Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis

Neurohumoral modulation of cardiovascular function is an important component of the hemodynamic alterations in patients with chronic congestive heart failure (CHF). Analysis of heart rate (HR) variability is a noninvasive means of investigating the autonomic control of the heart. The variability of HR and respiratory signals, both derived from ambulatory electrocardiographic recordings, were analyzed with power spectral analysis to evaluate autonomic control in 25 patients with chronic stable CHF (class III or IV) and 21 normal control subjects. In the patients with CHF, HR spectral power was markedly reduced (p less than 0.0001) at all frequencies examined (0.01 to 1.0 Hz, period 1 to 100 seconds) and virtually absent at frequencies greater than 0.04 Hz. Heart rate fluctuations at very low frequencies (0.01 to 0.04 Hz) less effectively differentiated CHF patients from control subjects, due to discrete (about 65 seconds, 0.015 Hz) oscillation in HR, which was associated with a similar pattern in respiratory activity in many of the patients with CHF. These findings demonstrate a marked derangement of HR modulation in patients with severe CHF. The frequency characteristics of HR fluctuations in these patients are consistent with abnormal baroreflex responsiveness to physiologic stimuli, and suggest that there is diminished vagal, but relatively preserved sympathetic, modulation of HR.     

Mental arithmetic stress as a test for evaluation of diabetic sympathetic autonomic neuropathy

The effects of a 1-min mental arithmetic stress test on heart rate change were studied in 72 Type 1 diabetic patients, 36 without and 36 with diabetic autonomic neuropathy (mean age 33 and 44 yr, respectively), and in 80 matched normal subjects. Variation in hand skin temperature was also recorded in 25 normal subjects and 30 diabetic patients without and 32 with autonomic neuropathy. While mental arithmetic rapidly reduced skin temperature of normal volunteers and of patients without autonomic neuropathy, no effect was found in autonomic neuropath (a drop of 0.63 +/- 0.05 (+/- SE), 0.52 +/- 0.04 and 0.16 +/- 0.02 degrees C (p less than 0.001), respectively). In control subjects and in diabetic patients without and with autonomic neuropathy the heart rate increase was 22.9 +/- 6.8 (+/- SD), 21.4 +/- 8.4 and 7.0 +/- 3.7 beats min-1, respectively (p less than 0.001). The ratio between maximum mental arithmetic-induced heart rate and basal heart rate was 1.29 +/- 0.10, 1.24 +/- 0.10 and 1.07 +/- 0.05 (p less than 0.001) for healthy subjects, non-neuropathic patients, and neuropathic patients. Cut-off values (the low normal limit for these variables) are proposed: skin temperature 0.23 degrees C, heart rate increase 11.6 beats min-1 and heart rate ratio 1.12. Anxiety state, blood glucose concentration (excluding hypoglycaemia), body position, basal heart rate, and age did not interfere with responses to mental arithmetic stress.     

Contrasting patterns of autonomic dysfunction in patients with mitral valve prolapse and panic attacks

Both mitral valve prolapse (MVP) and panic attacks have been reported to be associated with autonomic dysfunction, but previous studies have been limited by the lack of clear separation between patients with MVP and those with panic attacks and the use of noncomparable control subjects. Accordingly, heart rate and blood pressure responses to deep breathing, five minutes' quiet standing, and the Valsalva maneuver were studied in age- and cardiac symptom-matched groups of 33 control subjects, 66 patients with MVP, 20 patients with panic attacks, and 17 patients with both MVP and panic attacks. Compared with control subjects, patients with MVP exhibited more syncope (13 of 66, or 20 percent, versus none of 33, or 0 percent; p less than 0.01), more orthostatic hypotension during quiet standing (11 of 66, or 17 percent, versus one of 33, or 3 percent; p less than 0.01), loss of the normal decrease with age in vagally-mediated heart rate variability during deep breathing (r = 0.13, p = NS versus r = -0.44, p = 0.01), and lower 24-hour epinephrine excretion (6.1 +/- 0.7 versus 11.0 +/- 2.7 micrograms; p less than 0.01). In contrast, patients with panic attacks had greater increases than control subjects or patients with MVP without panic attacks in heart rate, mean blood pressure, and the product of heart rate and mean blood pressure during each minute of quiet standing and during the early strain phase of the Valsalva maneuver. These findings indicate that autonomic dysfunction occurs both in patients with MVP and in those with panic attacks in comparison with symptomatic control subjects, but that the patterns of abnormality differ. Patients with MVP exhibit decreased effectiveness of responses to orthostatic stress, reduced epinephrine excretion, and abnormal vagal tone, whereas patients with panic attacks have heightened cardiovascular responses to postural and positive intrathoracic pressure stresses.     

