Changes in blood tryptophan level during sleep deprivation

Prolonged sleep deprivation elicits a significant elevation of the plasma level of free tryptophan which appears to be involved in increased excretion of 5-HIAA during this state through enhanced 5-HT synthesis.     

Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea

BACKGROUND: Muscle sympathetic nerve activity (MSNA) is increased in patients with obstructive sleep apnea (OSA). We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in OSA. METHODS AND RESULTS: Using a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation (by comparing effects of breathing 100% oxygen for 15 minutes with effects of breathing room air for 15 minutes) on MSNA, heart rate, blood pressure, and minute ventilation in 14 untreated patients with OSA and in 12 normal subjects matched for age and body mass index. All control subjects underwent overnight polysomnography to exclude the existence of occult OSA. Baseline MSNA was markedly elevated in the patients with OSA compared with the control subjects (44+/-4 versus 30+/-3 bursts per minute; P=.01). In both control subjects and patients with OSA, heart rate decreased during administration of 100% oxygen but did not change during administration of room air. By contrast, both MSNA (P=.008) and mean arterial pressure (P=.02) were significantly reduced during chemoreflex deactivation by 100% oxygen only in patients with OSA but not in control subjects. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents may contribute to increased efferent sympathetic activity to muscle circulation in patients with OSA.     

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.     

Calcium antagonists and sympathetic activity in congestive heart failure

OBJECTIVE: To review the sympathetic abnormalities occurring in heart failure, their pathophysiological importance and clinical relevance, and the effects of drug treatment, with particular reference to calcium antagonists. SYMPATHETIC ACTIVATION IN HEART FAILURE: Indirect and direct approaches to study sympathetic function in humans have documented conclusively that sympathetic activation represents a hallmark of cardiac failure syndrome. Evidence indicates that sympathetic overactivity is associated with, and probably caused by, a baroreflex impairment and that it has adverse effects on patients' prognosis and survival. GOALS OF DRUG TREATMENT IN CONGESTIVE HEART FAILURE: In the past, drug treatment in heart failure was aimed at improving patients' survival by ameliorating cardiac hemodynamics. It is now established that a major goal of therapeutic intervention is also to reduce sympathetic activation characterizing heart failure. CALCIUM ANTAGONISTS IN HEART FAILURE: Studies with short-acting calcium antagonists show that they enhance sympathetic activation and that this has an adverse effect on patients' survival. In contrast, third generation calcium antagonists such as amlodipine, which have a slow onset and long duration of action, do not adversely affect sympathetic function and reflex cardiovascular control. Indeed, evidence suggests calcium antagonists with this profile may exert favorable clinical effects.     

Central neural regulation of heart and blood vessels in mammals

The study of the central regulation of the circulation in the past has been directed primarily at observing reflex responses to stimulation of peripheral receptors and at producing changes in cardiovascular parameters during electrical stimulation of central sites. These studies have demonstrated that the nervous system can regulate the circulation to different vascular beds with a high degree of specificity and that it has the ability to provide a range of coordinated responses which are appropriate to the metabolic needs of a particular behavioural pattern. In addition, it has become firmly established that the nervous system is capable of coupling cardiovascular changes with other autonomic and somatic activities to produce an integrated response. In the last decade it has become apparent that although the mode of operation of central cardiovascular regulation has been described in general terms, very little is known about the accurate anatomical localization of neuronal circuits and pathways and of impulse traffic corresponding to the changes in cardiovascular parameters that have been observed. This essay reviews recent information on discrete neuronal circuits and pathways and their mode of operation in electrophysiological terms. One of the most serious difficulties in this endeavour is the problem of demonstrating specificity of pathways and circuits because patterns of firing of afferent and efferent peripheral nerves can be usually identified, but the demonstration of specificity of central structures is a conceptual and technical challenge to the most skilled investigator. Several studies have been made in the last decade in an attempt to trace anatomically and functionally pathways involved in central cardiovascular regulation. Progress has been made especially with regard to the precise sites of termination of cardiovascular afferent fibres and the pattern of discharge of efferent cardiovascular neurons; some work has also been done to trace discrete pathways between the hypothalamus and the medulla and the medulla and the spinal cord. However, in view of the difficulties of establishing the specificity of cardiovascular pathways, progress will depend on the acquisition of a wiring diagram of simple cardiovascular reflex arcs before attempts are made to study the functional interactions of regions in the brain that have been traditionally associated with central regulation of the circulation. Future experiments should concentrate less on the demonstration of cardiovascular responses to stimulation or lesions in the central nervous system and more on the connections of discrete regions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration

BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime somnolence and cognitive impairment. It is also an independent marker of increased mortality in heart failure. This study evaluated the effectiveness of oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven patients with stable heart failure and Cheyne-Stokes breathing were studies. Oxygen and air were administered for 4 weeks in a double-blind, cross-over study. Sleep and disordered breathing was assessed by polysomnography. Symptoms were assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift scores. Cognitive function was assessed by neuropsychometric testing. Overnight urinary catecholamine excretion was used as a measure of sympathetic nerve activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p = 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs 4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen stabilized sleep disordered breathing and reduced sympathetic activity in patients with heart failure and Cheyne-Stokes respiration. We were unable to demonstrate an effect on either patient symptoms or cognitive function.     

