Optimal Oxygenation in Neonatal Lung Injury

描述（由申请人提供）：美国心脏协会最近发布了指南，建议在足月新生儿的初始复苏期间使用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新生儿护理中将PaO 2维持在50 - 80 mmHg之间。这些建议是基于在人类婴儿中使用氧饱和度的研究和通过在无肺部疾病的新生动物模型中的转化研究。从组织氧输送和氧毒性的角度来看，患有肺损伤/疾病的早产儿和足月新生儿复苏和通气期间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以满足组织需求，而不会有氧中毒的风险。本建议的首要目标是确定在新生羔羊肺实质性肺疾病/肺损伤复苏和通气过程中吸入氧气的最佳浓度。两种模式的新生儿肺损伤将在这个建议进行研究。在三只羔羊中，由于脐带阻塞和窒息（“窒息-MAS”组），在喘息呼吸期间吸入胎粪将诱导损伤。在妊娠126天（足月~ 145天）分娩的早产羔羊由于表面活性物质缺乏和呼吸窘迫综合征（“早产-RDS”组）而具有实质性肺损伤。将对羔羊进行复苏并使用21%氧气、100%氧气或调整吸入氧气浓度进行通气，以维持氧饱和度在85 - 89%、90 - 94%或95 - 99%之间。该建议的第一个具体目的是确定吸入氧浓度和饱和度对氧合、肺氧摄取和向组织的氧输送的影响。第二个具体目标是评价氧浓度和饱和度对肺、脑、冠状动脉和导管血流动力学的影响，并评估向各种重要器官输送氧气的情况。我们打算通过我们最后一个特定的目标来评估与不同氧水平相关的肺和脑中氧化剂损伤的风险。 公共卫生相关性：在患有肺部疾病的新生儿的复苏和随后的通气期间的氧气补充是提供足够的组织氧输送和形成压倒其缺乏的抗氧化防御系统的自由基之间的微妙平衡。最近发表的SUPPORT试验报告强调了对新生儿缺乏关于氧气补充，输送和毒性的特定生理知识的关注。从这项资助获得的数据将提供生理数据，并有助于建立未来的指导方针，为早产儿和足月新生儿肺部疾病的最佳氧气输送。

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. PUBLIC HEALTH RELEVANCE: Oxygen supplementation during resuscitation and subsequent ventilation of newborn infants with lung disease is a delicate balance between providing adequate tissue oxygen delivery and formation of free radicals that overwhelm their deficient antioxidant defense system. The recently published SUPPORT trial report has heightened concern about lack of specific physiological knowledge regarding oxygen supplementation, delivery and toxicity in newborn infants. Data obtained from this grant will provide physiological data and aid in establishment of future guidelines for optimal oxygen delivery in preterm and term neonates with lung disease.