Facilitating The Physiological Transition at Birth In Term And Preterm Neonates

描述（由申请人提供）：从胎儿到新生儿的转变是所有人类必须经历的最复杂和最具挑战性的转变之一。虽然大多数婴儿都能轻松地完成这种转变，但仍有相当数量的婴儿需要某种形式的干预才能生存。但不幸的是，这种干预可能会无意中伤害婴儿，导致终身残疾。我们相信，随着对相关过程的更好理解，有可能将受伤的风险降到最低。我们的主要目的是增加我们对从胎儿到新生儿生命过渡的生理学基础的理解，并利用这些信息来改进用于支持产房中婴儿的策略，在他们生命的这个重要阶段。最近由ILCOR提出的2010年新生儿复苏指南强调了新生儿复苏的许多领域，其中具体建议缺乏适当的证据来支持当前或拟议的实践。我们将努力填补其中一些重要的知识空白，使新生儿保健的改善以可靠的科学证据为基础。我们的独特建议将使用大型和小型动物模型来研究早产儿在出生时向新生儿生活过渡期间所经历的最关键问题。我们将：(1)确定在产房启动通风的最有效方法。具体来说，我们将专注于优化肺再生，促进肺血流动力学的增加和保护大脑免受血流动力学不稳定的程序。（II）确定重度窒息早产羔羊出生后第一次呼吸时的持续充气如何迅速恢复心脏功能，以及这种快速反应是否会增加脑损伤的风险（III）确定呼吸、心血管的生理基础

DESCRIPTION (provided by applicant): The transition from a fetus to a newborn is one of the most complex and challenging transitions that all humans have to undertake. While most infants make this transition with remarkable ease, a significant number of infants require some form of intervention to survive. But unfortunately, this intervention can inadvertently injure the infant causing life-long disability. We believe that with a better understanding of the processes involved, it is possible to minimize the risk of injury. Our primary aim is to increase our understanding of the physiology underpinning the transition from fetal to newborn life and to use this information to improve the strategies used to support infants in the delivery room, during this vital stage of their life. The recent 2010 neonatal resuscitation guidelines proposed by ILCOR has highlighted many areas of neonatal resuscitation where specific recommendations lack appropriate evidence to support current or proposed practices. We will endeavor to fill some of these critical gaps in knowledge so that improvements in neonatal health care are based on sound scientific evidence. Our unique proposal will use large and small animal models to investigate the most critical issues experienced by preterm infants during their transition to newborn life at birth. We will: (I) identify the most effective ways of initiating ventilation in te delivery room. Specifically we will focus on procedures that optimize lung recruitment, facilitate the increase in pulmonary hemodynamics and protect the brain from hemodynamic instability. (II) determine how a sustained inflation, given as the first breath after birth in severely asphyxi preterm lambs, rapidly restores cardiac function and whether this rapid response increases the risk of brain injury (III) determine the physiological basis underlying respiratory, cardiovascular and cerebral vascular improvements observed in response to delayed umbilical cord clamping, and determine the factors that alter these physiological responses. Our application incorporates a unique collaboration between clinicians, physiologists, physicists and engineers and utilizes the most advanced physiological, imaging and analytical capabilities currently available. Underpinning this application is our unique imaging capabilities, which allow for real-time assessment of lung aeration with a temporal and spatial resolution capable of imaging the smallest air sacs throughout a breath. Analysis of these images (developed by us) allows for accurate determination of regional lung volume, lung perfusion and lung tissue motion. Our proposal is focused on addressing the major issues facing clinicians and providing a strong physiological basis to improve the treatment of premature infants during the transition to newborn life at birth.