New biodegradable small-diameter artificial vascular prosthesis: a feasibility study

An in-house built instrument was used to fabricate a small internal diameter (2 mm) artificial vascular prosthesis from biodegradable chitosan. This new artificial vascular prosthesis has shown a good biocompatibility based on the studies of its cell compatibility, inflammatory reaction, and platelet adhesion. In an animal test, the prosthesis was used to replace a 4-cm-long section of femoral artery in each of the seven tested dogs. The patency of the replacement was monitored at regular intervals using Doppler ultrasound diagnostics. Nine months after the implantation, hematoxylin and eosin staining, immunohistochemical study, and scanning electron microscope observation were carried out. Complete decomposition of the prosthesis and replacement by a natural blood vessel were observed. The results suggests that the artificial vascular prosthesis displays many characteristics of the "ideal" small-diameter artificial vascular, and have the biocompatibility that can be tailored to match those desired in vascular replacement application.     

大鼠主要皮动脉的形态计量学及其相互关系

目的 探讨大鼠主要皮动脉的形态计量学特征及其血流动力学特点. 方法 SD大鼠12只, 行一次性全身血管造影并配合利用Photoshop 与Scion Image等电脑图像处理技术,分析不同类型皮动脉的供血范围、血管密度变化趋势及其供血趋向性等. 结果 6个主要皮动脉的平均外径为(0.53±0.12)mm,其营养体区周长为(18.74±4.84)cm,平均血管密度为(391.31±76.58)灰度/(像素·厘米厚度);皮动脉外径与其营养体区周长呈正相关,其回归方程为:y=32.441x+1.233(r=0.851,n=54,P<0.01). 结论 大鼠皮动脉外径和其营养区域的周长成正比,相同外径的皮动脉,其营养区域的周长相等,区域形状越接近于圆其面积越大.轴型血管营养皮瓣的平均血管密度高于分支型血管.     

下腔静脉人工血管置换术后放疗对血管内膜的影响

目的 观察术后放疗对犬下腔静脉人工血管置换术后人工血管内膜的影响.方法 犬16只完全随机法分为对照组(n=8)和放疗组(n=8),均行下腔静脉膨体聚四氟乙烯(ePTFE)人工血管置换术.放疗组于术后第2N行体外35 Gy放疗,对照组术后不予放疗.2N犬均于术后第8N采集标本,观察人工血管通畅率,并行HE染色、人工血管内膜厚度测量,增殖细胞核抗原(PCNA)及CD34免疫组化检测,计算人工血管内膜100μm内皮细胞数.结果 术后第8周,放疗组人工血管通畅率为100%(8/8),对照组为75%(6/8).放疗组各段人工血管内膜厚度较对照组明显减少[近心端:(610.69±32.90)μm比(753.39+10.36)μm,中段:(530.51±32.14)μm比(636.55±20.23)μm,远心端:(544.52±41.99)μm比(710.39±30.92)μm,均P＜0.01].放疗组各段人工血管内膜的PCNA阳性细胞百分率较对照组减低[近心端:(45.1±7.5)%比(56.3±7.8)%,中段:(29.2±4.1)%比(36.6±4.9)%,远心端:(33.8±5.5)%比(40.7±6.7)%,均P＜0.05].2组人工血管内膜100μm内皮细胞数的比较差异无统计学意义(P＞0.05).结论 下腔静脉人工血管术置换后35 Gy体外放疗不影响移植人工血管通畅率,对内膜血管平滑肌细胞的覆盖亦无明显影响,但可抑制人工血管内膜增生和PCNA的表达.     

Hemodynamic design requirements for in-series thoracic artificial lung attachment in a model of pulmonary hypertension

