H2S induced coma and cardiogenic shock in the rat

Effects of phenothiazinium chromophores

Takashi Sonobe, Philippe Haouzi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 un-anesthetized 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.

Original languageEnglish (US)
Pages (from-to)525-539
Number of pages15
JournalClinical Toxicology
Volume53
Issue number6
DOIs
StatePublished - Jul 1 2015

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Cardiogenic Shock
Methylene Blue
Chromophores
Coma
Rats
Cardiac Output
Sulfides
Animals
Hydrogen Sulfide
Urethane
Blood pressure
Ventricular Pressure
Electron Transport
Metabolites
Heart Arrest
Toxicity
Shock
Respiration
Coloring Agents
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

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title = "H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores",
abstract = "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 un-anesthetized 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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H2S induced coma and cardiogenic shock in the rat : Effects of phenothiazinium chromophores. / Sonobe, Takashi; Haouzi, Philippe.

In: Clinical Toxicology, Vol. 53, No. 6, 01.07.2015, p. 525-539.

Research output: Contribution to journalArticle

TY - JOUR

T1 - H2S induced coma and cardiogenic shock in the rat

T2 - Effects of phenothiazinium chromophores

AU - Sonobe, Takashi

AU - Haouzi, Philippe

PY - 2015/7/1

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N2 - 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 un-anesthetized 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.

AB - 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 un-anesthetized 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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