ischemic blood flow (radiolabeled microspheres) did not differ between LVS (0.05 +/- 0.02 ml/min/g) and LVAFW (0.05 +/- 0.03 ml/min/g), perivascular connective tissue (56 +/- 9 vs. 38+/-7 microm(2), p < 0.05) and the capillary-to-myocyte distance (1.65 +/- 0.23 vs. 1.18 +/- 0.23 mm, p < 0.05) were larger in LVS than in LVAFW. Interestingly, IS in LVS (9.3 +/- 9.6%, n = 24) and LVAFW (9.2 +/- 9.1%) were reduced to the same absolute extent by ischemic preconditioning with one cycle of 10 min ischemia and 15 min reperfusion, suggesting that a similar regional difference exists also in the protection afforded by ischemic preconditioning. The mechanism(s) for that remain(s) to be established. CONCLUSION : In pigs, regional differences in infarct development and protection from it exist in the LAD perfusion territory, which are independent of ischemic blood flow but apparently related to pre-existing structural differences.     

心肌缺血预适应对老年急性心肌梗塞近期预后的影响

本文分析８９例老年急性心肌梗塞（ＡＭＩ）病人心肌缺血预适应（ＭＩＰ）对其近期预后的影响，其中男５１例，女３８例，心肌梗塞前有ＭＩＰ者５８例（Ａ组），无ＭＩＰ者３１例（Ｂ组），资料分析显示，Ａ组在发生ＡＭＩ时，心肌坏死范围、心肌酶峰值、心功能损害、室性心律失常、心原性休克、室壁瘤形成及病死率均明显低于Ｂ组（Ｐ＜０．０５），两组有显著性差异，并对ＭＩＰ的临床意义和机理进行了讨论     

梗死前心绞痛对急性心肌梗死患者直接经皮冠状动脉介入治疗术后的影响

目的　探讨梗死前心绞痛对首次急性心肌梗死(AMI)患者直接经皮冠状动脉介入治疗(PCI)术后的近期影响。方法　将120例首次AMI患者分成有梗死前心绞痛史组(A组, 68例)和无梗死前心绞痛史组(B组, 52例),在发病12小时内行直接PCI术,分析梗死前心绞痛对肌酸肌酶(CK)峰值浓度、左心室功能和临床转归的影响。结果　(1)A组CK及CK MB峰值浓度均显著低于B组(P<0. 05); (2)A组冠状动脉自发再通率高于B组(P<0. 05),A组无再流现象发生率低于B组(P<0. 05); (3)A组左室射血分数高于B组(P<0. 05); (4)A组心力衰竭发生率及再梗死率低于B组(P<0. 05)。结论　梗死前心绞痛可能促进AMI患者梗死相关动脉自发再通的发生,减少直接PCI术后无再流现象发生,改善患者左心室功能和临床预后。