We have previously reported that methylene blue (MB) can counteract H2S intoxication induced circulatory failure. Due to 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 Ca2+ 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 µmoles/kg/min), produced a rapid fall in left ventricle ejection fraction (EF), determined by echocardiography, leading to a pulseless electrical activity (PEA). Blood concentrations of gaseous H2S reached 7.09 ± 3.53 microM when cardiac contractility started to decrease. Two to 3 Injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure and V O2 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 un-sedated rats. Applying a solution containing lethal levels of H2S (100 µM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca2+]i) transient amplitudes, and L-type Ca2+ currents (ICa) within 3 minutes of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca2+]i) transient, and ICa. The present results offer a new approach for countreacting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca2+ channels.
- sulfide toxicicty
- Cardiac contractility
- calcium channels
- Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology