Faculty Collaboration Database

99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment. Shock 2016 Oct;46(4):420-30

Date

03/15/2016

Pubmed ID

26974426

Pubmed Central ID

PMC5014734

DOI

10.1097/SHK.0000000000000605

Scopus ID

2-s2.0-84961231173 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Tc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf).For hyperoxia rats, HMPAO lung uptake increased after 24 h (134%) and 48 h (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 h after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.

Author List

Audi SH, Clough AV, Haworth ST, Medhora M, Ranji M, Densmore JC, Jacobs ER

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
John C. Densmore MD Professor in the Surgery department at Medical College of Wisconsin

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

Acute Lung Injury
Animals
Body Weight
Bronchoalveolar Lavage
Glutathione
Heart Rate
Hyperoxia
Lipopolysaccharides
Lung
Male
Oximes
Rats
Rats, Sprague-Dawley