Optimal Oxygenation in Neonatal Lung Injury

描述(由申请人提供)：美国心脏协会最近发布的指南建议在足月新生儿的初始复苏过程中使用21%的氧气，并使用混合补充氧气来维持早产儿的目标饱和度。美国儿科学会建议，在管理患病新生儿时，将PaO2保持在50至80毫米汞之间。这些建议是基于对人类婴儿氧饱和度的研究，以及对没有肺部疾病的新生儿动物模型的翻译研究。从组织氧输送和氧毒性的角度来看，早产儿和足月儿肺损伤/疾病复苏和机械通气过程中的最佳氧浓度和目标氧饱和度范围尚不清楚。氧疗的总体目标是提供足够的氧气来满足组织的需求，而不存在氧气中毒的风险。这项建议的主要目的是确定在复苏和换气期间患有实质性肺疾病/肺损伤的新生羔羊的最佳吸入氧气浓度。在这项建议中，将研究两种新生儿肺损伤类型。在TER羔羊中，脐带闭塞和窒息(“窒息-MAS”组)会在喘息时吸入胎粪而导致损伤。妊娠126d(足月~145d)早产羔羊因肺表面活性物质缺乏和呼吸窘迫综合征(“早产-呼吸窘迫综合征”)而导致肺实质损伤(“早产-RDS”)。羔羊将被复苏并用21%氧气、100%氧气或调整吸入氧气浓度来维持氧气饱和度在85%至89%、90%至94%或95%至99%之间。这项建议的第一个具体目标是确定吸入氧浓度和饱和度对氧合、肺摄氧量和组织氧输送的影响。第二个具体目标是评估氧气浓度和饱和度对肺、脑、冠状动脉和导管血流动力学的影响，并评估氧气向各个重要器官的输送。我们打算通过我们的最后一个特定目标来评估与不同水平的氧气相关的肺和大脑的氧化性损伤的风险。

DESCRIPTION (provided by applicant): The American Heart Association recently released guidelines recommending the use of 21% oxygen during initial resuscitation of term newborn infants and use of blended supplemental oxygen to maintain target saturations in premature infants. The American Academy of Pediatrics recommends maintaining PaO2 between 50 and 80 mmHg in the management of sick neonates. These recommendations are based on studies using oxygen saturations in human infants and through translational studies in neonatal animal models without lung disease. Optimal oxygen concentration and target oxygen saturation range during resuscitation and ventilation of preterm and term neonates with lung injury/disease from a standpoint of tissue oxygen delivery and oxygen toxicity is not known. The overall goal of oxygen therapy is to provide adequate oxygen to meet tissue demand without risking oxygen toxicity. The overarching aim of this proposal is to determine the optimal concentration of inspired oxygen during resuscitation and ventilation of a newborn lamb with parenchymal lung disease/ lung injury. Two patterns of neonatal lung injury will be studied in this proposal. In ter lambs injury will be induced by aspiration of meconium during gasping respirations induced as a consequence of umbilical cord occlusion and asphyxia ("asphyxia-MAS" group). Preterm lambs delivered at 126d gestation (term ~ 145d) have parenchymal lung injury as a consequence of surfactant deficiency and respiratory distress syndrome ("preterm-RDS" group). Lambs will be resuscitated and ventilated with 21% oxygen, 100% oxygen or adjusted inspired oxygen concentration to maintain oxygen saturations between 85 to 89%, 90 to 94% or 95 to 99%. The first specific aim of this proposal is to determine the effect inspired oxygen concentration and saturations on oxygenation, lung oxygen uptake and oxygen delivery to the tissues. The second specific aim is to evaluate the effect of oxygen concentration and saturations on pulmonary, cerebral, coronary and ductal hemodynamics and assess delivery of oxygen to various vital organs. We intend to evaluate the risk of oxidant injury in the lung and brain associated with various levels of oxygen through our last specific aim.