Methylene blue counteracts H sub( 2)S toxicity-induced cardiac depression by restoring L-type Ca channel activity

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2016-06, Vol.310 (11), p.R1030-R1030
• Main Authors: Judenherc-Haouzi, Annick, Zhang, Xue-Qian, Sonobe, Takashi, Song, Jianliang, Rannals, Matthew D, Wang, JuFang, Tubbs, Nicole, Cheung, Joseph Y, Haouzi, Philippe
• Format: Article
• Language: English
• ISSN: 0363-6119

We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H sub( 2)S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H sub( 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 the effects of MB on H sub( 2)S-induced cardiac toxicity and whether L-type Ca super( 2+) channels, one of the targets of H sub( 2)S, could transduce some of the counteracting effects of MB. In sedated rats, H sub( 2)S infused at a rate that would be lethal within 5 min (24 mu M.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 sub( 2)S reached 7.09 plus or minus 3.53 mu M when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and Vo sub( 2), allowing the animals to stay alive until the end of H sub( 2)S infusion. MB also delayed PEA by several minutes following H sub( 2)S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H sub( 2)S (100 mu M) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca super( 2+)] sub( i)) transient amplitudes, and L-type Ca super( 2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca super( 2+)] sub( i)) transient, and ICa. The present results offer a new approach for counteracting H sub( 2)S toxicity and potentially other conditions associated with acute inhibition of L-type Ca super( 2+) channels.