Biomedical subjects

S Akselrod

Publications and source records attributed to S Akselrod.

At least 73 records · Page 4Linked to original sources

PubMed1995

Interrelationships among measures of autonomic activity and cardiovascular risk factors during orthostasis and the oral glucose tolerance test.

Overstimulation of sympathetic nervous system activity is related to atherosclerotic cardiovascular disease risk, but the role of parasympathetic activity in this association is not clear. This study evaluated sympathetic and parasympathetic function by spectral analysis of heart rate variability and plasma levels of norepinephrine (NE) epinephrine (EPI), dihydroxyphenylglycol (DHPG), dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC). It also examined the interrelationships among these parameters and established atherosclerotic cardiovascular disease risk factors in 53 men (mean age 59.5 years). During supine rest, low-frequency power correlated positively with high-frequency power (r = 0.58, p < 0.001), plasma NE correlated with plasma DHPG (r = 0.41, p < 0.001) and plasma DOPA with DOPAC (r = 0.47, p < 0.001) but neither low- nor high-frequency power was correlated with plasma levels of any catechol. Among risk factors, plasma NE correlated with fasting insulin and mean arterial blood pressure, and urine NE correlated with body mass index. Both low- and high-frequency power correlated positively with insulin levels. Orthostasis decreased high-frequency power and increased low-frequency power and plasma NE levels. During the oral glucose tolerance test, both high- and low-frequency power increased, plasma NE levels were unchanged, and plasma EPI levels decreased [88.5 +/- 18 (SEM) versus 52.5 +/- 12 pM, p = 0.001]. The results suggest that orthostasis decreases and the oral glucose tolerance test increases parasympathetic outflows, whereas both stimuli increase sympathetic outflows. Among all atherosclerotic cardiovascular disease risk factors, hyperinsulinaemia showed the strongest association with autonomic nervous system activity, especially parasympathetic activity. Estimates of sympathetic responses obtained from power spectral analysis of heart rate variability agree poorly with those from plasma levels of catechols, possibly because of a parasympathetic contribution to low-frequency power and independence of sympathoneural outflows to the arm and heart.

Aged↗

PubMed1995

Insulin resistance and autonomic function in traumatic lower limb amputees.

This study examined plasma insulin response to oral glucose load and autonomic nervous system activity in male lower limb amputees (n = 52) aged 50-65 years, compared to matched controls (n = 53). The groups had similar body mass index, blood pressure and plasma lipid levels. The amputees had higher mean fasting plasma insulin levels (18.4 +/- 9.7 (SD) versus 13.7 +/- 5.1 mU/l, p = 0.005) and during an oral glucose tolerance test (OGTT) (1 h levels 88.1 +/- 45.3 versus 62.1 +/- 42.7, p = 0.016) with similar plasma glucose levels, indicating insulin resistance. At baseline with the subjects supine, there were no group differences in low- or high-frequency power of heart rate variability or in plasma levels of norepinephrine (NE) or epinephrine (EPI). In response to orthostasis, the groups had similarly increased plasma NE levels. During the OGTT, amputees had significantly larger increments in low-frequency power than did controls (2.2 +/- 1.3 versus 1.6 +/- 0.9 (beats/min)2 respectively, p < 0.01) and plasma NE levels increased significantly in amputees (1595 +/- 849 versus 1941 +/- 986 pM, p = 0.0008) but not in controls. At 1 h after glucose administration, plasma EPI levels were decreased significantly from baseline in both groups; at both 1 and 2 h after glucose administration, plasma EPI levels were higher in the amputees than controls. Amputees appear to have a combination of enhanced sympathoneural responsiveness and attenuated suppression of adrenomedullary secretion during glucose challenge. As catecholamines antagonize insulin effects, one possible explanation for insulin resistance in amputees is hyperglycaemia-induced sympathoneural activation and a failure of hyperglycaemia to decrease adrenomedullary secretion.

Aged↗

PubMed1995

Artefacts in standard and time-dependent spectral analysis of arterial blood pressure signals obtained by Finapres: importance and correction.

