Gomez, H and Kautza, B and Escobar, D and Nassour, I and Luciano, J and Botero, AM and Gordon, L and Martinez, S and Holder, A and Ogundele, O and Loughran, P and Rosengart, MR and Pinsky, M and Shiva, S and Zuckerbraun, BS
(2015)
Inhaled carbon monoxide protects against the development of shock and mitochondrial injury following hemorrhage and resuscitation.
PLoS ONE, 10 (9).
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-α 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.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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Gomez, H | | | | Kautza, B | | | | Escobar, D | | | | Nassour, I | | | | Luciano, J | | | | Botero, AM | | | | Gordon, L | | | | Martinez, S | | | | Holder, A | holder@pitt.edu | HOLDER | | Ogundele, O | | | | Loughran, P | pal32@pitt.edu | PAL32 | 0000-0001-9375-1724 | Rosengart, MR | mrr18@pitt.edu | MRR18 | | Pinsky, M | pinsky@pitt.edu | PINSKY | 0000-0001-6166-700X | Shiva, S | sss43@pitt.edu | SSS43 | | Zuckerbraun, BS | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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Editor | Raju, Raghavan | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Centers: |
Other Centers, Institutes, Offices, or Units > Vascular Medicine Institute |
Date: |
14 September 2015 |
Date Type: |
Publication |
Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
Journal or Publication Title: |
PLoS ONE |
Volume: |
10 |
Number: |
9 |
DOI or Unique Handle: |
10.1371/journal.pone.0135032 |
Institution: |
University of Pittsburgh |
Schools and Programs: |
School of Medicine > Critical Care Medicine School of Medicine > Pharmacology and Chemical Biology School of Medicine > Surgery |
Refereed: |
Yes |
Date Deposited: |
23 Aug 2016 14:38 |
Last Modified: |
06 Oct 2021 14:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/28386 |
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