Quantification of the dynamic behavior over time of narrow-band components present in heart rate variability by means of the instantaneous amplitude and frequency.

The statistical properties of the time- and frequency-domain characteristics of heart rate variability are known to vary over time. A method is presented to compute the time-varying spectral contents of the characteristic narrow-band frequency components of heart rate variability by means of the instantaneous amplitude and frequency at an optimal time resolution. The instantaneous frequency may show oscillatory, but also irregular periods in time. An index of the instantaneous bandwidth is computed to discriminate between oscillatory and irregular periods and to correct the instantaneous amplitude and frequency for irregular periods.

Cardiovascular, neuroendocrine, and sedative responses to four graded doses of clonidine in a placebo-controlled study.

Effects of four doses of the alpha 2-receptor agonist clonidine (CLO) (0.25, 0.5, 1, and 2 micrograms/kg IV) and placebo were studied in seven healthy men who volunteered in a double-blind randomized design in order to delineate possible presynaptic and postsynaptic components in the mechanism of action of CLO. Blood pressure, heart rate, plasma noradrenaline (NOR), plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma growth hormone (GH), and subjective sedation were monitored for a period of 1 hr following infusion of CLO. NOR and MHPG were also analyzed in urine, collected at 1 and 4 hr after the infusions. Dose-dependent decrements were observed in systolic and diastolic blood pressure and plasma NOR levels, and dose-dependent increases in subjective sedation and plasma GH. CLO did not influence plasma MHPG levels, whereas only urinary MHPG excretion was reduced 4 hr after infusion of 2 micrograms/kg CLO. Because no obvious differences between dose-response relations of plasma NOR (believed to be a presynaptic and peripheral effect), blood pressure (believed to be mainly a central presynaptic and postsynaptic effect), and subjective sedation (believed to be a central and probably postsynaptic effect) were observed, our results do not provide simple parameters to discern the multiple mechanisms of action of CLO. However, at a dose of 0.5 micrograms/kg CLO (a dose lower than that generally used) clear effects on plasma NOR, blood pressure, and sedation, but not on plasma GH (a central postsynaptic effect) or urinary MHPG (a presynaptic effect), were observed. When using CLO as a challenge test in psychiatric disorders, a design with 0.5 micrograms/kg CLO, in addition to the traditional 2 micrograms/kg CLO, may provide more information to characterize discrete abnormalities in the noradrenergic system at the level of the brainstem, the pituitary, or the peripheral sympathetic nervous system.

Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress.

Dose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male volunteers participated in a placebo and a lorazepam session, during which the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.6, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). Heart rate showed a dose-dependent decrease during rest with an ED50 of 0.13 mg lorazepam, while lorazepam had no effect on the cardiovascular and plasma catecholamine response magnitudes to the CWT. Subjective fatigue and reaction time increased significantly after 0.94 mg lorazepam, while at the same dose vigor decreased; state anxiety after the CWT was not influenced by lorazepam. These data show differential effects of lorazepam on cardiovascular, biochemical and psychological function. While heart rate was suppressed at low doses during rest and reaction time and subjective fatigue increased at doses which induced sedation, state anxiety and physiological response patterns to the CWT were not influenced by lorazepam.

Effects of lorazepam on cardiac vagal tone during rest and mental stress: assessment by means of spectral analysis.

Dose-dependent effects of intravenously administered lorazepam on haemodynamic fluctuations were studied by means of spectral analysis, in order to elucidate sympathetic and parasympathetic components in cardiovascular control during situations of rest and mental stress after benzodiazepine administration. In a double-blind randomized cross-over study, nine male volunteers participated in two sessions: a placebo and lorazepam session. During these sessions, the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.06, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). During the placebo session the subjects received five placebo injections. For five of the nine subjects the lorazepam session was their first session. Heat rate (HR), blood pressure (BP) and respiration were recorded continuously. Power spectra were calculated per 2.5-min periods for HR, systolic (SBP) and diastolic BP (DBP). Spectral density was assessed for three frequency bands: low (LFB: 0.02-0.06 Hz), mid (MFB: 0.07-0.14 Hz) and high (HFB: 0.15-0.40 Hz). During the consecutive periods of rest, lorazepam induced a dose-dependent decrease in HR, and a dose-dependent increase in LFB, MFB and HFB power of HR, but lorazepam had no effect on BP. The effects were significant after 0.44 mg lorazepam for HR and HFB power, and after 0.94 mg lorazepam for the HR fluctuations in the LFB and MFB. Lorazepam did not influence the cardiovascular responses to the CWT.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectral analysis of hemodynamics during infusions of epinephrine and norepinephrine in men.

