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Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.

Abstract

We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca(2+) channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg(-1)·min(-1)), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca(2+)]i) transient amplitudes, and L-type Ca(2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca(2+)]i) transient, and ICa The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca(2+) channels.

Authors+Show Affiliations

Heart and Vascular Institute, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania; phaouzi@hmc.psu.edu.Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania; and.Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania;Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania; and.Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania;Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania; and.Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania;Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania; and Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania;

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26962024

Citation

Judenherc-Haouzi, Annick, et al. "Methylene Blue Counteracts H2S Toxicity-induced Cardiac Depression By Restoring L-type Ca Channel Activity." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 310, no. 11, 2016, pp. R1030-44.
Judenherc-Haouzi A, Zhang XQ, Sonobe T, et al. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity. Am J Physiol Regul Integr Comp Physiol. 2016;310(11):R1030-44.
Judenherc-Haouzi, A., Zhang, X. Q., Sonobe, T., Song, J., Rannals, M. D., Wang, J., ... Haouzi, P. (2016). Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 310(11), pp. R1030-44. doi:10.1152/ajpregu.00527.2015.
Judenherc-Haouzi A, et al. Methylene Blue Counteracts H2S Toxicity-induced Cardiac Depression By Restoring L-type Ca Channel Activity. Am J Physiol Regul Integr Comp Physiol. 2016 06 1;310(11):R1030-44. PubMed PMID: 26962024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity. AU - Judenherc-Haouzi,Annick, AU - Zhang,Xue-Qian, AU - Sonobe,Takashi, AU - Song,Jianliang, AU - Rannals,Matthew D, AU - Wang,JuFang, AU - Tubbs,Nicole, AU - Cheung,Joseph Y, AU - Haouzi,Philippe, Y1 - 2016/03/09/ PY - 2015/12/15/received PY - 2016/03/08/accepted PY - 2016/3/11/entrez PY - 2016/3/11/pubmed PY - 2017/6/27/medline KW - calcium channels KW - cardiac contractility KW - sulfide toxicity SP - R1030 EP - 44 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 310 IS - 11 N2 - We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca(2+) channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg(-1)·min(-1)), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca(2+)]i) transient amplitudes, and L-type Ca(2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca(2+)]i) transient, and ICa The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca(2+) channels. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/26962024/Methylene_blue_counteracts_H2S_toxicity_induced_cardiac_depression_by_restoring_L_type_Ca_channel_activity_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00527.2015?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -