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Biomedical subjects

I Homma

Publications and source records attributed to I Homma.

At least 37 records · Page 2Linked to original sources

Vasopressin neuron activation and Fos expression by stimulation of the caudal ventrolateral medulla.

The present study demonstrates that projections ascending from the caudal ventrolateral medulla have direct effects on the expression of the immediate early gene c-fos and of the arginine-vasopressin gene in neurosecretory cells of the hypothalamic supraoptic nucleus. Intense Fos-like immunoreactivity (Fos-LI) was observed in many magnocellular neurons of the supraoptic nucleus after electrical stimulation of the caudal ventrolateral medulla. In sham-operated rats, Fos-LI was absent or present in very few magnocellular neurons in the supraoptic nucleus. Fos-LI was visible in neurons expressing arginine-vasopressin, and was seen rarely in oxytocin neurons by double-immunostaining method. This study showed that 76% of all Fos-positive cells were arginine-vasopressin immunoreactive, whereas only 4% of them showed oxytocin immunoreactivity in the supraoptic nucleus. With in situ hybridization, a high level of arginine-vasopressin mRNA was noted in the supraoptic nucleus 3 h after stimulation of the caudal ventrolateral medulla; the expression was highest 6 h after the stimulation compared with the same region in sham-operated animals. These findings suggest that noradrenaline, released from the axon terminals originating from the caudal ventrolateral medulla, may participate in the regulation of gene transcription of arginine-vasopressin in response to physiological stimuli.

Afferent Pathways↗

Possible synaptic connections of expiratory neurons in the medulla of newborn rat in vitro.

To elucidate synaptic interactions between expiratory (Exp) and other respiratory neurons in the ventrolateral medulla of brain stem-spinal cord preparations from newborn rats, we analyzed postsynaptic potentials in Exp and a subclass of inspiratory (Insp) neurons using whole-cell recordings. About 72% of the Exp neurons (Exp-p-i) showed Cl--dependent synaptic inhibition during the Insp and pre/post-Insp phases, corresponding to the active phase of the Insp and pre-inspiratory (Pre-I) neurons, respectively. The other 28% neurons (Exp-i) received Cl--dependent inhibition during the Insp phase only. Some Insp neurons showed reversed IPSPs during the active phase of Exp-p-i after Cl-loading. We suggest the existence of inhibitory connections from Pre-I and Insp to Exp and from Exp to Insp neurons. Basic synaptic connections among respiratory neurons similar to those in intact adult mammals may already exist in newborn rats.

Animals↗

The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat.

We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED50=0.5 microM) on the respiratory rhythm was stronger than NA (ED50=5 microM). The adrenaline respiratory rhythm depression was partially blocked by the alpha1-antagonist prazosin or by the alpha2-antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the alpha1-antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or depressed (n=5 of 39) by adrenaline, and excited by alpha1-agonist phenylephrine or depressed by alpha2-agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA(A)-antagonists bicuculline or picrotoxin, but not by the GABA(B)-antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through alpha-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via alpha1-receptors and inhibition via alpha2-receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA(A)ergic neurons.

Adrenergic alpha-Agonists↗

Modulation of respiratory rhythm by 5-HT in the brainstem-spinal cord preparation from newborn rat.

