远程缺血后处理的心肌保护作用

大量实验研究及初步临床观察表明,远程缺血后处理可以产生确切的心肌保护作用。通过对远程组织反复、短暂的缺血再灌注即可减轻心肌缺血再灌注后心肌坏死与功能障碍,缩小心肌梗塞面积,减少恶性心律失常的发生。本文综述了近年来有关远程缺血后处理在心肌保护作用及其临床应用方面的进展。     

缺血后处理的心肌保护作用及机制研究进展

近年来,关于缺血后处理心肌保护作用及机制的研究不断深入,在临床实验中提出了药物性缺血后处理和远程组织缺血后处理的概念,这些方法在防治心肌缺血/再灌注损伤中具有显著的保护作用和重要的应用价值,有些已在临床中被证明,但其作用机制复杂,许多细节尚不清楚,本文对近年来国内外有关远程组织缺血后处理心肌保护的机制简要综述。     

急性心肌梗死患者缺血预适应与Q-T离散度及恶性室性心律失常的关系

缺血预适应是指心肌短暂缺血对随后发生的持续严重缺血的保护作用,即限制心肌梗死范围、增加心肌收缩力及防止再灌注心律失常等.临床研究证实,心肌梗死前反复多次发作不稳定心绞痛可使缺血心肌处于预适应状态,并能减少心肌梗死后恶性心律失常、泵衰竭、心脏破裂的发生,降低死亡率.但缺血预适应对Q-T离散度(Q-Td)的影响国内外研究较少.本文就缺血预适应对急性心肌梗死患者Q-Td的影响及其与恶性室性心律失常的关系进行了探讨.     

糖尿病对大鼠心肌缺血预处理保护作用的影响

目的 探讨糖尿病对缺血预适应(IPC)在大鼠缺血再灌注心肌保护作用中的影响.方法 取糖尿病SD大鼠及非糖尿病SD大鼠各30只,分为非糖尿病对照组(A组)、非糖尿病缺血再灌注组(B组)、非糖尿病IPC组(C组)、糖尿病对照组(D组)、糖尿病缺血再灌注组(E组)、糖尿病IPC组(F组),每组10只.动物处死后建立离体心脏Langendorff灌注模型.对照组采用全心灌流90min,余不做任何处理;缺血再灌注组采用心脏平衡灌流30min后,缺血30min,再复灌30min;IPC组采用心脏平衡灌流10min,经2次缺血5min再灌注5rnin后,缺血30min,再复灌30min.比较各组复灌30min后心排血量(CO)、左室发展压(LVDP)、左室内压最大上升和下降速率(±dp/dtmax)的恢复率,检测缺血前及复灌30rain后冠脉流出液中肌酸激酶(CK)的活性和心肌组织中丙二醛(MDA)、超氧化物歧化酶(SOD)的含量,并计算心肌含水率.结果 与非糖尿病缺血再灌注组比较,非糖尿病IPC组CK活性、MDA含量、心肌含水率均明显降低,SOD含量明显增加,CO、LVDP、 dp/dtmax、-dp/dtmax恢复率明显增加(P<0.05).而糖尿病IFC组与糖尿病缺血再灌注组比较上述变化均不明显(P>0.05).结论 糖尿病可抑制IPC对大鼠缺血再灌注心肌的保护作用.     

心肌毛细血管六胺银染色法及缺血预适应对心肌毛细血管的影响

探讨显示心肌毛细血管的方法及用该法观察缺血预适应（ischemic preconditioning,IP)对毛细血管的影响,制备套扎前降支 脉犬模型,缺血再灌注（ischemia-reperfusion,IR)组予缺血1h,再灌注2h;IP组在缺血与再灌注之前,予缺血和再灌注各5min反复4次, 实验终点取缺血心肌进行六胺银染色显示毛细血管,并定量比较,结果六胺银法染色显示心肌毛细管清晰;IP组缺血心肌毛细血管数、周长和面积密度较IR一增加。认为六胺银法显示心肌毛细血管可靠实用;IP减轻缺血后毛细血管的破坏,提示具有毛细血管保护效应。     

