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Immunological and hemostatic responses to ventricular assist device support.

机译:对心室辅助装置支持的免疫和止血反应。

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摘要

Ventricular assist devices (VADs) are critical in the treatment of advanced heart failure, but continue to be plagued by infection, bleeding and thrombosis. Immunity may be affected by VADs, though most paradigms were developed in older-generation pumps and may not currently be applicable. Similarly, hemostasis and platelets may be impacted by device type, though the patient's health may also influence outcomes. Temporal immune cell activation and thrombosis biomarkers levels were evaluated across several contemporary pumps. This relationship was further studied in vitro through development of a method for visualizing cellular deposition onto opaque materials. An improved understanding of the cellular effects of VADs was sought through a comparative evaluation of these pumps, and this understanding may aid in the development of predictive indices of adverse events and influence future device design.;Patients implanted with a currently-utilized VAD did not experience changes to adaptive immunity reported with previous-generation devices. However, infection was still an ongoing risk for these patients. Further investigation found the impact of VADs on immunity was greater than that of similar surgeries, especially among innate immunity. Granulocyte activation was elevated following VAD implantation, and was significantly pronounced in one model, suggesting an influence of design on immune cells. Granulocyte activation promotes extravasation and apoptosis, suggesting a pathway for decreased cellular immunity.;Pre-operative hepatic dysfunction had immediate and long lasting hemostatic effects on VAD patients. Model for End-stage Liver Disease (MELD) score was found to be a positive pre-operative predictor of post-implant bleeding, blood product consumption and elevation of thrombosis biomarkers. MELD score was also found to be a stronger predictor of immediate post-operative bleeding than device type, underscoring the importance of patient pre-operative health on post-operative outcomes.;With this difficult hemostatic environment, improvement of the blood-contacting surfaces of rotary VADs may reduce complications. A flow chamber for real-time visualization of platelet deposition onto surfaces of opaque VAD materials under physiologically-relevant conditions was developed. This was accomplished through the novel combination of fluorescently-marked platelet-rich-plasma and translucent hemoglobin-depleted red blood cells. This method enables the hemocompatibility assessment of a wide range of implantable materials.
机译:心室辅助装置(VAD)在晚期心力衰竭的治疗中至关重要,但继续受到感染,出血和血栓形成的困扰。尽管大多数范例都是在较早的泵中开发的,但免疫力可能会受到VAD的影响,并且目前可能不适用。同样,止血和血小板可能会受到器械类型的影响,尽管患者的健康状况也可能会影响预后。在几个当代泵中评估了时间免疫细胞的活化和血栓形成生物标志物的水平。通过开发可视化细胞沉积在不透明材料上的方法,在体外进一步研究了这种关系。通过对这些泵的比较评估,寻求对VAD的细胞效应的更好理解,这种理解可能有助于不良事件的预测指标的发展并影响未来的设备设计。植入当前使用的VAD的患者并未体验上一代设备报告的自适应免疫的变化。然而,感染仍然是这些患者的持续危险。进一步的研究发现,VAD对免疫的影响大于类似手术的影响,特别是在先天免疫中。 VAD植入后,粒细胞激活升高,并且在一种模型中明显增强,表明设计对免疫细胞的影响。粒细胞活化促进外渗和凋亡,提示细胞免疫力降低。术前肝功能异常对VAD患者具有即刻和长期的止血作用。发现终末期肝病(MELD)评分模型是植入后出血,血液制品消耗和血栓形成生物标志物升高的阳性术前预测指标。还发现MELD评分比设备类型更能预示术后立即出血,强调了患者术前健康状况对术后预后的重要性。在这种困难的止血环境中,改善了患者血液接触表面旋转式VAD可以减少并发症。开发了一种流动室,用于在生理相关条件下实时观察血小板沉积在不透明VAD材料表面上的情况。这是通过富荧光的富血小板血浆和半透明的贫血红蛋白的红细胞的新颖组合来实现的。这种方法可以评估多种可植入材料的血液相容性。

著录项

  • 作者

    Woolley, Joshua Ryan.;

  • 作者单位

    University of Pittsburgh.;

  • 授予单位 University of Pittsburgh.;
  • 学科 Engineering Biomedical.;Biology Cell.;Health Sciences Surgery.;Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 183 p.
  • 总页数 183
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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