Collagen regulates the ability of endothelial progenitor cells to protect hypoxic myocardium through a mechanism involving miR‐377/VE‐PTP axis

The possibility to employ stem/progenitor cells in the cardiovascular remodelling after myocardial infarction is one of the main queries of regenerative medicine. To investigate whether endothelial progenitor cells (EPCs) participate in the restoration of hypoxia‐affected myocardium, we used a co‐culture model that allowed the intimate interaction between EPCs and myocardial slices, mimicking stem cell transplantation into the ischaemic heart. On this model, we showed that EPCs engrafted to some extent and only transiently survived into the host tissue, yet produced visible protective effects, in terms of angiogenesis and protection against apoptosis and identified miR‐377‐VE‐PTP axis as being involved in the protective effects of EPCs in hypoxic myocardium. We also showed that collagen, the main component of the myocardial scar, was important for these protective effects by preserving VE‐PTP levels, which were otherwise diminished by miR‐377. By this, a good face of the scar is revealed, which was so far perceived as having only detrimental impact on the exogenously delivered stem/progenitor cells by affecting not only the engraftment, but also the general protective effects of stem cells.     

Multicontrast endomyocardial imaging by single‐channel high‐resolution cross‐polarization optical coherence tomography

A single‐channel high‐resolution cross‐polarization (CP) optical coherence tomography (OCT) system is presented for multicontrast imaging of human myocardium in one‐shot measurement. The intensity and functional contrasts, including the ratio between the cross‐ and co‐polarization channels as well as the cumulative retardation, are reconstructed from the CP‐OCT readout. By comparing the CP‐OCT results with histological analysis, it is shown that the system can successfully delineate microstructures in the myocardium and differentiate the fibrotic myocardium from normal or ablated myocardium based on the functional contrasts provided by the CP‐OCT system. The feasibility of using A‐line profiles from the 2 orthogonal polarization channels to identify fibrotic myocardium, normal myocardium and ablated lesion is also discussed.      

运动性疲劳状态下大鼠心肌线粒体内膜变化的研究

采用递增负荷力竭性运动模型,观察了Ｓｐｒａｇｕｅ－Ｄａｗｌｅｙ大鼠急性运动至力竭后心肌线粒体内膜流动性、ＮＡＤＨ－ＣｏＱ还原酶及ＡＴＰ酶活性的变化。结果表明,大鼠心肌线粒体内膜荧光偏振值较安静时显著增高（Ｐ＜０．０１）,示膜流动性降低。线粒体内膜ＮＡＤＨ－ＣｏＱ还原酶和肌线粒体内膜功能改变,其膜流动性和呼吸链酶活性变化,可能是运动性疲劳的重要膜分子制之一。     

Renaissance of cytochemical localization of membrane ATPases in the myocardium

ATPases of cardiac cells are known to be among the most important enzymes to maintain the fluxes of vital cations by hydrolysis of the terminal high-energy phosphate of ATP. Biochemically the activities of Ca²⁺-pump ATPase, Ca²⁺/Mg²⁺-ecto ATPase, Na⁺,K⁺-ATPase and Mg²⁺-ATPase are determined in homogenates and isolated membranes as well as in myofibrillar and mitochondrial fractions of various purities. Such techniques permit estimation of enzyme activitiesin vitro under optimal conditions without precise enzyme topography. On the other hand, cytochemical methods demonstrate enzyme activityin situ, but not under optimal conditions. Until recently several cytochemical methods have been employed for each enzyme in order to protect its specific activity and precise localization but the results are difficult to interpret. To obtain more consistent data from biochemical and cytochemical point of view, we modified cytochemical methods in which unified conditions for each ATPase were used. The fixative solution (1% paraformaldehyde –0.2% glutaraldehyde in 0.1 M Tris Base buffer, pH 7.4), the same cationic concentrations of basic components in the incubation medium (0.1 M Tris Base, 2mM Pb(NO₂)₃, 5 mM MgSO₄, 5 mM ATP) and selective stimulators or inhibitors were employed. The results reveal improved localization of Ca²⁺-pump ATPase, Na⁺–K⁺ ATPase and Ca²⁺/Mg²⁺-ecto ATPase in the cardiac membrane.     

