The purpose of the project was to examine measures of heart rate variability (HRV) in male and female alcoholics admitted for drinking cessation. Our question was whether abstention from alcohol use for a period of 4 to 6 weeks would result in normalization of the cardiac signal complexity measure back to baseline, as defined by healthy comparison subjects or if the decreased signal complexity remained stable for a period of 4 to 6 weeks. Our outcome variable of interest was the Hurst exponent of the interbeat interval time series obtained from the EKG, which is a good measure of HRV. The Hurst exponent is a non-linear measure of the autocorrelation of the time series, and in our previous work was found to be increased in alcoholic subjects when obtained 48 hours after cessation of alcohol use with no symptoms of alcohol withdrawal syndrome present. We have determined that in alcoholic subjects, measures of signal complexity do not return to baseline at the end of 5 weeks, but reach an asymptote which is higher than controls. We also found that there were gender and age differences in this measure. We modeled this response over time and found a good fit to a sigmoid response construct. Work by other investigators has found that subjects with decreased measures of autocorrelation as found in this study in alcoholic subjects have a greater risk of sudden death, therefore we hypothesize that altered autonomic contol of heart rate in alcoholics may also be a risk factor for sudden death in this population, as has been determined from several large epidemiologic studies. We are terminating this project as we are moving to non-human primates and rodent models to answer several mechanistic questions resulting from this work. The final results related to this project have been published. (Karimullah K, George DT, DePetrillo PB. The time-course of electrocardiographic interbeat interval dynamics in alcoholic subjects after short-term abstinence. Eur J Pharmacol. 2001 Sep 21;427(3):227-233.)

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Intramural Research (Z01)
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Alcohol Abuse and Alcoholism
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Karimullah, K; George, D T; DePetrillo, P B (2001) The time-course of electrocardiographic interbeat interval dynamics in alcoholic subjects after short-term abstinence. Eur J Pharmacol 427:227-33
DePetrillo, P B; Bennett, A J; Speers, D et al. (2000) Ondansetron modulates pharmacodynamic effects of ketamine on electrocardiographic signals in rhesus monkeys. Eur J Pharmacol 391:113-9
DePetrillo, P B; White, K V; Liu, M et al. (1999) Effects of alcohol use and gender on the dynamics of EKG time-series data. Alcohol Clin Exp Res 23:745-50