Binge Drinking During Adolescence Induces Long-Lasting Oxidative Stress and Inflammation in the Heart and Promotes Cardiac Dysfunction in Rats
Hugo S. Díaz, Katherine V. Pereyra, Karla G. Schwarz, Rodrigo Iturriaga, Rodrigo Del RioBackground: It is not well-known whether cardiovascular alterations elicited by adolescent binge drinking (ABD) are reversible or if they persist following long-term abstinence until adult life. Thus, we studied the long-term impact of ABD on oxidative stress, inflammation and cardiovascular function. Methods: Twenty-four adolescent Sprague-Dawley rats underwent a controlled or ABD-like protocol, (ethanol 3.00 g/kg i.p.) starting at postnatal day 25 (PND25) to PND38, followed by long-term abstinence until PND70 (adulthood). Results: ABD resulted in overt cardiac dysfunction in adult rats. We found a decreased left ventricular compliance as evidenced by a marked reduction in the early-to-late mitral valve blood flow (E/A: 1.23 ± 0.14 vs. 1.51 ± 0.09, control vs. ABD, p < 0.05). Importantly, cardiac dysfunction was closely linked to adverse cardiac remodeling and fibrosis in ABD animals compared to control animals. Furthermore, we found that ABD resulted in a significant increase in cardiac arrhythmogenesis. Indeed, ABD rats showed a 2-fold increase in the incidence of cardiac arrhythmias compared to control rats (53.6 ± 12.7 vs. 21.7 ± 5.7 events/h, Control vs. ABD, p < 0.05). Finally, we found that cardiac functional impairments were accompanied by increases in cardiac tissue oxidative stress and upregulated levels of pro-inflammatory cytokines (i.e., IL-1β and TNF-α). Conclusions: Present results show that ABD drives long-lasting cardiac dysfunction that persists during early adulthood. Oxidative stress and inflammation may contribute to long-term cardiovascular alterations induced by ABD.