Methylene blue administration in septic shock

Preiser, Jean‐Charles; Lejeune, Philippe; Roman, Alain; Carlier, Eric; Backer, Daniel De; Leeman, Marc; Kahn, Robert J.; Vincent, Jean‐Louis

doi:10.1097/00003246-199502000-00010

Cited by 236 publications

(71 citation statements)

References 30 publications

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“…The powerful negative inotropic effects of H 2 S led to a complete electromechanical dissociation or PEA within minutes. As mentioned in the “Introduction” section, plausible mechanisms underlying NaHS-induced cardiac dysfunction comprise 1- an inhibition of calcium channels, 4,5,56 mimicking an intoxication by calcium channel blockers, and 2- a potentiation of the effects of NO by H 2 S 10,11 which in turn—just like in septic shock 42,43 —can lead to a profound depression in cardiac contractility. Finally, the reduction in ATP, via a complete blockage of the cytochrome C oxidase activity 6,7 could have led to a depressed cardiac contractility, akin to the effects of cardiac anoxia.…”

Section: Discussionmentioning

confidence: 99%

H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

Sonobe¹,

Haouzi²

2015

Clinical Toxicology

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Context Hydrogen sulfide (H2S) intoxication produces an acute depression in cardiac contractility-induced circulatory failure, which has been shown to be one of the major contributors to the lethality of H2S intoxication or to the neurological sequelae in surviving animals. Methylene blue (MB), a phenothiazinium dye, can antagonize the effects of the inhibition of mitochondrial electron transport chain, a major effect of H2S toxicity. Objectives We investigated whether MB could affect the immediate outcome of H2S-induced coma in unanesthetized animals. Second, we sought to characterize the acute cardiovascular effects of MB and two of its demethylated metabolites—azure B and thionine—in anesthetized rats during lethal infusion of H2S. Materials and methods First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached 40% of its baseline volume, MB, azure B, thionine, or saline were injected, while sulfide infusion was maintained until cardiac arrest occurred. Results Seventy-five percent of the comatose rats that received saline (n = 8) died within 7 min, while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized rats, arterial, left ventricular pressures and CO decreased during NaHS infusion, leading to a pulseless electrical activity within 530 s. MB produced a significant increase in CO and dP/dtmax for about 2 min. A similar effect was produced when MB was also injected in the pre-mortem phase of sulfide exposure, significantly increasing survival time. Azure B produced an even larger increase in blood pressure than MB, while thionine had no effect. Conclusion MB can counteract NaHS-induced acute cardiogenic shock; this effect is also produced by azure B, but not by thionine, suggesting that the presence of methyl groups is a prerequisite for producing this protective effect.

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Section: Discussionmentioning

confidence: 99%

H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

Sonobe¹,

Haouzi²

2015

Clinical Toxicology

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“…In septic shock patients, the administration of MB results in a transient and reproducible increase in arterial pressure, associated with an improvement in cardiac function, but does not increase cellular oxygen availability. The significant reduction in blood lactate concentration is probably related to the reductor effect of MB, rather than to an improvement in tissue oxygenation [63].…”

Section: Mb and Septic Shockmentioning

confidence: 96%

The Guanylyl Cyclase Inhibition by MB as Vasoplegic Circulatory Shock Therapeutical Target

Évora

Viaro

2006

CDT

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There were strong evidences that NO has capital importance in the progressive vasodilatation that associates to the varied circulatory shock forms. The decreased systemic vascular resistance observed in irreversible hemorrhagic (hypovolemic) and septic shock may be due to the excess production of nitric oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS) and ischemia reperfusion injury (cardiogenic shock, organ transplants), may involve nitric oxide overproduction. In these situations, the nitric oxide-induced loss of vascular sensitivity to catecholamines and myocardial depression contributes to lethal hypotension. As NO vasodilatation is cyclic GMP-mediated, there were two therapeutical options: a) The unspecific NO synthesis inhibition by L-arginine analogs, iNOS-specific inhibition by corticoids and/or aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis inhibition is associated to tissue necrosis and adverse hemodynamic effects and its clinical use was associated with high mortality, the second option using MB is safer and more rational. The elaboration of this text was motivated to suggest the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.

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“…Recently MB has been proposed as a potential treatment for cancer 25 , hepatopulmonary syndrome 26 , and septic shock 27,28 . Furthermore, the neuroprotective function of MB, which is able to traverse the BBB, has been reported 29 .…”

Section: Introductionmentioning

confidence: 99%

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress

Ryou¹,

Choudhury²,

Li³

et al. 2015

Neuroscience

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Brain ischemia and reperfusion (I/R) injury occurs in various pathological conditions, but there is no effective treatment currently available in clinical practice. Methylene blue (MB) is a century old drug with a newly discovered protective function in the ischemic stroke model. In the current investigation we studied the MB-induced neuroprotective mechanism focusing on stabilization and activation of hypoxia inducible factor-1α (HIF-1α) in an in vitro oxygen and glucose deprivation (OGD)-reoxygenation model. Methods HT22 cells were exposed to OGD (0.1% O2, 6h) and reoxygenation (21% O2, 24h). Cell viability was determined with the calcein AM assay. The dynamic change of intracellular O2 concentration was monitored by fluorescence lifetime imaging microscopy (FLTIM). Glucose uptake was quantified using the 2-[N-(7-Nitrobenz-2-Oxa- 1,3-Diazol-4-yl)Amino]- 2-Deoxy-D-Glucose (2-NBDG) assay. ATP concentration and glycolytic enzyme activity were examined by spectrophotometry. Protein content changes were measured by immunoblot: HIF-1α, prolyl hydroxylase 2(PHD2), erythropoietin (EPO), Akt, mTOR, and PIP5K. The contribution of HIF-1α activation in the MB-induced neuroprotective mechanism was confirmed by blocking HIF-1α activation with 2-methoxyestradiol-2 (2-MeOE2) and by transiently transfecting constitutively active HIF-1α. Results MB increases cell viability by about 50% vs. OGD control. Compared to the corresponding control, MB increases intracellular O2 concentration and glucose uptake as well as the activities of hexokinase and G-6-PDH, and ATP concentration. MB activates the EPO signaling pathway with a corresponding increase in HIF-1α. Phosphorylation of Akt was significantly increased with MB treatment followed by activation of the mTOR pathway. Importantly, we observed, MB increased nuclear translocation of HIF-1α vs. control (about 3 folds), which was shown by a ratio of nuclear:cytoplasmic HIF-1α protein content. Conclusion We conclude that MB protects the hippocampus derived neuronal cells against OGD-reoxygenation injury by enhancing energy metabolism and increasing HIF-1α protein content accompanied by an activation of the EPO signaling pathway.

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Methylene blue administration in septic shock

Cited by 236 publications

References 30 publications

H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

The Guanylyl Cyclase Inhibition by MB as Vasoplegic Circulatory Shock Therapeutical Target

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress

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Methylene blue administration in septic shock

Cited by 236 publications

References 30 publications

H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

The Guanylyl Cyclase Inhibition by MB as Vasoplegic Circulatory Shock Therapeutical Target

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress

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H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

H₂S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores