Alcohol and Neural Cardiovascular Control in Binge Drinkers

Not Applicable

Completed

Brief Summary: This study evaluates the impact of evening alcohol consumption on sympathetic activity and baroreflex function in binge drinkers. Our central hypothesis is that evening binge alcohol consumption will lead to sympathetic overactivity and blunted baroreflex function.

Detailed Description: This study will recruit male and female binge drinkers who will participate in a randomized, cross-over, double-blind, placebo-based study to examine the impact of an evening of alcohol vs. placebo/fluid-control on autonomic and cardiovascular control at night and the subsequent morning. The study will utilize established techniques for assessing sleep (polysomnography) and autonomic/cardiovascular control (microneurography, beat-to-beat finger plethysmography, electrocardiogram, etc.). All subjects will undergo a familiarization night in the sleep laboratory prior to their first randomized test session with either alcohol or placebo/fluid-control. Both men and women will be tested to address a secondary aim of determining the impact of sex (male vs. female) and ovarian cycle (early follicular vs. midluteal phase) on sympathetic neural responsiveness to evening alcohol in binge drinkers. Finally, as a tertiary/exploratory aim, participants that have a respiratory disturbance index of ≥5 episodes per hour during the alcohol treatment will be asked to consider one additional overnight session where they will be randomly assigned to either continuous positive airway pressure (CPAP) or sham-CPAP for one additional night of evening alcohol consumption.

Recruitment & Eligibility

Inclusion Criteria

Men and women age 21 - 40 years
Binge drinkers as defined by a pattern of consuming ≥4 drinks if female (≥5 drinks if males) in ≤ 2 hours on more than one occasion within the past 6 months, and at least once in the past 30 days. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) definition of a "drink" will be used.
Women must be eumenorrheic and premenopausal with regular and consistent menstrual cycles (i.e., ~25-30 days ovarian/uterine cycles that include 2-7 days of menstruation)
Willingness to abstain from exercise and caffeine at least 12 hours prior to any autonomic and cardiovascular testing, and abstain from alcohol 24 hours prior to any autonomic and cardiovascular testing (unless experimentally administered).

Exclusion Criteria

Body mass index ≥ 35 kg/m2
Smokers
A physician diagnosis of diabetes
Pregnancy
Taking any cardiovascular medications
Severe obstructive sleep apnea as determined by an apnea-hypopnea index of ≥ 30 episodes per hour
Moderate-to-severe Alcohol Use Disorder (AUD) as determined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
Individuals suspected to have mutant alcohol dehydrogenase 2 (ALDH2) isoenzyme as determined using a validated flushing questionnaire
Women using hormonal contraceptives (i.e., oral, intrauterine, etc.) in the prior 6 months

Arm && Interventions

Group	Intervention	Description
Fluid Control	Alcohol vs. Placebo	Participants first received a fluid control drink (i.e., juice) of the same volume of fluid as the alcohol condition. After at least a one-month washout period, they then received the alcohol condition.
Alcohol	Alcohol vs. Placebo	Participants first received the alcohol condition with 95% ethanol and fruit juice (1:3 ratio). After at least a one-month washout period, they then received the fluid control condition with a volume fluid match.

Primary Outcome Measures

Name	Time	Method
Sympathetic Nerve Activity Burst Frequency	1 month	Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode.
Sympathetic Nerve Activity Burst Incidence	1 month	Direct recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve using a microelectrode. Burst incidence is calculated as the number of sympathetic bursts per 100 heartbeats. This measure takes into account varying heart rates on sympathetic activity by normalizing to each individual's heartbeat. Higher calculated number equates to higher sympathetic activity.

Secondary Outcome Measures

Name	Time	Method
Spontaneous Sympathetic Baroreflex Sensitivity	1 month	The linear relationship between beat-to-beat blood pressure and sympathetic nerve activity expressed as bursts/100 heart beats. Sympathetic baroreflex sensitivity is determined using the slope of the weighted linear regression of diastolic blood pressure and MSNA burst incidence. Diastolic blood pressure values of individual cardiac cycles were binned into 3 mmHg intervals, and the MSNA burst incidence was determined and subsequently plotted against corresponding diastolic blood pressure bins.