CONICET | Buscador de Institutos y Recursos Humanos

Myocardial stunning occurs after a brief ischemic insult, manifested as a sustained contractile dysfunction. Substantial evidence supports that this dysfunction is triggered by Ca2+ overload (CaO) during reperfusion (R). However, the origin of CaO during R is not well defined. To address this issue, we performed 12 min of global no-flow ischemia (I) followed by R in Langendorff perfused mouse heart positioned on a Pulsed Local Field Fluorescence microscope, loaded with fluorescent dyes (Rhod-2 and Mag-fluo-4 to assess cytosolic or SR Ca2+, respectively). The results indicated an increase in cytosolic Ca2+ during I, which might contribute to increase SR Ca2+ load. During early R, there was an initial increase in diastolic Ca2+ (CaO) that gradually returned to pre-ischemic levels, associated with a rapid decrease in SR Ca2+ content, as a mirror image. Bilayer experiments showed a decrease in the open probability (Po) of the RyR2 in acidic conditions, similar to that observed during I, that fully recovered when pH returned to 7.4, as occurs at the beginning of R. The present findings indicate that the increase in diastolic Ca2+ that occurs upon R is due to a rapid SR Ca2+ release, which might be at least partially caused by the rapid disinhibition of RyR2 associated with pH normalization during early R.