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Biomedical subjects

S Iwase

Publications and source records attributed to S Iwase.

At least 127 records · Page 7Linked to original sources

Changes in spontaneous baroreflex sensitivity during sleep in humans.

To evaluate changes in the spontaneous baroreflex sensitivity for heart rate and for muscle sympathetic nerve activity (MSNA) during sleep, we simultaneously recorded MSNA from the tibial nerve and monitored ECG, EEG, EOG, EMG and blood pressure during the resting awake stage and sleep. Blood pressure, ECG and MSNA waves were changed to equidistant time series data of each second by cubic spline interpolation. Cross correlations between the MSNA and diastolic blood pressure and between the instantaneous heart rate and systolic blood pressure were analyzed. Spontaneous baroreflex sensitivities for MSNA and for heart rate were assessed from the slope of the regression lines for each. During sleep, the spontaneous baroreflex sensitivity for MSNA gradually decreased as the non-REM sleep stages advanced. Spontaneous baroreflex sensitivity for heart rate did not show any apparent changes. These results suggest that baroreflex modulations for heart rate and for MSNA differ during sleep.

Adult↗

[Skin sympathetic nerve activity in amyotrophic lateral sclerosis].

Skin sympathetic nerve activity (SSNA) was microneurographically analyzed in five patients with amyotrophic lateral sclerosis (ALS) (four men, one woman; age ranges between 36 and 68 years) and 16 age- and sex-matched controls. The duration of illness after the onset was ranged between 1 and 3 years. Three cases were the common form of ALS showing a moderate to severe involvement of the upper extremities and mild degree of bulbar signs. Two were the pseudopolyneuritic form with lower motor neuron sign predominant in the legs. All these patients could walk by alone and did not show any respiratory distress. SSNA was recorded directly by inserting a tungsten microelectrode into the tibial nerve at the popliteal fossa as described before. The sweat rate and skin blood flow on the area innervated by the tibial nerve were also monitored. Resting activity of the SSNA (bursts/minute) was significantly higher (p < 0.05) in patients with ALS as compared with the controls. The rate of increase in SSNA under the load of mental arithmetic, tone, electric stimulation of the median nerve and immersion of the hand into cold water were only slightly higher in ALS. The rate of increase in SSNA response by these stimuli against the basal SSNA, however, was not significant. These results indicate that skin sympathetic nerve functions are hyperactive in ALS particularly in the basal resting level, though the underlying mechanism is unclear.

Adult↗

Assessment of sympathetic nerve activity controlling blood pressure in the elderly using head-up tilt.

In order to assess age-related changes in sympathetic nerve activity controlling blood pressure, we recorded muscle sympathetic nerve activity, blood pressure, and heart rate during head-up tilt in 10 healthy elderly (69-75 years) and 16 healthy young (19-23 years) subjects. The elderly had significantly lower responsiveness of muscle sympathetic nerve activity to postural change than did the young subjects. In the elderly, marked rise in blood pressure without increase in muscle sympathetic nerve activity was observed in nearly upright position during head-up tilt, whereas this phenomenon was not observed in the young. We conclude that neural control function of blood pressure during head-up tilt in the elderly differs from that in the young, which may be due to age-related change in baroreflex function.

Adrenergic Fibers↗

Muscle sympathetic outflow in Buerger's disease.

One of the pathophysiological features in Buerger's disease, i.e. thromboangiitis obliterans (TAO), contains a sympathetic contribution which relates to vasospastic phenomenon. The purpose of this study is to clarify sympathetic mechanisms in TAO. Muscle sympathetic nerve activity (MSA) was recorded using a microneurographic technique in patients suffering from TAO. The cold pressor test (by immersing the hand of the subject into ice cold water) was used as a test to examine the sympathetic responsiveness to local cold stimulus. The basal level of the MSA in the TAO group was lower than that in the control group (control group vs. TAO group: 39.8 +/- 12.8 bursts/min vs. 26.1 +/- 12.1 bursts/min in burst rate, P < 0.05, 61.8 +/- 8.3 bursts/100 heart beats vs. 39.5 +/- 22.3 bursts/100 heartbeats in burst incidence, P < 0.05). The responsiveness of MSA to the cold pressor test in the TAO group was higher than that in the control group (TAO group vs. control group: 385 +/- 191% total MSA vs. 198 +/- 156% total MSA, P < 0.05). We directly demonstrated higher responsiveness of MSA to the local cold stimulus in patients with TAO. This hyperresponsive MSA might contribute to the pathophysiologic feature in TAO.