The non-invasive Finapres (finger arterial pressure) device is widely used for the measurement of arterial blood pressure (BP) in BP variability studies, in particular in experimental studies. In our work, we have noticed that the calibration pauses of the Finapres, occurring approximately every 80 heart beats, introduce artefacts in standard and time-dependent spectral analysis of the arterial BP signal. This report describes these artefacts and indicates their dependence on the heart rate (HR) of the subject. In standard spectral analysis, they appear principally for low HR subjects, whereas in time-dependent spectral analysis, they distort the time-dependent spectrum both for low and high HR subjects. A possible correction procedure is presented which eliminates these pauses, causing minimal distortion from the original arterial BP time series. This correction keeps the total time-duration of the corrected signal equal to that of the original signal, thus allowing reliable spectral analysis of arterial BP fluctuations to be performed.

Adult↗

PubMed1995

Effect of haemorrhage on the power of low frequency blood pressure fluctuations in young spontaneously hypertensive rats.

1. Before the onset of hypertension low frequency (0.04-0.1 Hz) MAP fluctuations are reduced in SHR when compared to WKY. We studied the effect of haemorrhage under alpha1 blockade or angiotensin converting enzyme inhibition (CEI) on the power spectra (PS) of each strain. 2. MAP was recorded from the caudal artery in conscious, 1 month old SHR and WKY. Three groups of rats were studied. Group 1, acute 2 mL haemorrhage; groups 2 and 3, injection of prazosin (0.25-2.5 mg/kg) or captopril (0.5-4 mg/kg), followed by haemorrhage, as in group 1. The PS was divided into 3 frequency bands, 0.004-0.04, 0.04-0.07 and 0.07-0.1 Hz. 3. In SHR, although the baseline MAP levels were similar to those of WKY, the PS was significantly damped in each of the 3 frequency bands. 4. Haemorrhage induced a similar MAP fall in both strains accompanied by an increase in the slow MAP fluctuations. However, in SHR the PS response was significantly greater than in WKY. The biggest response was in the slowest (0.004-0.04 Hz) frequency band, 8.7 +/- 1.7 vs 1.5 +/- 0.4 times baseline levels, respectively. 5. The difference between the two strains in the PS response to haemorrhage was eliminated by alpha1 blockade. The exaggerated response observed in haemorrhaged, unblocked SHR was reduced in the 3 frequency bands. 6. Captopril reduced the PS response to haemorrhage in SHR to the level observed in WKY in all 3 frequency bands. 7. The enhanced amplification of the MAP fluctuations in haemorrhaged SHR may indicate that SHR requires greater recruitment of control mechanisms than WKY to maintain MAP at a similar level to WKY.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1995

Development and maturation of the autonomic nervous system in premature and full-term infants using spectral analysis of heart rate fluctuations.

The changes in the power spectra of heart rate (HR) fluctuations, in particular the total power (within 0.02-2.0 Hz) and the power in the low- (0.02-0.2 Hz) and high- (0.2-2.0 Hz) frequency ranges, were computed from the ECG and respiratory signals of 59 premature and full-term infants. The objective of the study was to investigate the development and maturation of the autonomic nervous system from the first day of extrauterine life to several weeks of postnatal age. The study population was divided into four age groups. Group A: seven 1-d-old premature infants with gestational age of 34-35 wk. Group B: 28 premature infants 7-49 d old with a conceptional age of 34-35 wk. Group C: seven 1-d-old full-term infants of 39-41 wk gestation. Group D: six premature infants 35-97 d old with a conceptional age of 39-40 wk. Mean HR (+/- SEM) of groups C and D combined, i.e. 135 +/- 2 bpm, was significantly lower compared with groups A and B, i.e. 152 +/- 2 (p < 0.01). The mean (+/- SEM) of the low- to high-frequency power ratio obtained from the HR power spectrum decreased progressively from 71 +/- 31 in group A to 34 +/- 8 in group B, 16 +/- 3 in group C, and 17 +/- 2 in group D. The mean low to high ratio for the combined groups C and D, 17 +/- 1, was significantly lower compared with the combined group A and B, i.e. 44 +/- 9 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗

PubMed1995

Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability.