Effects of 5-hydroxytryptamine (5-HT) on inspiration-related nerve activity and membrane potential of respiratory neurons in the ventrolateral medulla were studied in brainstem-spinal cord preparations isolated from newborn rats. Bath application of 5-100 microM 5-HT induced a biphasic response in inspiratory nerve activity: a transient increase in respiratory frequency followed by a decrease in the rate of discharge. The excitatory effect of 5-HT was particularly prominent in preparations with a respiratory rate of less than 3 min-1, whereas the inhibitory effect was more pronounced in preparations with a higher respiratory rate. In pre-inspiratory (Pre-I) and inspiratory (Insp) neurons, 20 microM 5-HT induced a membrane depolarization of up to 10 mV accompanied by a significant decrease in the input resistance. Membrane depolarization by 5-HT was also evident in the presence of tetrodotoxin. In Pre-I neurons, 5-HT caused an increase in the burst rate, which was followed by a decrease in the intraburst firing frequency and burst amplitude, although the burst rate remained high. The burst rate in Insp neurons first increased and subsequently decreased without significant change in the intraburst firing frequency. Simultaneous intra- and extracellular recordings (in the contralateral medulla) of Pre-I/Pre-I neuron or Pre-I/Insp neuron pairs revealed that 5-HT disturbed the correlation between these neuron bursts. Increase in the respiratory rate induced by 20 microM 5-HT was completely blocked by pretreatment (5-15 min) with 5 microM ketanserin or 1 microM methysergide, but not by 10 microM propranolol. None of these antagonists blocked the inhibitory effects of 5-HT. A 5-HT2 agonist, 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10-100 microM) increased the respiratory rate. Perfusion with a 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT, 20-100 microM) induced an increase or a decrease in the respiratory rate. A 5-HT2C agonist, 1-(3-chlorophenyl)piperazine (m-CPP, 2-10 microM) induced an initial decrease in the respiratory rate followed by a further long- lasting decrease. Burst activity of Pre-I neurons was suppressed upon administration of 10 microM m-CPP and enhanced with 20 microM DOI. The results suggest that changes in the bursting properties of Pre-I and Insp neurons induced by 5-HT lead to modulation of the respiratory network, thus causing biphasic modulation of the respiratory rhythm. In addition to effects via 5-HT1A receptors, activation of 5-HT2A and 5-HT2C receptor subtypes might be involved in excitatory effects and inhibitory effects of 5-HT respectively.

Animals↗

Autoregulation of histamine release in medulla oblongata via H3-receptors in rabbits.

The release of histamine (HA) from the rostral ventrolateral medulla (RVL), the raphe nuclei (nR), and the solitary nucleus (nTS) was investigated in anesthetized rabbits using microdialysis and high-performance liquid chromatography. HA release upon electrical stimulation of the posterior hypothalamus (PH), where histaminergic cell bodies are located, was increased to 168% of the baseline level in the RVL (n = 6), 139% of the baseline level in the nR (n = 5), and 166% of the baseline level in the nTS (n = 4). Upon perfusion of thioperamide, an H3-receptor antagonist, via a microdialysis probe, HA release from the RVL, nR and nTS increased. The increase in HA release from the RVL, nR and nTS following thioperamide perfusion was suppressed by co-perfusion of thioperamide and an H3-receptor agonist, imetit. We found that HA is released from the RVL, nR and nTS, that the HA release from all three areas is increased upon stimulation of the PH, and that the HA release is locally influenced in opposite directions by thioperamide and imetit. These results suggest that HA release in the medulla oblongata is controlled by the PH and that H3-receptors participate in the autoregulation of HA release by providing negative feedback locally. Autoregulation of HA release via H3-receptors may be important for maintaining tonic output to the sympathetic nervous system.

Animals↗

Benefit of in-phase chest wall vibration on the pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Chest wall vibration of contracting intercostal muscles (in-phase vibration, (IPV)) improves O2 saturation in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the effect of IPV on the pulmonary hemodynamics in patients with COPD. METHODOLOGY: Twelve patients with COPD (FEV1%, 43.7 +/- 14.4%) underwent pulmonary artery catheterization in the supine position; hemodynamic variables as well as arterial and mixed venous gas tension were measured at baseline and after 15 min of IPV with IPV continued during the measurement. RESULTS: Mean pulmonary arterial pressure (Ppa, 21.3 +/- 5.0-19.1 +/- 4.8 mmHg and pulmonary vascular resistance (PVR, 294.6 +/- 196.0-228.5 +/- 101.7 dyne.sec.cm-5) decreased significantly, but there was no change in heart rate, cardiac index or systemic blood pressure. PaO2 increased (66.5 +/- 10.3-70.0 +/- 9.7 Torr) and PaCO2 decreased (46.6 +/- 8.9-45.0 +/- 10.1 Torr) significantly. Minute ventilation and tidal volume increased significantly in five out of the eight patients in whom ventilation was monitored throughout the study. CONCLUSION: IPV improves gas exchange and pulmonary circulation without affecting systemic circulation.

Aged↗

Effects of chest wall vibration on breathlessness during hypercapnic ventilatory response.

