Development of an Artificial Placenta

描述（由申请人提供）：美国每年有500万新生儿，其中50万为早产儿。早产与大量的死亡率、发病率和不断上升的成本有关。早产并发症导致大量呼吸、胃肠、免疫和中枢神经系统的发病率和显著的死亡率。特别是，早产儿呼吸衰竭的有效治疗仍然是一个未解决的问题。已经制定了几种策略来支持这些婴儿，包括改进机械通气和在严重呼吸衰竭时使用体外生命支持（ECLS）。ECLS仅限于妊娠3 -3周的婴儿，需要全身肝素化，不维持胎儿循环。为了规避这些挑战，开发一种通过脐带血管进入的泵驱动动静脉AV-ECLS电路形式的人工胎盘是一种很有吸引力的选择。在过去的40年里，许多研究人员试图制造人工胎盘，但由于技术有限，它从未超出概念阶段。我们的实验室开发了一种母胎羊模型，初步数据证明了解决这一问题的可行性。我们的目标是进一步表征和发展这个模型，为更长时间的实验做准备。我们意识到这是一个长期的项目，将对早产儿的护理产生重大影响。本研究的目的是建立一种通过脐带血管进行体外气体交换并维持血液动力学稳定性和正常胎儿循环的早产儿羔羊动物模型。本提案的具体目标是：1)开发一个原型动-静脉ECLS人工胎盘，包括脐血管通道和提供胎儿支持所需的技术；2)在AV- ECLS期间维持胎儿循环稳定24小时，特别注意识别那些限制实际长期应用的因素。

DESCRIPTION (provided by applicant): There are 5 million births in the United States each year of which 500,000 are premature. Premature delivery is associated with substantial mortality, morbidity and escalating cost. The complications of premature birth result in substantial respiratory, gastrointestinal, immune and central nervous system morbidity and significant mortality. In particular, effective treatment of respiratory failure in premature infants remains an unsolved problem. Several strategies have been developed to support these infants, including refinements in mechanical ventilation and the use of extracorporeal life support (ECLS) in severe respiratory failure. ECLS is limited to infants >34 weeks gestation for 2-3 weeks, requires systemic heparinization and does not maintain fetal circulation. To circumvent many of these challenges, the development of an artificial placenta in the form of a pump-driven arterio-venous AV-ECLS circuit with access via the umbilical vessels is an appealing alternative. For the last 40 years, many investigators have tried to make an artificial placenta but it has never gone beyond the concept phase because of limited technology. Our laboratory has developed a maternal-fetal sheep model with preliminary data demonstrating the feasibility to address this problem. We aim to further characterize and develop this model to prepare for longer duration experiments. We realize that this is a long term project which will impact substantially upon the care of premature newborns. The goal of this proposal is to develop an animal model in the preterm fetal lamb with full extracorporeal gas exchange via the umbilical vessels and maintenance of hemodynamic stability and normal fetal circulation. The specific aims of this proposal are 1) to develop a prototype arterio-venous ECLS artificial placenta including umbilical vessel access and the techniques necessary to provide fetal support; and 2) to maintain stable fetal circulation during AV- ECLS for 24 hours, with particular attention to identify those factors which will limit practical long-term application. PUBLIC HEALTH RELEVANCE: The complications associated with premature birth remain a major unsolved health problem. We propose development of a mechanical artificial placenta that would allow a premature infant to grow and thrive while avoiding the many complications using conventional treatment. Development of an artificial placenta would revolutionize the care of premature infants.