OBJECTIVE: The use of an efficient noninvasive method to investigate the autonomic nervous system and cardiovascular control during sleep. BACKGROUND: Beat-to-beat heart rate variability displays two main components: a low-frequency (LF) one representing sympathetic and parasympathetic influence and a high-frequency (HF) component of parasympathetic origin. Sympathovagal balance can be defined as LF/HF ratio. METHODS/DESIGN: We reviewed normal, standardly staged all-night polysomnograms from 10 healthy children aged 6 to 17 years. Recorded 256-second traces of heart rate and respiration were sampled. Power spectra of instantaneous heart rate and respiration were computed using a fast Fourier transform method. RESULTS: The study revealed a decrease in LF during sleep, with minimal values during non-REM slow-wave sleep and elevated levels similar to those of wakefulness during REM. HF increased with sleep onset, reaching maximal values during slow-wave sleep, and behaved as a mirror image of LF. LF/HF ratio displayed changes similar to those in LF. CONCLUSION: The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges toward mean awake levels during REM sleep. The autonomic balance is shifted toward parasympathetic predominance during slow-wave sleep. This noninvasive method used to outline autonomic activity achieves results that are in complete agreement with those obtained with direct invasive tools.

Adolescent↗

PubMed1994

Spectral analysis of the systolic blood pressure signal in secondary hypertension: a method for the identification of phaeochromocytoma.

OBJECTIVE: To seek in hypertensive patients rhythmic variations of the systolic blood pressure signal obtained by ambulatory blood pressure monitoring of any inherent cycle of intermediate value between 1 and 24 h. DESIGN: Subjects (62 hypertensive, 39 normotensive) were evaluated by 24-h ambulatory blood pressure monitoring. The hypertensive group consisted of 48 patients with essential hypertension, nine with renovascular hypertension and five with phaeochromocytoma. The groups were matched for age and weight. METHODS: The ambulatory systolic blood pressure recording served as the input for a filtering procedure that rejected unacceptable values according to predetermined criteria. The whole-day systolic blood pressure series thus obtained were subjected to Fourier analysis to obtain a spectral analysis of daily systolic blood pressure fluctuations. Daily (first 12 h), nightly (second 12 h) and whole-day average systolic blood pressure values were calculated and compared for the various groups. RESULTS: The average nocturnal systolic blood pressure was found to be lower than its daily counterpart in the normal subjects and in the patients with essential hypertension, whereas in the patients with renovascular hypertension or phaeochromocytoma no such nocturnal decrease was found. The power spectrum of patients with phaeochromocytoma was statistically different from that of other aetiologies of hypertension. This was achieved due mainly to a statistically significant difference in the power spectrum integral over the low-frequency band (0-0.2 cycles/h) of the power spectrum of the 24-h systolic blood pressure signal. Resection of the phaeochromocytoma normalized the power spectrum as found by analysis of the postoperative ambulatory blood pressure monitoring data in two patients who underwent a repeat recording. CONCLUSIONS: The technique described enables the discrimination of patients with phaeochromocytoma as a cause of hypertension from other aetiologies of hypertension. Patients with renovascular hypertension could not be distinguished from those with essential hypertension on the basis of their power spectrum. However, this technique may prove to be a valuable modality for characterizing hypertensive patients of different aetiologies.

Activity Cycles↗

PubMed1993

Spectral analysis of heart rate in vasovagal syncope: the autonomic nervous system in vasovagal syncope.

Spectral analysis of heart rate fluctuations was used to investigate the role of the autonomic nervous system in the pathogenesis of vasovagal syncope. Nine adolescents with a history of at least three episodes of vasovagal syncope and nine age-matched healthy controls were studied. All subjects were tested in supine position and at a 60 degrees inclination for 60 min or less if syncope developed. Blood pressure and heart rate were measured, while the ECG and respiration traces were recorded on magnetic tape for later spectral analysis. Baseline heart rate was lower in control subjects than in patients, increased with tilt in both groups, and remained lower in the control subjects throughout the experiment. Baseline systolic and diastolic blood pressure was similar in both groups. Diastolic blood pressure initially increased with tilt in all subjects and decreased significantly thereafter in patients. Pulse pressure was lower in patients throughout the experiment. The heart rate power spectra displayed a higher baseline level of low frequency fluctuations in the control group. The high frequency fluctuations component was similar in all subjects. The results of the test, regarding haemodynamic parameters and autonomic control of the heart rate, as expressed by low and high frequency fluctuations, are consistent with a reduced sympathetic reserve in the individuals with previous episodes of syncope.

Adolescent↗

PubMed1993

Myocardial regional blood flow: quantitative measurement by computer analysis of contrast enhanced echocardiographic images.

Quantitation of regional myocardial blood flow constitutes the missing link between the anatomy of coronary obstruction and its physiological effect on regional oxygen supply. Microscopic air bubbles, introduced into the coronary circulation, were shown to produce a transitory enhancement of the myocardial tissue contrast, easily detectable with standard ultrasonic imaging equipment. This study presents a new approach linking the tissue blood flow with the time-dependent changes in the intensity of the ultrasonic reflections produced by the microbubbles. The tissue blood flow is evaluated using the well-known indicator dilution relation, according to which flow equals the ratio between the intravascular fraction of the tissue sample volume and the mean transit time of the contrast agent. We derive these two parameters from the time curves representing the contrast induced variations in the mean videointensity measured in two regions of interest, a reference region in the left ventricular cavity and the region of interest within the myocardial tissue. The intravascular volume fraction is computed as the ratio of the total power of the above two intensity curves, as each of these is assumed to be proportional to the total amount of tracer traversing the corresponding region of interest. The mean transit time is computed using combined time- and frequency-domain processing, involving Fourier deconvolution of the response function of the myocardial tissue sample. This approach was validated in an in vivo model in a series of animal experiments involving left atrial injection of albumin coated air microbubbles (Albunex). Videointensity curves obtained during contrast enhancement of the myocardium were analyzed to provide values of regional myocardial blood flow (in mL/min/100 g) in 45 myocardial regions of interest defined in 7 experiments performed on 4 animals. The values obtained with our approach correlated well (r = 0.77, p < 0.001) with standard reference measurements based on radiolabeled microspheres. The intertechnique variability was found to be smaller than the intersegment variability characterizing our technique. The difference between the mean flow values obtained with microspheres for segments of the entire heart and the mean flow obtained with our technique for all regions of interest ranged between 1 to 19% in the 7 experiments. In its present form, based on left atrial or left ventricular injection of contrast solution, this method may allow, for the first time, quantitative evaluation of myocardial regional blood supply in the cardiac catheterization laboratory or the operation theater.(ABSTRACT TRUNCATED AT 400 WORDS)

Albumins↗

PubMed1993

Myocardial transit time of the echocardiographic contrast media.

The mean transit time of a tracer through a sample of tissue is a quantitative marker most closely related to regional tissue blood flow. Therefore, an accurate estimation of the mean time of transit of an ultrasonic tracer through a sample of myocardial tissue, obtained by contrast echocardiography, may provide a quantitative noninvasive estimate of myocardial perfusion. We hereby present an algorithm for the determination of the mean transit time by computerized analysis of a series of contrast-enhanced echocardiographic images. The algorithm comprises the evaluation of the echocardiographic impulse response function of a selected region of interest, using a deconvolution technique based on a fast Fourier transform and a frequency domain division of the videointensities measured in the sample, by that measured in a predetermined reference region. An extensive computer simulation study was designed to facilitate the optimization of the steps of analysis. We present the results of the evaluation study performed in order to assess the accuracy of the procedure in computer-simulated echocardiographic images. Within a wide range of parameters chosen to define these functions, the analysis is shown to be essentially independent of the rise and decay times of the impulse response function of the tissue sample as well as of the simulated intensities. The effects of random noise introduced into the simulated intensity curves and of their variable width were investigated. The mean transit time was found to be accurately evaluated within about 10% of error for the variety of widths and noise levels permitted. The reconvolution error did not correlate with the accuracy of the evaluation of the mean transit time, indicating that the reconvolution error cannot be used as an estimate of the accuracy of the procedure. The numerical methods and the results of the computer study are discussed in detail. The approach is proposed to be used as part of a more general technique for the quantitative measurement of regional myocardial tissue blood flow.

Algorithms↗

PubMed1993

An estimate of fetal autonomic state by spectral analysis of fetal heart rate fluctuations.