Spectral analysis of fluctuations in heart rate (HR) and arterial blood pressure (BP) during a 6-h infusion of epinephrine (15 ng.kg-1.min-1) or norepinephrine (30 ng.kg-1.min-1) in 10 normotensive males was used to analyze effects of peripheral sympathetic nervous system activity and adrenal medullary discharge on cardiovascular variability. Power spectra were calculated for each 5-min period for HR, systolic BP, and diastolic BP to yield power values for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.40 Hz). Infusion of epinephrine and norepinephrine induced plasma concentrations of epinephrine and norepinephrine, respectively, within the high physiological range. Spectral analysis showed that low-frequency fluctuations of BP during infusions of epinephrine and midfrequency fluctuations of BP during infusion of norepinephrine changed in opposite directions. These fluctuations may represent different components of short-term cardiovascular control mechanisms during situations that mimic increased sympathoadrenal activity. No changes were observed in HR fluctuations or high-frequency fluctuations of BP after either catecholamine. Our data imply that changes in concentrations of circulating catecholamines cannot be unequivocally labeled as indexes of an altered sympathoadrenal involvement in short-term cardiovascular control.

Characterization of stress reactions to the Stroop Color Word Test.

Sympatho-adrenal activation induced by stress contributes to the development of pathological states such as hypertension and anxiety disorders. The Stroop Color Word Test (CWT) is evaluated as a test for the study of stress-induced sympathetic effects, on the basis of psychological, physiological and biochemical responses. The CWT induced increases in plasma and urinary adrenaline, heart rate, respiration rate, electrodermal activity, electromyography, feelings of anxiety, and decreased finger pulse amplitude.

Heart rate variability spectra based on non-equidistant sampling: the spectrum of counts and the instantaneous heart rate spectrum.

This paper compares two methods to estimate heart rate variability spectra, i.e., the spectrum of counts and the instantaneous heart rate spectrum. Contrary to Fourier techniques based on equidistant sampling of the interbeat intervals, the spectrum of counts and the instantaneous heart rate spectrum are based on non-equidistant sampling: the values are determined at R-wave moments. A consequence of the non-equidistant occurrence of the R-peaks in a heart rate signal is the appearance of the sidebands of the harmonic components of the mean heart rate in the spectra. These sidebands contaminate the signal components in the spectrum. The sideband distortion in the instantaneous heart rate spectrum was found to be smaller than in the spectrum of counts. Simulations using the IPFM-model were made to quantify this difference. On the basis of these simulations, sideband distortion appeared to be dependent on the mean heart rate, the modulation depth and the modulation frequency.

The instantaneous frequency of cardiovascular time series: a comparison of methods.

The instantaneous frequency (IF) of cardiovascular time series is used to describe the time-varying spectral contents of the characteristic frequency bands that are of interest for psychophysiological and cardiovascular research. Four methods to compute IF of band-limited, monocomponent, and analytical cardiovascular time series were compared by means of simulated time series contaminated with additive noise. These four methods are: the method using the inverse Fourier transform of uncorrelated time-slices of the Wigner-Ville distribution, the discrete time-frequency transform, the circular mean direction of the time-slices of the Wigner-Ville distribution, and the central finite difference of the phase. The time resolution of the estimates is optimal and is inversely related to the bandwidth of the frequency components, as given by the uncertainty principle of Gabor. At periods in time where the signal fulfills the requirements of the model signal, the four estimates of IF are numerically equal; only the circular mean direction showed a slight deviation from the other estimates. Although the estimates of IF differ at sudden phase shifts at low amplitude, i.e. at points where the signal locally does not comply with the requirements of the model signal, overall the four methods produce comparable estimates of IF of a cardiovascular time series at an optimal time resolution.

The exponential distribution applied to nonequidistantly sampled cardiovascular time series.

Beat-to-beat fluctuations in cardiovascular time series comprise different frequency components which can be employed to describe autonomic regulatory processes. The Exponential Distribution (ED) is presented here as a specific time-frequency distribution which has the potential to describe the time-related changes in the frequency content of these cardiovascular fluctuations. The ED has as advantage that it gives a good suppression of the cross terms, a characteristic feature of bilinear time-frequency distributions. An implementation to apply the ED to nonequidistantly sampled cardiovascular time series is provided. Applications of the ED to various clinical and experimental human cardiovascular time series show that the ED can be an important aid to describe and interpret time-varying frequency components of cardiovascular signals such as heart rate, interbeat interval, blood pressure, and respiration.

A novel tool to quantify physical activities: ambulatory accelerometry in psychopharmacology.

Accelerometry by means of body-mounted piezoresistive sensors was evaluated as a new method to quantify physical activities (body posture and physical and locomotor activity) in relation to the sedative and cardiovascular effects of benzodiazepines, in an ambulatory study. In a double-blind, randomized, crossover study, 12 healthy men received either an oral dose of 2 mg lorazepam, 0.5 mg alprazolam, 1 mg alprazolam, or a placebo on 4 different days. By means of a portable digital recorder, each day 4 hours of continuous measurements of accelerometer signals and heart rate were performed in a living room in the hospital. Changes in subjective sleepiness were assessed at the beginning, halfway, and at the end of the recording period. A separate validation study of the ambulatory environment was performed in three subjects, in which computer classification of activities based on accelerometry was compared with visual evaluation of simultaneously recorded videotapes. In our validation study, comparison of the computer classification with visual analysis based on videotapes revealed an overall agreement for spontaneous and standardized activities of 88% and 96%, respectively. In our pharmacological study, the subjects spent more time in the lying position (p < 0.01) and less time in the sitting position (p < 0.01) after benzodiazepine administration; the effects were strongest for lorazepam. Motility during static activities was reduced (p < 0.025), with motility after lorazepam administration being lowest. Both lorazepam and alprazolam (0.5 and 1 mg) increased subjective sleepiness (p < 0.01). On average , lorazepam induced an overall increase in mean heart rate of about 6%, whereas alprazolam reduced mean heart rate by 2% versus placebo (p < 0.01); the effects were not dependent on posture. The validation study showed that accelerometry forms a reliable method to quantify aspects of normal daily activities. Our pharmacological study revealed that quantification of body postures, physical activity, and motility by means of ambulatory accelerometry proves to be an objective and promising tool to evaluate the psychological and cardiovascular effects of (psycho) pharmaca in relation to the postural and mobility activities of normal daily life.

