Altered Neutrophil Function in Ventricular Assist Devices

心室辅助装置中中性粒细胞功能的改变

• 批准号: 9252513
• 负责人: DAVID W SCHMIDTKE
• 金额: $ 17.76万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9252513
• 关键词: Adhesions; Adhesives; Affect; Alcoholic Hepatitis; American; Artificial Heart; Biochemical; Blood; Blood Cells; Blood Circulation; Blood flow; Catheters; Cause of Death; Chronic; Clinical; Complication; Congestive Heart Failure; Cytoplasmic Granules; Data; Destinations; Device Designs; Devices; Diagnosis; Disease; Epidemic; Evaluation; Exhibits; Exposure to; Foundations; Future; Generations; Gold; Heart; Heart Transplantation; Heart failure; Hemorrhage; Immune; Impairment; Individual; Infection; Inflammation; Intercellular adhesion molecule 1; Intervention; Invaded; Investigation; Measures; Mechanics; Medical; Microfluidic Microchips; Microfluidics; Modeling; Neutrophil Activation; Patients; Phagocytes; Pneumonia; Predisposition; Pump; Quality of life; Reporting; Research; Selectins; Sepsis; Site; Stroke; Survival Rate; Technology; Testing; Thrombosis; Time; Transplantation; Trauma; Urinary tract infection; Western World; alternative treatment; antimicrobial; cost; exhaustion; experience; fighting; healthy volunteer; implantation; improved; microbial; microorganism; millisecond; mortality; neutrophil; novel; premature; public health relevance; response; ventricular assist device

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a growing epidemic in the Western World, afflicting 6 million people in US, with an additional 550,000 new cases diagnosed each year. The one and five year mortality rates for CHF are 10% and 60%. Heart transplantation is gold standard therapy for advanced heart failure, but that remains limited by number (2,200 donor heart available each year) and cost. Ventricular assist devices (VADs) offer an alternative treatment for advanced heart failure by working in parallel with the failing ventricle. The current generation of rotary VADs uses a turbine rotor to impart blood flow, have one year survival rates approaching 85%; however, the technology is limited by cost, complexity, and complication. A leading long term cause of death with VAD therapy is infection and 30% of VAD recipients experience an infection each year. There is very little research which has examined why VAD patients remain so susceptible to infection. We have observed that the neutrophils of VAD recipients and advanced heart failure patients circulate in the blood in an activated state, which does not occur in healthy individuals. We have also developed novel microfluidic devices to simulate the extreme shear forces which blood cells experience when they pass through the VAD. Neutrophils from healthy individuals undergoing millisecond exposure to these forces, became activated, suggesting the high shear in VAD may cause neutrophil activation. However, it is not clear why neutrophil activation would contribute to an infectious susceptibility. To investigate these issues we propose 1) Measure changes in neutrophil activation following high shear exposure, 2) Quantify the adhesive capacity of healthy volunteer neutrophils after high shear exposure in comparison to those from Advanced Heart Failure and VAD patients, 3) Examine changes in neutrophil phagocytic function after high shear exposure and in Advanced Heart Failure and VAD patients.

描述（由申请人提供）：充血性心力衰竭（CHF）在西方世界是一种日益增长的流行病，在美国有600万人受到影响，每年诊断出另外550，000例新病例。CHF的1年和5年死亡率分别为10%和60%。心脏移植是晚期心力衰竭的金标准疗法，但仍受到数量（每年可提供2，200个供体心脏）和成本的限制。心室辅助装置（VAD）通过与衰竭的心室并行工作，为晚期心力衰竭提供了一种替代治疗方法。当前一代的旋转VAD使用涡轮机转子来赋予血液流动，具有接近85%的一年存活率;然而，该技术受到成本、复杂性和并发症的限制。VAD治疗的主要长期死亡原因是感染，每年有30%的VAD接受者经历感染。很少有研究探讨为什么VAD患者仍然如此容易感染。我们已经观察到VAD接受者和晚期心力衰竭患者的中性粒细胞以激活状态在血液中循环，这在健康个体中不会发生。我们还开发了新的微流体装置来模拟血细胞通过VAD时所经历的极端剪切力。来自健康个体的中性粒细胞经历毫秒暴露于这些力，变得活化，这表明VAD中的高剪切可能导致中性粒细胞活化。然而，尚不清楚为什么中性粒细胞活化会导致感染易感性。为了研究这些问题，我们提出1）测量高剪切暴露后中性粒细胞活化的变化，2）与来自晚期心力衰竭和VAD患者的中性粒细胞相比，量化高剪切暴露后健康志愿者中性粒细胞的粘附能力，3）检查高剪切暴露后以及晚期心力衰竭和VAD患者中中性粒细胞吞噬功能的变化。

项目成果

Oncostatin M: a Potential Biomarker to Predict Infection in Patients with Left Ventricular Assist Devices.

• DOI: 10.1097/mat.0000000000001608
• 发表时间: 2022-08-01
• 期刊: ASAIO JOURNAL
• 影响因子: 4.2
• 作者: Setiadi, Hendra;El-Banayosy, Ahmed M.;George, Susan;Schmidtke, David W.;El-Banayosy, Aly;Horstmanshof, Douglas A.;Long, James W.
• 通讯作者: Long, James W.