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

Objectives. This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy.Background. Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking.Methods. Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis.Results. There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean ± SD 7.24 ± 0.88 versus 7.59 ± 0.57 ln[ms²], p = 0.072). Although there was no significant difference in the high frequency component (5.31 ± 1.14 versus 5.40 ± 0.91 ln[ms²], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 ± 1.00 versus 6.72 ± 0.61 ln[ms²], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 ± 8% versus 43 ± 8%, p = 0.018) and the high frequency component significantly increased (16 ± 6% versus 12 = 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 ± 0.64 versus 1.33 ± 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients.Conclusions. Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.     

Effect of posture on spontaneous and thermally stimulated cardiovascular oscillations

STUDY OBJECTIVE--The aim of the study was to investigate the effect of posture on thermally stimulated cardiovascular oscillations. DESIGN--The effect of increased gravitational stress (rising from sitting to standing position) on the thermally stimulated cardiovascular oscillations was measured in young male volunteers. Extensive cardiovascular function data were obtained using a cardiovascular investigation protocol. SUBJECTS--The volunteers were five fit young men, aged 20-21 years. EXPERIMENTS AND MAIN RESULTS--Cardiovascular changes from sitting to standing indicated increased sympathetic and decreased parasympathetic influence on heart and skin blood vessels; mean heart rate increased, beat to beat heart rate variability diminished, high frequency periodic heart rate variability decreased, low frequency heart rate oscillations and ratio of low frequency to high frequency heart rate variability increased, mean skin blood flow and oscillations of skin blood flow decreased (all p less than 0.05). Thermal skin stimulation at 0.01-0.10 Hz frequency increased both sitting and standing 0.10 Hz periodic heart rate variability (p less than 0.05), and 0.10 Hz thermal stimulation entrained the heart rate oscillations in sitting and standing subjects (p less than 0.05). In contrast, skin blood flow oscillations in sitting subjects decreased, while in standing subjects it increased during 0.10 Hz thermal stimulation compared to the corresponding prestimulus values (p less than 0.04). CONCLUSIONS--On the basis of previous physiological experiments, these results suggest coupling between thermoregulatory and 0.10 Hz reflex activities.     

The child with recurrent syncope: autonomic function testing and beta-adrenergic hypersensitivity.

Recurrent syncope in the child with a normal heart poses both diagnostic and therapeutic problems. To assess autonomic contributions to syncope, formal autonomic function testing was performed in 22 children (aged 7 to 18 years) with recurrent syncope and a normal heart. Autonomic testing consisted of eight to nine separate tests; 14 of the 22 patients had reproduction of syncope or symptoms during testing. Patients with a positive test had a lower norepinephrine level while supine (334 +/- 86 versus 547 +/- 169 pg/ml, p less than 0.01) and lower norepinephrine level in the upright position (628 +/- 219 versus 891 +/- 270 pg/ml, p less than 0.05) than did patients with a negative test. The slope of heart rate response versus log isoproterenol dose was greater in patients with a positive test than in those with a negative test (1.70 +/- 0.70 versus 0.89 +/- 0.19, p less than 0.01). All five patients with a positive test who were given intravenous propranolol had elimination of syncope with repeat testing. Eight of 10 patients with a positive test were successfully treated with atenolol, including 2 patients without prior resolution of symptoms after pacemaker implantation for symptoms attributed to bradycardia. Beta-adrenergic hypersensitivity may cause recurrent syncope in young patients. Inappropriate heart rate response to standing may elicit the Bezold-Jarisch reflex, resulting in bradycardia or hypotension, or both, in some patients. Beta-adrenergic blockade is of benefit in many of these patients.     

