Does Biocompatibility Contribute to Transfusion-Related Adverse Effects?

项目摘要 美国每年进行近1500万次输血，约42.5万单位 只给儿科病人输血尽管输血频率很高，但也不是没有风险的。血液 输血并发症可能归因于大量暴露于塑料器械， 具有内分泌干扰特性的化学物质。该提案的主要假设是，塑料设备是 不具有普遍的生物相容性-并且对化学污染物的局部和全身反应有助于 输血相关并发症。该提案的目的是评估医疗器械的生物相容性 化学品暴露是心血管和自主神经功能障碍的潜在因素。该提案 还旨在确定更安全的生物材料，化学品和/或输血装置和血液的表面涂层 银行业务.在这项建议中，我们会在初步研究的基础上，提出三个具体目标：1）界定 生物材料浸出和化学暴露改变心血管和自主神经功能的程度， 使用体内和整个心脏模型。2)确定生物相容性和偶然化学暴露是否 与输血儿科患者的心血管和自主神经异常相关。3)比较和 对比替代生物材料，化学品和制造技术，以确定更安全的替代品， 输血相关器械。拟议的应用程序将量化生物相容性和化学的作用， 浸出对心血管和自主神经功能的影响-这两个目标对异生物质毒性非常敏感。 如果在拟议的研究中观察到不良结果，它将确定未来需要监测的其他变量 临床调查和流行病学研究。最后，本建议旨在为以下方面提供基础： 关于在医疗中使用具有内分泌干扰特性的化学添加剂的客观决策 科学、医学和监管团体的器械制造。拟议研究的结果可 激励和加速替代生物材料、添加剂和/或 制造技术，以提高输血患者的安全性。

Project Summary Nearly 15 million transfusions are performed in the United States each year, with approximately 425,000 units transfused to pediatric patients alone. Despite the frequency – transfusion procedures are not without risk. Blood transfusion complications may be attributed to heavy exposure to plastic devices, which are fabricated with chemicals that exert endocrine disrupting properties. The proposal's main hypothesis is that plastic devices are not universally biocompatible – and that local and systemic reactions to chemical contaminants contribute to transfusion-related complications. The proposal's objective is to assess whether medical device biocompatibility and chemical exposures are underlying contributors to cardiovascular and autonomic dysfunction. The proposal also aims to identify safer biomaterials, chemicals and/or surface coatings for transfusion devices and blood banking. In this proposal, we will build upon our preliminary studies to address three specific aims: 1) To define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function, using in vivo and whole heart models. 2) To determine if biocompatibility and incidental chemical exposures are correlated with cardiovascular and autonomic abnormalities in transfused pediatric patients. 3) To compare and contrast alternative biomaterials, chemicals and fabrication techniques in order to identify safer replacements for transfusion-related devices. The proposed application will quantify the role of biocompatibility and chemical leaching on cardiovascular and autonomic function – two targets that are highly susceptible to xenobiotic toxicity. If adverse outcomes are observed in the proposed study, it will pinpoint additional variables to monitor in future clinical investigations and epidemiological studies. Finally, this proposal aims to provide the foundation for objective decision making regarding the use of chemical additives with endocrine disrupting properties in medical device manufacturing by scientific, medical and regulatory communities. Results of the proposed studies can incentivize and accelerate the development and clinical adoption of alternative biomaterials, additives and/or fabrication techniques to improve transfusion patient safety.