Altered Autonomic Activity Research Articles

Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial.

We hypothesized that neurohormonal activity contributes to the initiation of sustained ventricular tachycardia (VT) as reflected in indices of heart rate variability (HRV). Autonomic nervous system activity participates in experimental arrhythmias but clinical studies have been inconsistent. Holter electrocardiograms from 53 patients with VT were analyzed. Heart rate variability indices were determined over 5 and 15 min and 24 h and examined for changes before the onset of VT. Heart rate variability indices in the frequency domain included ultra low frequency power (FP) (ULFP): 0-0.0033 Hz; very low FP (VLFP): 0.0033-0.04 Hz; low FP (LFP): 0.04-0.15 Hz; high FP (HFP): 0.15-0.4 Hz; total power (TP); normalized LFP (LFPn); normalized HFP (HFPn), and the ratio: LFP/HFP. Heart rate variability indices were severely diminished: TP: 12,009+/-11,076 ms2; ULFP: 10,087+/-9,565 ms2; VLFP: 1,416+/-1,571 ms2; LFP: 544+/-620 ms2; HFP: 161+/-176 ms2, and LFP/HFP: 3.68+/-2.83. Heart rate increased before VT (80.4+/-17.3 to 85.3+/-17.4 bpm, p < 0.001). Several HRV variables declined 30 min before VT compared to 24-h values (VLFP: -5.89+/-17.81%, p = 0.031; LFP: -5.23+/-14.3%, p = 0.003; HFP: -4.35+/-13.7%, p = 0.04). LFPn and the LFP/HFP ratio decreased significantly before the onset of VT (-17.7+/-46.9%, p = 0.035 and -8.24+/-38.8%, p = 0.037, respectively), whereas HFPn increased slightly (4.29+/-29.9%, p = 0.097). Heart rate rose, whereas LFP, LFPn and LFP/HFP fell before the onset of VT. This pattern of changes could be explained by a rise in sympathetic activity and saturation of the HRV signal resulting in dissociation of the average and rhythmical effects of sympathetic activity. These findings suggest that alterations in autonomic activity contributed to arrhythmogenesis in this group of patients.

Effects of chronic social separation on cardiovascular disease risk factors in female cynomolgus monkeys

A lack of social support is associated with increased risk of coronary heart disease morbidity and mortality in human beings. Similarly, chronic social separation (single cage housing) potentiates atherosclerosis in female monkeys. Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate this effect (as both are associated with increased atherosclerosis), heart rate and luteal phase plasma progesterone concentrations were measured in 12 female cynomolgus monkeys that were first socially housed, then individually housed, and finally returned to their original social groups. Afternoon heart rates increased during social separation compared to the social groupings ( P<0.001). Increased heart rates could not be explained by activity levels, which were lower during social separation than in social groupings ( P<0.001). Ovarian function (i.e. luteal-phase progesterone concentrations) was not influenced by housing condition. Single caging reduced the extent of social signaling, even though animals were in visual and auditory contact. Rates of affiliative behaviors increased and time spent alone decreased in post-reunion social groups compared to pre-separation social groups ( P's<0.01). The results indicate that chronic social separation in this group-living species may exacerbate atherosclerosis via altered autonomic activity, as evidenced by higher heart rates during social separation.

Contrasting expressions of aggressive behavior released by lesions of the central nucleus of the amygdala during wakefulness and rapid eye movement sleep without atonia in cats.

Whether damage to the central nucleus of the amygdala (Ace) contributes to the predatorylike attack sometimes observed in rapid eye movement sleep without atonia (REM-A), created in cats by bilateral pontine lesions, was examined. Such lesions eliminate REM sleep skeletal muscle atonia and release elaborate behavior. Unilateral damage to the Ace alone increased affective defensive aggressive behavior toward humans and conspecifics without altering predatory behavior in wakefulness. Pontine lesions added at loci normally not leading to aggression induced predatorylike attacks in REM-A as well as the waking affective defense. Alterations of autonomic activity, the absence of relevant environmental stimuli in REM-A, or both may explain the state-related differences.

Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study.

Cardiac autonomic activity, as assessed by heart rate variability, has been found to be associated with postmyocardial infarction mortality, sudden death, and all-cause mortality. However, the association of heart rate variability and the incidence of coronary heart disease (CHD) is not well described. The authors report on the association of baseline cardiac autonomic activity (1987-1989) with incident CHD after 3 years (1990-1992) of follow-up of the Atherosclerosis Risk in Communities Study cohort selected from four study centers in the United States by using a case-cohort design. The authors examined 137 incident cases of CHD and a stratified random sample of 2,252 examinees free of CHD at baseline. Baseline, supine, resting beat-to-beat heart rate data were collected. High- (0.16-0.35 Hz) and low- (0.025-0.15 Hz) frequency spectral powers and high-/low-frequency power ratio, estimated from spectral analysis, and standard deviation of all normal R-R intervals, calculated from time domain analysis, were used as the conventional indices of cardiac parasympathetic, sympatho-parasympathetic, and their balance, respectively. Incident CHD was defined as hospitalized myocardial infarction, fatal CHD, or cardiac revascularization procedures during 3 years of follow-up. The age, race, gender, and other CHD risk factor-adjusted relative risks (and 95% confidence intervals) of incident CHD comparing the lowest quartile with the upper three quartiles of high-frequency power, low-frequency power, high-/low-frequency power ratio, and standard deviation of R-R intervals were 1.72 (95% confidence interval (CI) 1.17-2.51), 1.09 (95% CI 0.72-1.64), 1.25 (95% CI 0.84-1.86), and 1.39 (95% CI 0.94-2.04), respectively. The findings from this population-based, prospective study suggest that altered cardiac autonomic activity, especially lower parasympathetic activity, is associated with the risk of developing CHD.

Regional vascular and cardiac responses to systemic neuropeptide-Y in normal and diabetic rats.

Diabetes is associated with altered autonomic activity, and both the peripheral and central nervous content of NPY is altered in diabetes suggesting that part of the cardiovascular dysfunction of diabetes may be associated with altered responses to NPY. We evaluated the mean arterial pressure (MAP), heart rate (HR) and regional blood flow (BF) in response to NPY in normal and diabetic rats. Male Wistar rats were made diabetic using streptozotocin and maintained without insulin treatment for 28-30 days. Normal and diabetic animals were anesthetized, the femoral artery cannulated, and flow probes placed around the iliac, renal and superior mesenteric arteries. Dose dependent responses to NPY infusion were determined for MAP, HR and BF. Conductance was calculated from BF/MAP. In normal rats NPY increased the MAP in a dose-dependent fashion but did not alter the HR. NPY decreased the BF in the iliac artery in a dose-dependent fashion while the renal BF was decreased only at the highest dose, and the superior mesenteric BF was not affected. The conductances in all vascular beds were decreased dose dependently. NPY in diabetic rats also increased MAP and did not affect HR. In diabetic rats NPY also decreased BF in iliac and renal arteries but contrastingly increased BF in the superior mesenteric artery. Again conductances in all three vascular beds were decreased by NPY. When comparing diabetic response to NPY to normals we noted that the MAP response was less in the diabetic, but the HR and regional BF were not different. The vascular conductances in response to NPY were attenuated in the diabetic vessels especially the iliac and superior mesenteric. We conclude that systemic NPY increases MAP as a result of decreased vascular conductance and this vasopressive effect of NPY is diminished in diabetics.

