Vikram K. Yeragani

Effect of age on long-term heart rate variability

OBJECTIVE Previous studies on short-term time series of heart rage suggest an inverse relationship between age and spectral powers of heart rate variability in various frequency bands. In this study, we examined the relationship between age (6-61 years) and long-term heart rate variability. METHODS We obtained 24-h Holter ECG in 33 healthy human subjects (11 children and 22 adults). The heart rate data were analyzed by using spectral analysis and fractal dimensions of the time series. RESULTS We found a significant negative correlation between age and very low frequency (VLF, 0.0033-0.04 Hz), low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) powers and fractal dimensions during awake as well as sleep periods, and a positive correlation between age and LF/HF ratios. Age and ultra-low frequency (ULF, < 0.0033 Hz) were modestly and negatively correlated only during the awake period. CONCLUSIONS Sleep ULF power is not significantly affected by age, whereas VLF, LF and HF powers and fractal dimensions of heart rate significantly decrease with age during awake as well as sleep periods.

Decreased heart-period variability in patients with panic disorder: a study of Holter ECG records

This study investigated cardiac autonomic function in patients with panic disorder and normal controls using Holter ECG records. A decrease in ultra-low frequency power (< 0.0033 Hz) is known to be associated with an increased risk for cardiovascular mortality in humans. Twenty-four-hour ECG was recorded in 29 patients with panic disorder and 23 normal controls using Holter records. Data for 20 h and also 20000 s of awake and 20000 s of sleep periods were analyzed using spectral analysis to quantify absolute and relative heart-period variability in ultra low (ULF: < 0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. The patients with panic disorder had significantly lower total and absolute ULF power, which was more pronounced during sleep. The patients also had significantly lower relative ULF power and significantly higher relative LF power during sleep. There was a significant increase of relative LF power from awake to sleep period only in the patient group. The decrease in total and ULF power may increase the risk of mortality and sudden arrhythmic death in patients with panic disorder if they experience a cardiac event. The higher relative LF power during sleep also suggests a possible higher sympathetic drive in the patients during sleep.

Effect of Posture and Isoproterenol on Beat-to-Beat Heart Rate and QT Variability

Rationale: Recent literature emphasizes the utility of QT variability to study ventricular electrophysiologic function. In this investigation, we sought to test the hypothesis that beat-to-beat fluctuations in QT intervals are mediated by sympathetic activity in normal subjects using postural challenge and isoproterenol infusions. Subjects and Methods: We obtained ECG in the supine and standing postures during spontaneous breathing, at 12, 15 and 20 per minute controlled breathing (n = 19), and before and after infusions of isoproterenol, a β-adrenergic agent, in the supine posture during spontaneous breathing (n = 11) using lead II configuration in healthy human adult subjects. Heart rate (HR) and QT time series data were analyzed by spectral analysis of 256 s of real-time data. Beat-to-beat QT intervals were measured by automated analysis of ECG. A QT variability index (QTvi) was calculated for each subject as the logarithm of the ratio of normalized QT variance to normalized HR variance. We also calculated fractal dimensions of QT time series during spontaneous breathing. Results: QTvi was significantly higher in the standing than in the supine posture (–1.93 ± 0.27 vs. –1.47 ± 0.41; p = 0.0001), and also during isoproterenol infusions in the supine posture (–1.83 ± 0.39 vs. –1.27 ± 0.43; p = 0.0001). Fractal dimensions of QT time series were also significantly higher during standing (p = 0.00001) and isoproterenol infusions (p = 0.0002). Respiratory rate or tidal volume did not account for the increased QT variability seen in the standing posture. Conclusions: A change from the supine to the standing posture as well as infusion of isoproterenol significantly increased the absolute as well as normalized QT variability, which appears to be due to an increase in sympathetic activity associated with these conditions.

Heart Rate and Blood Pressure Variability: Implications for Psychiatric Research

Symptoms of anxiety suggest autonomic dysfunction and most of the psychotropic agents used to treat anxiety and affective disorders have strong autonomic effects. This article describes the utility and importance of analysis of heart rate and blood pressure time series to study cardiac autonomic function in psychiatric research. The variability of heart rate between 0.15 and 0.5 Hz is related to respiratory sinus arrhythmia, and is modulated by cholinergic activity in both supine and standing postures, while the variability between 0.04 and 0.15 Hz is dually influenced by cholinergic and adrenergic mechanisms which can be used as a relative measure of sympathetic activity in standing posture. Analysis of beat-to-beat control of heart rate and blood pressure gives important information about cardiac sympathetic and parasympathetic interaction, which could be used to study the possible link between anxiety and depressive disorders and increased cardiovascular morbidity.

