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ABSTRACT: Aims
Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation.Results
Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-? and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets).Conclusion
These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.
SUBMITTER: Gomez H
PROVIDER: S-EPMC4569171 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Gomez Hernando H Kautza Benjamin B Escobar Daniel D Nassour Ibrahim I Luciano Jason J Botero Ana Maria AM Gordon Lisa L Martinez Silvia S Holder Andre A Ogundele Olufunmilayo O Loughran Patricia P Rosengart Matthew R MR Pinsky Michael M Shiva Sruti S Zuckerbraun Brian S BS
PloS one 20150914 9
<h4>Aims</h4>Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation.<h4>Results</h4>Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resusc ...[more]