Journal of the autonomic nervous system最新文献

The aim of this study was to investigate if sensory stimulation in the form of manual acupuncture could influence urge- or mixed-type incontinence among elderly women who were not satisfactorily relieved by standard pharmacological and non-pharmacological treatments given at a specialised incontinence unit. The study is an open clinical follow-up study. The study included 15 elderly women who were treated with manual acupuncture 12 times. Both subjective scorings and objective measurements in the form of leakage in grams (48 h Inco-test) were used. Evaluations were performed at discharge and 1 and 3 months thereafter. Almost all outcome measurements were significantly improved even at follow-up 3 months after the last treatment. Global scorings showed that 12 of the 15 women considered themselves improved even at the follow-up 3 month after treatments were completed. The possible mechanisms of action are discussed, as is the way to perform more studies in this field.

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). α1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective α1 blocker) and moxisylyte (an α1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than −30 mmHg at trial entry (P<0.05). Modulation of α1-receptors may function in the management of lower urinary tract dysfunction in MSA.

Visceral relay neurons in the nucleus of the solitary tract (NTS) regulate behavior and autonomic reflex functions. NTS projections have been extensively characterized in animal studies but not in humans. For the first time, NTS fiber trajectories in the human medulla oblongata were revealed with an “in vitro” postmortem tracing method. Local intramedullary pathways were labeled by direct pressure injections of free horseradish peroxidase centered on the medial subnucleus at a level adjacent to true obex. Labeled elements were resolved by peroxidase histochemistry as a dark brown intracellular reaction product. A prominent transtegmental system of axons emerged from the NTS injection sites and entered the intermediate reticular zone, a region corresponding to an autonomic reflex center in other mammals. A medial system of axons arched across the dorsomedial reticular formation toward the dorsal medullary raphe and projected ventrally toward the nucleus gigantocellularis. A small lateral fiber trajectory coursed towards the dorsomedial zone of spinal trigeminal nucleus caudalis. Presumptive terminals appeared as dustings of fine punctate processes within the NTS, dorsomotor nucleus and reticular formation. NTS projections in humans resemble those identified in other mammals including primates. Axonal tracing studies predict that visceral impulses in humans may transmit over evolutionarily conserved pathways involved in autonomic feedback control and stress adaptation.

To examine whether the cardiovascular neurons of the ventral medulla consist of functionally different kinds of neurons, single neuronal activity of the ventral medulla, activity of the renal sympathetic nerves (RSNA), blood flow of the ear (EarBF) and arterial pressure (AP) were recorded in urethane-anesthetized, vagotomized and immobilized rabbits during electrical stimulation of the aortic nerve (AN, baroreceptor afferent fibers) and electrical stimulation of the dorsomedial hypothalamus (DMH) that reduced EarBF but less affected on AP and RSNA. The dorsolateral funiculus of the second cervical cord was stimulated to evoke antidromic spikes of medullary neurons. Two kinds of reticulo-spinal neurons were identified. Activities of one kind of neurons were facilitated by stimulation of DMH (latency 48.6±27.6 ms, n=11) but they did not respond to stimulation of the AN. Therefore, it was presumed that these neurons controlled vasomotion of the ear through the vasoconstrictor neurons in the spinal cord but did not participate in regulation of systemic AP. Activities of the other neurons were inhibited by stimulation of the AN (latency 47.8±8 4 ms, n=16) but they did not respond to the DMH stimulation. These neurons were identical to those reported previously as the RVLM neurons, and they contributed to regulate systemic AP but might not participate in control of cutaneous vascular movement. The former neurons were located medially to the latter in the reticular formation of the rostral ventral medulla. These results provided evidence at the single neuronal level that the cardiovascular neurons in the ventral medulla were consisted of functionally different sympatho-excitatory neurons and they were located at the different sites in the rostral ventral medulla.

The effects on cardiovascular functions of noxious stimulation to the orofacial areas innervated by trigeminal afferent nerves were analyzed in urethane-anesthetized, spinal cord-intact rats and in rats acutely spinalized at the second cervical level. In the spinal cord-intact rats, pinching of the upper lip produced increases in both heart rate (HR) and mean arterial pressure (MAP). Both responses were considered to be due to activation of sympathetic efferent nerves to the cardiovascular organs. Both responses were attenuated but did not disappear after spinalization at the C2 level. In spinalized rats, sympathetic preganglionic neurons emerging from the thoracolumbar spinal cord could not receive any neural influences from the brain. The HR response in the spinal rats was abolished after either bilateral vagotomy or intravenous injection of a peripherally acting muscarinic cholinergic receptor antagonist, methylatropine. This suggests that the increase in HR was elicited via vagal cholinergic efferent fibers, probably by decreasing tonic activity of vagus nerves to the heart. In spinal rats, neither vagotomy nor cholinergic blockade affected the increase in MAP, but i.v. injection of the vasopressin V1 receptor antagonist, OPC-21268, abolished the response of MAP. This suggests that the response of MAP was due to peripheral vasoconstriction elicited by vasopressin secreted from the posterior pituitary lobe. The present study demonstrated that, in rats acutely spinalized at the C2 level, noxious stimulation of orofacial areas innervated by the trigeminal nerve could produce reflex increases both in HR, by decreasing cholinergic vagal nerve activity to the heart, and blood pressure, by secreting vasopressin from the pituitary gland, even though sympathetic efferent innervation to the cardiovascular organs could not be directly affected by trigeminal afferent nerve excitation.

