# Optimal Oxygenation in Neonatal Lung Injury

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $685,208

## Abstract

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.

## Key facts

- **NIH application ID:** 10893610
- **Project number:** 5R01HD072929-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Satyanarayana Lakshminrusimha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,208
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893610

## Citation

> US National Institutes of Health, RePORTER application 10893610, Optimal Oxygenation in Neonatal Lung Injury (5R01HD072929-13). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10893610. Licensed CC0.

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