Effects of using the unloaded configuration in predicting the in vivo diastolic properties of the heart

Computational models are increasingly being used to investigate the mechanical properties of cardiac tissue. While much insight has been gained from these studies, one important limitation associated with computational modeling arises when using in vivo images of the heart to generate the reference state of the model. An unloaded reference configuration is needed to accurately represent the deformation of the heart. However, it is rare for a beating heart to actually reach a zero-pressure state during the cardiac cycle. To overcome this, a computational technique was adapted to determine the unloaded configuration of an in vivo porcine left ventricle (LV). In the current study, in vivo measurements were acquired using magnetic resonance images (MRI) and synchronous pressure catheterization in the LV (N = 5). The overall goal was to quantify the effects of using early–diastolic filling as the reference configuration (common assumption used in modeling) versus using the unloaded reference configuration for predicting the in vivo properties of LV myocardium. This was accomplished by using optimization to minimize the difference between MRI measured and finite element predicted strains and cavity volumes. The results show that when using the unloaded reference configuration, the computational method predicts material properties for LV myocardium that are softer and less anisotropic than when using the early-diastolic filling reference configuration. This indicates that the choice of reference configuration could have a significant impact on capturing the realistic mechanical response of the heart.     

Inhibitors of adenosine catabolism improve recovery of dog myocardium after ischemia

Summary The effects of inhibitors of adenosine catabolism on contractile function and metabolites were assessed during 15 minutes of ischemia followed by 30 minutes of reperfusion in the open-chest dog heart. As compared to sham treatment, pretreatment with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and dipyridamole (DP) protected contractile function during ischemia, and improved recovery of high energy phosphate content and contractile fucntion during reperfusion following ischemia. Testing EHNA and DP in a free-radical generating system indicated both compounds have some scavenging ability, suggesting the effect of EHNA + DP may not be on adenosine nucleotide metabolism alone. Comparison of end diastolic segment lengths to contractile function indicated the results were not affected by changes in preload resulting from peripheral vasodilation.With the technical assistance of Dennis Dahmen.     

Neurohormonal regulation of calcium in the cell

Neurohormone C (NC) is a glycopeptide isolated from bovine hypothalamus, which inhibits Ca-calmodulin (CaM)-dependent cAMP and cGMP phosphodiesterase (PDE) and is a regulator of Ca in the cell. Distribution of [⁴⁵Ca]CaCl₂ in the mitochondria and reticulum (SR) of heart and brain mitochondria and changes of Ca-binding proteins in these organelles under NC influence have been studied in the myocardium before and after isoproterenol-induced necrosis. Intraperitoneal administration of 80–100 mU of PDE inhibitory activity of NC to rats did not cause any noticeable changes in the protein content of intracellular organelles, but altered the affinity of certain proteins to⁴⁵Ca²⁺. This property of NC was especially noticable after isoproterenol necrosis. Necrotic injury of the myocardium induced Ca²⁺ storage in the mitochondria and SR of brain, and decreased the Ca²⁺ concentration in myocardial mitochondria. NC injection to the animals with necrosis was followed by Ca²⁺ release from all the studied organelles.     

高血压大鼠心肌2型小电导-Ca2+-激活-K+通道蛋白(SK2)表达的变化*

目的:观察高血压大鼠心肌细胞2型小电导-Ca²⁺-激活-K⁺(SK2)通道蛋白表达情况。方法:12只健康成年雄性SD大鼠随机分为对照组(5只)和实验组(7只),实验组采用N’-硝基-L-精氨酸(L-NNA 15 mg/(kg·d))腹腔注射制备高血压模型,对照组以等体积生理盐水腹腔注射,每天称量大鼠体重,每周测量血压及心电图变化,4周后处死大鼠取心脏;采用Western blot的方法检测心肌SK2通道蛋白表达水平。结果:给药4周后,与对照组相比,实验组大鼠血压明显升高(P＜0.05),心电图QRS时长和R-R间期延长,实验组大鼠心房组织和心室组织SK2通道的表达均明显升高(1.12±0.18 vs 0.52±0.99,1.64±0.26 vs 0.99±0.22, P＜0.05)。结论:高血压模型大鼠心房和心室SK2通道表达增加,其可能是导致高血压模型大鼠出现心律失常的机制之一,为高血压疾病的治疗和预后提供新的思路和策略。