Effects of isoproterenol infusions on heart rate variability in patients with panic disorder

Some evidence suggests that patients with panic disorder have a decreased cardiac vagal and a relatively higher sympathetic activity. In this study, spectral analysis of the time series of heart rate before and after isoproterenol infusions was used to study heart rate variability in six panic disorder patients and 11 normal control subjects. These preliminary data reveal a significant increase of sympathovagal ratios only in the patient group after isoproterenol administration. The findings suggest a relative increase in cardiac sympathetic and a relative decrease in cardiac vagal function in patients with panic disorder during isoproterenol infusions.

Depression and heart rate variability

Since there is evidence suggesting an increased incidence of cardiovascular morbidity in patients with major depression and phobic anxiety (Dalack et al 1990: Kawachi et al 1994), we have been conducting studies on cardiac autonomic function in these disorders using noninvasive techniques such as spectral analysis of heart rate (HR). Low frequency (LF:0.01-0.05 Hz) power has been related to renin angiotensin and thernmregulatory mechanisms, midfrequency (MF:0.07-0.15 Hz) power to baroreceptor control, and high-frequency (HF:0.16-0.5 Hz) power to respiratory sinus arrhythmia (Malliani et al 1991). Our previous findings suggest that patients with panic disorder have decreased variance of heart rate time series, higher standing re lame midfrequency power, and higher increases in standing midfrequency power when challenged v, ith yohimbine (Yeragani et al 1992, 1993). We have also found that patients with panic disorder have exaggerated vagal withdrawal and higher sympathovagal ratios during sodium lactate and isoproterenol infusions (Yeragani et al 1994, 1995). In a previous report on time domain measures of heart rate variability, we did not find any significant differences in the standard deviation of heart rate between patients with depression and normal controls (Yeragani et al 199l). However, the data acquisition and determination of R-R intervals were done manually, and we did not use spectral analysis of HR in this study. In the present relx)rt, we compare heart rate variability data on 16 patients with major depression with no current or past history of panic attacks, and 29 patients with panic disorder without a current history of major depression. The data on these 16 patients with depression have not been published elsewhere. However.

Sodium lactate increases sympathovagal ratios in normal control subjects: Spectral analysis of heart rate, blood pressure, and respiration

We used spectral analysis of heart rate (HR), blood pressure (BP), and respiration to examine the effects of lactate on cholinergic and adrenergic influences on HR and BP variability, a technique found to be very useful in cardiovascular research. We specifically used high frequency (0.2-0.5 Hz) and midfrequency (0.07-0.15 Hz) powers to study cholinergic and adrenergic activity in nine normal control subjects before and after lactate and placebo infusions. Our results demonstrate a marked decrease in cholinergic activity and a significant increase in sympathovagal ratios of HR modulation after lactate infusions. This altered sympathovagal balance may contribute to the panicogenic effects of lactate in panic disorder patients.

Imipramine-induced jitteriness and decreased serum iron levels.

Jitteriness appears to be a specific side effect of tricyclic antidepressant treatment in panic disorder patients. In addition, the patients with jitteriness have lower serum iron levels compared to those that do not develop jitteriness (p = 0.01).

Power spectrum of the QRS complex in patients with panic disorder and normal controls.

We performed spectral analysis on the QRS complex of the electrocardiogram obtained using standard limb leads, sampled at 500 Hz with 12 bit precision in 20 normal subjects and 15 patients with panic disorder. We divided the frequency range of the QRS into two bands based on spectral patterns before and after the postural challenge-mid frequency (MF): 7.8-20 Hz; and high frequency (HF): 21-250 Hz. Postural change from supine to standing produced a significant increase in absolute (P = 0.003) and relative HF power (P = 0.00001). Patients with panic disorder had a significantly decreased QRS HF power (P = 0.003). The increase in QRS HF power may have been due to the shortening of the QRS interval in standing posture. The decreased QRS HF power in patients with panic disorder should be further investigated due to the recent reports of an association of phobic anxiety and fatal coronary heart disease, and the possible association of decreased high frequency components of QRS in myocardial infarction.

Effects of lactate on cross-spectral analysis of heart rate, blood pressure, and lung volume in normal volunteers

Baroreceptor reflex sensitivity, coherence functions, and transfer functions between respiration and heart rate, and between respiration and blood pressure, were studied in nine normal volunteers before and after intravenous sodium lactate infusions. Cross-spectral analysis was used to examine heart rate, finger blood pressure, and respiration obtained with the subjects in a supine posture during spontaneous breathing. Sodium lactate produced a significant decrease of the modulus between respiration and heart rate (beats/min/l). There was no such change for the placebo infusions. The absence of a significant difference in the modulus between systolic blood pressure and heart rate for placebo or lactate indicated that there were no significant changes in the baroreceptor sensitivity index. These findings suggest that lactate infusions are associated with a decrease in cardiac vagal function.