Immediate and Complex Cardiovascular Adaptation to an Acute Alcohol Dose.

THE LONG-term, detrimental effects of chronic heavy alcohol use on cardiovascular function are well established and broadly appreciated (e.g., American Heart Association, 2015; Corrao et al., 2004; National Institute on Alcohol Abuse and Alcoholism, 2015; Rehm et al., 2010). These chronic effects arise over time as the result of repeated bouts of acute intoxication and withdrawal, but each drinking episode is also acutely linked to its own complex time-and dose-dependent neural, muscular, and biochemical alterations within the cardiovascular system (Kahkonen et al., 2011; Kawano, 2010). Initially, these acute cardiovascular alterations are transient (Kawano, 2010), and system redundancies can effectively compensate for disruptions to any one given element (Joyner and Pedersen, 2011; Quinn and Kohl, 2012). Over time, however, these alterations can persist and become clinically evident as one of several diagnosable chronic cardiovascular diseases that are highly comorbid with alcohol dependence (Corrao et al., 2004; Rehm et al., 2010). In this study, we examined the early effects of an oral dose of alcohol on the cardiovascular system, with particular emphasis on changes in system variability and sensitivity, in a sample of healthy, young adult drinkers. Interest in biological variability has exploded over the past decade, with significant literature now focusing on neural (Wang, 2010) and cardiovascular (Lehrer and Eddie, 2013; Rickards and Tzeng, 2014) oscillations. Greater variability in biological functions is generally thought to demonstrate more intact regulatory systems that are appropriately detecting and dynamically responding to perturbation (Kitano, 2004; Lehrer and Eddie, 2013; Thayer and Lane, 2000). In other words, more variability often implies a high degree of flexibility in a well-functioning biological system (Tapanainen et al., 2002; Vaschillo et al., 2011). Heart rate variability (HRV; i.e., changes in the time intervals between consecutive heart beats) is perhaps the best known and most easily measured index of physiological variability. HRV reflects the continual, bidirectional communication between the heart and brain, which allows the individual to precisely adapt to changes in his/her internal milieu and external environment by integrating neural and cardiovascular reactions. In the resting state, it is a robust biomarker of health (Kemp and Quintana, 2013; Thayer et al., 2010). Following oral alcohol consumption, resting state HRV is reduced (reviewed in Romanowicz et al., 2011), as is HRV reactivity to emotionally valenced visual cues (Vaschillo et al., 2008). The cardiovascular system, however, does not adapt solely by modulating HRV. Rather, it can flexibly respond to challenge by changing stroke volume, vascular tone, and blood pressure (BP) variability in addition to or in lieu of changing HRV (Liu et al., 2004; Ma and Zhang, 2006; Rickards and Tzeng, 2014; Vaschillo et al., 2012). System redundancy ensures that the cardiovascular system can buffer itself against internal (e.g., cognitive emotional) and external (e.g., pharmacological) challenges, and thus protect the brain from stroke and the heart from myocardial infarction. These system elements (i.e., heart rate [HR], vascular tone) may work independently or in tandem to generate fine-grained, real-time adjustments to optimize cardiovascular responding. Importantly, variability in each of these processes is linked through the baroreflex system, which is comprised of multiple parallel, closed-loop branches that control BP through changes in HR (i.e., the HR baroreflex loop), stroke volume (i.e., the stroke volume baroreflex loop), and vascular tone (i.e., the vascular tone baroreflex loop) (Casadei et al., 1992; Eckberg and Sleight, 1992; Vaschillo et al., 2012; Yambe et al., 2009). In addition, the baroreflex controls sympathetic nervous system activity. For example, the baroreflex decreases muscle sympathetic nerve activity when BP increases, and increases it when BP decreases (Hart et al., 2009). Under normal conditions, the baroreflex coordinates cardiovascular processes. When challenged by alcohol, however, it is unclear whether cardiovascular processes remain coordinated and/or whether the sensitivity of the baroreflex system to detect changes is compromised. This study sought to provide a first step in characterizing system-wide cardiovascular disruption by examining the effects of acute alcohol intoxication on average HR, stroke volume, vascular tone, and BP, variability in each of these cardiovascular processes, and sensitivity in the HR, stroke volume, and vascular tone baroreflex branches. The effects of acute alcohol on the cardiovascular system were assessed on the ascending limb of the blood alcohol curve, a period of maximal alcohol absorption that is associated with stimulant/euphoric subjective experiences. Prior studies suggest that cardiac responses to alcohol are more tightly linked to the stimulant, compared to sedative effects of alcohol (Brunelle et al., 2007). Our general hypothesis was that the reactions of individual cardiovascular parameters and baroreflex feedback loops to acute alcohol intoxication would be disparate but coordinated, such that they maintain general cardiovascular homeostasis. For average cardiovascular responses, based on prior studies using oral alcohol administration protocols and similar assessment time points, we hypothesized an increase in HR (Conrod et al., 2001), a decrease in stroke volume (Morvai et al., 1988), and vasodilation (Agewall et al., 2000). For variability, we predicted global suppression based on the premise that greater variability implies greater adaptability and better health (Lehrer and Eddie, 2013; Thayer and Lane, 2000; Vaschillo et al., 2011). Previous oral alcohol administration studies have observed a reduction in HRV following alcohol administration (Vaschillo et al., 2008). To our knowledge, no one has assessed whether stroke volume variability or vascular tone variability is disrupted during alcohol intoxication. Finally, oral alcohol administration has been shown to reduce HR baroreflex sensitivity (Fazio et al., 2001), and likewise it is possible that, due to its pharmacological actions on the nitric oxide pathway (Bau et al., 2005) and smooth muscle (Goslawski et al., 2013), alcohol would also reduce sensitivity in the vascular tone and stroke volume baroreflex branches. Thus, we tentatively hypothesized that alcohol would reduce baroreflex sensitivity across all baroreflex branches.