Document Detail

Methylene blue reverses endotoxin-induced hypotension.
MedLine Citation:
PMID:  8187278     Owner:  NLM     Status:  MEDLINE    
Hypotension in septic shock is a reflection of unregulated nitric oxide (NO) production and vascular smooth muscle guanylyl cyclase activation. We examined the effect of methylene blue on lipopolysaccharide (LPS)-induced shock in anesthetized rabbits. Shock was induced with 150 micrograms/kg LPS after measurement of mean arterial pressure, platelet cGMP, and total plasma NO (nitrogen monoxide+S-nitrosothiol) content. Measurements were repeated before and after the intravenous administration of 1, 5, and 10 mg/kg methylene blue in response to a 55% reduction in mean arterial pressure. At baseline, mean +/- SEM arterial pressure was 88 +/- 3 mm Hg, which fell to 51 +/- 3 mm Hg after LPS (P < .05). Methylene blue at doses of 1, 5, and 10 mg/kg produced a prompt dose-dependent increase in mean arterial pressure to 69 +/- 2, 77 +/- 3, and 81 +/- 2 mm Hg, respectively (P < .05 versus mean arterial pressure after LPS) in association with normalization of plasma total NO content (P < .05); however, methylene blue did not significantly affect intraplatelet cGMP levels. Thus, methylene blue restores normal arterial pressure in rabbits with septic shock. This effect is associated with persistent elevation of intraplatelet cGMP levels and normalization of total plasma NO content. These data are consistent with methylene blue-mediated inhibition of NO synthase and/or degradation of NO in this model and suggest a novel therapeutic approach to the treatment of septic shock.
J F Keaney; J C Puyana; S Francis; J F Loscalzo; J S Stamler; J Loscalzo
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  74     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-06-23     Completed Date:  1994-06-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1121-5     Citation Subset:  IM    
Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
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MeSH Terms
Blood Pressure / drug effects
Cyclic GMP / blood
Hypotension / chemically induced,  drug therapy*
Lipopolysaccharides / toxicity*
Methylene Blue / therapeutic use*
Nitric Oxide / blood
Shock, Septic / drug therapy
Sulfhydryl Compounds / blood
Grant Support
Reg. No./Substance:
0/Lipopolysaccharides; 0/Sulfhydryl Compounds; 10102-43-9/Nitric Oxide; 61-73-4/Methylene Blue; 7665-99-8/Cyclic GMP

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