Vibratory stimulation applied to the chest wall during inspiration reduces the intensity of breathlessness, whereas the same stimulation during expiration has no effect or may increase breathlessness. The purpose of the present study was to determine whether vibration reduced the intensity of breathlessness during progressive hypercapnia with and without the addition of an external resistive load. A second objective was to see whether the mouth occlusion pressure at 0.2 s (P0.2) was reduced by the vibratory stimulation. Hypercapnic ventilatory response was conducted in 10 healthy male volunteers with simultaneous measurement of visual analog scale, P0.2, and minute ventilation. Hypercapnic ventilatory response was performed and randomly combined with or without vibratory stimulation (100 Hz) as well as with or without inspiratory load. With inspiratory load, in-phase vibration did not cause any significant changes in the slopes of P0.2 and minute ventilation to CO2, whereas the slope of visual analog scale to CO2 significantly decreased from 0.47 +/- 0.15 to 0.34 +/- 0.11 (SE) cm/Torr (P < 0.05). We conclude that in-phase vibration could decrease the slope of breathlessness elicited by inspiratory load combined with hypercapnia without changing motor output.

Adult↗

In-phase chest wall vibration decreases dyspnea during arm elevation in chronic obstructive pulmonary disease patients.

In-phase chest wall vibration (IPV) is known to decrease dyspnea in patients with chronic obstructive pulmonary disease (COPD) at rest and during leg exercise. In the present study, the effects of IPV (100 Hz) on dyspnea and arm fatigue during upper extremity activity were studied in 9 patients with COPD (mean FEV1, 0.95 l). Dyspnea and arm fatigue (modified Borg scale) and ventilatory variables were measured during arm elevation (AE) with weights lifted straight above the head with and without IPV. Mean dyspnea during AE was 3.3 without IPV and 2.1 with IPV (p<0.05), but, arm fatigue, oxygen saturation and end-tidal FCO2 were not affected by IPV. Minute ventilation during AE was significantly increased with IPV in 5 of 9 patients. The results suggest that IPV decreases dyspnea during AE.

Afferent Pathways↗

Anxiety and respiratory patterns: their relationship during mental stress and physical load.

In the present study we investigated the effect of mental stress on respiration using unpleasant sounds. To compare the center output of each stimuli, subjects took part in one session divided into two phases: a mental stress test and a physical loading test. The purpose of this study was not only to investigate ventilatory response in emotions caused by mental stress and physical load, but also to determine the relationship between respiratory pattern and personality. Ten normal subjects were measured for VE (minute ventilation), VT (tidal volume), RR (respiratory rate), Vo2 (O2 consumption), Vco2 (CO2 production) and FETco2 (end-tidal CO2 concentration) on a breath-by-breath basis; the subjects were given Spielberger's State Trait Anxiety Inventory (STAI) before beginning this experiment. Unpleasant emotions caused by mental stress altered the breathing pattern. VE increase was achieved by the combination of VT and RR disregarding the subjects' personality. However, subjects with high anxiety RR increased more than VT resulting in a positive correlation between the trait anxiety score and RR. We found that a dominant RR increase was observed not only in the mental stress test but also in the physical loading test. In the physical load, there was a positive correlation between the state anxiety score and RR. These results indicate that respiratory patterns are related to personality anxiety. These findings may provide important evidence relating respiratory function to psychological aspects.

Adult↗

Neuronal mechanisms of respiratory rhythm generation: an approach using in vitro preparation.

The respiratory network in the ventrolateral medulla of the brainstem-spinal cord preparation from newborn rat involves pre-inspiratory (Pre-I) neurons, three types of inspiratory (Insp I, II, III) neurons and two types of expiratory (Exp-i, Exp-p-i) neurons as major subtypes, which were classified according to patterns of postsynaptic potentials. The neuronal respiratory-related membrane potential fluctuations of these cells indicate at least four distinguishable phases of the in vitro respiratory cycle: pre-inspiratory, inspiratory, post-inspiratory (E1), and late-expiratory (E2). A current hypothesis for the central pattern generator of respiration proposed by our group is that Pre-I neurons in the rostral ventrolateral medulla, with intrinsic burster properties, produce the primary respiration rhythm. This rhythm triggers an inspiratory pattern generator composed of Insp neurons in the rostral and caudal ventrolateral medulla. Respiratory neurons possess several types of ionic channels which are involved in the generation of rhythm and burst pattern. Particularly, P-type Ca2+ channels and TTX-sensitive persistent Na+ channels are postulated to contribute to the intrinsic burst generation of Pre-I neurons. N-type Ca2+ channels may be involved in the maintenance and termination of inspiratory burst activity via the activation of Ca2(+)-dependent K+ channels. Respiratory neuron networks in this preparation were compared with those of different in vitro preparations, like rhythmic slices or perfused brainstems and of adult mammals in vivo. Many types of synaptic connections among respiratory neurons in adult mammals were also found in the (rostral) ventrolateral medulla of a brainstem-spinal cord preparation from newborn rat. The characteristics of the inspiratory burst pattern and inspiratory off switch mechanisms in newborn rat preparations might be explained by insufficient inhibitory (or excitatory) synaptic inputs to the inspiratory pattern generator due to an immature neuron network and/or deafferentiation.

