Biology of Long-Term Mechanical Circulatory Support

长期机械循环支持生物学

• 批准号: 7422301
• 负责人: YOSHIFUMI NAKA
• 金额: $ 246.98万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-25 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422301
• 关键词: Biology; Long; Term; Mechanical; Circulatory

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a highly prevalent and morbid condition. Randomized trials have shown that the one-year mortality in the subset of heart failure patients with refractory endstage disease ranges from 50 to 75%. Outcomes are worse than those for breast, colon and even lung cancer. Pharmacological treatment offers limited benefit to these patients while heart transplantation is severely limited by the shortage of human donors. Implantable left ventricular assist devices (LVADs) have been developed and clinically investigated in order to fill the obvious gap in our clinical armamentarium. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Trial recently demonstrated significant survival and quality of life benefit in LVAD recipients compared to medically managed patients. However, the trial also documented the remaining serious adverse events associated with LVAD therapy, which, if overcome, would add substantially to its effectiveness while reducing costs. The proposed SCCOR seeks to elucidate and modulate the biology of the interface between implanted long-term mechanical circulatory support devices and patients with end-stage heart failure. A combination of closely linked animal model and human clinical trials is planned. Studies will evaluate novel interventions directed at the adverse impact of infection and coagulopathy that result from this interface. Furthermore, the feasibility of improving native myocardial function through cellular transplantation in order to facilitate device removal will be explored. While observations and interventions will focus on end-stage heart failure, the exploration of coagulation in this setting could enhance interventions to prevent and manage bleeding and thrombo-embolism while exploration of cellular transplantation has the potential to improve therapeutic approaches to less severe forms of heart failure. The planned research on infection has broader implications for prosthetic implants in general.

描述(由申请人提供)： 充血性心力衰竭(CHF)是一种非常普遍和病态的疾病。随机试验 研究表明，在患有难治性终末期疾病的心力衰竭患者中，一年的死亡率从50%到75%不等。结果比乳腺癌、结肠癌甚至肺癌更糟糕。药物治疗对这些患者的益处有限，而心脏移植则受到人类供体短缺的严重限制。可植入左心室辅助装置(LVADs)的研制和临床应用，填补了我国临床研究的空白。最近进行的机械辅助治疗充血性心力衰竭(REMATCH)试验的随机评估显示，与医疗管理的患者相比，LVAD接受者的存活率和生活质量都有显著改善。然而，该试验也记录了与LVAD治疗相关的其余严重不良事件，如果克服这些不良事件，将大大增加其有效性，同时降低成本。拟议的SCCOR旨在阐明和调节植入的长期机械循环支持设备与终末期心力衰竭患者之间的接口生物学。计划将密切联系在一起的动物模型和人类临床试验结合起来。研究将评估针对这一界面导致的感染和凝血障碍的不利影响的新干预措施。此外，还将探讨通过细胞移植改善天然心肌功能以促进装置移除的可行性。虽然观察和干预措施将集中在终末期心力衰竭上，但在这种情况下探索凝血可以加强预防和管理出血和血栓栓塞症的干预措施，而探索细胞移植则有可能改进治疗方法，以治疗不太严重的心力衰竭。计划中的感染研究总体上对假肢植入物具有更广泛的影响。

项目成果

Challenges of long-term mechanical circulatory support therapy.

长期机械循环支持治疗的挑战。

• DOI: 10.1586/17434440.5.4.413
• 发表时间: 2008
• 期刊: Expert review of medical devices
• 影响因子: 3.1
• 作者: Latif,Farhana;Cadeiras,Martin;vonBayern,ManuelPrinz;Shahzad,Khurram;Sinha,Anshu;Deng,MarioC
• 通讯作者: Deng,MarioC

Cardiac transplantation: any role left?

• DOI: 10.1016/j.hfc.2007.04.004
• 发表时间: 2007-07-01
• 期刊: Heart failure clinics
• 影响因子: 3.4
• 作者: Cadeiras, Martin;von Bayern, Manuel Prinz;Deng, Mario C
• 通讯作者: Deng, Mario C

Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment.

泵，渡槽和干旱管理：血管认知障碍的血管生理。

• DOI: 10.1161/strokeaha.110.595645
• 发表时间: 2011-01
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Marshall RS;Lazar RM
• 通讯作者: Lazar RM

Vaccination with clumping factor A and fibronectin binding protein A to prevent Staphylococcus aureus infection of an aortic patch in mice.

• DOI: 10.1086/590210
• 发表时间: 2008-08-15
• 期刊: The Journal of infectious diseases
• 作者: Arrecubieta C;Matsunaga I;Asai T;Naka Y;Deng MC;Lowy FD
• 通讯作者: Lowy FD

Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia.

• DOI: 10.1111/j.1582-4934.2010.01241.x
• 发表时间: 2011-10
• 期刊: Journal of cellular and molecular medicine
• 影响因子: 5.3
• 作者: See F;Seki T;Psaltis PJ;Sondermeijer HP;Gronthos S;Zannettino AC;Govaert KM;Schuster MD;Kurlansky PA;Kelly DJ;Krum H;Itescu S
• 通讯作者: Itescu S