芪参益气滴丸对缺血性心肌细胞保护的研究进展

目前大多研究者认为心肌缺血再灌注损伤的主要发生机制是氧自由基、钙超载、心肌能量代谢异常、炎性反应、细胞凋亡。为了研究复合中药制剂芪参益气滴丸是否对缺血再灌注心肌细胞有保护作用,并进一步阐明其作用机制,本文对芪参益气滴丸中的黄芪、丹参、三七、降香等药物对急性心肌缺血再灌注损伤模型均有抑制细胞凋亡、抑制炎症反应、保护心肌组织、清除自由基、保护血管内皮、逆转心室重构、维持正常能量代谢等药理活性进行归纳总结,得出芪参益气滴丸因将四种中药合理配比运用,对缺血再灌注损伤的心肌有着良好的保护作用。相信随着我们研究工作的深入开展,加强临床方面的研究和复方制剂的综合研究,有望能发现其他新的抗心肌缺血再灌注损伤药物。     

人类心肌缺血预适应的研究进展

心肌缺血预适应(ischemicpreconditioning,IP)是指反复短暂的缺血使心肌产生快速适应,对随后较长时间的缺血和再灌注损伤有保护作用。Murry等〔1〕首先在狗心脏中发现,随后在多种动物模型中都发现这种现象。IP对心肌的保护作用包括缩小缺血心肌梗死范围(MIS)、促进心肌收缩功能的恢复和减少室性心律失常等。IP的机制目前仍不清楚,可能与心肌内源性物质及其内在的信息传递途径有关。Yellon等〔2〕首先报告,反复主动脉钳夹对随后持续缺血的人心肌有保护作用,提示人类心肌也存在IP现象。1　人类心肌缺血预适应现象1.1　离体心肌细胞和肌…     

铁紫红素7对肾脏缺血再灌注损伤保护作用的实验研究

肾缺血再灌注过程中产生大量的氧自由基,而氧自由基正是构成肾脏缺血再灌注损伤的重要因素〔１〕。目前临床及实验研究中证实许多自由基清除剂和抗氧化剂具有保护肾脏缺血再灌注损伤的作用。本实验通过建立大白鼠肾缺血再灌注损伤模型,观察铁紫红素７对急性肾脏缺血再灌...     

坎地沙坦对缺血-再灌注心脏搏出液心肌酶谱以及组织形态学的影响

目的观察坎地沙坦对离体家兔心脏缺血-再灌注后心肌酶指标的影响,评价其对心肌的保护作用。方法制作全心缺血-再灌注模型,观察坎地沙坦3个剂量组对心肌细胞酶学的影响,同时观察其对缺血再灌注后心肌细胞结构的影响。结果坎地沙坦100nmol·L-1剂量组能明显降低家兔缺血再灌注时LDH;坎地沙坦10和100nmol·L-1剂量组能明显降低家兔缺血再灌注时GOP的升高;100nmol·L-1剂量组对家兔缺血再灌注时CK和CKMB的升高无统计学意义。结论通过降低家兔离体心脏缺血-再灌注后心肌酶学水平的升高,是坎地沙坦保护心肌的作用途径之一。     

IGF-1后处理与缺血后处理对缺血再灌注心肌保护作用的对比研究

目的 比较胰岛素样生长因子-1后处理(IGF-1-POST)与缺血后处理(I-POST)对缺血再灌注心肌的保护作用,探讨两者抑制缺血再灌注心肌凋亡的可能机制.方法 采用垫扎球囊法建立模型,将48只SD大鼠随机均分成4组(n=12):假手术组、I/R组、I-POST组、IGF-1-POST组.除假手术组外其余各组均缺血4...     

Imaging of ischemic heart disease

Despite advances in the understanding and treatment of ischemic cardiomyopathy, characterized by extensive coronary artery disease and left ventricular (LV) dysfunction, the prognosis remains poor with only a 50-60% 5-year survival rate. The composition of atherosclerotic lesions is currently regarded as being more important than the degree of stenosis in determining acute events. If imaging techniques could distinguish vulnerable from stable plaques, then high-risk patient subgroups could be identified. Another important concept is that LV dysfunction may be the result of either scarring due to necrosis or to the presence of myocardial hibernation, in which there is sufficient blood flow to sustain viable myocytes, but insufficient to maintain systolic contraction. This concept of myocardial viability is critical for making optimal clinical management decisions. This review describes how noninvasive imaging methods can be used to distinguish regions of irreversibly injured myocardium from viable but hibernating segments. Technical advances in CT and MR have made imaging of the beating heart possible. Considerable clinical progress has already been made and further cardiac applications are expected. Radiologists therefore have new opportunities for involvement in cardiac imaging but must recognize the political implications as well as the diagnostic potential of these modalities not only for the heart, but also for the whole vascular system. This review focuses on imaging myocardial injury. It compares state-of-the-art CT and MR with more established yet contemporary echocardiography and nuclear scintigraphy.     

