| Elucidating the role of reversible protein phosphorylation in sepsis-induced myocardial dysfunction. | |
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MedLine Citation:
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PMID: 19533850 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mortality in children with sepsis is most often related to diminished cardiac output with cardiovascular collapse, resulting in impaired oxygen delivery and, ultimately, end-organ failure. Although cardiovascular "collapse" is commonly observed in individuals with septic shock, the hemodynamic causes of this differ greatly. In children, intrinsic myocardial dysfunction is most commonly present, whereas the systemic vascular resistance is typically high. This pattern is distinct from adults with sepsis where the principal hemodynamic profile shows elevated cardiac output, but substantially reduced systemic vascular resistance. Various studies support the concept that myocardial dysfunction, as occurs in pediatric septic patients, is due to intrinsic abnormalities in cardiomyocyte function and is not related to hypoperfusion as a result of low systemic vascular resistance. Importantly, when examined more closely, data from adults with septic shock also reveal that intrinsic myocardial dysfunction may play a larger role than previously appreciated. As a result, cardiovascular support, especially in pediatric sepsis, requires a treatment strategy directed at the underlying mechanism(s) responsible for this dysfunction. Thus, it is imperative to gain a better understanding of the myocardial derangements that occur during sepsis to identify targets that will ultimately influence the management of children with septic shock and favorably alter the associated mortality. We hypothesize that key signaling pathways that control myocardial calcium flux, regulated to key kinases and phosphatases, influence myocyte contractility in sepsis. Thus, we review the data relevant to the sepsis-induced intracellular alterations in calcium flux in the cardiomyocyte, with an emphasis on changes in the phosphorylation state of the contractile proteins regulated by the balance between kinases and phosphatases. We believe that therapies modulating the activity of these key proteins may provide an improvement in calcium handling and myocardial contractility and alter the clinical outcomes in sepsis. |
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Authors:
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Angela Lorts; Timothy Burroughs; Thomas P Shanley |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 32 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-16 Completed Date: 2009-09-02 Revised Date: 2011-06-07 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 49-54 Citation Subset: IM |
Affiliation:
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Division of Pediatric Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. Angela.Lorts@cchmc.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 4-Kinase
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metabolism Cardiomyopathies / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism Humans Phosphorylation / physiology Protein Phosphatase 2 / metabolism Sepsis / physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM066839-06/GM/NIGMS NIH HHS; R01 GM066839-09/GM/NIGMS NIH HHS; R01 GM66839-01/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.7.1.67/1-Phosphatidylinositol 4-Kinase; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.1.3.16/Protein Phosphatase 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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