Recent thoracic artificial lung (TAL) prototypes have impedances lower than the natural lung. With these devices, proximal pulmonary artery (PA) to distal PA TAL attachment may be possible in patients without right ventricular dysfunction. This study examined the relationship between pulmonary system impedance and cardiac output (CO) to create TAL design constraints. A circuit with adjustable resistance and compliance (C) was attached in a PA-PA fashion with the pulmonary circulation of seven sheep with chronic pulmonary hypertension. The pulmonary system zeroth harmonic impedance modulus (Z(0)) was increased by 1, 2.5, and 4 mmHg/(L/min) above baseline. At each Z(0), C was set to 0, 0.34, and 2.1 ml/mmHg. The change in pulmonary system zeroth and first harmonic impedance moduli (ΔZ(0) and ΔZ(1)), the percent change in CO (%ΔCO), and the inlet and outlet anastomoses resistances were calculated for each situation. Results indicate that ΔZ(0) (p < 0.001) but not ΔZ(1) (p = 0.5) had a significant effect on %ΔCO and that %ΔCO = -7.45*ΔZ(0) (R(2) = 0.57). Inlet and outlet anastomoses resistances averaged 0.77 ± 0.16 and 0.10 ± 0.19 mmHg/(L/min), respectively, and the relationship between %ΔCO and TAL resistance, R(T), in mmHg/(L/min) was determined to be %ΔCO = -(7.45f)×(R(T) + 0.87), in which f = the fraction of CO through the TAL. Thus, newer TAL designs can limit %ΔCO to less than 10% if f < 0.75.     

Differential structural adaptation to haemodynamics along single rat cremaster arterioles

We tested the hypothesis that under physiological conditions, arterioles match their diameter to the level of shear stress. Haemodynamic and anatomical data were obtained in segments of the first-order arteriole of the rat cremaster muscle. Along this segment of ∼10 mm in length, local blood pressure decreased from 68 ± 4 mmHg upstream to 54 ± 3 mmHg downstream ( n = 5). Pulse pressure decreased from 8.2 ± 1.3 mmHg upstream to 4.1 ± 0.6 mmHg downstream. At the same locations, an increase in arteriolar diameter was measured in vivo, from 179 ± 4 μm upstream to 203 ± 4 μm downstream ( n = 10). In vitro pressure-diameter relations of maximally dilated vessels showed that the passive diameter was larger in downstream than upstream segments over a 15–125 mmHg pressure range ( n = 18). The wall stress was similar for the upstream vs. downstream location: 266 ± 16 vs. 260 ± 14 mN mm⁻². However, shear stress decreased from 30 ± 5 to 21 ± 5 dyn cm⁻² (3.0 ± 0.5 to 2.1 ± 0.5 N m⁻²; n = 4) along the artery. In conclusion, these results demonstrate that shear stress is not the only factor in determining vascular calibre. We suggest that arteriolar calibre may rather depend on an interplay between shear stress and the local pressure profile.     

椎体骨密度与抗压强度的关系及临床意义

目的探讨椎体骨密度(BMD)与抗压强度的关系。方法18具完整腰段脊柱标本(L1～L5),用DEXA测试每个椎体的BMD,游离成单个椎体,按骨质疏松试行诊断标准分成正常对照组、轻中度骨质疏松组和重度骨质疏松组;测试椎体静态压缩下的最大抗压力和刚度。结果正常对照组、轻中度骨质疏松组和重度骨质疏松组平均骨密度分别为(0.916±0.191)、(0.594±0.116)和(0.402±0.096)g/cm     

Attenuated inspiratory muscle metaboreflex in endurance-trained individuals

The inspiratory metaboreflex is activated during loaded breathing to task failure and induces sympathetic activation and peripheral vasoconstriction that may limit exercise performance. Inspiratory muscle training appears to attenuate the inspiratory metaboreflex in healthy subjects. Since whole body aerobic exercise training improves breathing endurance and inspiratory muscle strength, we hypothesized that endurance-trained individuals would demonstrate a blunted inspiratory muscle metaboreflex in comparison to sedentary individuals. We studied 9 runners (23±0.7 years; maximal oxygen uptake [VO2 max] = 53 ± 4 ml kg(-1) min(-1)) and 9 sedentary healthy volunteers (24±0.7 years; VO2 max = 37 ±2 ml kg(-1) min(-1)). The inspiratory muscle metaboreflex was induced by breathing against an inspiratory load of 60% of maximal inspiratory pressure (MIP), with prolonged duty cycle. Arterial pressure, popliteal blood flow, and heart rate were measured throughout the protocol. Loaded breathing to task failure increased mean arterial pressure in both sedentary and endurance-trained individuals (96±3 to 100±4 mmHg and 101±3 to 110±5 mmHg). Popliteal blood flow decreased in sedentary but not in trained individuals (0.179±0.01 to 0.141±0.01 cm/s, and 0.211±0.02 to 0.214±0.02 cm/s). Similarly, popliteal vascular resistance increased in sedentary but not in trained individuals (559±35 to 757±56 mmHg s/cm, and 528±69 to 558±64 mmHg s/cm). These data demonstrate that endurance-trained individuals have an attenuated inspiratory muscle metaboreflex.     