Single-vessel coronary artery stenosis: myocardial perfusion imaging with Gadomer-17 first-pass MR imaging in a swine model of comparison with gadopentetate dimeglumine

PURPOSE: To evaluate the ability of Gadomer-17 to depict perfusion defects in a closed-chest swine model of single-vessel coronary artery disease. MATERIALS AND METHODS: Twelve pigs underwent closed-chest placement of a flow reducer for 70%-90% luminal stenosis in the proximal left anterior coronary artery. Magnetic resonance (MR) perfusion imaging with Gadomer-17 and gadopentetate dimeglumine, microsphere blood flow (MBF) testing, and technetium 99m ((99m)Tc) 2 methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) were performed during dipyridamole vasodilation. Comparisons of percentage signal intensity (SI) increase (PSIC) in remote and ischemic myocardium were made with repeated measurements analysis of variance after injection of both tracers. RESULTS: Perfusion defects and reduced PSIC in the anterior ischemic versus the inferior remote myocardium could be identified after injection of both Gadomer-17 (PSIC, 66% +/- 30 [mean +/- SD] vs 100% +/- 32, respectively; P <.001) and gadopentetate dimeglumine (PSIC, 49% +/- 31 vs 81% +/- 43, respectively; P <.005). The size of perfusion defect depicted with both tracers was highly correlated with defect size at (99m)Tc MIBI SPECT (r = 0.69, P <.05 for Gadomer-17 and r = 0.60, P =.05 for gadopentetate dimeglumine) and with areas of reduced MBF (r = 0.70, P <.05 for Gadomer-17 and r = 0.80, P <.05 for gadopentetate dimeglumine). PSIC also correlated with MBF (r = 0.89, P <.001 for Gadomer-17 and r = 0.75, P <.001 for gadopentetate dimeglumine). Gadomer-17 allowed differentiation of ischemic from nonischemic myocardium, as demonstrated by reduced PSIC (PSIC, 48% +/- 38 vs 72% +/- 31, respectively; P <.001) until 20 minutes after contrast material injection. In contrast, differentiation of ischemic from nonischemic myocardium was possible only until 55 seconds after injection of gadopentetate dimeglumine (PSIC, 36% +/- 24 vs 56% +/- 27, respectively; P <.005) but not at any time point thereafter. CONCLUSION: With the study conditions, Gadomer-17 provided more prolonged differentiation of ischemic from remote myocardium than that with gadopentetate dimeglumine.     

A cytochemical method for the identification of ischemic and necrotic myocardial fibres

Summary The author studied the nickel-dimethylglioxim reaction in ischemic and necrotic myocardium fibres in dogs, following ligature of the left anterior descending coronary artery. The nickel-dimethylglioxim reaction was positive in ischemic fibers, but not in necrotic ones. The cytochemical reaction, observed in ischemic fibers, was localized in the intracellular compartment and in the mitochondria.     

脑创伤病人心脏应激反应的临床研究

目的：研究脑创伤时心脏的应激反应，并探讨其发生机制。方法：141例各型脑创伤病人，采用血液循环动力学信息检测仪检测其心肌耗氧量（MVO）、心肌缺血阈值（MIT）、身血分数（EF）、左室机械效率（LME）、心肌变力系数（MIC）、心肌负变力系数（MNC）等。并设141例正常健康人为对照组。结果：W现人MVO、MNC比对照组明显增高（P＜0．01），EF、MIT、LME、MIC较对照组显著降低（P＜0．01）。结论脑创伤病人明显的心脏应激反应，表现为MVO增加、心肌供血障碍、心脏效率低下、心肌负变力效应增加等，具有潜在的危险性。长期、严重的心脏应激反应，必将影响心脏功能，仍至引发心功能衰竭。     

远程缺血预处理对心肌保护的研究进展

近年来,随着远程缺血预处理(remote ischemic preconditioning,RIPC)的心肌保护作用及机制研究的不断深入,RIPC对心肌保护作用的临床意义也逐渐受到重视。为此,作者就RIPC对心肌保护作用及其可能的机制研究进展作一综述。     

Imaging of intracellular sodium with shift reagent aided (23)Na CSI in isolated rat hearts.