The assessment of the functional state of the autonomic nervous system (ANS) in real time, by means of spectral analysis of fetal heart rate variability, may serve to improve the diagnosis of pathologic conditions of importance to the perinatologist. The combination of two approaches, namely an efficient method for detecting fetal ECG from the abdominal maternal signal, followed by spectral analysis of heart rate variability, is tested as a new noninvasive tool to assess fetal viability in real time. This study demonstrates a pattern of ANS development via the spectral contents of heart rate variability. It is shown that during "quiet state," the "young" fetuses (gestational age = 23.5 +/- 1 wk) present twice as much power of heart rate fluctuations at all frequencies from 0.2 to 1.0 Hz as "mature" fetuses (gestational age = 39.75 +/- 1.5 wk). This finding is coherent with the evolution of a stable and mature ANS activity. At frequencies below 0.1 Hz, a 1/f alpha power law relationship (alpha = 0.85, r2 > 0.9) between spectral density and frequency is displayed in the two age groups. A respiratory peak has been observed in some of the short (64-s) traces we analyzed. However, no respiratory peak was ever observed in a long (256-s) trace, due to the episodic nature of the fetal breathing and immaturity of the ANS.

Algorithms↗

PubMed1992

Digital path-dependent recompensation of contrast-enhanced echocardiographic images.

The regional video intensity of two-dimensional (2D) ultrasonographic images is directly affected by energy losses from the ultrasonic beam propagating between the transducer and the specific region of interest (ROI). These losses are mainly dependent on the scattering and absorption properties of the more proximal tissues. The commonly utilized automatic time-gain compensation (TGC) procedures, based on the assumption of uniform scattering and energy conversion throughout the investigated tissues and organs, seem to be largely inadequate in the contrast echocardiographic studies which attempt to quantitate the contrast enhancement of myocardial tissue. We hereby present an algorithm for the non-linear adaptive path-dependent recompensation of the ultrasonographic video intensity for the non-uniform scattering and absorption in images obtained using automatic TGC. The variable energy losses are estimated in our technique according to the reflections from the different points along the acoustic beam. The proposed algorithm is a post-processing function. It was developed considering beam attenuation by scattering and absorption and comparing correction procedures necessary with and without the assumption of uniform attenuation. We hereby present the results obtained by applying this algorithm to contrast enhanced echocardiographic images of canine hearts. The artifacts produced by the inadequate automatic TGC are essentially reduced by the recompensation procedure. The recompensation allows the observation of the changes in video intensity induced in the myocardial tissue by contrast-enhancing media, which are otherwise severely obscured by contrast transit altering the propagation effects.

Albumins↗

PubMed1992

Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations.

The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.

Adult↗

PubMed1992

Evidence for instability of the autonomic nervous system in patients with migraine headache.

Autonomic impairment in migraine is well documented. In order to evaluate the autonomic control in migraine, spectral analysis of heart rate fluctuations was performed on ten migraine patients, drug-free and during the inter-headache phase. They were compared to nine healthy controls and eight tension headache patients. A 24h Holter recording of ECG was performed for each subject. Every half hour, a short ECG subtrace was digitized and submitted to R wave detection, followed by computation of heart rate power spectrum. The spectral analysis of heart rate fluctuations disclosed significant differences between control subjects and patients with migraine. The migraine patients displayed markedly enhanced low frequency fluctuations (below 0.1 sec-1), during day hours (p less than 0.01) and especially at night (p less than 0.0006). In the respiratory frequency band (between 0.2 and 0.4 sec-1) no significant change was observed. Tension headache patients however, resembled the controls in that they did not display enhanced low frequency fluctuations. The enhancement at low frequencies fluctuations only, a frequency range known to be related to vasomotor control, suggests that the migraine patients are characterized by a clear sympathetic instability. This finding supports the hypothesis that migraine is of neural origin and is consistent with the observation of large variations in regional cerebral flow. Spectral analysis of heart rate fluctuations allows us to specify and quantitate this autonomic imbalance and may provide a useful tool for the evaluation of drug therapy in migraine.

Adult↗

PubMed1992

Propranolol in the prophylaxis of migraine--evaluation by spectral analysis of beat-to-beat heart rate fluctuations.