In spectral analysis of heart rate variability (HRV), the ratio between power in the low-frequency (LF) and power in the high-frequency (HF) regions is widely used to assess the balance between cardiovagal and sympathetic activity (LF/HF ratio). We studied the variation between three observers in the analysis of seven healthy volunteers and eight patients with renovascular hypertension under three conditions (rest, nitroprusside and phenylephrine infusion), in order to determine whether manual selection of the most representative and steady periods increases the reliability of the method. For each condition a period of 6 min of assumed steady-state ECG activity was marked for further analysis. LF/HF ratios were calculated for 3-min periods, using three analysis methods: ‘all manual’, ‘fixed frequency’ and ‘automatic’. In ‘all manual’, the observer selected the optimal 3-min period as well as the LF and HF regions. In ‘fixed frequency’, the manually selected optimal 3-min periods were used with fixed frequency regions for LF (0.04–0.15 Hz) and HF (0.15–0.40 Hz). In ‘automatic’, the fixed frequency regions (0.04–0.15 and 0.15–0.40 Hz) were used and the periods were systematically selected regardless of HR data. The variance in this ‘automatic’ analysis is considered to reflect intrasubject variability. For all analysis methods, the mean LF/HF ratio was highest in the nitroprusside condition, in which the largest interobserver as well as intrasubject variations were found. Calculated per method and per patient condition, the standard deviation between observers was always >25% of the corresponding mean LF/HF ratio. The smallest interobserver variations were found for the ‘fixed frequency’ method. The data showed that it is advantageous to select the 3-min ECG periods but not to select the frequency regions. Selection of the latter led to an increase in interobserver variation. The results of this study give a realistic impression of the intrasubject and interobserver variation to be expected when measuring the LF/HF ratio. This variation is considerable.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21–36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30° and 60° (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7±3.2 to 40.9±3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0.005). A significant diastolic blood pressure fall at 5th min of 60° HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60° HUT. He showed gradual blood pressure fall 10 s after 60° HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Indexes of heart rate variability (HRV) and the slope of cardiac baroreflex are extensively used for non invasive assessment of circulatory autonomic control in pathophysiology. We performed this study (1) to assess the sensitivity of these indexes towards small graded postural stimulations and (2) to delineate the informations provided about the settings of both vascular tone and cardiac activity. Twenty heathly subjects were randomly tilted for eight minutes at each of the six angles: −10°, 0° (supine), 10°, 30°, 45°, and 60°. Instant RR-interval and finger blood pressure (BP) were continuously recorded, and venous blood was collected at the end of each 8 min position for catecholamines determination. Group average heart rate, noradrenaline and diastolic BP (DBP) increased linearly with head-up tilt angle from 10°. Systolic BP (SBB) ranked only two distinct series −10°, 0°, 10° versus 30°, 45°, 60°, as did the number of spontaneous baroreflex (SBR) sequences. The spectral power of the low-frequency (LF) and high-frequency (HF) of RR variability and the ratio LF/HF changed rather abruptly from either 30° or 45°, depending on each individual. Both HF/tot i.e. the ratio of HF to total spectral RR variability and the slope of SBR decreased markedly from 10° to 30° and less but more gradually from 30° to 60°. Thus, our observations argue for gradual adjustments of vascular tone as reflected by highly consistent changes in plasma noradrenaline and diastolic arterial pressure, contrasting with a main discontinuous autonomic setting of cardiac activity as reflected by changes in the harmonic components of spectral RR variability and in the slope of cardiac baroreflex. The pattern of changes in systolic arterial pressure attested the discontinuous cardiac autonomic control rather than the gradual setting of arterial tone. We submit that these different patterns of autonomic adjustments should be considered when assessing pathophysiological states.

Transgenic (TG) mice overexpressing β₂-adrenoceptors (AR) in the heart have enhanced β-adrenergic activity. Since the degree of β-adrenergic activation influences the negative chronotropic control of heart rate (HR), we studied the inhibitory effect of cholinergic and purinergic stimulation on HR in TG and wild-type (WT) control mice. Bradycardia in response to vagal nerve stimulation and administration of acetylcholine or adenosine was studied in anesthetised animals and perfused hearts. Basal HR was significantly higher in TG than WT mice (P<0.01). Electrical stimulation of vagal nerves (1–32 Hz) induced a Hz-dependent reduction in HR and the response was more pronounced in TG than WT groups (P<0.01). In perfused hearts, HR reduction by acetylcholine (ACh) was more pronounced with EC₅₀ 110-fold lower in TG than WT hearts. Adenosine-induced bradycardia, which was abolished by a P₁ antagonist, was more pronounced in TG hearts. After pre-treatment with pertussis toxin (PT, 100 μg/kg), bradycardia by vagal nerve stimulation or ACh remained unchanged in WT, but markedly inhibited in TG hearts (both P<0.01). Conversely, inhibiting guanylyl cyclase with LY83583 (30 μM) or nitric oxide synthase with l-NMMA (100 μM) attenuated HR reduction by vagal nerve stimulation in WT but not in TG hearts. Immunobloting assay showed similar G_iα2 abundance in TG and WT hearts. Thus, cardiac overexpression of β₂AR with high β-adrenergic activity leads to hypersensitivity of inhibitory receptors controlling HR due to increase in activity of PT-sensitive G-proteins.