Chloroethylclonidine and alpha-adrenoceptor agonist interaction in blood vessels following heart failure

We compare and contrast the putative mechanisms underlying CO2 chemoreceptor function in air breathing vertebrates and terrestrial pulmonate snails. We discuss the role of intracellular pH (pHi) in central respiratory responses to CO2 and describe a variety of patterns of pHi regulation in chemosensory areas. One pattern, in which pHi retains a fixed relationship to the CO2 stimulus over time, seems well suited to chemoreceptor cells. Alphastat regulation of ventilation is apparent in both air breathing vertebrates and terrestrial pulmonate snails. Diethyl pyrocarbonate inhibits respiratory responses to hypercapnia in both groups of animals. The neuronal basis of chemosensitivity is similar, in that putative chemoreceptor cells depolarize during hypercapnic stimulation, but the ionic basis of excitability appears to be a potassium conductance in the vertebrates studied to date and a calcium conductance in the snails. Despite divergent evolutionary histories, chemosensory responses and mechanisms are remarkably similar in air breathing vertebrates and terrestrial pulmonate snails.     

Changes in plasma dopamine-beta-hydroxylase activity during the perioperative period of cardiac surgery: an index of sympathetic nerve activity

To evaluate the usefulness of plasma dopamine-beta-hydroxylase (DBH) activity as an index of sympathetic nerve activity during cardiac operations, we examined the serial changes in plasma DBH activity, in relation to the plasma noradrenaline (NA) level and hemodynamic parameters, in patients who underwent cardiac surgery. The plasma DBH activity decreased significantly after cardiopulmonary bypass, and remained low during dopamine (DA) infusion until 72 h after the operation. However, recovery of the hemodynamic parameters, being the mean arterial pressure, heart rate and cardiac index, was seen as early as 1-3 h postoperatively. It was therefore assumed that the plasma DBH activity takes a long time to recover after an operation. The time-course changes in the plasma NA level were quite different from the changes in DBH activity, with an apparent negative correlation being observed between them. Thus, there is a possibility that exogenously administered DA, as well as increased plasma NA, might inhibit DBH activity during cardiac surgery. Moreover, since catecholamines are often administered upon completion of cardiac surgery, measurement of the plasma catecholamine level would be inappropriate for evaluating real sympathetic nerve activity. From the results of this study, it is surmised that measurement of the plasma DBH activity could be useful for estimating the intrinsic sympathetic nerve activity of patients who have undergone cardiac surgery.     

Colonic motor activity in women during sleep

Regulators of G-protein signalling (RGS) are recently identified proteins that shorten the lifetime of the activated G protein. We now show that rat cardiac myocytes express mRNA for at least 10 RGS. The mRNA for RGS-r is barely detectable in rat ventricles, but increases more than 20-fold during the 60- to 90-min process of isolating ventricular myocytes, and after 90 min of culture of atrial pieces in medium with Ca2+. Both in myocytes and in atria, the rise in RGS-r is transient. The mRNA for cardiac RGS5, but not RGS-r, is developmentally regulated. These studies suggest that rapid regulation of RGS levels may be a new mechanism that governs how signals are transmitted across the cardiac cell membrane.     

Changes in resistance and capacitance functions of skeletal muscle vessels during the amplitude-frequency modulation of the perfusion blood flow

Changes of venous outflow, pre- and postcapillary resistance of the skeletal muscle vessels were found to depend on values of amplitude and frequency of the perfusion blood flow in cats. Three types of the responses were distinguished: either increase, or decrease, or absence of them. The findings suggest a possibility to affect haemodynamic parameters with the aid of amplitude-frequency deviations in the organ blood flow.     

Changes in EEG power density during sleep laboratory adaptation

First- and second-night effects on the electroencephalogram (EEG) were investigated by means of polygraphic sleep recordings and all-night spectral analysis. Eighteen normal subjects were studied for three consecutive nights in a hospital sleep laboratory. Visual sleep scoring showed that there was a first-night effect in normal subjects similar to that reported previously [increased wakefulness; decreased total sleep time, sleep efficiency, and rapid eye movement (REM) sleep]. Spectral analysis of the sleep EEG revealed important changes, most of which occurred in REM sleep. Increased delta, theta, and beta1 power densities accompanied by decreased mean frequency were seen in REM sleep in the second night. On the basis of REM sleep deprivation results previously published, our data suggest that the second night could be affected by partial REM sleep deprivation that occurred in the first night. Delta and theta power density values decreased in the first non-rapid eye movement episode of nights 1 and 2; this could result from increased REM sleep pressure. The overall consistency of spectral data in the first and second night with REM sleep findings derived from visual scoring in the first night lends further support to this hypothesis. The sleep disturbance experienced during the first night in a sleep laboratory may be a useful and valid model of transient insomnia. Therefore, we conclude that data from all nights recorded should be included in assessing a subject's sleep.     

