AMPK activation is harmful for postischemic recovery of isolated rat atria subjected to simulated ischemia-reperfusion (Is-Rs) when palmitate is available as energy substrate

HERMANN, ROMINA; MESTRE CORDERO, VICTORIA E.; REZNIK, FEDERICO; FERNÁNDEZ PAZOS, M.MERCEDES; VÉLEZ, DÉBORA E.; SAVINO, ENRIQUE A.; MARINA PRENDES, M.GABRIELA; VARELA, ALICIA

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

AMPK is a cellular ?fuel gauge? enzyme, that regulates cellularfatty acid and glucose metabolism. The effects of AMPKin myocardial ischemia and reperfusion, when fatty acid levelsare elevated, as observed in patients suffering acute myocardialinfarction, are less well established.We explored the effects of the pharmacological inhibitor,Compound C (CC;10 μM), in isolated rat left atria subjectedto 75min Is-75min Rs, on inotropic response to isoproterenol(ISO) 2 mM (contractile reserve: CR), tissue ATP content, mitochondrialATP synthesis and pyruvate dehydrogenase (PDH)activity after Is-Rs.SD rats weighing 220?270 g were used. Atria were incubatedin Krebs?Ringer containing glucose 10 mM (G) or G and 1,2 mMpalmitate-3% BSA (P), 95% O2?5% CO2, pH 7,4. For Is, the incubationmedium contained 10 mM 2-deoxy-D-glucose, 95% N 2?5%CO2, pH 6,8. ANOVA, n=6.Results showed a significant increase in AMPK activityduring Is, remaining activated during Rs. CC prevented AMPKactivation. CR was attenuated by Is-Rs, P increased this attenuation.CC increased the attenuation of CR in the presenceof G as sole exogenous substrate, but reversed theharmful effect of P (Systolic force%: Rs:91±9; Rs+CC:67±7*;Rs+P:66±8*; Rs+CC+P:92±5;*p