Effects of 3-methyladenine on isolated left atria subjected to simulated ischaemia-reperfusion.

HERMANN R; TATIANA RUSIECKI; M FERNANDEZ PAZOS; V MESTRE CORDERO; D VELEZ; M.G MARINA PRENDES; E. SAVINO; A VARELA

Foz de Iguazu

Congreso; 1st PanAmerican Congress of Physiological Sciences. Physiology without borders.; 2014

Although autophagy is a prominent feature of myocardial ischaemia and reperfusion, the functional significance is unclear and controversial. In order to gain a deeper insight into the role of autophagy in myocardial ischaemia-reperfusion, we explored the effects of the pharmacological inhibitor 3-methyladenine (3-MA) in isolated rat left atria subjected to simulated ischaemia (75min)-reperfusion (75min) (Is-Rs). A significant enhance in the LC3-II/LC3-I ratio, indicator of autophagosome formation, occurred during Rs. This was prevented by 3-MA which also increased p62 protein, one of the specific substrates that are degraded through the autophagy-lysosomal pathway. Electron micrographs showed double membrane autophagosome like structures during Rs, which were absent in the presence of 3-MA. These findings suggest that this agent inhibited the autophagic flux under the present experimental conditions. Inhibition of autophagy during Is-Rs was accompanied by a high incidence of tachyarrhythmias during Rs and a decrease in the maximal inotropic response to β-adrenergic and to calcium stimulation at the end of Is-Rs. A deterioration of mitochondrial morphology and function, without affecting cell viability, was observed in the atria subjected to Is-Rs in the presence of 3-MA. Present results suggest an association between the inhibition of autophagy and functional alterations of the cells that have undergone sublethal stress and were able to recover in this experimental model of Is-Rs.