Basement membrane of blood vessels during distraction osteogenesis

A canine model of distraction osteogenesis has recently been developed that permitted the evaluation of bone formation and its vascularization during bifocal callotasis. In this model, the authors examined the composition of the blood vessels during distraction osteogenesis of the mandible for laminin and for Type IV collagen, both constituents of the vascular basement membrane. At the fibrous distraction site, at the juncture of the free cortical surface and the regenerated bone, and at the abutting cortical surfaces at the distal margin of the defect, laminin and Type IV collagen were present in all vessels.     

Changes in luminescence of the undiluted blood in patients with ischemic heart disease during laser therapy

AIMS: To examine the course taken by individual retinal ganglion cell axons through the human lamina cribrosa. METHODS: Retinal ganglion cell axons were labelled using the retrograde tracer horseradish peroxidase applied directly to the optic nerve in two normal human eyes removed during the course of treatment for extraocular disease. RESULTS: A majority of axons took a direct course through the lamina cribrosa but a significant minority, in the range 8-12%, deviated to pass between the cribrosal plates in both central and peripheral parts of the optic disc. CONCLUSIONS: It is postulated that these axons would be selectively vulnerable to compression of the lamina cribrosa in diseases such as glaucoma in which the intraocular pressure is increased.     

Changes in blood sugar and ammonium levels after ligation of the afferent hepatic vessels

Certain aspects of the development of Ehrlichia canis, causative agent of canine ehrlichiosis (tropical canine pancytopenia) in Rhipicephalus sanguineus ticks were studied. It was found that partial feeding of nymphs infected as larvae with E canis was a desirable, if not necessary, preliminary treatment for successful infection of dogs with ground-up ticks. It remains unclear whether feeding increased the number or altered the virulence of ehrlichiae within tick tissues. Ehrlichia canis organisms were detected by immunofluorescent microscopy in the midgut and hemocytes and by electron microscopy in the midgut and salivary glands of partially engorged adult ticks which had been infected as larvae and nymphs. Organisms were not observed in the ovary. Intracytoplasmic inclusions contained 1 to 80 elementary bodies, each provided with 2 distinct membranes. Infection of the midgut and salivary gland was confirmed by injecting homogenates of these tissues into susceptible dogs. Staining of gut smears of partially engorged adult ticks by fluorescein-conjugated anti-E canis antibody was found to be a reliable indicator of the infection.     

Development of heart rate in newborn infants during quiet sleep

The small number of investigations of the development of heart rhythm during the first half year of life provide only rough ideas regarding the maturation of heart rate control. In the present study, in 10 newborns, ECG and respiratory effort were recorded in 13 sessions from birth up to the sixth month. The total power (TP), power in the low (LF) and high frequency range (HF), and the ratio LF/HF were used from the heart rate power spectra. All parameters reveal no linear developmental patterns: TP, LF, and HF increase during the first days to a maximum, then decrease subsequently and remain low until the second month. TP and HF increase between the second and sixth month. LF/HF increases up to the second month followed by a decrease down to the sixth month. The developmental courses of TP, HF and LF/HF correlate with the course of breathing rate (BR), whereby high BR is associated with low HF and TP. The results hint at a maturated cardiorespiratory system.     

Effects of microinjection of L-NNA and SNP into ventrolateral medulla on blood pressure, heart rate and renal sympathetic nerve activity in rats

The effects of microinjection of a NO synthase inhibitor--N-nitro-L-arginine (L-NNA) and NO donor-sodium nitroprusside (SNP) into ventrolateral medulla on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were examined in anesthetized rats to define the role of L-arginine: NO pathway in the central regulation of BP and to explore the underlying mechanism. The results obtained were as follows: (1) Following microinjection of L-NNA into rostral ventrolateral medulla (RVLM), both of MAP and RSNA were increased. The effects lasted for more than 30 min and could be reversed by prior intravenous injection of L-arginine. (2) In response to microinjection of SNP into RVLM, MAP and RSNA were decreased, while HR showed no significant change. (3) During microinjection of L-NNA into caudal ventrolateral medulla (CVLM), MAP, HR and RSNA were decreased. (4) Upon injection of SNP into CVLM, MAP and RSNA were increased, but HR showed no significant change. The above-mentioned results indicate that the L-arginine: NO pathway may exhibit a modulatory action on the activity of ventrolateral medulla neurons.