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.     

Radionuclide assessment of left ventricular diastolic filling in diabetes mellitus with and without cardiac autonomic neuropathy

Indexes of left ventricular diastolic filling were measured by radionuclide ventriculography in 28 patients with insulin-dependent diabetes mellitus without evidence of ischemic heart disease. Six patients (21%) had abnormal diastolic filling and differed from diabetic patients with normal filling in their greater severity of cardiac autonomic neuropathy, assessed by noninvasive means, and their lower plasma norepinephrine levels in the supine (131.1 +/- 24.7 versus 356.2 +/- 58.4 pg/ml, p less than 0.01) and upright (224.9 +/- 47.8 versus 673.3 +/- 122.3 pg/ml, p less than 0.005) positions. The diabetic patients determined as having cardiac autonomic neuropathy (n = 15) had depressed left ventricular diastolic filling compared with subjects free of autonomic neuropathy, whether measured as the time to peak filling rate (154.2 +/- 12.0 versus 119.1 +/- 10.6 ms, p less than 0.05) or the time to peak filling rate normalized to the cardiac cycle length (24.3 +/- 2.2 versus 16.2 +/- 1.5%, p less than 0.01). Of the various tests of autonomic nervous system function, the strongest correlate of impaired diastolic filling was orthostasis, measured as the decrease in systolic blood pressure with standing (r = 0.584, p less than 0.001). Thus, in patients with diabetes mellitus, alterations in sympathetic nervous system activity are associated with abnormalities of left ventricular diastolic filling.     

Spectrum analysis of heart rate. A method of studying the role of the autonomic nervous system in the regulation of blood circulation]

Spectral analysis of heart rate variability has recently been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular automatic regulatory responses. In 12 ambulant normotensive healthy young males (mean age 23 +/- 1 years) after a period of 10 min. for stabilisation, a continuous ecg recording (lead CM-5) for 8 min. was obtained in the supine and standing position, with a controlled respiration rate 15/min. Power spectrum of 512 point time series (R-R intervals) in both positions was calculated using a fast Fourier transform-based window periodogram method. Based upon results from the literature the power spectrum analysis was performed on two components: low frequency LF (0.05-0.15 Hz) and high frequency HF (0.15-0.50 Hz). Mean R-R interval decreased on standing position from 0.79 +/- 0.10 s to 0.59 +/- 0.11 s (p less than 0.001). The ratio HF/LF in supine was 0.63 +/- 0.70 and on standing position 2.54 +/- 0.73 (p less than 0.001). The relative LF component of the total HR power spectrum increased from 22.8% +/- 12.1% to 42.9 +/- 14.4% (p less than 0.001) after changing the position from supine to standing, and the relative HF component decreased from 56.3 +/- 22.4% to 25.5 +/- 16.2 (p less than 0.001). The total power was significantly lower when standing in comparison to supine position (681 +/- 519 s2, 1188 +/- 963 s2 respectively, p less than 0.05). Our results suggest that heart rate fluctuations in supine position in normal men are mainly vagally determined (HF power spectrum component).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BACKGROUND. Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. METHODS AND RESULTS. To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. CONCLUSIONS. Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.     

Cholinergic bronchomotor tone and airway caliber in insulin-dependent diabetes mellitus.

