REMOTE ISCHEMIC PRECONDITIONING MODIFIES EARLY VENTRICULAR REMODELING POST MYOCARDIAL INFARCTION BY ATTENUATION OF THE INFLAMMATORY RESPONSE AND OXIDATIVE STRESS

MARIANA GARCES; BIN, ELIANA; MAGNANI NATALIA; GELPI RICARDO; DONATO MARTIN; EVELSON PABLO

Congreso; Redox Biology in translation annual meeting of the society for free radical research-Europe; 2023

It is known that remote ischemic preconditioning (rIPC) reduces infarct size inexperimental models of myocardial infarction (MI) but the effect of rIPC on postinfarction ventricular remodeling is unknown. The aim of this work was toevaluate the effect of rIPC on early ventricular remodeling, considering MIexpansion. Male FVB mice, 2-6 months old, were underwent to MI by permanentligation (7 days) of the left anterior coronary artery; in a second group, a rIPCprotocol (3 cycles of 5 min ischemia/reperfusion in the left lower limb) wasperformed prior to MI. A third group was undergoing to left thoracotomy, butwithout MI (Sham). Lastly, the same procedures were performed in dominantnegative mutant mice of thioredoxin-1 (DN group). We evaluated infarct area,ventricular functions, MMPs 2 and 9. While oxidative damage to macromolecules, TNF-α, IL-6 and IL-10 levels were measured in serum. MI decreased ejection fraction and fractional shortening (p0,05 vs sham), while rIPC protocolimproved both parameters (p0,05 vs IM). The relationship between end-systolic stress and ejection fraction was plotted, observing a significant improvement in the rIPC group, compared MI group. Moreover, rIPC reducedsignificantly MMP-9 expression (p0,001 vs sham). Finally, rIPC decreasedoxidation of proteins and lipids (p0,01; p0,05) as well as TNF-α and IL-6 levelsin serum compared to MI group (p0,0001; p0,01). Regarding IL-10 levels,rIPC showed an increase compared with Sham and MI group (p0,01). Meanwhile, inhibition of endogenous thioredoxin-1 in the heart of transgenic miceabolish the cardioprotection observed in ischemic preconditioning (DN-rIPCgroup) as observed by a decreased in ejection fraction and increased damage toproteins and TNF-α levels when comparing to DN-Sham group (p0,05;p0,001; p0,05). rIPC has a beneficial effect on early remodeling, improvingventricular function. These beneficial effects could be related to a reducedoxidative stress and inflammatory response