ROLE OF AUTOPHAGY IN MYOCARDIAL ISCHEMIA- REPERFUSION (Is-Rs): INFLUENCE OF AVAILABLE ENERGY SUBSTRATES

ROMINA HERMANN; FEDERICO JOAQUÍN REZNIK; MARÍA DE LAS MERCEDES FERNÁNDEZ PAZOS; VICTORIA EVANGELINA MESTRE CORDERO; DÉBORA ELISABET VELEZ; MARÍA GABRIELA MARINA PRENDES; ALICIA VARELA

Congreso; Reunión Anual de Sociedades de Biociencias; 2017

Autophagy is a prominent feature of myocardial Is-Rs.However, the functional significance is still unclear and controversial.In this study, we explored effects of autophagy in isolated rat leftatria subjected to 75 min Is-75 min Rs, when atria were incubated inthe presence of 10 mM glucose (G) or G and 1,2 mM palmitate (P),as observed in most clinical situations of acute myocardial infarction,which are less well established. For this aim, the effects of theautophagy inhibitor 3-methyladenine (3-MA, 5 mM) were assessed.ANOVA, n=8.Results showed a significant enhance in the LC3-II/LC3-I ratio, anestablished indicator of autophagy, during Rs, which was achievedmore slowly in the presence of P. These results were accompaniedby a concomitant decrease of p62, a specific substrate degradedthrough the autophagy-lysosomal pathway, in both groups. 3-MAprevented LC3 ratio increase and produced p62 accumulation inboth metabolic conditions. Electron micrographs showed autophagosomelike structures during Rs, which were absent in the presenceof 3-MA. Autophagy inhibition was accompanied by a deteriorationof mitochondrial morphology and function, although theseresults were not affected by P. ATP content recovery during Rs wasreduced by P and 3-MA in both metabolic conditions, being this resultconsistent with attenuation in contractile reserve at the end ofRs. In the presence of 3-MA, either in the atria incubated with G or P,spontaneous tachyarrhythmias (270-300 contractions per min) wereobserved throughout Rs, which were attenuated by the inner membraneanion channel blocker PK11195, suggesting an involvementof mitochondria in the 3-MA-induced arrhythmias. These resultswere not affected by P.Present results suggest that autophagy is induced during reperfusiondeveloping cardioprotective effects. P present at high concentrationsas an exogenous energy substrate, would not have significanteffects on this process in the ischemic-reperfused myocardium.