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Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury

Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury

Authors :
Hiroshi Morimatsu
Hiroko Shimizu
Shigeru Maeda
Atsunori Nakao
Kiyoshi Morita
Kenji Sato
Susumu Kawanishi
Masaki Matsumi
Toru Takahashi
Emiko Omori
Source :
Molecular Medicine Reports. 7:3-10
Publication Year :
2012
Publisher :
Spandidos Publications, 2012.

Abstract

Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-γ, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-γ protein expression.

Details

ISSN :
17913004 and 17912997
Volume :
7
Database :
OpenAIRE
Journal :
Molecular Medicine Reports
Accession number :
edsair.doi.dedup.....e3e86bf5ab125d92a3e7ce9912628e97
Full Text :
https://doi.org/10.3892/mmr.2012.1173