Facilitating The Physiological Transition at Birth In Term And Preterm Neonates

描述(申请人提供)：从胎儿到新生儿的转变是所有人类必须进行的最复杂和最具挑战性的转变之一。虽然大多数婴儿非常轻松地完成了这一转变，但相当数量的婴儿需要某种形式的干预才能存活下来。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。我们认为，通过更好地了解所涉及的过程，有可能将受伤的风险降至最低。我们的主要目标是增加我们对支持从胎儿向新生儿过渡的生理学的理解，并利用这些信息来改进用于在婴儿生命的这一关键阶段在产房支持婴儿的策略。ILCOR最近提出的2010年新生儿复苏指南强调了新生儿复苏的许多领域，在这些领域中，具体建议缺乏适当的证据来支持当前或拟议的做法。我们将努力填补知识中的一些关键差距，以便新生儿保健的改善建立在可靠的科学证据的基础上。我们独特的建议将使用大小动物模型来调查早产儿在出生时过渡到新生儿生活过程中经历的最关键的问题。我们将：(I)确定在TE产房启动通风的最有效方法。具体地说，我们将专注于优化肺招募、促进肺血流动力学增加和保护大脑免受血液动力学不稳定影响的程序。(Ii)确定严重窒息早产羔羊出生后第一次呼吸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、心血管疾病的生理基础 以及在延迟夹住脐带时观察到的脑血管改善，并确定改变这些生理反应的因素。我们的应用结合了临床医生、生理学家、物理学家和工程师之间的独特合作，并利用了目前可用的最先进的生理、成像和分析能力。支撑这一应用的是我们独特的成像能力，它允许实时评估肺充气情况，时间和空间分辨率能够成像整个呼吸过程中最小的气囊。对这些图像的分析(由我们开发)可以准确地确定区域肺体积、肺血流灌注和肺组织运动。我们的建议侧重于解决临床医生面临的主要问题，并为改善早产儿在出生时向新生儿生活过渡期间的治疗提供强有力的生理学基础。

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.