GLUCOCORTICOID RECEPTOR ANTAGONISM BY MIFEPRISTONE ALTERS PHOSPHOCREATINE BREAKDOWN DURING SEPSIS

Citation
T. Mitsuo et al., GLUCOCORTICOID RECEPTOR ANTAGONISM BY MIFEPRISTONE ALTERS PHOSPHOCREATINE BREAKDOWN DURING SEPSIS, Archives of surgery, 131(11), 1996, pp. 1179-1185
Citations number
21
Categorie Soggetti
Surgery
Journal title
ISSN journal
00040010
Volume
131
Issue
11
Year of publication
1996
Pages
1179 - 1185
Database
ISI
SICI code
0004-0010(1996)131:11<1179:GRABMA>2.0.ZU;2-X
Abstract
Objective: To determine the role of glucocorticoids in the regulation of myocellular energetics induced by sepsis by means of the glucocorti coid receptor antagonist mifepristone (RU 38486). Design: Randomized c ontrolled study. Setting: University laboratories. Participants: Thirt y-two adult male Wistar rats. Methods: Animals were randomly assigned to 1 of 4 groups. In 2 groups, mifepristone (10 mg/kg) was administere d by gavage feeding 2 hours before cecal ligation and single 18-gauge needle puncture or sham operation. The other 2 groups of animals recei ved placebo gavage feedings 2 hours before their surgical procedures. Twenty-four hours after operation, high-energy phosphate ratios, intra cellular pH, the forward rate constant for the creatine kinase reactio n, and phosphocreatine breakdown rates were measured in the gastrocnem ius muscle by in vivo phosphorus 31 magnetic resonance spectroscopy. T issue and blood samples were collected to measure creatine and adenosi ne 5'-triphosphate concentrations, Na+-K+ adenosine triphosphatase act ivity, and circulating corticosterone levels. Results: Circulating cor ticosterone levels were twice as high in septic animals as in sham-ope ration control rats (P<.01). Phosphocreatine breakdown rates and Na+-K + adenosine triphosphatase activity were significantly higher (40% and 75%, respectively; P<.01) in placebo-treated septic rats than in sham -operation control rats. However, phosphocreatine breakdown rates and Na+-K+ adenosine triphosphatase activity in mifepristone-treated septi c animals were not significantly elevated above control levels. Conclu sion: Pretreatment with mifepristone reduces the demand for adenosine triphosphate production from phosphocreatine breakdown and downregulat es Na+-K+ adenosine triphosphatase activity during sepsis.