Protection by inhaled hydrogen therapy in a rat model of acute lung injury can be tracked in vivo using molecular imaging

Said H. Audi*, Elizabeth R. Jacobs, Xiao Zhang, Amadou K.S. Camara, Ming Zhao, Meetha M. Medhora, Benjamin Rizzo, Anne V. Clough

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Inhaled hydrogen gas (H2) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a ratmodel of ALI.Our objective was to evaluate the ability of 99mTc-hexamethylpropyleneamineoxime(HMPAO) and 99mTc-duramycin to track the effectiveness ofH2 therapy in vivo in the hyperoxia ratmodel ofALI. Ratswere exposed to roomair (normoxia), 98%O22%N2 (hyperoxia) or 98%O2 2%H2 (hyperoxiaH2) for up to 60 h. In vivo scintigraphy imageswere acquired following injection of 99mTc-HMPAO or 99mTc-duramycin. For hyperoxia rats, 99mTc-HMPAO and 99mTc-duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 h, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxiaH2 rats. Hyperoxia exposure increased glutathione content in lung homogenate (36%) more than hyperoxiaH2 (21%), consistent with increases measured in 99mTc-HMPAO lung uptake. In 60-h hyperoxia rats, pleural effusion,whichwas undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue 3-nitrotyrosine expression increased by 790%. Increaseswere reduced by 69%and 59%, respectively, in 60-h hyperoxiaH2 rats. This study detects and tracks the anti-oxidant and anti-apoptotic properties ofH2 therapy in vivo after as early as 24 h of hyperoxia exposure. The results suggest the potential utility of theseSPECTbiomarkers for in vivo assessment of key cellular pathways in the pathogenesis ofALI and for monitoring responses to therapies.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalShock
Volume48
Issue number4
DOIs
StatePublished - Oct 1 2017

Keywords

  • Acute respiratory distress syndrome
  • Hyperoxia
  • SPECT imaging
  • Tc-HMPAO
  • Tc-durmaycin

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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