Migraine patients seem to suffer from a continuous autonomic imbalance. Sympathetic instability, expressed by enhanced low frequency fluctuations, which exists during the headache free intervals, was observed in our previous study by spectral analysis of heart rate (HR) fluctuations. Propranolol--a beta adrenoceptor antagonist, is widely used in migraine prophylaxis. In order to specify and quantitate propranolol efficacy in migraine, spectral analysis of heart rate fluctuations was performed on 10 migraine patients before and during the treatment with propranolol. They were compared to 10 healthy control patients and 6 migraine patients who were treated for several months with propranolol and then discontinued the medication. The analysis was carried out on a 24h Holter ECG recording, which was performed for each subject during a headache free interval. Short 256 sec subtraces, taken every 30 min from the 24h ECG signal, were submitted to A/D conversion, R wave detection and computation of heart rate power spectrum. Propranolol achieved a marked effect, when comparing the power spectra of HR fluctuations in treated versus untreated migraine patients. A strong reduction (to normal level) in the low frequency HR fluctuations in the range below 0.1 Hz., was apparent in patients treated with propranolol. Subjects who had received propranolol in the past and discontinued the drug, displayed a carry-over effect of reduced fluctuations even 2-3 months after its discontinuation. It seems that the propranolol efficacy in migraine is associated with the mechanism of stabilizing the fluctuations within the frequency band related to sympathetic activity, hereby moderating the vascular instability in migraine.

Adult↗

PubMed1991

A new method for fetal ECG detection.

Presented in this work is the theoretical basis of a new method we propose for the analysis of fetal ECG (FECG). This method is intended to detect the fetal HR from a weak FECG signal, and to supply us with an average FECG complex. The FECG signals studied in this work were recorded from the maternal abdominal wall. The core of our method is the computation of a triple parametric transform, using analyzing functions which have a greater correlation with the ECG signal than the correlation of the standard sine and cosine functions used in a Fourier transform. The functions used are trains of square waves characterized by the width of the square wave, their periodicity, and some initial phase value. This method, applied here to a medical problem, can be more generally applied to handle weak quasiperiodic sharp signals of any origin.

Electrocardiography↗

PubMed1991

Modulation of the dose-dependent effects of atropine by low-dose pyridostigmine: quantification by spectral analysis of heart rate fluctuations in healthy human beings.

The interaction between a low-dose cholinesterase inhibitor, pyridostigmine (PYR), and atropine was investigated by spectral analysis of heart rate fluctuations in eight healthy humans. Each subject was given increasing boluses of IV atropine during treatment with PYR (30 mg.3/day) or placebo. PYR attenuated the bimodal dose-dependent changes in the respiratory peak (which respresents the parasympathetic control) in response to atropine. We suggest that spectral analysis can be used for quantifying the complex dose-dependent cholinergic agonist-antagonist interactions, and may help to disclose an asymptomatic low-dose intoxication with acetylcholinesterase inhibitors.

Adult↗

PubMed1991

Pharmacological modulation of vagal cardiac control measured by heart rate power spectrum: a possible bioequivalent probe.

The autonomic cardiac control was studied as a sensitive parameter of anticholinergic treatment in humans, using heart-rate (HR) power spectrum. A cross-over placebo controlled study was performed in 8 young volunteers who received increasing bolusdoses of IV atropine (from 1.3 micrograms/kg to 29.9 micrograms/kg) or placebo. Computing the HR power spectrum and integrating over specific frequency bands, we focused in particular on the respiratory frequency band (usually between 0.2-0.4 Hz) which is purely of vagal mediation. At small atropine doses (less than 5.2 micrograms/kg), the respiratory peak increased, relative to baseline, with maximal response at 2.6 micrograms/kg (from 1.0 to 1.9 +/- 0.9). Larger doses of atropine (greater than or equal to 6.5 micrograms/kg) reduced the power of the respiratory peak, by a few orders of magnitude, in a dose-dependent way. Corresponding changes were observed in mean HR but in the opposite direction i.e., a maximal bradycardia at 2.6 micrograms/kg and a nearly two fold increase in mean HR at 29.9 micrograms/kg. We conclude that atropine has a bimodal dose-dependent effect on parasympathetic cardiac control. Since the use of HR spectral analysis has been demonstrated in various animal species, we suggest that it can be used as a sensitive noninvasive probe for animal to man transformation studies.

Adult↗