覆膜支架腔内修复术与药物保守治疗对Stanford B型主动脉夹层动脉瘤患者肝肾功能、炎性因子以及预后的影响

目的:比较覆膜支架腔内修复术与药物保守治疗对Standford B型主动脉夹层动脉瘤的疗效及对患者肝肾功能、炎性因子及预后的影响。方法:选择2012年1月～2014年8月我院收治的Standford B型主动脉夹层动脉瘤患者68例,按照随机数字表法分为对照组与研究组,各34例。对照组入院后采取药物保守治疗,研究组应用覆膜支架腔内修复术治疗。观察两组住院期间死亡率、再次手术或介入率以及治疗前、治疗2周后肝肾功能、血清炎性因子变化。所有患者随访36个月,比较两组患者预后情况。结果:研究组再次手术或介入率为2.94%,低于对照组的22.58%(P0.05)。治疗2周后,研究组丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、胱抑素C、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、γ-干扰素(INF-γ)、C反应蛋白(CRP)水平较治疗前降低(P0.05),且研究组低于对照组(P0.05)。两组患者均随访36个月,随访12个月时两组患者生存率分别为100.00%和80.65%,随访36个月时两组患者生存率分别为91.18%和29.03%,经Log Rank分析显示,两组生存率比较差异有统计学意义(P0.05)。结论:覆膜支架腔内修复术治疗Standford B型主动脉夹层动脉瘤的疗效确切,能够改善患者肝肾功能,降低炎症反应,患者近中期随访生存率较高,其效果优于保守治疗。     

Sodium (±)‐5‐bromo‐2‐(α‐hydroxypentyl) benzoate ameliorates pressure overload‐induced cardiac hypertrophy and dysfunction through inhibiting autophagy

Sodium (±)‐5‐bromo‐2‐(a‐hydroxypentyl) benzoate (generic name: brozopine, BZP) has been reported to protect against stroke‐induced brain injury and was approved for Phase II clinical trials for treatment of stroke‐related brain damage by the China Food and Drug Administration (CFDA). However, the role of BZP in cardiac diseases, especially in pressure overload‐induced cardiac hypertrophy and heart failure, remains to be investigated. In the present study, angiotensin II stimulation and transverse aortic constriction were employed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial cell autophagy. We observed that BZP administration ameliorated cardiomyocyte hypertrophy and excessive autophagic activity. Further results indicated that AMP‐activated protein kinase (AMPK)‐mediated activation of the mammalian target of rapamycin (mTOR) pathway likely played a role in regulation of autophagy by BZP after Ang II stimulation. The activation of AMPK with metformin reversed the BZP‐induced suppression of autophagy. Finally, for the first time, we demonstrated that BZP could protect the heart from pressure overload‐induced hypertrophy and dysfunction, and this effect is associated with its inhibition of maladaptive cardiomyocyte autophagy through the AMPK‐mTOR signalling pathway. These findings indicated that BZP may serve as a promising compound for treatment of pressure overload‐induced cardiac remodelling and heart failure.     

Traction Force Measurements of Human Aortic Smooth Muscle Cells Reveal a Motor-Clutch Behavior

The contractile behavior of smooth muscle cells (SMCs) in the aorta is an important determinant of growth, remodeling, and homeostasis. However, quantitative values of SMC basal tone have never been characterized precisely on individual SMCs. Therefore, to address this lack, we developed an in vitro technique based on Traction Force Microscopy (TFM). Aortic SMCs from a human lineage at low passages (4-7) were cultured 2 days in conditions promoting the development of their contractile apparatus and seeded on hydrogels of varying elastic modulus (1, 4, 12 and 25 kPa) with embedded fluorescent microspheres. After complete adhesion, SMCs were artificially detached from the gel by trypsin treatment. The microbeads movement was tracked and the deformation fields were processed with a mechanical model, assuming linear elasticity, isotropic material, plane strain, to extract the traction forces formerly applied by individual SMCs on the gel. Two major interesting and original observations about SMC traction forces were deduced from the obtained results: 1. they are variable but driven by cell dynamics and show an exponential distribution, with 40% to 80% of traction forces in the range 0-10 μN. 2. They depend on the substrate stiffness: the fraction of adhesion forces below 10 μN tend to decrease when the substrate stiffness increases, whereas the fraction of higher adhesion forces increases. As these two aspects of cell adhesion (variability and stiffness dependence) and the distribution of their traction forces can be predicted by the probabilistic motor-clutch model, we conclude that this model could be applied to SMCs. Further studies will consider stimulated contractility and primary culture of cells extracted from aneurysmal human aortic tissue.     

In situ diode laser fenestration: An ex‐vivo evaluation of irradiation effects on human aortic tissue

The in situ laser fenestration is an interesting option for the endovascular treatment of short‐necked aneurysms with an intraoperative modification of a standard endograft. According to literature evidence, diode laser emitting in the near‐infrared wavelength (810 nm) can be successfully used to fenestrate the endograft fabric. This paper describes a three‐dimensional navigation system for the accurate targeting of the fenestration site, then reports results of an ex vivo study to assess whether the laser operative conditions, which ensure the fabric fenestration, are harmless for the biological tissue surrounding the endoprosthesis. Two hundred twenty‐five samples of human aorta, including healthy specimens and abdominal aortic aneurysm samples, were irradiated ex vivo using a 810 nm diode laser. Energy and pulse duration were varied. Irradiated tissues were fixed in formaldehyde, sectioned and subjected to histological examination. Only 7.5% of the irradiated samples exhibited a thermal damage, which was always confined to the contact point between the laser fiber tip and the aortic wall. These experiments suggest that the diode laser can be safely used for the proposed surgical application.     

Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve

Recent data suggest that angiogenesis plays an important role in the pathogenesis of valvular disease. However, the cellular mechanisms underlying this process remain unknown. This study aimed at identifying and characterizing the cellular components responsible for pathological neovascularization in calcific aortic valves (CAV). Immunohistochemical analysis of uncultured CAV tissues revealed that smooth muscle alpha-actin (alpha-SMA)-positive cells, which coexpressed Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2), can be identified prior to the initiation of capillary-like tube formation. In a second step, leaflets of CAV and non-calcific aortic valves (NCAV) were cultured and the cells involved in capillary-like tube formation were isolated. The majority of these cells displayed the same phenotype as non-cultured cells identified in CAV tissues, i.e., expression of alpha-SMA, Tie-2, and VEGFR-2. In comparison to cells isolated from cultures of NCAV leaflets, these cells showed enhanced angiogenic activity as demonstrated by migration and tube assays. The coexpression of VEGFR-2 and Tie-2 together with alpha-SMA suggests both endothelial and mesenchymal properties of the angiogenically activated cells involved in valvular neovascularization. Hence, our findings might provide new insights into the process of pathological angiogenesis in cardiac valves.     

Secular trends of obesity and cardiovascular risk factors in a Mediterranean population

Objective: To evaluate time trends of obesity, abdominal obesity, and cardiovascular risk factors (CRFs) according to BMI and waist circumference (WC) categories in a Mediterranean population. Research Methods and Procedures: Subjects were Spanish men (n = 2383) and women (n = 2525) 25 to 74 years old, examined in 1994 to 1995 and 1999 to 2000 in two independent population‐based cross‐sectional surveys in the northeast of Spain. Lifestyle measures, CRFs, and anthropometric variables were analyzed. Results: Over the 5 years of the study, mean age‐standardized BMI increased by 1.0 units in men and by 0.8 units in women. At the same time the prevalence of obesity increased from 15.4% to 21.9% in men and from 15.4% to 21.4% in women. An upward trend was observed for WC and abdominal obesity (WC > 102 cm in men and WC > 88 cm in women) only in men. The proportion of men and women with hypercholesterolemia, diabetes, and low high‐density lipoprotein‐cholesterol plasma concentration remained stable within BMI and WC categories. The proportion of hypertension and smoking in obese men significantly increased from 1995 to 2000. Discussion: The 5‐year increase in BMI and WC is of considerable magnitude in the present population, although several CRFs remained stable within BMI and WC categories.     

Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity

Objective: The aim of this study was to test the hypothesis that baroreflex sensitivity (BRS), assessed by indirect measurement of aortic pressure, is blunted in obesity. Additionally, the potential effect of cardiac autonomic nervous system (ANS) activity, aortic compliance, and metabolic parameters on BRS of obese subjects was investigated. Research Methods and Procedures: A group of 30 women with BMI >30 kg/m² and a group of 30 controls with BMI <25 kg/m² were examined. BRS was estimated by the sequence technique, cardiac ANS activity by short‐term spectral analysis of heart rate variability (HRV), and aortic compliance by the method of applanation tonometry. Results: BRS was lower in obese women (9.18 ± 3.77 vs. 19.63 ± 9.16 ms/mm Hg, p < 0.001). The median values (interquartile range) of the power of both the high‐frequency and low‐frequency components of the HRV were higher in the lean than in the obese participants [1079.2 (202.7 to 1716.9) vs. 224.1 (72.7 to 539.6) msec², p = 0.001 and 411.8 (199.3 to 798.0) vs. 235.8 (99.4 to 424.5) msec², p = 0.01 respectively]. Low‐to‐high‐frequency ratio values were higher in the obese subjects [0.82 (0.47 to 2.1) vs. 0.57 (0.28 to 0.89), p = 0.02]. Aortic augmentation values were not significantly different between lean and obese subjects. Multivariate analysis demonstrated a significant and independent association between BRS and age (p = 0.003), BMI (p < 0.001), and high‐frequency power of HRV (p < 0.001). These variables explained 72% of the variation of BRS values. Discussion: BRS is severely reduced in obese subjects. BMI, age, and the parasympathetic nervous system activity are the main determinants of BRS. Baroreflex behavior is of clinical relevance because an attenuated BRS represents a negative prognostic factor in cardiovascular diseases, which are common in obesity.     

Development of a novel MATLAB-based framework for implementing mechanical joint stability constraints within OpenSim musculoskeletal models

The Static Optimization (SO) solver in OpenSim estimates muscle activations and forces that only equilibrate applied moments. In this study, SO was enhanced through an open-access MATLAB interface, where calculated muscle activations can additionally satisfy crucial mechanical stability requirements. This Stability-Constrained SO (SCSO) is applicable to many OpenSim models and can potentially produce more biofidelic results than SO alone, especially when antagonistic muscle co-contraction is required to stabilize body joints. This hypothesis was tested using existing models and experimental data in the literature. Muscle activations were calculated by SO and SCSO for a spine model during two series of static trials (i.e. simulation 1 and 2), and also for a lower limb model (supplementary material 2). In simulation 1, symmetric and asymmetric flexion postures were compared, while in simulation 2, various external load heights were compared, where increases in load height did not change the external lumbar flexion moment, but necessitated higher EMG activations. During the tasks in simulation 1, the predicted muscle activations by SCSO demonstrated less average deviation from the EMG data (6.8% −7.5%) compared to those from SO (10.2%). In simulation 2, SO predicts constant muscle activations and forces, while SCSO predicts increases in the average activations of back and abdominal muscles that better match experimental data. Although the SCSO results are sensitive to some parameters (e.g. musculotendon stiffness), when considering the strategy of the central nervous system in distributing muscle forces and in activating antagonistic muscles, the assigned activations by SCSO are more biofidelic than SO.