Animals↗

Reconstruction of tonic vibration reflex in the biceps brachii reinnervated by transferred intercostal nerves in patients with brachial plexus injury.

The transfer of intercostal nerves to musculocutaneous nerves has been performed to reconstruct elbow flexion in patients with brachial plexus injury. In nine of 15 such patients, 2-3 Hz tapping of the distal tendon of the biceps muscle reinnervated by the transferred intercostal nerves (IC-biceps) induced a mode in the correlogram between tap and EMG pulse of IC-biceps. In five of the mode-positive patients, tapping of various frequencies induced gradual augmentation of integrated EMG of IC-biceps. This reflex was consistent with the tonic vibration reflex (TVR) in normal controls. Conduction velocity and frequency property of the reflex were compatible with the speculation that rapid-conducting muscle afferents (group Ia or II or both) reinnervate mechanoreceptors, such as muscle spindles. The clinical significance of muscle sensory reinnervation is not clear; however, the reconstruction of TVR following this operation is worthy in that it confirms the specific sensory reinnervation of denervated muscle in humans.

Adolescent↗

Optical imaging of respiratory burst activity in newborn rat medullary block preparations.

We report on the optical imaging of excitation propagation induced by electrical stimulation of the nucleus tractus solitarius (NTS) area and subsequent inspiratory burst activity in the ventrolateral medulla (VLM) of a medullary block preparation. A medullary block preparation with a thickness of 1.0-1.4 mm was made from brainstems isolated from 0- to 4-day-old rats and stained with a fluorescent voltage-sensitive dye, RH795. Neuronal responses in the VLM evoked by electrical stimulation were recorded as a fluorescence change using an optical recording apparatus with a 128 x 128 photodiode array and a maximum time resolution of 0.6 ms. Motoneuronal activity was simultaneously recorded at the contralateral hypoglossal nerve roots. Neuronal excitation evoked by stimulation of the NTS area propagated to the VLM through the intermediate reticular zone (IRt). In contrast, caudal VLM stimulation induced excitation which propagated to the rostral VLM without any detectable excitation propagation in the IRt toward the NTS area from the VLM. NTS stimulation also induced an inspiratory burst activity in the hypoglossal nerve root activity with a 150-200 ms delay. Fluorescence changes corresponding to the inspiratory burst activity were observed in the VLM which coincided with the area in which the localization of many respiratory neurons had been demonstrated in previous studies using whole-brainstem preparations. The present results show the feasibility of using optical recordings for the analysis of respiratory neuron activity as well as for analysis of the transmission pathway of afferent and/or efferent information in the medulla.

Animals↗

Vibration-induced finger flexion reflex and inhibitory effect of acupuncture on this reflex in cervical spinal cord injury patients.

The vibration-induced finger flexion reflex (VFR) and the inhibitory effect of acupuncture on this reflex were studied in five cervical spinal cord injury patients (C-SCIs). VFR, which is a tonic finger flexion reflex induced by vibratory stimulation on the finger tip, was induced before and after acupuncture was carried out on the same hand. A stainless steel needle was inserted to the Hoku point. As in healthy subjects, VFR was performed and it was significantly inhibited by acupuncture in the C-SCIs; mean maximum VFR was 204.2 +/- S.E. 68.6 g before and 119.8 +/- S.E. 42.2 g after acupuncture. The present results suggest that at least part of the reflex center for VFR is located in the spinal cord and that part of VFR inhibition by acupuncture may be mediated via the spinal cord.

Acupuncture Therapy↗

[Clinical effects of four weeks of respiratory muscle stretch gymnastics in patients with chronic obstructive pulmonary disease].