Adult↗

A mild case of nesidioblastosis with diagnostic and therapeutic difficulty.

A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia.

Combined Modality Therapy↗

Skin sympathetic nerve activity in acquired idiopathic generalized anhidrosis.

We recorded skin sympathetic nerve activity (SSNA) microneurographically from the right tibial nerve of a patient with acquired idiopathic generalized anhidrosis (AIGA). The patient did not show any spontaneous sweating or pilocarpine- and nicotine-induced sweat response. Histopathologic examination showed degenerated eccrine glands associated with surrounding inflammatory cellular infiltration. Electrical nerve stimulation produced a two-peak pattern of SSNA reflex discharge representing sudomotor and vasoconstrictor components. The frequency of spontaneous SSNA bursts (burst rate), presumably of a sudomotor nature, at the ambient temperature of 25 degrees C was significantly higher than in a healthy control subject and was further increased at a temperature of over 38 degrees C. Thus, sudomotor sympathetic nerve activity is well preserved or even increased in AIGA. We conclude that anhidrosis of AIGA results from the generalized sweat gland dysfunction rather than decreased sympathetic outflow to the skin.

Adult↗

Role of the sympathetic nervous system in the generation of one-minute wave in body fluid volume during upright standing.

In clarifying the role of sympathetic nerve outflow to the muscles in the genesis of one-minute waves in body fluid volume, power spectral analysis of muscle sympathetic nerve activity (MSNA) was performed. MSNA was recorded by microneurography in an upright standing position simultaneously with the measurements of body circumference, venous pressure at the dorsum pedis veins, intrathoracic fluid volume, soleus EMG, and calf fluid volume. Subjects were seven healthy male volunteers aged 18 to 32 years. Spectral analysis revealed the one-minute oscillation in MSNA as well as in other variables. Cross spectral analysis between the soleus EMG and each variable revealed a phase order of the one-minute oscillations. It was as follows: 1) an increase in calf fluid volume; 2) a decrease in intrathoracic fluid volume; 3) an increase in venous pressure at the dorsum pedis veins; 4) an increase in the soleus EMG activation; 5) an activation of MSNA; 6) a decrease in calf fluid volume; and 7) an increase in intrathoracic fluid volume. It is concluded that sympathetic nerve activity as well as cardiovascular variables have a cyclic rhythm with a duration of one minute to maintain hemodynamic homeostasis in humans in an upright standing position.

Adolescent↗

Cardiovascular function in the elderly during water immersion.

In attempting to clarify the effects of aging on the regulatory functions of the cardiovascular system, we measured blood pressure, heart rate and stroke volume during thermoneutral head-out water immersion in seven healthy elderly and eight healthy young subjects. In the young subjects water immersion resulted in a marked increase in stroke volume, a deceleration of the heart rate and stable blood pressure values. In the elderly group the blood pressure increased significantly during shoulder-level water immersion. Compared to the young subjects, the elderly presented a less pronounced elevation of the stroke volume, and no change in the heart rate. These results indicate that the vasodepressive mechanisms regulated by baroreflexes diminish with aging, resulting in an elevation of blood pressure.

Adult↗

Effect of metoclopramide on muscle sympathetic nerve activity in humans.

For determining the effect of the activation of the central cholinergic system on the sympathetic nervous system, we measured muscle sympathetic nerve activity (MSNA) together with heart rate and blood pressure before and after an intravenous injection of metoclopramide. Immediately after metoclopramide injection, short-term increases in MSNA and heart rate followed a transient decrease in blood pressure, suggesting that increased sympathetic nerve activity may result from the unloading of arterial baroreceptors. Approximately 7 min after injection, MSNA and heart rate were again notably increased, followed by an increase in blood pressure. This late increase in MSNA may result from central activation of the sympathetic nervous system, but not as a result of the unloading of arterial baroreceptors. The results of this study suggest that metoclopramide activates the sympathetic nervous system by mediating the central cholinergic system in humans.

Adult↗

Effect of L-dopa on human muscle sympathetic nerve activity.

