Takashi Sonobe1, Philippe Haouzi. 1. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Pennsylvania State University, College of Medicine , Hershey, PA , USA.
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.
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 H2Stoxicity. 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 comatoserats 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.
Authors: T Kofidis; M Strüber; M Wilhelmi; M Anssar; A Simon; W Harringer; A Haverich Journal: J Thorac Cardiovasc Surg Date: 2001-10 Impact factor: 5.209
Authors: Arne Warth; Benjamin Goeppert; Christian Bopp; Peter Schirmacher; Christa Flechtenmacher; Jürgen Burhenne Journal: Virchows Arch Date: 2009-02-03 Impact factor: 4.064
Authors: Kevin W Swan; Bryant M Song; Allen L Chen; Travis J Chen; Ryan A Chan; Bradley T Guidry; Prasad V G Katakam; Edmund K Kerut; Thomas D Giles; Philip J Kadowitz Journal: Am J Physiol Heart Circ Physiol Date: 2017-06-30 Impact factor: 4.733
Authors: Joseph Y Cheung; JuFang Wang; Xue-Qian Zhang; Jianliang Song; John M Davidyock; Fabian Jana Prado; Santhanam Shanmughapriya; Alison M Worth; Muniswamy Madesh; Annick Judenherc-Haouzi; Philippe Haouzi Journal: Cardiovasc Toxicol Date: 2018-10 Impact factor: 3.231
Authors: Philippe Haouzi; Nicole Tubbs; Matthew D Rannals; Annick Judenherc-Haouzi; Larry A Cabell; Joe A McDonough; Takashi Sonobe Journal: Shock Date: 2017-03 Impact factor: 3.454