Features of autonomic cardiovascular control during cognition in major depressive disorder

Previous research has suggested reduced parasympathetic cardiac regulation during cognitive activity in major depressive disorder (MDD). However, little is known about possible abnormalities in sympathetic control and cardiovascular reactivity. This study aimed to provide a comprehensive analysis of autonomic cardiovascular control in the context of executive functions in MDD. Thirty six MDD patients and 39 healthy controls participated. Parameters of sympathetic (pre‐ejection period, PEP) and parasympathetic control (high and low frequency heart rate variability, HF HRV, LF HRV; and baroreflex sensitivity, BRS) as well as RR interval were obtained at rest and during performance of executive function tasks (number‐letter task, n‐back task, continuous performance test, and Stroop task). Patients, as compared to controls, exhibited lower HF HRV and LF HRV during task execution and smaller shortenings in PEP and RR interval between baseline and tasks. They displayed longer reaction times during all conditions of the tasks and more omission errors and false alarms on the continuous performance test. In the total sample, on‐task HF HRV, LF HRV and BRS, and reactivity in HF HRV, LF HRV, and PEP, were positively associated with task performance. As performance reduction arose independent of executive function load of the tasks, the behavioral results reflect impairments in attention and processing speed rather than executive dysfunctions in MDD. Abnormalities in cardiovascular control during cognition in MDD appear to involve both divisions of the autonomic nervous system. Low tonic parasympathetic control and blunted sympathetic reactivity imply reduced physiological adjustment resources and, by extension, provide suboptimal conditions for cognitive performance.     

Relationships between features of autonomic cardiovascular control and cognitive performance

The study investigated relationships between autonomic cardiovascular control and attentional performance. In 60 healthy subjects R-wave to pulse interval (RPI), respiratory sinus arrhythmia (RSA), heart rate variability in the mid-frequency (MF) band and sensitivity of the cardiac baroreflex (BRS) were assessed at rest and during a visual attention test. All parameters decreased markedly during test execution. Lower values of resting BRS predicted increased performance. On-task RPI, RSA, MF power and BRS were inversely related to attentional functioning, with RSA accounting for the largest portion of test score variance. The inverse association between resting BRS and performance is discussed as reflecting the bottom-up modulation of cerebral function by baroreceptor activity. The results concerning the on-task measures suggest that a pattern of cardiovascular adjustment including enhanced sympathetic and reduced vagal cardiovascular influences, as well as baroreflex inhibition may induce an adaptive state associated with improved cognitive-attentional functioning.     

The effects on cardiovascular autonomic control of repetitive arousal from sleep

STUDY OBJECTIVES: To quantitatively assess autonomic cardiovascular control in normal young adults following exposure to repetitive acoustically-induced arousals from sleep. DESIGN: Respiration, R-R interval (RRI) and noninvasive measurements of continuous arterial blood pressure were monitored in subjects during the transition from relaxed wakefulness to stable Stage 2 sleep. These measurements were made under undisturbed conditions or conditions in which transient arousals were induced repetitively by acoustic stimulation. A mathematical model was used to partition the fluctuations in RRI into a component ("RSA") correlated with respiration and a component ("A representing baroreflex control of heart rate. The magnitudes and forms of each component before and after exposure to repetitive arousals were compared SETTING: Sleep disorders laboratory in a university setting. PATIENTS OR PARTICIPANTS: Ten healthy young adults (5 male, 5 female) with an average age of 20.4 +/- 2.0 y and mean body-mass index of 23.8 +/- 2.9 kg/m2. INTERVENTIONS: Each subject participated in multiple sleep studies consisting of 4 conditions with 2 nights in each condition. The first condition consisted of undisturbed sleep (control), while in the other 3 conditions, the subjects were aroused from sleep by repetitive auditory stimuli applied continuously over a duration of 50 minutes, with periodicities of 30 seconds, 1 minute, and 2 minutes of sleep. MEASUREMENTS AND RESULTS: Exposure to repetitive arousal (RA) did not alter mean heart rate or blood pressure. However, ABR and RSA gains estimated using the model, increased from the onset of Stage 1 sleep to the start of stable Stage 2 sleep under the control condition, but remained unchanged in all RA conditions. There were also significant increases in low-frequency oscillations of systolic blood pressure in the RA conditions versus no change in the control condition. CONCLUSIONS: Exposure to RA over durations approximating an hour produces cumulative effects on autonomic control that are subtle and can only be detected when advanced signal processing methods are employed. More specifically, the increases in ABR and RSA gains that accompany increasing sleep depth in normal sleep are prevented from occurring.     

