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The aim of this study was to clarify 1) the effects of MB on H<jats:sub>2<\/jats:sub>S-induced cardiac toxicity and 2) whether L-type Ca<jats:sup>2+<\/jats:sup>channels, one of the targets of H<jats:sub>2<\/jats:sub>S, could transduce some of the counteracting effects of MB. In sedated rats, H<jats:sub>2<\/jats:sub>S infused at a rate that would be lethal within 5 min (24 \u03bcM\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H<jats:sub>2<\/jats:sub>S reached 7.09 \u00b1 3.53 \u03bcM when cardiac contractility started to decrease. Two to three injections of MB (4 mg\/kg) transiently restored cardiac contractility, blood pressure, and V\u0307o<jats:sub>2<\/jats:sub>, allowing the animals to stay alive until the end of H<jats:sub>2<\/jats:sub>S infusion. MB also delayed PEA by several minutes following H<jats:sub>2<\/jats:sub>S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H<jats:sub>2<\/jats:sub>S (100 \u03bcM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) transient amplitudes, and L-type Ca<jats:sup>2+<\/jats:sup>currents ( I<jats:sub>Ca<\/jats:sub>) within 3 min of exposure. MB (20 mg\/l) restored the cardiomyocyte function, ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) transient, and I<jats:sub>Ca<\/jats:sub>. The present results offer a new approach for counteracting H<jats:sub>2<\/jats:sub>S toxicity and potentially other conditions associated with acute inhibition of L-type Ca<jats:sup>2+<\/jats:sup>channels.<\/jats:p>","DOI":"10.1152\/ajpregu.00527.2015","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T04:08:59Z","timestamp":1457582939000},"page":"R1030-R1044","source":"Crossref","is-referenced-by-count":32,"title":["Methylene blue counteracts H<sub>2<\/sub>S toxicity-induced cardiac depression by restoring L-type Ca channel activity"],"prefix":"10.1152","volume":"310","author":[{"given":"Annick","family":"Judenherc-Haouzi","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Translational Medicine, Temple 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