Document Detail

Acute effects of high-dose methylprednisolone on diaphragm muscle function.
MedLine Citation:
PMID:  18671291     Owner:  NLM     Status:  MEDLINE    
The time- and dose-dependent effects of acute high-dose corticosteroids on the diaphragm muscle are poorly defined. This study aimed to examine in rabbits the temporal relationships and dose-response effects of acute high-dose methylprednisolone succinate on diaphragmatic contractile and structural properties. Animals were assigned to groups receiving: (1) 80 mg/kg/day methylprednisolone (MP80) intramuscularly for 1, 2, and 3 days; (2) 10 mg/kg/day methylprednisolone (MP10, pulse-dose) for 3 days; or (3) saline (placebo) for 3 days; and (4) a control group. Diaphragmatic in vitro force-frequency and force-velocity relationships, myosin heavy chain (MyHC) isoform protein and mRNA, insulin-like growth factor-1 (IGF-1), muscle atrophy F-box (MAF-box) mRNA, and volume density of abnormal myofibrils were measured at each time-point. MP80 did not affect animal nutritional state or fiber cross-sectional area as assessed in separate pair-fed groups receiving methylprednisolone or saline for 3 days. Compared with control values, MP80 decreased diaphragmatic maximum tetanic tension (Po) by 19%, 24%, and 34% after 1, 2, and 3 days (P < 0.05), respectively, whereas MP10 decreased Po modestly (12%; P > 0.05). Vmax and MyHC protein proportions were unchanged in both the MP80 and MP10 groups. Maximum power output decreased after 2 and 3 days of MP80. Suppression of IGF-1 and overexpression of MAF-box mRNA occurred in both MP groups. Significant myofibrillar disarray was also observed in both MP groups. The decline in Po was significantly associated with the increased volume density of abnormal myofibrils. Thus, very high-dose methylprednisolone (MP80) can produce rapid reductions in diaphragmatic function, whereas pulse-dose methylprednisolone (MP10) produces only modest functional loss.
Catherine S H Sassoon; Ercheng Zhu; H Tony Pham; Renee S Nelson; Liwei Fang; Michael J Baker; Vincent J Caiozzo
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Muscle & nerve     Volume:  38     ISSN:  0148-639X     ISO Abbreviation:  Muscle Nerve     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-28     Completed Date:  2008-11-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7803146     Medline TA:  Muscle Nerve     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1161-72     Citation Subset:  IM    
Department of Medicine, VA Long Beach Healthcare System, 5901 East 7th Street, Long Beach, California 90822, USA.
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MeSH Terms
Analysis of Variance
Diaphragm / cytology*
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Insulin-Like Growth Factor I / genetics,  metabolism
Methylprednisolone / pharmacology*
Muscle Contraction / drug effects*
Muscle Fibers, Skeletal / metabolism
Muscle, Smooth / cytology,  drug effects*,  metabolism
Myosin Heavy Chains / genetics,  metabolism
Neuroprotective Agents / pharmacology*
RNA, Messenger / metabolism
SKP Cullin F-Box Protein Ligases / genetics,  metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Myosin Heavy Chains; 0/Neuroprotective Agents; 0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; 83-43-2/Methylprednisolone; EC Cullin F-Box Protein Ligases

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