Hyperoxia-induced alterations in cardiovascular function and autonomic control during return to normoxic breathing

Hyperoxia causes hemodynamic alterations. We hypothesized that cardiovascular and autonomic control changes last beyond the end of hyperoxic period into normoxia. Ten healthy volunteers were randomized to breathe either medical air or 100% oxygen for 45 min in a double-blind study design. Measurements were performed before (baseline) and during gas exposure, and then 10, 30, 60, and 90 min after gas exposure. Hemodynamic changes were studied by Doppler echocardiography. Changes in cardiac and vasomotor autonomic control were evaluated through changes in spectral power of heart rate variability and blood pressure variability. Cardiac baroreflex sensitivity was assessed by the sequence method. Hyperoxia significantly decreased heart rate and increased the high frequency power of heart rate variability, suggesting a chemoreflex increase in vagal activity since the slope of cardiac baroreflex was significantly decreased during hyperoxia. Hyperoxia increased significantly the systemic vascular resistances and decreased the low frequency power of blood pressure variability, suggesting that hyperoxic vasoconstriction was not supported by an increase in vascular sympathetic stimulation. These changes lasted for 10 min after hyperoxia (p < 0.05). After the end of hyperoxic exposure, the shift of the power spectral distribution of heart rate variability toward a pattern of increased cardiac sympathetic activity lasted for 30 min (p < 0.05), reflecting a resuming of baseline autonomic balance. Cardiac output and stroke volume were significantly decreased during hyperoxia and returned to baseline values (10 min) later than heart rate. In conclusion, hyperoxia effects continue during return to normoxic breathing, but cardiac and vascular parameters followed different time courses of recovery.     

Stress cardiovascular/autonomic interactions in mice

Studies evaluated the role of the autonomic nervous system in the cardiovascular response to stress using radiotelemetric blood pressure (BP) recording coupled with autoregressive spectral analysis. Conscious male C57/BL6 mice with carotid arterial telemetric catheters were exposed to acute episodes of shaker stress before and after administration of cholinergic, beta1-adrenergic and alpha1-adrenergic receptor antagonists. Pulse interval (PI) and systolic arterial pressure (SAP) were analyzed for variance and the low frequency (LF: 0.1-1.0 Hz) and high frequency (HF: 1-5 Hz) spectral components. Stress (5 min) increased BP and heart rate (HR) as well as PI and SAP variability. PI variance increased from 41+/-6 to 75+/-14 ms2 while SAP variance increased from 25+/-5 to 55+/-9 mm Hg2. Autonomic blockade had specific effects on stress-induced changes in PI and SAP and their respective variability. Atropine reduced the tachycardia and abolished the increase in PI variance and its LF component. Data documents that in mice the cholinergic system is fundamental for the maintenance of HR variability. Atropine had no effects on the BP responses, either the increase in SAP or the variance associated with stress. Atenolol blocked the increase in PI and SAP variability induced by stress. Prazosin reduced the tachycardia produced by stress and blocked the increase in PI (only LF) and SAP variability. Using quantitative spectral analysis of telemetrically collected BP data in mice along with pharmacological antagonism, we were able to accurately determine the role of autonomic input in the mediation of the stress response. Data verify the role of sympathetic/parasympathetic balance in stress-induced changes in HR, BP and indices of variance.     

Changes in cardiac autonomic regulation after prolonged maximal exercise.