It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulin-dependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (Gaw/VL) induced by aerosol administration of atropine sulfate. In all of the patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p less than 0.05) in group D-2 (2.48 +/- 0.12 s-1.kPa-1 [mean +/- SE]) than in group D-1 (2.11 +/- 0.10 s-1.kPa-1). Aerosol atropine caused a significant increase (p less than 0.001) in airway caliber in all three groups; however, the increase in Gaw/VL was significantly lower in group D-2 (0.26 +/- 0.05 s-1.kPa-1) when compared with group D-1 (0.63 +/- 0.09 s-1.kPa-1; p less than 0.01) and group C (0.67 +/- 0.06 s-1.kPa-1; p less than 0.001). A weak but significant (p less than 0.02) correlation was observed between the increases in Gaw/VL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared to patients without AN.     

Cardiac autonomic control in obstructive sleep apnea: effects of long-term CPAP therapy.

To determine how long-term treatment with continuous positive airway pressure (CPAP) affects cardiac autonomic function, we measured R-R interval (RRI), respiration, and blood pressure in 13 awake patients with moderate-to-severe obstructive sleep apnea (OSA) in both supine and standing postures, before and after 3 to 9 mo of home therapy. Using visual feedback, the subjects controlled their respiration to track a randomized breathing pattern. From the RRI spectrum, we computed high-frequency power and the ratio of low-frequency to high-frequency power (LHR). To correct for differences in breathing, the average transfer gain relating respiration to RRI changes (G(RSA)) and the modified low-frequency to high-frequency ratio (MLHR) were also derived. CPAP therapy did not change the conventional spectral indices of heart rate variability (HRV). However, G(RSA) increased with average nightly CPAP use in supine (p < 0.01) and standing (p < 0.03) postures, whereas MLHR decreased with CPAP compliance during standing (p < 0.03). Supine mean heart rate decreased with compliance (p < 0.03). None of the estimated parameters was correlated with duration of therapy when actual CPAP use was not taken into account. These results suggest that CPAP treatment improves vagal heart rate control in patients with OSA and that the degree of improvement varies directly with compliance level.     

Abnormal cardiovascular regulation in the mitral valve prolapse syndrome

Studies of patients with mitral valve prolapse syndrome have suggested autonomic nervous system dysfunction, but a precise definition of mechanisms is lacking. We measured supine and standing heart rate, blood pressure, cardiac output, oxygen consumption, plasma catecholamines, and blood volume in 23 symptomatic women with both echocardiographic and phonographic signs of MVP and in 17 normal control subjects. An analysis of the results revealed 2 distinct subgroups of patients: those with normal heart rates but increased vasoconstriction (Group I, n = 10) and those with orthostatic tachycardia (Group II, n = 13). Group II patients had heart rates at rest supine of 97 ± 3 compared with 79 ± 2 in Group I patients and 78 ± 8 in control subjects. Estimated total blood volumes were lowest in Group I patients, intermediate in Group II patients, and highest in control subjects (p<0.05). Other measurements at rest supine were similar in patients and controls. After standing for 5 minutes, patients had a higher mean plasma epinephrine value, diastolic blood pressure (81 ± 2 versus 74 ± 3 mm Hg, p < 0.05), and peripheral resistance (1,878 ± 114 versus 1,414 ± 92, dynes s cm^?5, p < 0.01), wider arteriovenous oxygen difference (6.7 ± 0.4 versus 5.3 ± 0.5 vol%), and lower stroke volume index (26 ± 2 versus 33 ± 2 ml/m², p < 0.01) than did the control subjects. Cardiac output was normal in Group II patients but reduced in Group I patients, who demonstrated marked vasoconstriction. No patient had evidence of a “hyperkinetic” circulatory state. A cycle of decreased forward stroke volume, vasoconstriction, and blood volume contraction appears to be present in at least some symptomatic patients with MVP.     

Relationship between fluctuations in heart rate and asymptomatic nocturnal ischaemia

In order to quantify autonomic changes related to asymptomatic nocturnal myocardial ischaemia, we analyzed heart rate fluctuations recorded during Holter monitoring in 9 subjects with coronary heart disease (21 episodes) and in 11 age-matched controls. R-R interval spectral analysis was computed in sequences of 256 heart beats, taken during the ischaemic episode, 4, 8 and 60 minutes before, and 4 and 60 minutes after. Mean heart rate, R-R interval variability (assessed by R-R interval standard deviation), low and high (respiration-linked) frequency components of R-R interval spectrum were evaluated. Mean heart rate and R-R interval variability increased only during ischaemia (from 62.9 to 73.3 beats/minute, P less than 0.02, and from 39 to 88 msec, P less than 0.01, respectively). While high-frequency components of heart rate variability remained unchanged, low-frequency peak increased during ischaemia (from 9.4 to 43.3 sec2 X 10(-3)/Hz, P less than 0.01) and also 8 minutes (P less than 0.05) and 4 minutes before (P less than 0.05). Despite a moderate increase of heart rate occurring only during ischaemia, the early rearrangement of heart rate fluctuations suggests the occurrence of changes of autonomic tone before the electrocardiographic onset of ischaemia. Due to its limited amount, this phenomenon appears to be a consequence, most likely unspecific, of factors responsible for the genesis of myocardial ischaemia.     

Study of the autonomous nervous system with heart rate spectral analysis in acute myocardial infarction]

OBJECTIVES: Characterize power spectrum pattern of heart rate variability (HRV) and assessment of relative cardiac nervous system in patients with acute myocardial interaction of sympathetic and parasympathetic infarction. We also compared the spectral power with some known prognostic risk variables. STUDY DESIGN: Study of patients with acute myocardial infarction (AMI) and sedentary healthy subjects sex matched. SUBJECT AND METHODS: 19 postinfarction patients aged 55.7 +/- 10.5 years and 19 healthy subjects controls aged 53.9 +/- 11.0. ECG signals were recorded after 15 minutes of supine rest with controlled breathing at 15 cycles/min. Signal acquisition was done at 300 samples/sec. From 512 consecutive sinus beats, we calculated the average, standard deviation, maximum and minimum values and rate between the longest and shortest R-R interval (E/I). We also calculated, after computing the fast Fourier transform, the total spectrum power, low frequency component (LF, from 0.01 to 0.15 Hz), high frequency component (HF, from 0.15 to 0.50 Hz) and its ratio (LF/HF). Thereafter, we correlated these results with radionuclide ejection fraction, duration of treadmill test, Holter ventricular premature complex and localization of infarction. RESULTS: The average R-R interval was 757.9 +/- 116.3 and 850.9 +/- 133.9 msec (p less than 0.05), the R-R corrected standard deviation was 15.3 +/- 6.0 and 38.2 +/- 8.5 msec (p less than 0.001) and ratio E/I was 1.13 +/- 0.06 and 1.32 +/- 0.09 (p less than 0.001) in AMI and control group, respectively. In AMI group, low frequency spectral band was very decreased (LF = 0.03 +/- 0.02 sec2) and high frequency was virtually absent (HF = 0.01 +/- 0.01 sec2) compared with control group (LF = 0.13 +/- 0.06 and HF = 0.14 +/- 0.15 sec2), p less than 0.001; ratio LF/HF was increased in AMI group. There were no significant differences between groups for normalized LF (LF%) and HF (HF%). CONCLUSIONS: These results showed that spectral pattern in AMI patients had very low LF and HF power density. Decreased HRV in that group was mainly due to diminished parasympathetic influence in cardiac regulation; nevertheless ratio LF/HF was increased which represents an imbalance of sympatho-vagal activity with predominance of sympathetic tone. We found poor correlation between frequency domain indices and other risk variable; best correlation was between total spectral power and radionuclide ejection fraction (r = 0.642, p less than 0.01), which could express independent prognostic value in AMI patients risk stratification.     

