2005 Fiscal Year Final Research Report Summary
Diaphragmatic Contractility and Fatigue in Sepsis.
Project/Area Number |
15591915
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Emergency medicine
|
Research Institution | Okayama University |
Principal Investigator |
UJIKE Yoshito Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (10201352)
|
Co-Investigator(Kenkyū-buntansha) |
ICHIBA Shingo Okayama University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (30284102)
|
Project Period (FY) |
2003 – 2005
|
Keywords | Diaphragm / Sepsis / Fatigue |
Research Abstract |
We investigated the effects of several pharmacological agents on diaphragmatic contractility during sepsis. 1) We evaluated the effects of theophylline and aminophylline on diaphragmatic contractility and cAMP levels during sepsis. Theophylline and aminophylline attenuated CLP-induced diaphragm dysfunction. Theophylline and aminophylline increased diaphragmatic cAMP levels. Dibutyryl cAMP attenuated CLP-induced diaphragm dysfunction. These results demonstrated theophylline and aminophylline improves diaphragmatic contractility by increasing diaphragmatic cAMP concentrations. 2) We evaluated the effects of induction of heat shock protein (HSP) 70 expression by geranylgeranylacetone (GGA) on diaphragmatic dysfunction during sepsis. Induction of HSP70 attenuated CLP-induced diaphragm dysfunction and increased malondialdehyde (MDA) concentrations in a dose-dependent manner. These results demonstrated that HSP70 induced by GGA attenuates septic diaphragm dysfunction by inhibiting the production of oxygen-derived free radicals. 3) We evaluated the effects of pentoxifylline (PTX) on endotoxin-induced diaphragmatic dysfunction and MDA levels. The PTX attenuated endotoxin-induced diaphragmatic dysfunction and increased MDA concentrations. These results demonstrated that pentoxifylline attenuated endotoxin-induced diaphragmatic dysfunction by inhibiting the production of oxygen-derived free radicals.
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