| Local wound p38 MAPK inhibition attenuates burn-induced cardiac dysfunction. | |
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MedLine Citation:
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PMID: 19789038 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Topical inhibition of activated p38 MAPK within burn wounds attenuates the local and systemic inflammatory response. In this study, we investigated the effects of local activated p38 MAPK inhibition on burn-induced cardiac dysfunction. METHODS: Using a standardized rat model of scald burn injury, rats were given a 30% total body surface area partial thickness burn or sham injury, and the wounds were treated with an activated p38 MAPK inhibitor (SB) or vehicle. Systemic blood pressure measurements were recorded in vivo followed by in vitro assessment of sarcomere contraction in single-cell suspensions of isolated cardiomyocytes. RESULTS: Systolic blood pressure or maximum left ventricular pressures in vivo and peak cardiomyocyte sarcomere contractility in vitro were significantly reduced after burn injury. These functional deficits were abolished 24 h after burn injury following local p38 MAPK inhibition. In vitro incubation of normal cardiomyocytes with homogenate from burned skin or burn serum resulted in a similar pattern of impaired cardiomyocyte contractility. These effects were reversed in normal cardiomyocytes exposed to burn skin homogenates treated topically with a p38 MAPK inhibitor. A Western blot analysis showed that cardiac p38 MAPK activation was not affected by dermal blockade of activated p38 MAPK, arguing against systemic absorption of the inhibitor and indicating the involvement of systemic cytokine signaling. CONCLUSION: Topical activated p38 MAPK inhibition within burned skin attenuates the release of proinflammatory mediators and prevents burn-induced cardiac dysfunction after thermal injury. These results support the inhibition of burn-wound inflammatory signaling as a new therapeutic approach to prevent potential postthermal injury multiorgan dysfunction syndrome. |
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Authors:
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Laszlo M Hoesel; Aladdein F Mattar; Saman Arbabi; Andreas D Niederbichler; Kyros Ipaktchi; Grace L Su; Margaret V Westfall; Stewart C Wang; Mark R Hemmila |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Surgery Volume: 146 ISSN: 1532-7361 ISO Abbreviation: Surgery Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-30 Completed Date: 2009-10-14 Revised Date: 2013-02-04 |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: United States |
Other Details:
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Languages: eng Pagination: 775-85; discussion 785-6 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Burns / physiopathology* Imidazoles / pharmacology* Male Myocardial Contraction / drug effects* Protein Kinase Inhibitors / pharmacology* Pyridines / pharmacology* Rats Rats, Sprague-Dawley Sarcomeres / drug effects Ventricular Function, Left / drug effects* p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors* |
| Grant Support | |
ID/Acronym/Agency:
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K08 GM078610/GM/NIGMS NIH HHS; K08 GM078610-01/GM/NIGMS NIH HHS; K08 GM078610-02/GM/NIGMS NIH HHS; K08 GM078610-03/GM/NIGMS NIH HHS; K08-GM078610/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; 0/Imidazoles; 0/Protein Kinase Inhibitors; 0/Pyridines; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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