Optimal Oxygenation in Neonatal Lung Injury

新生儿肺损伤的最佳氧合

• 批准号: 10734639
• 负责人: Satyanarayana Lakshminrusimha
• 金额: $ 68.78万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734639
• 关键词: 3-nitrotyrosine; Accounting; Animal Model; Antioxidants; Apoptotic; Asphyxia Neonatorum; Blood flow; Brain; Brain Injuries; California; Canada; Cerebrum; Cessation of life; Childhood; Clinical Trials; Data; Drug Kinetics; Duct (organ) structure; Electroencephalography; European; Exposure to; Extracorporeal Membrane Oxygenation; Future; Gases; Goals; Hippocampus; Hour; Hypoxanthines; Hypoxemic Respiratory Failure; Impairment; Incidence; Infant; Intravenous; Lung; Meconium Aspiration; Mediating; Methionine; Modeling; Morbidity - disease rate; Neurodevelopmental Impairment; Neurological outcome; Neurons; Nitric Oxide; Oligodendroglia; Outcome; Oxidative Stress; Oxygen; Pharmaceutical Preparations; Plasma; Property; Pulmonary Vascular Resistance; Pulmonary artery structure; Rattus; Recommendation; Regimen; Rodent Model; Secondary to; Temperature; Therapeutic; Uganda; Vasodilation; Vasodilator Agents; Xanthines; arm; cerebral hemodynamics; design; hemodynamics; improved; indexing; inhaled nitric oxide; lamb model; methionine sulfoxide; mortality; natural hypothermia; neonatal hypoxic-ischemic brain injury; neonatal lung injury; neonatal pulmonary hypertension; neonate; neuron loss; neuroprotection; nitrosative stress; phosphodiesterase V; pulmonary vascular disorder; pulmonary vasoconstriction; pup; response; sildenafil; standard of care; ventilation

Project summary: Optimal oxygenation in neonatal lung injury Whole-body hypothermia is currently the standard of care for moderate to severe hypoxic-ischemic encephalopathy (HIE). HIE is commonly associated with meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of the newborn (PPHN). Therapeutic hypothermia can cause pulmonary vasoconstriction and exacerbate PPHN and is currently the leading indication for extracorporeal membrane oxygenation in California. The optimal target SpO2, and pulmonary vasodilator regimen that results in improvement in both pulmonary and neurological outcomes in PPHN and HIE is not known. We hypothesize that targeting 95-98% SpO2 (compared to 91-95% - current standard of care) and intravenous (IV) sildenafil will minimize brain injury and enhance pulmonary vasodilation. The first specific aim focuses on changes in gas exchange and cerebral hemodynamics with two SpO2 target ranges during 72-hours of whole-body hypothermia. The second specific aim focuses on oxidative stress and neuroprotection offered by iNO and sildenafil following birth asphyxia during hypothermia and ventilation at two different SpO2 targets. The final specific aim evaluates the impact of hypothermia on pulmonary hemodynamics and pharmacokinetics of sildenafil. Hypoxemic respiratory failure secondary to MAS and PPHN is common during whole-body hypothermia. Results from this study will inform the design of future clinical trials by defining the optimal SpO2, temperature, and pulmonary vasodilators while managing neonates with PPHN and HIE. The therapeutic potential of a commonly available and less expensive agent such as sildenafil in improving both pulmonary and neurological outcomes following birth asphyxia will be explored in this proposal.

项目总结：新生儿肺损伤的最佳氧合 全身低温是目前治疗中度至重度缺氧缺血性脑病的标准方法。 脑病（HIE）。HIE通常与胎粪吸入综合征（MAS）相关， 新生儿持续性肺动脉高压（PPHN）。治疗性低温会导致 肺血管收缩并加重PPHN，目前是PPHN的主要适应症。 体外膜肺氧合技术在加州的应用最佳目标SpO 2和肺动脉 血管扩张剂方案可改善PPHN的肺部和神经系统结局 而他，也不知道。 我们假设，SpO 2达到95-98%（与当前标准治疗91-95%相比）， 静脉注射（IV）西地那非将使脑损伤最小化并增强肺血管舒张。第一 特定目标侧重于气体交换和脑血流动力学的变化，具有两个SpO 2目标 72小时的全身低温第二个具体目标集中在氧化应激 iNO和西地那非在出生窒息后低温期间提供的神经保护作用， 在两个不同的SpO 2目标下进行通气。最终的具体目标是评估低温对 西地那非的肺血流动力学和药代动力学。 继发于MAS和PPHN的低氧性呼吸衰竭在全身低温期间很常见。 本研究的结果将通过定义最佳SpO 2为未来临床试验的设计提供信息， 体温和肺血管扩张剂，同时管理新生儿PPHN和HIE。治疗 一种普遍可用且较便宜的药物（如西地那非）在改善这两种疾病方面的潜力 本提案将探讨出生窒息后的肺部和神经系统结局。

项目成果

Laryngeal mask airway: an alternate option for all phases of neonatal resuscitation.

• DOI: 10.1038/s41390-021-01917-5
• 发表时间: 2022-09
• 期刊: PEDIATRIC RESEARCH
• 影响因子: 3.6
• 作者: Vali, Payam;Laskminrusimha, Satyan
• 通讯作者: Laskminrusimha, Satyan

Epidemiology and Clinical Research Design, Part 2: Principles.

流行病学和临床研究设计，第 2 部分：原则。

• DOI: 10.1542/neo.16-2-e94
• 发表时间: 2015
• 期刊: NeoReviews
• 作者: Manja,Veena;Lakshminrusimha,Satyan
• 通讯作者: Lakshminrusimha,Satyan

Cyclic stretch stimulates mitochondrial reactive oxygen species and Nox4 signaling in pulmonary artery smooth muscle cells.

• DOI: 10.1152/ajplung.00097.2014
• 发表时间: 2015-07
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: S. Wedgwood;S. Lakshminrusimha;P. Schumacker;R. Steinhorn

Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord.

• DOI: 10.3390/children8050353
• 发表时间: 2021-04-29
• 期刊: Children (Basel, Switzerland)
• 作者: Nair J;Davidson L;Gugino S;Koenigsknecht C;Helman J;Nielsen L;Sankaran D;Agrawal V;Chandrasekharan P;Rawat M;Berkelhamer SK;Lakshminrusimha S
• 通讯作者: Lakshminrusimha S

Oral Dextrose Gel Reduces the Need for Intravenous Dextrose Therapy in Neonatal Hypoglycemia.

• DOI: 10.1159/000448511
• 发表时间: 2016-09
• 期刊: Biomedicine hub
• 作者: Rawat M;Chandrasekharan P;Turkovich S;Barclay N;Perry K;Schroeder E;Testa L;Lakshminrusimha S
• 通讯作者: Lakshminrusimha S