23Na chemical shift imaging (CSI) in conjunction with shift reagents was used to obtain images of intracellular (Na(i)) and extracellular sodium (Na(e)) in isolated rat hearts. It was demonstrated that the increase of Na(i) concentration in ischemic myocardium can be detected with this technique. 3D acquisition-weighted (23)Na CSI datasets with a nominal spatial resolution of 1.7 x 1.7 x 2.9 mm were acquired in 30 min in normoxic hearts and in globally or locally ischemic hearts. The shift reagent Tm(DOTP)(5-) was used to discriminate Na(i) and Na(e) signals. Na(i) maps could be generated in ischemic hearts, but not in normoxic hearts as the signal-to-noise ratio is too low. The Na(i) signal increased by more than 100% and the Na(e) signal decreased by more than 50% in myocardium of globally ischemic hearts (n = 3) compared to normoxic hearts (n = 3). In hearts with an acute occlusion of the left anterior descending coronary artery (n = 3), there was a local Na(i) signal increase in the anterior wall in the range of 60-110% compared to remote, normoxic tissue.     

Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention

This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi.^99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial^99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release^99mTc-sestamibi from the mitochondrial fraction, with an IC₅₀ of 2.54±0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of^99mTc-sestamibi was found to increase from 10.5% ± 3.0% to 61.2% ± 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium overload and loss of mitochondrial metabolic function,^99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.     

Contrast-enhanced magnetic resonance imaging in the assessment of myocardial infarction and viability

Contrast-enhanced magnetic resonance imaging (MRI) can be used to visualize the transmural extent of myocardial infarction with high spatial resolution. The aim of this review is to provide an overview of the use of contrast-enhanced MRI for characterization of ischemic myocardial injury in comparison to other imaging methods and its relevance in clinical syndromes related to coronary artery disease. Infarcted myocardium appears hyperenhanced compared with normal myocardium when imaged by a delayed-enhancement MRI technique with the use of an inversion-prepared T₁-weighted sequence after injection of gadolinium chelates, such as gadolinium-diethylenetriamine pentaacetic acid. Experimental and clinical studies indicate that the extent of delayed enhancement is reproducible and closely correlates with the size of myocardial necrosis or infarct scar as determined by established in vitro and in vivo methods. Furthermore, MRI appears to be more sensitive than other imaging methods in detecting small subendocardial infarctions. The transmural extent of delayed enhancement potentially predicts functional outcome after revascularization in acute myocardial infarction and chronic ischemic heart disease, indicating that it can accurately discriminate between infarction and dysfunctional but viable myocardium. Further experience from clinical trials is needed to understand the association of delayed enhancement with clinical outcomes. Financial assistance was provided by EC-FP6-project DiMl (LSHB-CT-2005-512146) and Finnish Foundation for Cardiovascular Research.     

The Japanese experience with metabolic imaging in the clinical setting

Conclusions  Reduced utilization of fatty acids at rest often is observed in severely ischemic myocardium and possibly postischemic myocardium despite normal perfusion at rest. The role of metabolic imaging in identifying postischemic insult as ischemic memory imaging has been the focus of recent investigations. A number of reports from Japan show quite acceptable diagnostic accuracy of BMIPP imaging for detecting coronary patients without prior MI. In addition, recent data indicate that BMIPP imaging has prognostic value when applied in patients with documented or suspected coronary disease. The major advantage of BMIPP imaging is to demonstrate ischemic myocardium as an area of altered metabolism at rest. Thus this study is of clinical importance for elderly patients or for patients not suitable for a stress study. Furthermore, this radiopharmaceutical tracer may hold promise in demonstrating early alteration of energy metabolism in a variety of myocardial disorders.     

Acute myocardial ischemia and reperfusion: MR imaging with albumin-Gd- DTPA

The utility of a macromolecular, intravascular contrast agent, albumin-gadolinium diethylenetriaminepentaacetic acid (DTPA), for the differentiation of acutely ischemic and reperfused myocardium on magnetic resonance (MR) images was investigated. Regional, reversible myocardial ischemia was produced in rats and confirmed. After reperfusion, flow to the compromised myocardial segment returned to baseline. Normal myocardium could not be differentiated from ischemic myocardium on nonenhanced MR images (n = 12). After 5 minutes of myocardial ischemia and after administration of albumin-Gd-DTPA, the ischemic zone involving the free wall of the left ventricle was characterized by the absence of significant enhancement. Normal myocardium appeared homogeneously enhanced (by 145%). This pattern persisted for up to 1 hour of myocardial ischemia. In six rats that underwent myocardial reperfusion after 5 minutes of ischemia, the normal and reperfused myocardium became isointense. Radiotracer studies with albumin-Gd-153-DTPA confirmed the decreased distribution of contrast agent to the ischemic myocardium, possibly due to decreased blood pool or a blocked primary delivery system in the ischemic myocardium.