Faculty Collaboration Database

In vivo molecular imaging stratifies rats with different susceptibilities to hyperoxic acute lung injury. Am J Physiol Lung Cell Mol Physiol 2022 Oct 01;323(4):L410-L422

Date

08/10/2022

Pubmed ID

35943727

Pubmed Central ID

PMC9484995

DOI

10.1152/ajplung.00126.2022

Scopus ID

2-s2.0-85138459754 (requires institutional sign-in at Scopus site)

Abstract

^99mTc-hexamethylpropyleneamine oxime (HMPAO) and ^99mTc-duramycin in vivo imaging detects pulmonary oxidative stress and cell death, respectively, in rats exposed to >95% O₂ (hyperoxia) as a model of acute respiratory distress syndrome (ARDS). Preexposure to hyperoxia for 48 h followed by 24 h in room air (H-T) is protective against hyperoxia-induced lung injury. This study's objective was to determine the ability of ^99mTc-HMPAO and ^99mTc-duramycin to track this protection and to elucidate underlying mechanisms. Rats were exposed to normoxia, hyperoxia for 60 h, H-T, or H-T followed by 60 h of hyperoxia (H-T + 60). Imaging was performed 20 min after intravenous injection of either ^99mTc-HMPAO or ^99mTc-duramycin. ^99mTc-HMPAO and ^99mTc-duramycin lung uptake was 200% and 167% greater (P < 0.01) in hyperoxia compared with normoxia rats, respectively. On the other hand, uptake of ^99mTc-HMPAO in H-T + 60 was 24% greater (P < 0.01) than in H-T rats, but ^99mTc-duramycin uptake was not significantly different (P = 0.09). Lung wet-to-dry weight ratio, pleural effusion, endothelial filtration coefficient, and histological indices all showed evidence of protection and paralleled imaging results. Additional results indicate higher mitochondrial complex IV activity in H-T versus normoxia rats, suggesting that mitochondria of H-T lungs may be more tolerant of oxidative stress. A pattern of increasing lung uptake of ^99mTc-HMPAO and ^99mTc-duramycin correlates with advancing oxidative stress and cell death and worsening injury, whereas stable or decreasing ^99mTc-HMPAO and stable ^99mTc-duramycin reflects hyperoxia tolerance, suggesting the potential utility of molecular imaging for identifying at-risk hosts that are more or less susceptible to progressing to ARDS.

Author List

Audi SH, Taheri P, Zhao M, Hu K, Jacobs ER, Clough AV

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Kurt Hu MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Lung Injury
Animals
Hyperoxia
Molecular Imaging
Oximes
Rats
Rats, Sprague-Dawley