CALDERON SANCHEZ, EVA MARIA, Dominguez-Rodriguez, Alejandro , Lopez-Haldon, Jose , Jimenez-Navarro, Manuel F. , Gomez, Ana M. , Smani, Tarik , Ordonez, Antonio
No
Rev. Esp. Cardiol.
Article
Científica
0.146
01/01/2016
000367528800008
Introduction and objectives: Ranolazine is used as a complementary treatment for angina in symptomatic patients who are inadequately controlled with first-line antianginal therapies. Ranolazine inhibits sodium voltage-dependent channels, suggesting their possible involvement in the reperfusion process by preventing the sodium and calcium overload that occurs during ischemia. In this study, we characterized the effect of ranolazine on calcium homeostasis in isolated adult cardiac myocytes from rats subjected to a simulated ischemia and reperfusion protocol. Methods: The effects of ranolazine on changes in intracellular calcium concentration were evaluated at different times using field electrostimulation. The study of intracellular calcium was performed using microfluorimetry with the fluorescent indicator, Fura-2, and by confocal microscopy with the indicator, Fluo-3. Results: We found that cardiomyocytes subjected to ischemia-reperfusion showed an increase in the diastolic calcium concentration and a decrease in the amplitude of intracellular calcium transients. The application of ranolazine during ischemia significantly improved intracellular calcium handling, preventing intracellular calcium overload, decreasing the diastolic calcium concentration, increasing the sarcoplasmic reticulum calcium load, and preserving the amplitude of the intracellular calcium transient, which was reflected by successful recovery in the process of excitation-contraction coupling during reperfusion. However, these effects of ranolazine did not occur when it was applied during reperfusion or when applied in both ischemia and reperfusion. Conclusions: Ranolazine shows beneficial effects in cardiomyocytes exposed to ischemia/reperfusion but only when applied during ischemia. This effect is achieved through its improvement of calcium handling during ischemia. (C) 2015 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.
Ischemia-reperfusion; Cardioprotection; Ca2+; Ranolazine