Harmful cardiac events occurs frequently after exercise. However, the cardiac autonomic regulation after vigorous exercise is not well known. This study was designed to assess heart rate (HR) variability before and after a 75 km cross-country skiing race. HR variability was assessed by using standard statistical measures along with spectral and quantitative Poincarè plot analysis of HR variability in 10 healthy male subjects (age 36 +/- 11 years). The average HR was at the same level 1 day after the race as before the race, but on the second day, HR was significantly lower (P<0.001) compared with the prerace and 1 day after values. The normalized high-frequency (HF) spectral component of HR variability (nuHF) was lower (P<0.01) on the first day after the maximal exercise compared with the pre-exercise values but returned to or even exceeded the prerace level on the second day (P<0.01). The changes in short-term R-R interval variability analysed from the Poincaré plot were similar to those observed in the HF spectral component. The normalized low-frequency (LF) spectral component of HR variability (nuLF) was higher (P<0.01) on the first day after the exercise compared with the prerace levels and it also returned to the pre-exercise level or even dropped below it on the second day after the race. The mean time it took the HF spectral component to return to the pre-exercise level was 4.2 +/- 4.2 h (ranging from 0 to 12 h). This recovery time correlated inversely with the maximal oxygen consumption (VO2max) measured during the bicycle exercise test before the skiing race (r=-0.712, P<0.016). The cardiac vagal outflow is blunted for several hours after prolonged vigorous exercise. The recovery time of reduced vagal outflow depends on individual cardiorespiratory fitness and there is an accentuated rebound of altered autonomic regulation on the second day after prolonged exercise.     

Testing of autonomic cardiovascular regulation--methodological considerations

The different analyses of the results on autonomic nervous function tests were evaluated in 43 male and 32 female diabetic patients and in 24 male and 24 female control subjects, aged 47-67 years, all without any known heart disease. The Valsalva ratio of the first effort did not differ from the mean Valsalva ratio of three efforts. During deep breathing, heart rate variation and max/min R-R interval ratio determined from the first three breathing cycles did not differ from the respective variables calculated from six consecutive breathing cycles. Diastolic blood pressure response to isometric handgrip was greater during the third minute than during the first and the first two minutes. In conclusion, the tests for the evaluation of autonomic nervous function can be simplified without losing their diagnostic value.     

Post-exercise recovery of autonomic cardiovascular control: a study by spectrum and cross-spectrum analysis in humans

The recovery of the baseline autonomic control of cardiovascular activity after exercise has not been extensively studied. In 12 healthy subjects, we assessed the time-course of recovery by autoregressive spectrum and cross-spectrum analysis of heart period and systolic blood pressure during the 3 h after the end of 20 min of steady-state exercise at 50% (light workload, LW) and 80% (moderate workload, MW) of the individual's anaerobic threshold. The electrocardiogram and non-invasive blood pressure were simultaneously recorded during 10 min periods in the sitting position, at rest before exercise, and at 15, 60 and 180 min of recovery after exercise. At 15 min we observed a persistent tachycardia and relative hypotension; after MW, at 60 min heart rate was still slightly higher. Spectrum and cross-spectrum analysis showed, at 15 min, an increase in the low frequency component of systolic blood pressure, a reduction in the high frequency component of heart rate (larger in MW), and a decrease in baroreceptor sensitivity. After 60 and 180 min none of these parameters was significantly different from those at rest, although, in MW, some subjects still displayed signs of sympathetic activation after 1 h. We concluded that, after 15 min of recovery, the cardiovascular reflexes were blunted, that sympathetic nerve activity was still enhanced, and that the tone in the vagus had not fully recovered. Only the persistent vagal restraint seemed to be exercise intensity-dependent. For complete restoration of autonomic control after LW 1 h of rest was sufficient, and just enough after MW. Accepted: 2 November 2000     

Two types of cardiovascular autonomic regulatory responses to the war.

In war, many people are not directly hurt, but they feel fear of various intensities for a long time. The response of the cardiovascular autonomic system to these conditions, produced by the bombardment of Yugoslav cities by NATO for 78 days in spring 1999, was investigated. A group of 12 active medical professionals was examined 1 and 5 weeks after the beginning of bombardment and 10 days after the end of bombardment by spectral analysis of heart rate variability. Two types of cardiovascular autonomic responses emerged. One type included a fast reaction and then adaptation; the increased activity of symphaticus compared to parasymphaticus in the beginning of war was followed by a balance of these activities after 1 month and a small increase immediately after the end of bombardment. The other type did not show an increased activity of symphaticus compared to parasymphaticus during the war, but at the end of bombardment the prevalence of vagal tone was observed.     