Differential effects of ketamine and midazolam on heart rate variability

Alterations in autonomic activity caused by anaesthesia can be assessed by spectral analysis of heart rate variability (HRV). This study examined the effects of ketamine and midazolam on HRV. Thirty patients of ASA PS 1 were studied. Fifteen were given ketamine (2 mg.kg-1) and 15 received midazolam (0.3 mg.kg-1), iv. The RR intervals of ECG were measured before and after induction of anaesthesia for ten minutes during spontaneous respiration. Power spectral density of the data was computed using fast Fourier transform. The spectral peaks within each measurement were calculated: low frequency area (LF, 0.04-0.15 Hz), high frequency area (HF, 0.15-0.5 Hz), and total power (TP, 0.04-0.5 Hz). Normalized unit power was derived as follows: low frequency area (nuLF): LF/TP x 100%, high frequency area (nuHF): HF/TP x 100%. Both ketamine and midazolam caused reductions in all measurements of HRV power (P < 0.05). However, ketamine increased nuLF from 64 +/- 14% to 75 +/- 13% (P < 0.05) and decreased nuHF from 36 +/- 14% to 25 +/- 13% (P < 0.05), while midazolam decreased nuLF from 66 +/- 15% to 54 +/- 14% (P < 0.05) and increased nuHF from 34 +/- 15% to 46 +/- 14% (P < 0.05). These results documented that both ketamine and midazolam reduced the total power and all frequency components of power in spite of their opposing effects on autonomic nervous activity. However, normalized unit power showed the expected sympathetic activation with ketamine and sympathetic depression with midazolam since ketamine increased nuLF and midazolam decreased nuLF.

Haemodynamic changes caused by alteration of autonomic activity in patients with heart failure.

In 14 patients with heart failure (New York Heart Association class 2-3) and sinus rhythm the carotid sinus baroreceptors were stimulated to induce a reflex mediated decrease of sympathetic efferent activity and a simultaneous increase in vagal tone. Five patients were in severe heart failure (New York Heart Association class 3) with raised plasma concentrations of noradrenaline at rest (2.99 (0.86) nmol/l (mean (SD)) and nine patients had less severe heart failure (class 2.2 (0.2)) and normal plasma concentrations of noradrenaline at rest. The haemodynamic responses during arterial baroreceptor stimulation were different in both groups. In all five patients with severe heart failure cardiac output increased whereas in the nine patients with less severe heart failure it was unchanged or decreased. The increase of cardiac output in the group with severe heart failure was solely the result of a significant increase of stroke volume index (by 9 (2) ml/m2). In the nine patients with less severe heart failure stroke volume remained unchanged but heart rate decreased significantly by 7 (2) beats/min during baroreceptor stimulation. These data show that an integrated change of autonomic activity consisting of a decrease in sympathetic tone and an increase in vagal activity leads to an increase of stroke volume in patients with severe heart failure and hence to haemodynamic improvement.

Transient ST-segment elevation in subarachnoid hemorrhage

Electrocardiographic manifestation mimicking the hyperacute phase of myocardial infarction and the electrical alternans of the elevated ST-segment in association with subarachnoid hemorrhage were reported in two patients with no evidence of heart disease. In both cases the ST-segment changes were transient and there were no persistent changes suggestive of underlying myocardial damage or ischemia. These findings suggested that the electrocardiographic changes were probably secondary to subarachnoid hemorrhage and not an expression of primary myocardial disease. The electrocardiographic abnormalities could be explained by altered autonomic activity to coronary arteries or directly to the myocardium.

Body fat and the activity of the autonomic nervous system.

The cause of most cases of human obesity is unknown. Specific alterations in the activity of the autonomic nervous system may mediate and perhaps cause obesity in animal models. We therefore looked for alterations in autonomic activity in human obesity. Fifty-six healthy men with various percentages of body fat underwent autonomic testing while at rest. Significant correlations were found between the percentage of body fat and the variation in the R-R interval after beta-adrenergic blockade (r = -0.30, P less than 0.03), the heart rate (r = 0.30, P less than 0.03), the plasma norepinephrine concentration (r = -0.30, P less than 0.05), the plasma epinephrine concentration (r = -0.49, P less than 0.001), and the pupillary latency period (r = 0.39, P less than 0.01). Each of these variables reflects the activity of the sympathetic nervous system or parasympathetic nervous system or both. Depressions in sympathetic and parasympathetic activity were significantly but weakly associated with increasing percentages of body fat. These associations indicate that in obese persons, autonomic changes, though not necessarily causal, involve several organ systems. We suggest that autonomic alterations are important in human obesity, as they are in animal obesity. A disordered homeostatic mechanism may promote excessive storage of energy by decreasing sympathetic activity, while defending against weight gain by decreasing parasympathetic activity. The use of autonomic profiles holds promise for classifying human obesity and identifying obese patients at increased risk for various disorders.