Relationship between phasic changes in human skin blood flow and autonomic tone

Heart rate beat-to-beat oscillations synchronous with respiration and blood pressure waves, have been found to be a marker of sympathovagal interaction in man and animals. Oscillations of heart rate, respiration, and cutaneous blood flow were simultaneously recorded to assess the relationship between autonomic nervous control and cutaneous circulation in a group of 21 healthy subjects and in a group of 6 healthy patients after brachial plexus anesthesia and consequent sympathetic blockade. In the first group, changes in posture were employed to modify autonomic tone. Relative changes in cutaneous blood flow were recorded by laser-Doppler flowmetry. Spectral analysis techniques (cross-correlation) were used to quantify the relationship between oscillations common to the recorded signals. A standing maneuver induced a significant decrease of the cross-correlation between respiratory and heart rate fluctuations (from 4.93 +/- 0.16 to 4.44 +/- 0.16 a.u.; P less than 0.001), and a significant increase of the cross-correlation between heart rate and skin blood flow fluctuations (from 0.64 +/- 0.31 to 1.33 +/- 0.21 a.u.; P less than 0.001), but did not modify the cross-correlation between respiratory and skin blood flow fluctuations (from 2.87 +/- 0.15 to 3.04 +/- 0.14 a.u.; NS). After the standing maneuver the maximum correlation between heart rate and skin blood flow was always due to oscillations in the range of 0.1 Hz (or 10-sec period), similar to the oscillations described in large arteries. Sympathetic blockade reduced significantly the cross-correlation between heart rate and skin blood flow (P less than 0.001). These results suggest that the cross-correlation between skin blood flow and heart rate at 10-sec period fluctuations can be used as an index of the influence of the autonomic tone on skin blood circulation.     

Power spectrum analysis of heart rate variability in human cardiac transplant recipients

Beat-to-beat heart rate variability was studied by power spectral analysis in 17 orthotopic cardiac transplant patients. Heart rate power spectra were calculated from eighty-four 256-second recordings and compared with those taken from six normal subjects. The power spectra from the control subjects resolved into discrete peaks at 0.04-0.12 Hz and 0.2-0.3 Hz, whereas those of heart transplant recipients resembled broad-band noise without peaks. Log total power in the 0.02-1.0 Hz range was greater in the control subjects (0.982 +/- 0.084 [0.206], mean +/- SEM [SD]) than in the transplanted subjects (-0.766 +/- 0.059 [0.541]), (p less than 0.0001). Fifty-five electrocardiographic recordings from transplant patients were done within 48 hours of an endomyocardial biopsy. When the power spectra of those patients whose endomyocardial biopsies showed evidence of myocardial rejection were compared with those from patients who were found to be free of rejection, a significant difference was found in log total power (-0.602 +/- 0.090 [0.525] vs. -0.909 +/- 0.136 [0.577], p less than 0.02). We conclude that denervation of the heart significantly reduces heart rate variability and abolishes the discrete spectral peaks seen in untransplanted control subjects and that the development of allograft rejection may significantly increase heart rate variability.     

Vinca alkaloid-induced cardiovascular autonomic neuropathy

To determine the incidence of vinca alkaloid (VA)-induced cardiovascular autonomic neuropathy (CAN), neoplastic patients were studied. Thirty-three of them were receiving chemotherapy regimens including VAs, and 30 were receiving chemotherapy without VA and were considered controls. Abnormal variation in blood pressure on standing, heart rate during deep breathing, and heart rate on standing was found in 27 (82%), 16 (48%), and 16 (48%) patients receiving VA versus nine (30%; P less than 0.01), three (10%; P less than 0.05), and one (P less than 0.001) controls, respectively. Of 198 tests performed, 100 were abnormal in patients receiving VA (51%) versus 33 of 180 tests in the controls (18%; P less than 0.001). Although abnormal clinical or electrocardiographic tests for CAN appeared significantly more frequently in patients who received high doses of VA (P less than 0.01), their incidence was not significantly different in patients greater than or equal to 60 years of age, in those who received doxorubicin, or in those who showed abnormal deep tendon reflexes. The consequences of VA-induced CAN might be especially important for potentially curable cancer patients.     