Development of autonomic control of fetal circulation.

Development of parasympathetic and sympathetic reflexes controlling heart rate, vascular pressures, and blood flows was investigated in fetal lambs weighing 300-5,800 g (65-165 days' gestation). Cardiovascular responses to veratridine injections, atrial stretching, bilateral cervical vagotomy, and cholinergic blockade with atropine were used to test parasympathetic activities. Responses to propranolol and phenoxybenzamine were used to test beta- and alpha-adrenergic activities. Autonomic ganglionic blockade and stimulation provided additional information on both cholinergic and adrenergic systems. Fetal responses to various tests were compared to those of the mother. Results show: a) little parasympathetic tone on resting heart rate and other circulatory functions exists prior to fetal maturity; b) despite the feeble resting tone, the parasympathetic system is capable of exerting significant control when stimulated in both premature and mature fetuses, the capability increases as fetus approaches term; c) alpha- and beta-adrenergic tone in control of resting heart rate and peripheral circulation exists in early fetal life and increases as the fetus reaches maturity, and both adrenergic receptors respond strongly to stimuli in immature, premature, and mature fetuses; d) in immature fetuses, veratridine does not elicit a vagally mediated reflex; instead, it produces a centrally mediated alpha- and beta-adrenergic stimulation; e) the fetal cardiovascular response to any given test is dampened by the existence of the various vascular shunts, the umbilicoplacental circulation and, possibly, by incomplete maturation of vasomotor tone.     

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.     

Maturation of autonomic control in preterm infants

In order to investigate the development of autonomic control and its relation to postnatal illness, healthy term, healthy preterm, and preterm infants who had recovered from respiratory distress syndrome (RDS) were seen around the expected date of their birth, 40 weeks conceptional age (C.A.), and again at 3 months conceptional age. Three minutes of resting EKG were collected at each age point while the infant was in a quiet, alert state. Measures of resting heart period and heart period variability were derived. Results revealed the influence of maturity and illness on autonomic activity. RDS and healthy preterm infants, at 40 weeks C.A. exhibited a pattern of small heart period compared to healthy term. RDS preterm infants at 40 weeks C.A. exhibited less overall variability than either healthy group and across age displayed less short-term variability than the healthy infants. The data suggest that autonomic activity during the early months of life may be affected by both pre-maturity and postnatal illness. The significance of these data in understanding term/preterm differences in the neonatal period is discussed.     

Simulation of the autonomic neural control of insulin secretion.

A seventh order, nonlinear, highly isomorphic, dynamic systems model of insulin secretion was used to test specific mechanistic hypotheses about the sites of action of sympathetic and parasympathetic autonomic neural input on glucose-induced insulin secretion. The application of neural input was modeled by changing only those specific model parameters that correspond to the hypotheses under study as a function of the input magnitude. The results of these simulations suggest that sympathetic and parasympathetic inputs modify glucose-induced insulin secretion by decreasing the maximal rate of calcium uptake and increasing the affinity of calcium uptake to glucose, respectively.     

Effects of dietary copper on human autonomic cardiovascular function

Summary Heart rate and blood pressure responses during supine rest, orthostasis, and sustained handgrip exercise at 30% maximal voluntary contraction were determined in eight healthy women aged 18–36 years who consumed diets varying in copper and ascorbic acid content. Copper retention and plasma copper concentration were not affected by diet. Enzymatic, but not immunoreactive, ceruloplasmin was lower (p<0.05) after the low copper and high ascorbic acid diet periods. Diet had no effect on resting supine heart rates, orthostatic responses in heart rate and blood pressure, or standing resting blood pressure. Systolic and diastolic blood pressures were increased significantly (p<0.05) during the handgrip test at the end of the low copper and ascorbic acid supplementation periods. Also, the ratio of enzymatic to immunoreactive ceruloplasmin decreased significantly during these dietary treatments. The mean arterial blood pressure at the end of the handgrip test was negatively (p<0.0004) correlated with the ceruloplasmin ratios. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion.