新型机械心脏瓣膜的研究

目前临床使用的各种机械心脏瓣膜的主要问题是血栓栓塞和与抗凝治疗有关的出血,其缺陷在于瓣膜开启时,碟片和支架将瓣膜的整个血流通道分隔成三至四个较小的血流通道。在这种受阻隔的血流通宫,形成容易诱发血栓的高剪应力区、紊流和滞流区。我们研制的两种机械心脏瓣膜在瓣膜开启时,没有任何支架和碟片分隔瓣膜的血流通道,使血流与天然心脏瓣膜中的相类似,可减少对血液的危害,从而可减少换瓣病人对抗凝治疗的依赖程度。     

Mineralization by mesenchymal stromal cells is variously modulated depending on commercial platelet lysate preparations

Background aims

Numerous cellular models have been developed to investigate calcification for regenerative medicine applications and for the identification of therapeutic targets in various complications associated with age-related diseases. However, results have often been contradictory due to specific culture conditions, cell type ontogeny and aging status. Human platelet lysate (hPL) has been recently investigated as valuable alternative to fetal bovine serum (FBS) in cell culture and bone regeneration. A parallel comparison of how all these multiple factors may converge to influence mineralization has yet to be reported.

Regulation of the growth of nonmuscle heart cells in culture

Summary Primary cultures of neonatal rat hearts contain both striated muscle (myocytes) as well as nonmuscle heart cells (NMHC). Although myocytes do not divide in culture, NMHC do increase in number. The growth of NMHC is dependent on the concentration of serum in the media over a range of 1 to 10%. When compared to growth in 10%, cells in 1% serum have a prolonged doubling time and reach a maximum density that is 70% less. Thus, 1% serum which supports normal myocyte development is a useful culture media to also maintain muscle heart cell homogeneity by its failure to support optimum NMHC division. Dr. Klein is a Clinical Investigator of The Veteran’s Administration supported in part by The Western Pennsylvania Heart Association and NIH Grant 5T32 HL07557.     

Morphological and biochemical analysis of human cardiac valve allografts after an increment of the cryostorage temperature

Cryopreserved human cardiac valve allografts could suffer lethal damages if the temperature is elevated during cryostorage. This work describes the functional and morphological alterations suffered by human cardiac valve allografts after a gradual increment of the cryostorage temperature from −147 °C to −47 °C due to a technical failure. Three experimental groups of human pulmonary and aortic allografts were compared: fresh, cryopreserved (−147 °C) and cryopreserved with temperature changes from −147 °C up to −47 °C and back to −147 °C. Fibroblast functionality was studied to asses the degree of valvular damages. Collagen network was also analyzed with bright light field and polarized microscopy; an immunohistochemistry for procollagen I was performed and the MTT colorimetric assay was used to evaluate fibroblast mitochondrial enzymatic activity. Porcine heart grafts valves were used to set the MTT colorimetric assay.With bright light field microscopy, disorganized collagen network was seen together with interstitial edema in cryopreserved groups. Polarized microscopy showed that fresh allografts had abundant collagen type I and III, cryopreserved group had less amount of collagen type I and in allografts that suffered cryopreservation temperature elevation collagen type I synthesis could not been demonstrated. Procollagen I was present in fibroblast cytoplasm of fresh group, but it was diminished in cryopreserved group and was absent in the group that suffered temperature elevation.Temperature changes during the cryopreservation period of human cardiac valve allografts induced fibroblast activity reduction. When the cryopreservation temperature is elevated during cryostorage, fibroblasts lost their functionality and the allografts may be not suitable for transplant.     

Regulation of valvular interstitial cell phenotype and function by hyaluronic acid in 2-D and 3-D culture environments

Disruption of the extracellular matrix (ECM) is frequently found in calcific aortic valve disease (CAVD), yet the role of ECM components in valvular interstitial cell (VIC) function and dysfunction remains poorly understood. This study examines the contributions of exogenous and endogenous hyaluronic acid (HA), in both two-dimensional (2-D) and 3-D environments, in regulating the phenotype and calcification of VICs. VIC calcification was first assessed in a 2-D setting in which the cells were exposed to different molecular weights of exogenous HA presented in either an immobilized or soluble form. Delivery of HA suppressed nodule formation in a molecular weight-dependent manner, while blocking VIC recognition of HA via an antibody to CD44 abolished these nodule-suppressive effects and stimulated other hallmarks of valvular dysfunction. These 2-D results were then validated in a more physiologically-relevant setting, using an approach that allowed the characterization of VIC phenotype in response to HA alterations in the native 3-D environment. In this approach, leaflet organ cultures were analyzed following treatment with anti-CD44 or with hyaluronidase to specifically remove HA. Disruption of VIC-HA interactions upregulated markers of VIC disease and induced leaflet mineralization. Similarly, HA-deficient leaflets exhibited numerous hallmarks of CAVD, including increased VIC proliferation, apoptosis, increased expression of disease-related markers, and mineralization. These findings suggest that VIC-HA interactions are crucial in maintaining a healthy VIC phenotype. Identification ECM components that can regulate VIC phenotype and function has significant implications for understanding native valve disease, investigating possible treatments, and designing new biomaterials for valve tissue engineering.     

Pregnancy in women with prosthetic heart valves

Pregnancy in women with mechanical valve prostheses has a high maternal complication rate including valve thrombosis and death. Coumarin derivatives are relatively safe for the mother with a lower incidence of valve thrombosis than un-fractionated and low-molecular-weight heparin, but carry the risk of embryopathy, which is probably dose-dependent. The different anticoagulation regimens are discussed in this review. When valve thrombosis occurs during pregnancy, thrombolysis is the preferable therapeutic option. Bioprostheses have a more favourable pregnancy outcome than mechanical prostheses but due to the high re-operation rate in young women they do not constitute the ideal alternative. When women with native valve stenosis need pre-pregnancy intervention, mitral balloon valvuloplasty is the best option in mitral stenosis, while the Ross operation or homograft implantation may be the preferable surgical regimen in aortic stenosis. (Neth Heart J 2008;16:406-11.)     

1600例重症心脏瓣膜置换术中的体外循环管理

目的报告1600例重症心脏瓣膜置换术中的体外循环管理技术。方法CPB中采用低液面预充、中度血液稀释、浅低温、HCT22～25％,心肌保护为高钾含血停跳液灌注。对心胸比例超过85％,合并肝大、腹水、肺长期淤血的患者,CPB中采用超滤法。结果体外循环时间90～357min,主动脉阻断时间50～170min,心脏停跳时间54～175min,术中灌注压55～70mmHg,中心静脉压0～5cm H2O,尿量平均200～800ml,自动复跳1047例,占65％。结论为了提高重症心脏瓣膜手术的体外循环质量,增加手术成功率,强调：(1)中度血液稀释,提高胶体渗透压;(2)CPB中用高钾含血停搏液作为心肌保护,必须做到按时、足量灌注;(3)及时补充碱性药物和电解质;(4)补充充足的镁离子可增加细胞内的钾离子浓度。     

421例重症心脏瓣膜替换术中的体外循环探讨

本文报告1993－1996年12月施行421例重症心脏瓣膜术替换术的体外循环经验。病人年龄26－66岁,体重39－88kg。其中作二尖瓣替换术208例;二尖瓣和主动脉瓣双瓣替换术148例;主动脉瓣替换术59例;其余6例行双瓣伴作冠状动脉搭桥手术。体外循环转流时间90－357min,主动脉阻断时间50－170min,心脏停跳时间54－175min。术中灌注压8－12kPa,中心静脉压0－0．98kPa。自动复跳245例,占60％。全组421例中,手术死亡数16例,病死率为3．8％。为了提高重症心脏手术的体外 循环质量,增加手术成功率,作者强调：①选用优质模式肺,以保证长时间转流,②长时间转流必须采用高流量灌注,维持良好动脉压;③选用顺灌伴逆灌的心肌保护方法;④适当延长辅助循环时间。     

Effects of β1 →4 Linked Galactooligosaccharides on Use of Magnesium and Calcification of the Kidney and Heart in Rats Fed Excess Dietary Phosphorus and Calcium

Magnesium deficiency was induced in male Wistar rats by adding an excess of phosphorus and calcium to the diet (1.195 g of phosphorus and 1.04g of calcium/100g of diet). Feeding of these animals with a diet containing β1→4 linked galactooligosaccharides (4′-GOS) (5g of 4′-GOS/100g of diet) increased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur, and reduced accumulation of calcium in the kidney and heart. We speculate that the use of magnesium increased by feeding 4′-GOS to a limited extent prevented the lower magnesium status and the severity of calcification of the kidney and heart caused by excess dietary phosphorus and calcium.     

Transplantation of Pulmonary Valve Using a Mouse Model of Heterotopic Heart Transplantation

Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed results. However, the cellular and molecular mechanisms of the neotissue development, valve thickening, and stenosis development are not researched extensively. To answer the above questions, we developed a murine heterotopic heart valve transplantation model. A heart valve was harvested from a valve donor mouse and transplanted to a heart donor mouse. The heart with a new valve was transplanted heterotopically to a recipient mouse. The transplanted heart showed its own heartbeat, independent of the recipient’s heartbeat. The blood flow was quantified using a high frequency ultrasound system with a pulsed wave Doppler. The flow through the implanted pulmonary valve showed forward flow with minimal regurgitation and the peak flow was close to 100 mm/sec. This murine model of heart valve transplantation is highly versatile, so it can be modified and adapted to provide different hemodynamic environments and/or can be used with various transgenic mice to study neotissue development in a tissue engineered heart valve.     

颈动脉粥样硬化及主动脉瓣钙化与动脉粥样硬化性肾动脉狭窄的关系

目的:探讨颈动脉粥样硬化、主动脉瓣膜钙化(aortic valve calcification,AVC)与动脉粥样硬化性肾动脉狭窄(atherosclerotic renal artery stenosis,ARAS)的关系。方法:对我院162例行选择性冠脉造影合并肾动脉造影的患者进行颈动脉超声和超声心动图检查,测量颈动脉内中膜厚度(carotid artery intima-media thickness,CIMT)和主动脉瓣钙化的情况,根据患者是否患有ARAS进行分组,比较两组的性别、年龄、吸烟、病史、血脂水平、CIMT、颈动脉粥样硬化发生率和AVC发生率,计算颈动脉粥样硬化和AVC对ARAS的预测价值。结果:ARAS组高血压病史患者的构成比、胆固醇水平、CIMT、颈动脉粥样硬化发生率、AVC发生率均显著高于对照组,有明显的统计学差异(P0.05)。颈动脉粥样硬化预测ARAS的灵敏度较高,特异度偏低;AVC的灵敏度低,而特异度高;二者联合特异度明显增高。结论:颈动脉粥样硬化、AVC对ARAS的诊断有一定的参考价值,可用于排除诊断。