Abstract

Harmful alcohol abuse is associated with serious psychosocial and health damage, including cardiac and neurological morbidities. Americans drink 40% more than the global average and adolescents are the heaviest drinkers, displaying a pathological consumption pattern termed “binge drinking”, consisting in short episodes of heavy alcohol intake followed by long withdrawal periods. Despite adolescent binge drinking (ABD) drives severe impairments in neurological and cardiorespiratory function, there are no current health policies to prevent ABD or its physiological consequences. Indeed, little is known about the long-term consequences of ABD in adulthood physiology. Therefore, we aimed to investigate the potential harmful effects of ABD on cardiac and respiratory (patho)physiology in the adult life. Sixteen male juvenile Sprague-Dawley rats underwent ABD-like alcohol administration protocol or control treatment, consisting of 2-days “ON” and 2-days “OFF” doses of ethanol (3.0 g/kg, 25% w/v in saline administered i. p.) beginning on post-natal day (PND) 25 until PND 38. Once rats reached adulthood (PND80), respiratory and cardiac function were respectively assessed by whole-body plethysmography and intraventricular pressure-volume loops. Compared to controls, adult rats exposed to ABD displayed no differences in resting blood pressure, heart rate and pulmonary ventilation, but they showed a significant (p<0.05) increase in the breath-to-breath interval variability (40.8 ± 2.8 vs. 25.6 ± 2.3 ms; ABD vs. Control, respectively) and in the incidence of apneas/hypoapneas (AHI: 5.83 ± 0.40 vs. 2.50 ± 0.37 events/h; ABD vs. Control, respectively). Intraventricular cardiac function analysis using PV-loops revealed a reduction in left ventricular compliance in ABD animals, evidenced by the augmented slope of the end diastolic pressure-volume relationship (EDPVR: 0.0303 ± 0.006 vs. 0.009 ± 0.001 mmHg/µL; ABD vs. Control). Also, we found that ABD induced cardiac autonomic imbalance estimated by low/high frequency ratio of heart rate variability (LFHRV/HFHRV: 1.59 ± 0.23 vs. 1.01 ± 0.08) and increased arrhythmia incidence (53.6 ± 12.7 vs. 21.7 ± 5.7 events/h; ABD vs. Control). Our results shows that binge drinking in adolescence causes long-lasting cardiorespiratory dysfunction that includes at least cardiac diastolic dysfunction, autonomic imbalance, and generation of irregular breathing all of them persisting until the adulthood.