Physiological adaptation to physical conditioning. Old problems revisited.

Three classical problems in the field of man's adaptive response to exercise are reviewed. A case is made for the pump capacity of the heart limiting maximal oxygen uptake in man. This conclusion is based on findings that the capacity of skeletal muscle of man markedly surpasses that of the heart supplying it with a flow and thereby oxygen. It is suggested that only one third of the muscle mass of man can fully tax the capacity of the heart and consume the oxygen delivered by the heart. If a larger muscle mass is intensely engaged in the exercise, vasoconstriction must occur in the arterioles of the exercising limbs to avoid a reduction in blood pressure. Evidence is presented that a decrease in heart rate at submaximal exercise-observed after a period of physical conditioning, is caused by an altered autonomic chronotropic activity to heart, which most likely is due to a less potent feed back reflex from exercising muscles. The enlarged stroke volume is secondary to a larger diastolic filling, which via a Frank-Starling mechanism results in an elevation in the stroke volume. Last, it is argued that the altered metabolic response to exercise after physical conditioning, i.e. the larger lipid oxidation and reduced lactate production, results from local regulatory mechanisms rather than from changes in supply of oxygen, substrates, or hormones. Further, the muscle metabolic response to exercise is thought to play a major role in modulating systemic cardiovascular regulation in exercise.

Cardiac rhythm, rate and ventricular repolarization properties in infants at risk for sudden infant death syndrome: Comparison with age- and sex-matched control infants

Using 24-hour ambulatory electrocardiographic recordings and 120-lead body surface potential maps, prevailing cardiac rate and rhythm, incidence and frequency of dysrhythm and rate and pattern of ventricular repolarization at the body surface were compared in 17 infants at risk for sudden infant death syndrome (SIDS) and 17 age- and sex-matched control subjects. Sinus rhythm was the prevailing rhythm in both study groups and there were no intergroup differences in average overall awake or asleep sinus rates, nor in temporal variability of sinus rate. Atrial and ventricular ectopic activity were equally uncommon in both study groups. Although there were smooth and bipolar body surface distributions of ST-T and QRST time integrals in both study groups, the average rate of ventricular repolarization (QTc), measured from the 12-lead electrocardiogram, 120-lead body surface potential maps and 24-hour electrocardiography, was consistently shorter in the at-risk group than in the control group. However, temporal variability of QTc was not different between the 2 groups. Thus, significant cardiac dysrhythm and QT prolongation are not found in infants at increased risk for SIDS. Rather, there is an abbreviated ventricular repolarization interval in at-risk infants. In combination with the findings of intergroup similarity of average sinus rate and temporal variability of sinus rate and ventricular repolarization rate, the data suggest a subtle, constant difference in cardiac autonomic activity, most likely an Increase in sympathetic tone, in at-risk subjects. The role of this altered cardiac autonomic activity in the causation of SIDS remains undetermined.

CARDIOVASCULAR RESPONSES DURING THE MENOPAUSAL HOT FLUSH

Circulatory responses during spontaneous and stress induced menopausal flushes were measured by a plethysmographic technique. With the onset of symptoms there was an immediate and marked increase in hand blood flow which was sustained over three to four minutes and then fell to control levels over a further three minutes. Forearm and calf flow increased simultaneously through to a lesser extent and regained control levels within four-and-a-half minutes from the onset of symptoms. Mean pulse rate also increased during the flush but fell to control values at a time when limb flow was still elevated. There was no significant change in blood pressure during or after the flush. The peripheral circulatory exchanges are attributed to altered autonomic activity and may in part reflect a disturbance of thermoregulatory control in the menopause of which the flush is but one manifestation.