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Methylene blue reverses endotoxin-induced hypotension
J F Keaney1, J C Puyana, S Francis
1Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
Circulation Research
|June 1, 1994
Summary
Methylene blue effectively reversed hypotension in a rabbit model of septic shock by normalizing nitric oxide levels. This suggests methylene blue as a potential treatment for septic shock.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Biochemistry
Background:
- Septic shock involves unregulated nitric oxide (NO) production, leading to hypotension.
- Vascular smooth muscle guanylyl cyclase activation contributes to the pathophysiology of septic shock.
Purpose of the Study:
- To investigate the efficacy of methylene blue in treating lipopolysaccharide (LPS)-induced septic shock in rabbits.
- To assess the impact of methylene blue on mean arterial pressure, platelet cyclic guanosine monophosphate (cGMP), and total plasma NO levels.
Main Methods:
- Septic shock was induced in anesthetized rabbits using 150 µg/kg LPS.
- Measurements of mean arterial pressure, platelet cGMP, and total plasma NO were taken before and after intravenous administration of methylene blue (1, 5, and 10 mg/kg).
Main Results:
- LPS administration caused a significant reduction in mean arterial pressure.
- Methylene blue administration resulted in a dose-dependent increase in mean arterial pressure.
- Methylene blue normalized total plasma NO content but did not significantly alter intraplatelet cGMP levels.
Conclusions:
- Methylene blue effectively restores normal arterial pressure in a rabbit model of septic shock.
- The therapeutic effect of methylene blue is linked to the normalization of plasma NO levels.
- These findings suggest methylene blue as a potential therapeutic agent for septic shock by inhibiting NO synthase or NO degradation.