Methylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action.
Animals
Antidotes
/ administration & dosage
Cytochromes c
/ blood
Echocardiography
Female
Gas Poisoning
/ blood
Hemoglobins
/ analysis
Hydrogen Sulfide
/ poisoning
Membrane Potential, Mitochondrial
/ drug effects
Methylene Blue
/ administration & dosage
Myocardial Contraction
/ drug effects
Myocytes, Cardiac
/ drug effects
Sheep
Ventricular Dysfunction, Left
/ blood
Hydrogen Sulfide Intoxication
Methylene Blue
Toxic Cardiac Failure
Journal
Toxicological sciences : an official journal of the Society of Toxicology
ISSN: 1096-0929
Titre abrégé: Toxicol Sci
Pays: United States
ID NLM: 9805461
Informations de publication
Date de publication:
01 04 2019
01 04 2019
Historique:
pubmed:
28
12
2018
medline:
13
3
2020
entrez:
28
12
2018
Statut:
ppublish
Résumé
Exposure to toxic levels of hydrogen sulfide (H2S) produces an acute cardiac depression that can be rapidly fatal. We sought to characterize the time course of the cardiac effects produced by the toxicity of H2S in sheep, a human sized mammal, and to describe the in vivo and in vitro antidotal properties of methylene blue (MB), which has shown efficacy in sulfide intoxicated rats. Infusing NaHS (720 mg) in anesthetized adult sheep produced a rapid dilation of the left ventricular with a decrease in contractility, which was lethal within about 10 min by pulseless electrical activity. MB (7 mg/kg), administered during sulfide exposure, maintained cardiac contractility and allowed all of the treated animals to recover. At a dose of 350 mg NaHS, we were able to produce an intoxication, which led to a persistent decrease in ventricular function for at least 1 h in nontreated animals. Administration of MB, 3 or 30 min after the end of exposure, whereas all free H2S had already vanished, restored cardiac contractility and the pyruvate/lactate (P/L) ratio. We found that MB exerts its antidotal effects through at least 4 different mechanisms: (1) a direct oxidation of free sulfide; (2) an increase in the pool of "trapped" H2S in red cells; (3) a restoration of the mitochondrial substrate-level phosphorylation; and (4) a rescue of the mitochondrial electron chain. In conclusion, H2S intoxication produces acute and long persisting alteration in cardiac function in large mammals even after all free H2S has vanished. MB exerts its antidotal effects against life-threatening sulfide intoxication via multifarious properties, some of them unrelated to any direct interaction with free H2S.
Identifiants
pubmed: 30590764
pii: 5258482
doi: 10.1093/toxsci/kfy308
pmc: PMC6516679
doi:
Substances chimiques
Antidotes
0
Hemoglobins
0
Cytochromes c
9007-43-6
Methylene Blue
T42P99266K
Hydrogen Sulfide
YY9FVM7NSN
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
443-459Subventions
Organisme : NINDS NIH HHS
ID : U01 NS097162
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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