Energetic study of cardioplegic hearts under ischaemia/reperfusion and [Ca²⁺] changes in cardiomyocytes of guinea‐pig: mitochondrial role

Abstract

CPG, diazoxide and clonazepam improve postischaemic recovery, respectively, by increasing the Ca(2+) cycling and by reducing the mitochondrial Ca(2+) uptake either by uniporter or by mNCX. The mitochondria compete with the leaky sarcoplasmic reticulum (SR) as sink of Ca(2+) in guinea-pig hearts, affecting the postischaemic contractility. CPG also prevented the ouabain-induced dysfunction by avoiding the Ca(2+) overload. Ouabain reduced the synergism between CPG and clonazepam suggesting that [Na(+)]i and SR load influence the mNCX role.

Benzothiazepine CGP37157 and its 2′-isopropyl analogue modulate Ca2+ entry through CALHM1

“…These effects are presumably due to the interaction of CGP37157 with other biological targets, e.g. mNCX or sarco-endoplasmic Ca 2þ ATPase (SERCA), and the subsecuent Ca 2þ cell dynamics alteration when administered at higher micromolar concentrations (Ragone et al, 2013). Moreover, though we have discarded that CCGP37157 exerts its modulatory effect on CALHM1 indirectly through mitochondria, further experiments need to be addressed to confirm a direct action on CALHM1.…”

Effects of pyruvate on the energetics of rat ventricles stunned by ischemia–reperfusion

“…The hearts were immediately excised and perfused using the Langendorff method with Krebs solution at a constant flow rate of 6 mL·min −1 ·g −1 , using a peristaltic pump (Gilson Minipuls 3) (Ponce-Hornos et al 1995;Consolini et al 2001;Consolini and Bonazzola 2008;Bonazzola and Takara 2010;Ragone et al 2013). The atria were removed, and spontaneous beating was stopped by a little cut on the interventricular septum close to the aorta.…”

“…Whenever mitochondrial free Ca 2+ was tested, cells were loaded with Rhod-2 AM (3 mol·L −1 ; Molecular Probes-Invitrogen) during 1 h at 4°C followed by wash-up for at least 1 h at 37°C (Trollinger et al 1997;Ragone et al 2013). Cells were placed on a laminin-precoated perfusion chamber and superfused with Krebs-24-HEPES solution containing 2 mmol·L −1 Ca 2+ until stabilization.…”

“…The aim of this work was to evaluate whether Pyr and CPG are additive as cardioprotectives in the stunned heart, and the energetic consequences on post-ischemic hearts. Online calorimetry was employed, since it was extensively used for studying the energetics of Ca 2+ movements in resting and beating hearts (Ponce-Hornos et al 1982, 1995Bonazzola and Takara 2010), as well as under ischemia and hypoperfusion (Consolini et al 2001(Consolini et al , 2007Ragone et al 2013). The myothermic analysis in ventricles was complemented with measurements of mitochondrial and cytosolic [Ca 2+ ] in ventricular cardiomyocytes to suggest the underlying mechanisms of Pyr, either added to a cold cardioplegia or as a unique pretreatment in a model of cardiac stunning.…”

Eudistomin D and Penaresin Derivatives as Modulators of Ryanodine Receptor Channels and Sarcoplasmic Reticulum Ca2+ATPase in Striated Muscle

“…In contrast, Pen derivatives do not appear to have strong potential to generate caffeine-like agonists of RyRs. Still, their effects on SERCA and their very mild agonism of RyRs resemble that of benzothiazepines, agents associated with cardioprotection Lv et al, 2013;Ragone et al, 2013).…”