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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
- 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.
- Subjects :
- Male
Cancer Research
Resuscitation
Pathology
medicine.medical_specialty
Mean arterial pressure
Acute Lung Injury
Nitric Oxide Synthase Type II
Apoptosis
Pulmonary Edema
Inflammation
Shock, Hemorrhagic
Lung injury
Biochemistry
Edema
Genetics
medicine
Animals
Hypoxia
Lung
Molecular Biology
Carbon Monoxide
Inhalation
Tumor Necrosis Factor-alpha
business.industry
Hemodynamics
Interleukin-10
Rats
PPAR gamma
Disease Models, Animal
medicine.anatomical_structure
Carboxyhemoglobin
Gene Expression Regulation
Neutrophil Infiltration
Oncology
Molecular Medicine
Inflammation Mediators
medicine.symptom
business
Subjects
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