Document Type

Article

Publication Date

2025

Publisher

Frontiers Media S.A.

Source Publication

Frontiers in Physiology

Source ISSN

1664-042x

Abstract

Introduction:

Exposure of adult rats to hyperoxia is a well-established model of human Acute Respiratory Distress Syndrome (ARDS). Although rats exposed to 100% O2 display clinical evidence of lung injury after ∼40 h and death by 72 h, rats exposed to 60% O2 for up to 7 days show little sign of injury. However, when subsequently exposed to hyperoxia, these pre-exposed rats become more susceptible to ARDS. The objective of this study is to evaluate the ability of imaging biomarkers to track this hyperoxia susceptibility and to elucidate underlying mechanisms.

Methods:

Sprague-Dawley rats were exposed to either room air (normoxia), >95% O2 for 24 h (hyperoxia), 60% O2 for 7 days (H-S), or H-S followed by 24 h of hyperoxia (H-S+24). Following i.v. injection of 99mTcduramycin (marker of cell death) and/or 99mTc-hexamethylpropelyneamine oxime (99mTc-HMPAO, marker of lung tissue redox status), in vivo scintigraphy images were acquired and lung uptake of these biomarkers was determined from the images.

Results:

99mTc-HMPAO uptake was 84% greater in hyperoxic rats compared to normoxic controls. Uptake in H-S rats was 34% higher than normoxics, but with no change with subsequent exposure to hyperoxia (HS+24). 99mTc-duramycin uptake was 40% greater in hyperoxic rats than normoxics. Uptake in H-S rats was not different from normoxics but increased by 160% with H-S+24 in conjunction with enhanced hyperoxia susceptibility. 99mTc-HMPAO and 99mTc-duramycin uptake correlated with expression of 3- nitrotyrosine (oxidative stress) and cleaved-caspase 3 (cell death) measures acquired independently.

Discussion:

Overall, these results suggest the potential utility of 99mTc-HMPAO and 99mTc-duramycin imaging for identifying those hosts that are more, or less, susceptible to progression to severe ARDS at a time of mild symptoms of lung injury.

Comments

Published version. Frontiers in Physiology, Vol. 16 (2025). DOI. © 2025 Clough, Taheri, Sharma, Zhao, Jacobs and Audi.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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