Development of an artificial placenta IV: 24 hour venovenous extracorporeal life support in premature lambs

An extracorporeal artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that a venovenous extracorporeal life support (VV-ECLS) artificial placenta would maintain fetal circulation, hemodynamic stability, and adequate gas exchange for 24 hours. A near-term neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors, average mean arterial pressure was 69 ± 10 mm Hg for the first 4 hours and 36 ± 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 ± 30. Mean VV-ECLS flow was 94 ± 20 ml/kg/min. Using a gas mixture of 50% O(2)/3% CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 ± 0.09, with Po(2) of 35 ± 12 mm Hg and Pco(2) of 48 ± 12 mm Hg. Necropsy revealed a patent ductus arteriosus in all cases, and there was no gross or microscopic intracranial hemorrhage. Complications in failed attempts included technically difficult cannulation and multisystem organ failure. Future studies will enhance stability and address the factors necessary for long-term support.     

Porcine extracellular matrix scaffolds in reconstructive urology: An ex vivo comparative study of their biomechanical properties

Functional reconstruction of the human urinary bladder has been attempted by replacing defective bladder tissue with tissue-engineered xenogenic extracellular matrix (ECM) scaffolds. However, experimental studies that demonstrate the effects of implanted ECMs on important biomechanical properties such as total bladder capacity (TBC) and compliance (C) are lacking. In the current study, the effects of ECM scaffold surface area (SA) on TBC and C was assessed, ex vivo, in an ovine model (n=5). TBC and C were measured at pressures (P) of 5, 10, 15 and 20 mm?Hg prior to performing a 3×3?cm (9?cm(2)) partial cystectomy defect. Equal-sized 3×3?cm (9?cm(2)) and larger 6×6?cm (36?cm(2)) urinary bladder matrix (UBM) scaffolds of porcine origin replaced the 3×3?cm cystectomy defect, and TBC and C were re-recorded for comparative analysis. The results showed that TBC decreased by 39.6%±0.005% (122.9?ml±15?ml, p<0.05) and C by 38.9%±0.51%, (ΔP=0-5mmHg, p<0.05) in ovine bladders reconstructed with 3×3?cm UBM scaffolds compared to their native values. It was also found that TBC increased by 25.6±0.64% (64.2?ml ± 8.8?ml, p>0.05) and C by 24.5±0.43% (ΔP=0-5mmHg, p>0.05) in the 6×6?cm UBM scaffold group compared to the 3×3?cm UBM scaffold group; however, these values were not statistically significant. The present work demonstrates that a fourfold increase in ECM scaffold SA relative to its intended defect does not lead to a significant improvement in TBC and C values.     

Development of a compliant and cytocompatible micro-fibrous polyethylene terephthalate vascular scaffold

Bioengineering approaches have been intensively applied to create small diameter vascular grafts using artificial materials. However, a fully successful, high performing and anti-thrombogenic structure has not been achieved yet. In this study, we have designed and fabricated a novel non-woven fibrous vascular graft with biomechanical properties closely resembling those of native vessels. Vascular cell growth, preservation of cell phenotype, retention of vasoactive properties, as well as the effect of gelatin coating on the cellular interaction with the scaffolds under static and shear stress conditions were investigated. The non-woven fibrous scaffolds were made from melt blown polyethylene terephthalate fiber webs stacked by means of a consolidation technique. The scaffold variables were fiber diameter distribution and the number of consolidated web stacks. SEM analysis confirmed various fiber diameter and pore size ranges corresponding to the different conditions. The scaffolds showed burst pressure values of ～1500 mmHg and compliance (8.4 ± 1.0 × 10(-2) % mmHg(-1) ) very similar to those of native arteries (～8 × 10(-2) % mmHg(-1) ). The structure with the smallest fiber diameter range (1-5 μm) and pore size range (1-20 μm) was the most suitable for the growth of human brain endothelial cells and aortic smooth muscle cells. The cells maintained their specific cell phenotype, expressed collagen and elastin and produced cAMP in response to α-calcitonin gene-related peptide. However, under shear stress conditions (0.9 dyne cm(-2) ), only 30% of the cells were retained in both uncoated and gelatin-coated scaffolds indicating the need for improving the cell retention capacity of these structures, which is our future research direction. This study indicates that the biomechanical and biocompatible properties of this novel vascular scaffold are promising for the development of a vascular graft with similar characteristics to those of native vessels.     

Intradermal microdialysis of hypertonic saline attenuates cutaneous vasodilatation in response to local heating

We tested the hypothesis that microdialysis of hypertonic saline would attenuate the skin blood flow response to local heating. Seventeen healthy subjects (23 ± 1 years old) were studied. In one group (n = 9), four microdialysis fibres were placed in the forearm skin and infused with the following: (1) Ringer solution; (2) normal saline (0.9% NaCl); (3) hypertonic saline (3% NaCl); and (4) 10 mm l-NAME. A second group (n = 8) was infused with the following: (1) normal saline; (2) hypertonic saline; (3) normal saline + l-NAME; and (4) hypertonic saline + l-NAME. Red blood cell flux was measured via laser Doppler flowmetry during local heating to 42°C. Site-specific maximal vasodilatation was determined by infusing 28 mm sodium nitroprusside while the skin was heated to 43°C. Data were expressed as the percentage of maximal cutaneous vascular conductance (%CVC(max)). The local heating response at the Ringer solution and normal saline sites did not differ (n = 9; initial peak Ringer solution, 69 ± 6 versus normal saline, 66 ± 2%CVC(max); plateau Ringer solution, 89 ± 4 versus normal saline, 89 ± 5%CVC(max)). Hypertonic saline reduced the initial peak (n = 9; normal saline, 66 ± 2 versus hypertonic saline, 54 ± 4%CVC(max); P < 0.05) and plateau (normal saline, 89 ± 5 versus hypertonic saline, 78 ± 2%CVC(max); P < 0.05) compared with normal saline. Plateau %CVC(max) was attenuated to a similar value at the normal saline + l-NAME and hypertonic saline + l-NAME sites (n = 8; normal saline + l-NAME, 39 ± 6 and hypertonic saline + l-NAME, 39 ± 5%CVC(max)). The nitric oxide contribution (plateau %CVC(max) - l-NAME plateau %CVC(max)) was lower at the hypertonic saline site (normal saline, 55 ± 6 versus hypertonic saline, 35 ± 4; P < 0.01). These data suggest an effect of salt on the cutaneous response to local heating, which may be mediated through a decreased production and/or availability of nitric oxide.     

In vivo performance of a phospholipid-coated bioerodable elastomeric graft for small-diameter vascular applications

There remains a great need for vascular substitutes for small-diameter applications. The use of an elastomeric biodegradable material, enabling acute antithrombogenicity and long-term in vivo remodeling, could be beneficial for this purpose. Conduits (1.3 mm internal diameter) were obtained by electrospinning biodegradable poly(ester urethane)urea (PEUU), and by luminally immobilizing a non-thrombogenic, 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer. Platelet adhesion was characterized in vitro after contact with ovine blood. The conduits were implanted as aortic interposition grafts in the rat for 4, 8, 12, and 24 weeks. Surface treatment resulted in a 10-fold decrease in platelet adhesion compared to untreated material. Patency at 8 weeks was 92% for the coated grafts compared to 40% for the non-coated grafts. Histology at 8 and 12 weeks demonstrated formation of cellularized neotissue consisting of aligned collagen and elastin. The lumen of the grafts was confluent with cells qualitatively aligned in the direction of blood flow. Immunohistochemistry suggested the presence of smooth muscle cells in the medial layer of the neotissue and endothelial cells lining the lumen. Mechanically, the grafts were less compliant than rat aortas prior to implantation (4.5 ± 2.0 × 10(-4) mmHg(-1) vs. 14.2 ± 1.1 × 10(-4) mmHg(-1) , respectively), then after 4 weeks in vivo they approximated native values, but subsequently became stiffer again at later time points. The novel coated grafts exhibited promising antithrombogenic and mechanical properties for small-diameter arterial revascularization. Further evaluation in vivo will be required to demonstrate complete remodeling of the graft into a native-like artery.     