This study was undertaken to clarify the mechanism of orthostatic hypotension, one of the side effects frequently encountered after administration of levodopa (L-dopa). Muscle sympathetic nerve activity (MSNA) was measured concomitantly with blood pressure (BP), heart rate (HR) and calf blood flow (calf BF). The responses of these variables to head-up tilting (HUT) were analyzed before and after intravenous administration of L-dopa (50 mg) in eight healthy subjects. L-dopa induced significant increases in MSNA, with concomitant decreases in BP and no changes in calf BF in the supine position. At each angle of HUT, both MSNA and the calf BF increased, following administration of L-dopa. The pattern of MSNA changes was dissociated from that of the calf BF under the influence of L-dopa. These results suggest that peripheral, rather than central, mechanisms are involved in L-dopa-induced orthostatic hypotension.

Adult↗

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activity in humans.

To clarify the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine (NE), the effect of this drug on microneurographically recorded muscle sympathetic nerve activity (MSA) from the tibial nerve was analyzed in ten healthy male volunteers. A single dose of 600 mg of L-threo-DOPS was orally administered and the effect of this norepinephrine precursor on MSA at resting and at upright standing positions, as well as the MSA responsiveness to head-up tilting was examined by comparing the data obtained after administration of the drug with those obtained under control conditions. The plasma NE levels were determined in two subjects. The results were as follows: (1) resting MSA increased significantly 80 min after administration of L-threo-DOPS and was accompanied by an increase in plasma NE levels; (2) standing MSA when treated with the drug was not significantly different from values obtained under control conditions; and (3) MSA responsiveness to orthostasis was reduced after L-threo-DOPS. We conclude from the activation of MSA by L-threo-DOPS that this drug raised blood pressure not only through an increase in metabolized plasma NE levels, but also through the enhancement of MSA by activation of descending noradrenergic or adrenergic pathways proximal to the recording site of the sympathetic discharge.

Adult↗

Enhanced muscle sympathetic nerve activity during sleep apnea in the elderly.

To examine how muscle sympathetic nerve activity (MSNA) becomes modified during sleep apnea in the elderly, we analyzed polysomnographic recording simultaneously with microneurographically recorded MSNA. Subjects were three healthy elderly males aged 72, 75, and 76. MSNA was suppressed with deeper non-REM sleep stages in these elderly subjects. In all three subjects, sleep apnea for 10 s or longer was observed during sleep of 00:00-06:00. During sleep apnea, MSNA was enhanced concomitantly with a blood pressure fall and a reduction in saturation rate of oxyhemoglobin. With the termination of sleep apnea, MSNA was maximally enhanced with a transient elevation of blood pressure. We conclude that sleep apnea induces an enhancement of MSNA, which may be responsible for hypertensive episodes during sleep.

Aged↗

Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test.

We measured muscle sympathetic nerve activity (MSA) to clarify the mechanisms of the blood pressure rise during cold pressor test (CPT), simultaneously with impedance cardiography and blood pressure wave measurement in 10 healthy subjects. MSA remained unchanged during the initial period of 0-30s of the CPT and increased remarkably during the later period of 30-90s of the CPT, while cardiac output exhibited a slight increase during the initial period but not during the later period. Mean blood pressure increased significantly throughout the entire period of CPT and reached the maximal level during 90-120s of the CPT. The mean blood pressure and total peripheral resistance during the CPT showed a linear correlation with MSA. In conclusion, an increase of cardiac output elevates blood pressure at the initial period of the CPT with little increase in MSA, while an increase of MSA plays an essential role to elevate the blood pressure at the later period of the CPT.

Adult↗

[Laser-Doppler flowmetry].

Laser-Doppler flowmetry (LDF) is a non-invasive technique for measuring the tissue blood flow. It has been shown in the skin that LDF discloses blood flow fluctuations due to vasomotor nerve activity. LDF can give measurements of blood flow at various sites of different tissue. Furthermore, LDF may enable selective measurement of blood flow at different depths within the tissue, when the device and the probe are appropriately chosen. Thus, LDF is available for examining vasomotor responses at various tissue sites. For clinical application, a method for calibrating the LDF signal in absolute units should be established.

Autonomic Nervous System Diseases↗

Involvement of a nuclear factor-kappa B-like protein in induction of the macrophage colony-stimulating factor gene by tumor necrosis factor.

The macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes. Previous studies have demonstrated that tumor necrosis factor (TNF) induces transcription of the M-CSF gene in human myeloid cells. The present work examined the effects of TNF on cis-acting elements in the M-CSF promoter. Deleted forms of the M-CSF promoter were linked to the chloramphenicol acetyltransferase (CAT) gene and transfected by electroporation into HL-60 promyelocytic leukemia cells. The results demonstrate that an enhancer responsive to TNF stimulation is located between positions -406 and -344 upstream to the transcription start site. The fragment from positions -419 to -304 was cloned 5' to the heterologous thymidine kinase (TK) promoter and linked to the CAT gene. Both orientations of this fragment enhanced TK-promoter activity in TNF-treated HL-60 cells. The results of gel mobility shift assays with the -419 to -304 fragment demonstrate binding of a constitutive nuclear protein. A TNF-inducible protein also bound to this fragment and resulted in a different mobility pattern. Binding of the TNF-induced nuclear protein to the -419 to -304 fragment was inhibited by an oligonucleotide containing the nuclear factor-kappa B (NF-kappa B) consensus sequence. DNA footprinting demonstrated protection of an NF-kappa B binding site at positions -377 to -368. Methylation interference assays showed that the TNF-induced protein made contact points with guanine residues in the same NF-kappa B sequence. Taken together, the findings provide evidence for involvement of an NF-kappa B-like factor in transcriptional regulation of the M-CSF gene.

Base Sequence↗

Neural and humoral controlling mechanisms of cardiovascular functions in man under weightlessness simulated by water immersion.

To clarify how neural and humoral mechanisms operate to control cardiovascular functions in man under weightlessness, the response of sympathetic nerve activity was observed in healthy human subjects by means of microneurographic technique with the changes of several hemodynamic parameters and hormonal responses during thermoneural head-out water immersion. Muscle sympathetic nerve activity was markedly suppressed by head-out immersion, concomitantly with a reduction of the leg volume, an increase of the stroke volume and a reduction of total peripheral resistance. At the same time, plasma level of norepinephrine, vasopressive and antidiuretic hormones (ADH, aldosterone, renin activity, angiotensin I-II) were reduced, while vasodepressive and diuretic hormone (ANP) was markedly increased. The systemic blood pressure was maintained almost unchanged during head-out water immersion. The suppressive response of sympathetic nerve activity seemed to be age-dependent. This response was less prominent in the elderly than in young subjects. It is concluded that the suppressive response of muscle sympathetic activity plays an important role to maintain hemodynamic homeostasis under weightlessness to compensate for the cephalad fluid shift and the resultant increase of the stroke volume in cooperation with the hormonal responses.

Adolescent↗

Telescience testbed in human space physiology.

The present telescience testbed study was conducted to evaluate the feasibility of physiological experimentation under restricted conditions such as during simulated weightlessness induced by using a water immersion facility, a reduced capacity of laboratory facilities, a delay and desynchronization of communication between investigator and operator, restrictions of different kinds of experiments practiced by only one operator following a limited time line and so on. The three day's experiments were carried out following the same protocols. The operators were changed every day, but was the same the first and the third day. The operators were both medical doctors but not all round experts in the physiological experimentation. The experimental objectives were: 1) ECG changes by changing water immersion levels, 2) blood pressure changes, 3) ultrasonic Echo-cardiographic changes, 4) laser Doppler skin blood flowmetry in a finger, 5) blood sampling to examine blood electrolytic and humoral changes. The effectiveness of the testbed experiment was assessed by evaluating the quality of the obtained data and estimating the friendliness of the operation of the telescience to investigators and operators.

Aerospace Medicine↗

Long-acting alpha 1-adrenoceptive sympathomimetic agent suppresses sympathetic outflow to muscles in humans.

To clarify the effect of a long-acting selective alpha 1-adrenoceptive sympathomimetic agent on sympathetic outflow to muscles (muscle sympathetic activity, MSA) in humans, 5 mg of midodrine hydrochloride was injected intravenously in ten healthy male subjects aged 19-25. Spontaneous MSA was significantly suppressed as well as plasma norepinephrine level without changing heart rate, or systemic blood pressure. The suppression continued for more than 90 min, and this is supposed to be due to negative feedback action on the baroreflex loop. The absence of significant changes in heart rate or systemic blood pressure in healthy subjects suggests that hemodynamic homeostasis is maintained by reducing the MSA in response to a long-acting sympathomimetic agent, like midodrine hydrochloride, which constricts peripheral vessels directly.

Adrenergic alpha-Agonists↗