Sleep patterns and blood pressure variability in patients with pure autonomic failure.

Sleep patterns and 24-h blood pressure variability were studied in four female patients (age range: 56-82 years) with pure autonomic failure. All patients had severe symptomatic postural hypotension, without neurological deficits. In these patients the following patterns were observed: (i) a reversed diurnal blood pressure pattern, with the highest values observed at sleep onset; (ii) a prolonged sleep latency and increased amount of stage 3 sleep; (iii) difficulty with getting up after awakening in the morning, due to severe postural hypotension; (iv) an absence of prominent respiratory abnormalities during sleep; and (v) a dissociation between respiratory and haemodynamic findings. It is concluded that isolated deficiency of presumed postganglionic autonomic function influences sleep architecture, probably through absence of buffering of diurnal haemodynamic alterations, such as by postural hypotension and its consequences for body fluid volume regulation. This may be of relevance when sleep patterns are studied in other types of autonomic failure with postural hypotension involving central or preganglionic lesions, as in patients with the Shy-Drager syndrome or multiple system atrophy.

Psychological, cardiovascular, and endocrine changes during 6 hours of continuous infusion of epinephrine or norepinephrine in healthy volunteers.

Psychological, cardiovascular, endocrine, and metabolic reactions to a sustained infusion of epinephrine (E) and norepinephrine (NE) were studied in 10 healthy male volunteers in a placebo-controlled randomized design. The subjects participated each in three sessions during which they received 6-hr infusion of either E (82 pmol/kg/min), NE (178 pmol/kg/min), or placebo (PLA) (saline, 5.4 ml/hr). Heart rate and intra-arterial blood pressure were recorded continuously. Blood samples for assay of catecholamines, cortisol, prolactin, growth hormone, insulin, triglycerides, and glucose were obtained at regular intervals. Changes in subjective mood were assessed with the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI). During infusion of E, arterial plasma epinephrine levels increased 10-fold, which induced significant increases in heart rate, plasma insulin, and glucose levels, and decreases in mean arterial pressure (MAP) and diastolic pressure (DAP). NE infusion caused a 5-fold arterial plasma norepinephrine increase and induced a significant decrease in heart rate and increases in MAP, DAP, and glucose levels. The effects were present shortly after initiation of the infusions, remained fairly constant during the 6-hr infusion period and disappeared within 1 hr after the infusions had been stopped. Changes in subjective mood were not observed during the infusions, nor after the infusions had been stopped. Infusion of E or NE also had no significant effect on systolic blood pressure, plasma prolactin, growth hormone, cortisol, and triglycerides. Our results show that moderate cardiovascular and metabolic effects can be caused by sustained increases in circulating catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular variability after clonidine challenge: assessment of dose-dependent temporal effects by means of spectral analysis.

Effects of four intravenous (i.v.) doses (0.25, 0.5, 1, and 2 micrograms/kg) of the alpha 2-adrenoceptor agonist clonidine (CLO) were studied in 7 normotensive male volunteers in a placebo-controlled double-blind randomized design to evaluate the role of alpha 2-adrenoceptors in spontaneous short-term cardiovascular fluctuations. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP; Finapres device), stroke volume (SV) and total peripheral resistance (TPR) were monitored for 1 h after infusion of CLO while the subjects rested in a semirecumbent position. For HR, SBP, and DBP, power spectra and variation coefficients were calculated for consecutive time segments of 2.5 min. Power density was assessed for three frequency bands: low (LFB, 0.02-0.06 Hz), mid (MFB, 0.07-0.14 Hz), and high (HFB, 0.15-0.40 Hz). Per time-segment, baroreflex sensitivity (BRS) was estimated as the gain (or modulus) in MFB between systolic pressure values and R-R interval times. Decreases in mean levels of SBP and DBP were observed within 15 min after infusion of > or = 0.5 micrograms/kg CLO. HR first showed a slight increase 15 min after infusion of 0.5, 1, and 2 micrograms/kg CLO, but decreased subsequently as in all doses, including placebo. SV and TPR decreased after a dose of 2 micrograms/kg CLO. LFB and MFB power of HR were reduced after 2 micrograms/kg CLO, but only during the first 30 min after infusion; during this period, respiratory depth was also diminished, indicating that these effects may reflect a reduction in sympathetic outflow as well as a reduction in vagal outflow.(ABSTRACT TRUNCATED AT 250 WORDS)