Enhanced vagal activity and normal arginine vasopressin response in carotid sinus syndrome: implications for a central abnormality in carotid sinus hypersensitivity

The relation between arginine vasopressin and vagal activity in carotid sinus syndrome was studied in 10 patients and 17 age matched controls using head up tilt as a stimulus. Of the controls, seven had unexplained syncope and 10 were healthy elderly subjects with no previous history of syncope. Subjects were studied supine for 45 min and thereafter during 120 min head up tilt to 40 degrees. Phasic arterial pressure and heart rate were monitored throughout. Serum was sampled at frequent intervals to measure arginine vasopressin, noradrenaline, and adrenaline concentrations. Seventy per cent of carotid sinus patients had vasovagal syncope at (mean(SD)) 25(4) min after tilt compared with 43% of subjects with unexplained syncope and one healthy elderly control. The maximum (mean(SD)) fall in systolic blood pressure and heart rate was 70(20) mmHg and 20(7) beats.min-1 (p less than 0.001 and p less than 0.01 respectively). Arginine vasopressin, noradrenaline, and adrenaline concentrations rose significantly in syncopal subjects (p less than 0.001, p less than 0.01, and p less than 0.05 respectively). Changes in systolic blood pressure, heart rate, and hormone concentrations were similar for patients with carotid sinus syndrome and control subjects. For those who completed the tilt period without the development of symptoms, systolic blood pressure and arginine vasopressin and adrenaline concentrations were unchanged, whereas noradrenaline concentrations and heart rate rose significantly. Vasovagal activity is thus appreciably increased in carotid sinus syndrome. Furthermore, the afferent limb of the carotid sinus reflex appears to be intact in patients with carotid sinus syndrome since the pattern of arginine vasopressin release was not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac effects of acute ethanol ingestion unmasked by autonomic blockade.

We assessed the effects of ethanol and autonomic blockade on left ventricular function in nine normal subjects, age 20--35 years, using M-mode echocardiography and systolic time intervals. On day 1, measurements were made of heart rate, mean velocity of circumferential fiber shortening, and left ventricular pre-ejection period and left ventricular ejection time ratio (PEP/LVET), during a control period and after autonomic blockade. Autonomic blockade was produced with intravenous propranolol (0.2 mg/kg body weight) and atropine (0.04 mg/kg body weight). On day two, measurements were again made during a control period, then with ethanol alone, followed by addition of autonomic blockade to ethanol. One hundred eighty milliliters of ethanol were ingested over 60 minutes, resulting in a mean blood ethanol level of 110 mg/dl (range 77--135 mg/dl) at 60 minutes post-ingestion. There were no significant differences between the control data on days 1 and 2. Blood pressure was unchanged throughout the study. study. On day 1, autonomic blockade alone resulted in the expected increase in heart rate (p less than 0.001), with a proportional increase in mean velocity of circumferential fibr shortening (p less than 0.01), and an increase in PEP/LVET (p less than 0.01). On day 2, ethanol alone resulted in no significant changes except for a slight increase in PEP/LVET (p less than 0.02). Ethanol plus autonomic blockade, (day 2), compared with autonomic blockade alone (day 1), revealed a decrease in mean velocity of circumferential fiber shortening (p less than 0.05), and an increase in PEP/LVET (p less than 0.01), with a decrease in intrinsic heart rate (p less than 0.001). We conclude that in normal subjects: 1) autonomic blockade does not directly affect contractility; 2) acute ethanol ingestion alone does not produce important changes in cardiac function; and, 3) ethanol in the autonomic blockaded heart causes a significant decrease in contractility. Thus, we infer that ethanol has a negative inotropic effect which is masked by catecholamines and/or autonomic nervous system discharge.