We developed a program of respiratory muscle stretch gymnastic (RMSG), and measured lung function, exercise capacity, dyspnea, and quality of life before and after 4 weeks of training with this program. Thirteen patients with chronic obstructive pulmonary disease (mean FEVi, 1.24 liters) began the program. They participated in three sessions of RMSG each day. Twelve patients completed all 4 weeks. RMSG significantly (p < 0.01) decreased functional residual capacity (from 4.19 +/- 1.27 to 3.88 +/- 1.03 liters), total lung capacity (from 5.98 +/- 1.35 to 5.66 +/- 1.20 liters), residual volume (from 3.29 +/- 1.16 to 2.89 +/- 0.89 liters), and residual volume as a percent of total lung capacity (from 53.9 +/- 11.2% to 50.6 +/- 9.74%). The distance walked in 6 min increased by an average of 43 +/- 30 meters (+ 15%, p < 0.01). Dyspnea after a 6-minute walk (measured with a 150-mm visual analog scale) decreased significantly (from 65.1 +/- 40.8 to 36.1 +/- 36.8, p < 0.05). Quality of life was measured with the Chronic Respiratory Disease Questionnaire of Guyatt, et al., and was found to have improved significantly. Respiratory muscle stretch gymnastics may be useful in pulmonary rehabilitation.

Aged↗

Posterior hypothalamic control of rabbit tracheal tension and involvement of central histaminergic neurons.

The hypothalamus is involved in the control of the cardiovascular system, but airway tone is less well defined. In the posterior hypothalamus, histaminergic neuronal cell bodies are located. Effects of electrical stimulation in the posterior hypothalamus on tracheal tension and the cardiovascular system were examined in anesthetized, paralyzed and artificially ventilated rabbits. Tracheal tension was determined from pressure exerted on a balloon inserted in the trachea and measured by a pressure transducer. Electrical stimulation of the posterior hypothalamus caused tracheal tension to decrease, arterial blood pressure to increase, and mild tachycardia followed by bradycardia. The tracheal tension decrease induced by posterior hypothalamic stimulation was not affected by atropine nor by transection of either the superior laryngeal nerve or the vagus nerve, but was depressed by adrenoceptor blockade. Tracheal tension decrease was also reduced by pyrilamine, a histamine H1-receptor antagonist, administered into the fourth ventricle, but was not affected by cimetidine, a histamine H2-receptor antagonist. The stimulation sites where these effects were evoked were interspersed among the loci of histamine immunoreactive cell bodies previously reported. Results suggest that posterior hypothalamic neurons decrease tracheal tension through the sympathetic nervous system, and involve the histaminergic neurons in this route.

Animals↗

Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats.

In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by "perforated" whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca2+ concentration was lowered to 0.2 mM and the Mg2+ concentration was increased to 5 mM. In low-Ca2+, high-Mg2+ solution (referred to here as "low Ca"), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5-12 mV in low Ca, at a rate of 12 +/- 6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonic-type neurons was 2.3 +/- 1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1-1 microM tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n = 3) were also silent with 1 microM TTX perfusion. Inspiratory neurons either became silent (n = 4) or fired tonically (n = 1) in low Ca. The present study by "perforated" whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.

Animals↗

Effect of acupuncture at the Hoku point on vibration-induced finger flexion reflex in man: comparison between press needle technique, electroacupuncture, and in-situ technique.

Effects of press needle technique (PN), electroacupuncture (EA), or in-situ technique (IS) on vibration-induced finger flexion reflex (VFR) were examined in 31 healthy adults. VFR, which is tonic finger flexion evoked by vibration applied to the finger tip, was induced by vibrating the volar side of the middle finger tip before and after acupuncture. Acupuncture was applied to the Hoku point on both sides. The three techniques, each studied on separate days, inhibited VFR and there was no significant difference in VFR inhibition among the three techniques (percentage of pre-acupuncture VFR was 71.5 +/- SE 2.2% after PN, 72.6 +/- SE 2.4% after EA, and 75.6 +/- SE 2.8% after IS). The results suggest that afferent signals from muscles contracting due to electrical stimulation had no significant effect on the reflex arcs of VFR; and that the intradermal stimulation by acupuncture played a significant role in VFR inhibition.

Acupuncture Therapy↗