The purpose of the project is to examine measures of heart rate variability (HRV), continuously and noninvasively, in male and female alcoholics admitted for drinking cessation. The project serves to test the hypothesis that measures of HRV might serve to distinguish a priori sub-groups of patients at risk for more severe alcohol withdrawal in the absence of clinically apparent symptomatology. The peripheral manifestations of alcohol withdrawal syndrome (AWS) are characterized by rapidly changing autonomic influences. These may vary, minute to minute and hour to hour, depending on the severity and stage of AWS. Consequently, the development of HRV measures, which are relatively insensitive to non-stationarity of signal and could capture relevant data during short periods of measurement, was necessary prior to the protocol implementation. An algorithm, using phase-space decomposition, was developed that characterizes the type of noise exhibited in time-series measures such as inter-beat interval (IBI). In agreement with other workers using different methodologies, it was found that healthy subjects generate IBI time-series with noise characteristics between noise and noise. The algorithm was found to be sensitive, distinguishing between healthy comparison subjects measured in an eyes open or eyes closed paradigm. Relatively short measurement times are required to extract the noise characteristics from the time-series within an acceptable degree of error. Relative insensitivity to non-stationarity of signal was demonstrated. A manuscript outlining this method and its application is in preparation. The methodology was used to retrospectively analyze the IBI from EKG's obtained from 264 subjects performed under eyes-open and eyes-closed paradigm. Subjects were stratified based on demographic parameters and presence/absence of alcohol dependence. As this data is analyzed, it will provide additional information on the validity and stability of the method. Noise parameters are being compared and contrasted adjusting for age, gender, years of alcohol use, and psychopathology. The results of this analysis will provide valuable information regarding population-based variances of the noise parameter. These results will be applied to the design of the inpatient phase of the study, which will compare and contrast HRV parameters studied in healthy comparison subjects and alcoholics. IBI will be measured in patients for three consecutive 96-hour periods every 7 days during the course of treatment. Application of the phase-space algorithm to a heart beat window of 250 - 350 beats throughout the periods of measurement will allow the analysis of correlations between the noise characteristics and symptoms of AWS. Coarse-graining spectral analysis (CGSA) methodology will also be utilized to simultaneously evaluate parasympathetic and sympathetic nervous system (PNS/SNS) indicators.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Intramural Research (Z01)
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Special Emphasis Panel (LCS)
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National Institute on Alcohol Abuse and Alcoholism
United States
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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