Optimal Oxygenation in Neonatal Lung Injury

新生儿肺损伤的最佳氧合

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要：新生儿肺损伤的最佳氧合全身低温目前是中度至重度缺氧缺血的护理标准脑病（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）。治疗性低温可导致肺血管收缩并加剧 PPHN，目前是 PPHN 的主要适应症加利福尼亚州的体外膜氧合。最佳目标 SpO2 和肺功能血管扩张剂治疗方案可改善 PPHN 的肺部和神经系统结果 HIE 未知。我们假设目标 SpO2 为 95-98%（相比之下，目前的护理标准为 91-95%）并且静脉注射（IV）西地那非将最大限度地减少脑损伤并增强肺血管舒张。第一个具体目标侧重于气体交换和脑血流动力学的变化，有两个 SpO2 目标 72小时全身低温期间的范围。第二个具体目标侧重于氧化应激 iNO 和西地那非在低体温和出生窒息后提供的神经保护作用两个不同 SpO2 目标的通气量。最终的具体目标是评估低温对身体的影响西地那非的肺血流动力学和药代动力学。 MAS 和 PPHN 继发的低氧性呼吸衰竭在全身低温期间很常见。这项研究的结果将通过定义最佳 SpO2 为未来临床试验的设计提供信息，在管理患有 PPHN 和 HIE 的新生儿时，应注意体温和肺血管扩张剂。治疗性的西地那非等常用且较便宜的药物在改善两者方面的潜力该提案将探讨出生窒息后的肺部和神经系统结局。

项目成果

期刊论文数量（92）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
作者：
Manja,Veena;Lakshminrusimha,Satyan
通讯作者：
Lakshminrusimha,Satyan

Comorbidities and Late Outcomes in Neonatal Pulmonary Hypertension.

新生儿肺动脉高压的合并症和后期结果。

DOI：
10.1016/j.clp.2023.10.002
发表时间：
2024
期刊：
Clinics in perinatology
影响因子：
2.1
作者：
Stieren,EmilyS;Sankaran,Deepika;Lakshminrusimha,Satyan;Rottkamp,CatherineA
通讯作者：
Rottkamp,CatherineA

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
影响因子：
0
作者：
Rawat M;Chandrasekharan P;Turkovich S;Barclay N;Perry K;Schroeder E;Testa L;Lakshminrusimha S
通讯作者：
Lakshminrusimha S

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)
影响因子：
0
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

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