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Methylene blue counteracts H 2 S toxicity-induced cardiac depression by restoring L-type Ca channel activity
We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H 2 S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H 2 S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if...
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Published in: | American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2016-06, Vol.310 (11), p.R1030-R1044 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H
2
S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H
2
S 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 H
2
S-induced cardiac toxicity and 2) whether L-type Ca
2+
channels, one of the targets of H
2
S, could transduce some of the counteracting effects of MB. In sedated rats, H
2
S 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 H
2
S 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 V̇o
2
, allowing the animals to stay alive until the end of H
2
S infusion. MB also delayed PEA by several minutes following H
2
S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H
2
S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca
2+
]
i
) transient amplitudes, and L-type Ca
2+
currents ( I
Ca
) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca
2+
]
i
) transient, and I
Ca
. The present results offer a new approach for counteracting H
2
S toxicity and potentially other conditions associated with acute inhibition of L-type Ca
2+
channels. |
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ISSN: | 0363-6119 1522-1490 |
DOI: | 10.1152/ajpregu.00527.2015 |