Splenic neurohormonal modulation of mesenteric vascular tone

In portal hypertension, development of a hyperdynamic circulation is preceded by transient mesenteric vasoconstriction. Portal hypertension increases splenic venous outflow pressure. We hypothesized that this causes direct reflex activation of mesenteric vasoconstrictor nerves and splenorenal reflex-mediated activation of the renin-angiotensin system. In anaesthetized male rats, we measured mesenteric efferent nerve activity and mesenteric vascular conductance (MVC) after selectively elevating splenic venous pressure. Partial splenic vein occlusion raised splenic venous pressure (from 4.8 ± 0.4 to 24.1 ± 0.3 mmHg; n = 18) and induced a significant increase in mesenteric efferent nerve activity (from 23.2 ± 3.3 to 31.6 ± 3.5 spikes s(-1); n = 11); this response was abolished by prior splenic denervation (from 32.4 ± 2.4 to 31.2 ± 1.6 spikes s(-1); n = 7). Mesenteric vascular conductance, the ratio of superior mesenteric artery blood flow to mean arterial pressure, fell upon splenic vein occlusion (ΔMVC = -0.0120 ± 0.0014 ml min(-1)mmHg(-1); P < 0.05, n = 10). This was attenuated by splenic denervation (ΔMVC = -0.0044 ± 0.0018 ml min(-1)mmHg(-1); P < 0.05, n = 8), but unaffected by mesenteric denervation (ΔMVC = -0.0145 ± 0.0020 ml min(-1)mmHg(-1); n = 6) or bilateral renal denervation (ΔMVC = -0.0106 ± 0.0021 ml min(-1)mmHg(-1); n = 5). Localized blockade of mesenteric vascular angiotensin II type 1 (AT(1)) receptors significantly attenuated the response (ΔMVC = -0.0058 ± 0.0017 ml min(-1)mmHg(-1); P < 0.05, n = 5), whereas blockade of both AT(1) and α(1)-adrenergic receptors caused a significant increase in mesenteric conductance (ΔMVC = +0.0033 ± 0.0010 ml min(-1)mmHg(-1); P < 0.05, n = 6). Our evidence suggests that increased splenic venous outflow pressure reflexly activates adrenergic/angiotensinergic mesenteric nerves, vasodilator mesenteric nerves and the renin-angiotensin system. We propose that obstruction to splenic venous outflow, such as would normally accompany portal hypertension, induces reflex mesenteric vasoconstriction independently of the increase in portal venous pressure.     

Ischemic exercise hyperemia in the human forearm: reproducibility and roles of adenosine and nitric oxide

The roles of local metabolites in reactive and exercise hyperemia remain incompletely understood. A maximum metabolic stimulus caused by ischemic exercise (IE) could potentially fully activate all vasodilator pathways and limit potential redundancy amongst vasoactive substances. We tested the hypotheses that IE elicits a reproducible hyperemic response in the forearm and that adenosine (ADO) and nitric oxide (NO) contribute to this response. In separate protocols, forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and rhythmic forearm handgrip exercise (performed during last 2 min of ischemia). In protocol 1 (n = 8), FBF was measured after three trials of IE. In protocol 2 (n = 9), subjects performed IE during control (saline), aminophylline (APH; adenosine receptor antagonist), and combined APH/N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) infusions. In protocol 1, coefficients of variation for total (area under the curve) ΔFBF and ΔFVC (forearm vascular conductance) following IE were 10.4 ± 1.0% and 14.9 ± 1.0%, respectively. In protocol 2, peak ΔFBF was similar for saline and APH trials. Peak ΔFBF for the APH+L: -NMMA trial was greater than that of the APH trial (P = 0.03), and peak ΔFVC was marginally non-significant (P = 0.053). Total ΔFBF (54.8 ± 3.9, 55.2 ± 5.4, and 60.4 ± 4.8 ml 100 ml(-1); P = 0.43) and ΔFVC (51.4 ± 3.5, 52.1 ± 5.5, and 56.5 ± 5.0 ml 100 ml(-1) 100 mmHg(-1); P = 0.52) were similar for saline, APH, and APH+L: -NMMA, respectively. Our data suggest that (1) the hyperemic response to IE is reproducible and (2) inhibition of ADO alone or combined ADO and NO does not blunt the hyperemic response following IE.     

保留自身关节的定制型假体与新轴心式膝关节假体在股骨远端骨肉瘤保肢治疗中的应用效果比较

目的:对比分析保留自身关节的定制型假体和新轴心式膝关节假体在股骨远端骨肉瘤保肢治疗中的临床疗效。方法:回顾性队列研究。纳入2012年8月—2019年3月上海市第六人民医院股骨远端骨肉瘤患者32例,其中男22例、女10例,年龄8～73(22.1±15.9)岁。本组32例新辅助化疗均有效,均行股骨远端瘤段切除假体重建术治疗...     

骨髓间充质干细胞构建组织工程化小口径血管

目的采用在动物体外构建初级组织工程化血管、体内强化的方法,探讨构建小口径组织工程化血管的可能性.方法体外培养骨髓间充质干细胞(BMSC),用含全反式维甲酸(AT-RA)、双丁酰环磷酸腺苷(db-cAMP)的DMEM-LG培养液和含血管内皮细胞生长因子(VEGF)的培养液诱导BMSC分别向血管平滑肌样细胞和血管内皮样细胞分化.免疫荧光观察平滑肌样细胞β肌动蛋白的表达和内皮样细胞vWF的表达.电镜观察超微结构的改变.诱导的血管平滑肌样细胞和血管内皮样细胞,分层种植于胶原包埋聚乙醇酸(PGA)的复合支架表面,将细胞和支架复合体种植于动物皮下,于植入后第4、8周再次麻醉动物,取出植入皮下的组织工程化血管,行组织学检查、压力实验及免疫荧光检查.结果诱导14 d后,BMSC能够分化为血管平滑肌样细胞和血管内皮样细胞:β肌动蛋白和vWF呈阳性表达,电镜证实细胞出现了相应的形态学改变.人工血管组织学观察见管壁结构清晰.单纯支架组可承受100～150 mm Hg(1mm Hg=0.133 kPa)的血管腔内压力,实验组则均可承受200mm Hg的血管腔内压力不破裂.实验组皮下培养8周Brdu标记细胞的免疫荧光结果显示部分细胞核呈现明亮的黄绿色荧光.结论以动物皮下为生物反应器可构建出组织工程化血管,其大体结构和天然血管相似.     

Calpain inhibition preserves talin and attenuates right heart failure in acute pulmonary hypertension

Right heart failure from right ventricular (RV) pressure overload is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We tested the hypothesis that right heart failure during 4 hours of RV pressure overload is associated with alterations of the focal adhesion protein talin, and that the inhibition of calpain attenuates RV dysfunction and preserves RV talin. Anesthetized open-chest pigs treated with the calpain inhibitor MDL-28170 (n = 20) or inactive vehicle (n = 23) underwent 4 hours of RV pressure overload by pulmonary artery constriction (initial RV systolic pressure, 64 ± 1 and 66 ± 1 mm Hg in MDL-28170 and vehicle-treated pigs, respectively). Progressive RV contractile dysfunction was attenuated by MDL-28170: after 4 hours of RV pressure overload, RV systolic pressure was 44 ± 4 mm Hg versus 49 ± 6 mm Hg (P = 0.011), and RV stroke work was 72 ± 5% of baseline versus 90 ± 5% of baseline, (P = 0.027), in vehicle-treated versus MDL-28170-treated pigs, respectively. MDL-28170 reduced the incidence of hemodynamic instability (death or systolic blood pressure of < 85 mm Hg) by 46% (P = 0.013). RV pressure overload disrupted talin organization. MDL-28170 preserved talin abundance in the RV free wall (P = 0.039), and talin abundance correlated with the maintenance of RV free wall stroke work (r = 0.58, P = 0.0039). α-actinin and vinculin showed similar changes according to immunohistology. Right heart failure from acute RV pressure overload is associated with reduced talin abundance and disrupted talin organization. Calpain inhibition preserves the abundance and organization of talin and RV function. Calpain inhibition may offer clinical utility in treating acute cor pulmonale.     

The vascular prosthesis without pseudointima prepared by antithrombogenic phospholipid polymer

On the luminal surface of the common synthetic vascular prostheses, blood coagulation can occur and a thrombus membrane is formed when blood flow passes through it. The thrombus membrane should be organized according to the wound healing process and it becomes a pseudointima which could serve as a blood conduit. However, the small-diameter vascular prosthesis may be quickly occluded by the initial thrombus. Therefore, no clinically applicable small-diameter prostheses have been developed to date. 2-Methacrylovloxyethyl phosphoryleholine (MPC) polymers resemble the structure of an outer cell membrane similar to the fluid mosaic model and demonstrate excellent antithrombogenicity. The purpose of this study is to develop a clinically applicable small-diameter prosthesis based on the new concept of the MPC polymer. We prepared vascular prostheses (2mm ID) from polymer blend composed of segmented polyurethane and the MPC polymer. The prostheses were placed in rabbit carotid arteries. The luminal surface retrieved at eight weeks after implantation was clear without thrombus and pseudointima. We now realize that the vascular prosthesis having the MPC polymer can be applied as a small-diameter prosthesis because it functions without thrombus and pseudointima formation.     

The attenuation of restenosis following arterial gene transfer using carbon nanotube coated stent incorporating TAT/DNA(Ang1+Vegf) nanoparticles

This study report the development of a nanobiohybrid hydrogel based endovascular stent device capable of preventing postangioplasty in-stent restenosis (ISR) by promoting significant vascular endothelial recovery in a site-specific manner. The hydrogel is comprised of fibrin matrices, assembled layer-by-layer (LbL) on stent surface with alternate layers carrying endosomolytic Tat peptide/DNA nanoparticles (NPs) or NPs hybridized to polyacrylic acid (PAA) wrapped single-walled carbon nanotubes (NP-CNT). Here, the hydrogel works as a reservoir to carry, protect, and simultaneously deliver pro-angiogenic, vascular endothelial growth factor (Vegf) and Angiopoietin-1(Ang1), gene carrying NPs to the target site. In?vitro results demonstrated that CNTs incorporated in the hydrogel layers play a major role in tuning the bioactivity of the stent. In addition, the developed stent formulation can significantly reduce the loss of therapeutics while traversing through the vessel and during deployment. In?vivo experiments in balloon-injured canine femoral artery demonstrated that the NCS (+) group, carrying NP(vegf+Ang1), can significantly enhance re-endothelialization of injured artery compared to control NCS (-), carrying NP(Null), and bare metal stent (BMS) groups, attenuate stenosis (18.5±9.03% vs 39.56±13.8 vs 45.34±8.3%; n=8, p<0.05) and prevent neointima formation (1.53±0.36mm(2) vs 2.51±0.27mm(2) vs 2.66±0.14mm(2); n=8, p<0.05) as analyzed angiography and histomorphometric analysis. These data collectively implicate that this new technology can be useful for stent and other biomedical devices through controlled delivery of multiple biotherapeutics.     

Heavy and moderate interval exercise training alters low-flow-mediated constriction but does not increase circulating progenitor cells in healthy humans

Moderate-intensity endurance exercise training improves vascular endothelial vasomotor function; however, the impact of high-intensity exercise training has been equivocal. Thus, the effect of the physiological stress of the exercise remains poorly understood. Furthermore, enhanced vascular repair mediated by circulating progenitor cells may also be improved. To address whether the physiological stress of exercise training is an important factor contributing to these adaptations, 20 healthy participants trained for 6 weeks. Training involved either moderate (MSIT; n = 9) or heavy metabolic stress (HSIT; n = 11) interval exercise training programmes matched for total work and duration of exercise. Before and after training, flow-mediated dilatation, low-flow-mediated constriction and total vessel reactivity were measured at the brachial artery using Doppler ultrasound. Circulating progenitor cells (CD34(+), CD133(+) and CD309/KDR(+)) were measured by flow cytometry (means ± SD). Relative (MSIT pre- 5.5 ± 3.4 versus post-training 6.6 ± 2.5%; HSIT pre- 6.6 ± 4.1 versus post-training 7.0 ± 3.4%, P = 0.33) and normalized (P = 0.16) flow-mediated dilatation did not increase with either training programme. However, low-flow-mediated constriction was greater after training in both groups (MSIT pre- -0.5 ± 3.2 versus post-training -1.9 ± 3.1%; HSIT pre- -1.0 ± 1.7 versus post-training -2.9 ± 3.0%, P = 0.04) and contributed to greater total vessel reactivity (MSIT pre- 7.4 ± 3.3 versus post-training 10.1 ± 3.7%; HSIT pre- 10.9 ± 5.9 versus post-training 12.7 ± 6.2%, P = 0.01). Peak reactive hyperaemia and the area under the shear rate curve were not different between groups, either before or after training. Although circulating progenitor cell numbers increased following heavy-intensity interval exercise training, variability was great amongst participants [MSIT pre- 16 ± 18 versus post-training 14 ± 12 cells (ml whole blood)(-1); HSIT pre- 8 ± 6 versus post-training 19 ± 23 cells (ml whole blood)(-1), P = 0.50]. Overall, vasoconstrictor function may be augmented by moderate- and heavy-intensity interval exercise training in young adults. However, circulating progenitor cell numbers were not increased, suggesting that these cells are not likely to be upregulated as a result of training.