LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in breath.
(9/2868)
Laser magnetic resonance spectroscopy (LMRS) is a sensitive and isotope-selective technique for determining low concentrations of gaseous free radicals with high time resolution. We used this technique to analyze the nitric oxide (NO) concentration profile while simultaneously measuring the flow and expired volume during several single breathing cycles. Eight healthy, nonallergic volunteers were investigated. An initial NO peak was found in all breathing cycles before the NO concentration dropped to a relatively stable plateau in the late phase of expiration. The nasal NO peak was significantly higher than the oral NO peak. The nasal NO plateau was always higher than the oral NO plateau. The height of the initial nasal and oral NO peak rose with increasing duration of breath hold, whereas the late expiratory NO plateau changed only little for either the nasal or the oral breathing cycles. Our findings demonstrate, in line with other reports using other techniques, that the nose is the primary source for NO within the airways. (+info)
Respiratory and cardiac modulation of single sympathetic vasoconstrictor and sudomotor neurones to human skin.
(10/2868)
1. The firing of single sympathetic neurones was recorded via tungsten microelectrodes in cutaneous fascicles of the peroneal nerve in awake humans. Studies were made of 17 vasoconstrictor neurones during cold-induced cutaneous vasoconstriction and eight sudomotor neurones during heat-induced sweating. Oligounitary recordings were obtained from 8 cutaneous vasconstrictor and 10 sudomotor sites. Skin blood flow was measured by laser Doppler flowmetry, and sweating by changes in skin electrical resistance within the innervation territory on the dorsum of the foot. 2. Perispike time histograms revealed respiratory modulation in 11 (65 %) vasoconstrictor and 4 (50 %) sudomotor neurones. After correcting for estimated conduction delays, the firing probability was higher in inspiration for both classes of neurone. Measured from the oligounitary recordings, the respiratory modulation indices were 67. 7 +/- 3.9 % for vasoconstrictor and 73.5 +/- 5.7 % for sudomotor neurones (means +/- s.e.m.). As previously found for sudomotor neurones, cardiac rhythmicity was expressed by 7 (41 %) vasoconstrictor neurones, 5 of which showed no significant coupling to respiration. Measured from the oligounitary records, the cardiac modulation of cutaneous vasoconstrictor activity was 58.6 +/- 4.9 %, compared with 74.4 +/- 6.4 % for sudomotor activity. 3. Both vasoconstrictor and sudomotor neurones displayed low average firing rates (0.53 and 0.62 Hz, respectively). The percentage of cardiac intervals in which units fired was 38 % and 35 %, respectively. Moreover, when considering only those cardiac intervals when a unit fired, vasoconstrictor and sudomotor neurones generated a single spike 66 % and 67 % of the time. Rarely were more than four spikes generated by a single neurone. 4. We conclude that human cutaneous vasoconstrictor and sudomotor neurones share several properties: both classes contain subpopulations that are modulated by respiration and/or the cardiac cycle. The data suggest that the intensity of a multi-unit burst of vasoconstrictor or sudomotor impulses is probably governed primarily by firing incidence and the recruitment of additional neurones, rather than by an increase in the number of spikes each unit contributes to a burst. (+info)
Selective potentiation of peripheral chemoreflex sensitivity in obstructive sleep apnea.
(11/2868)
BACKGROUND: The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Abnormalities in chemoreflex mechanisms may be implicated in increased cardiovascular stress in patients with obstructive sleep apnea (OSA). We tested the hypothesis that chemoreflex function is altered in patients with OSA. METHODS AND RESULTS: We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 16 untreated normotensive patients with OSA and 12 normal control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with OSA than in the control subjects (43+/-4 versus 21+/-3 bursts per minute; P<0. 001). During hypoxia, patients with OSA had greater increases in minute ventilation (5.8+/-0.8 versus 3.2+/-0.7 L/min; P=0.02), heart rate (10+/-1 versus 7+/-1 bpm; P=0.03), and mean arterial pressure (7+/-2 versus 0+/-2 mm Hg; P=0.001) than control subjects. Despite higher ventilation and blood pressure (both of which inhibit sympathetic activity) in OSA patients, the MSNA increase during hypoxia was similar in OSA patients and control subjects. When the sympathetic-inhibitory influence of breathing was eliminated by apnea during hypoxia, the increase in MSNA in OSA patients (106+/-20%) was greater than in control subjects (52+/-23%; P=0.04). Prolongation of R-R interval with apnea during hypoxia was also greater in OSA patients (24+/-6%) than in control subjects (7+/-5%) (P=0.04). Autonomic, ventilatory, and blood pressure responses to hypercapnia and the cold pressor test in OSA patients were not different from those observed in control subjects. CONCLUSIONS: OSA is associated with a selective potentiation of autonomic, hemodynamic, and ventilatory responses to peripheral chemoreceptor activation by hypoxia. (+info)
The rostral ventrolateral medulla mediates the sympathoactivation produced by chemical stimulation of the rat nasal mucosa.
(12/2868)
1. We sought to outline the brainstem circuit responsible for the increase in sympathetic tone caused by chemical stimulation of the nasal passages with ammonia vapour. Experiments were performed in alpha-chloralose-anaesthetized, paralysed and artificially ventilated rats. 2. Stimulation of the nasal mucosa increased splanchnic sympathetic nerve discharge (SND), elevated arterial blood pressure (ABP), raised heart rate slightly and inhibited phrenic nerve discharge. 3. Bilateral injections of the broad-spectrum excitatory amino acid receptor antagonist kynurenate (Kyn) into the rostral part of the ventrolateral medulla (RVLM; rostral C1 area) greatly reduced the effects of nasal mucosa stimulation on SND (-80 %). These injections had no effect on resting ABP, resting SND or the sympathetic baroreflex. 4. Bilateral injections of Kyn into the ventrolateral medulla at the level of the obex (caudal C1 area) or into the nucleus tractus solitarii (NTS) greatly attenuated the baroreflex and significantly increased the baseline levels of both SND and ABP. However they did not reduce the effect of nasal mucosa stimulation on SND. 5. Single-unit recordings were made from 39 putative sympathoexcitatory neurons within the rostral C1 area. Most neurons (24 of 39) were activated by nasal mucosa stimulation (+65.8 % rise in discharge rate). Responding neurons had a wide range of conduction velocities and included slow-conducting neurons identified previously as C1 cells. The remaining putative sympathoexcitatory neurons were either unaffected (n = 8 neurons) or inhibited (n = 7) during nasal stimulation. We also recorded from ten respiratory-related neurons, all of which were silenced by nasal stimulation. 6. In conclusion, the sympathoexcitatory response to nasal stimulation is largely due to activation of bulbospinal presympathetic neurons within the RVLM. We suggest that these neurons receive convergent and directionally opposite polysynaptic inputs from arterial baroreceptors and trigeminal afferents. These inputs are integrated within the rostral C1 area as opposed to the NTS or the caudal C1 area. (+info)
Inspiration-promoting vagal reflex under NMDA receptor blockade in anaesthetized rabbits.
(13/2868)
1. This study describes a novel vagal respiratory reflex in anaesthetized rabbits. In contrast to the well-known inspiratory (I) off-switching by vagal afferent excitation, this vagal reflex initiates and maintains the central I activity of phrenic nerve discharges in rabbits pre-treated with antagonists of N-methyl-D-aspartate-type excitatory amino acid receptors (NMDA-Rs). 2. Under NMDA-R blockade with either dizocilpine (0.025-0.3 mg kg-1), D-2-amino-5-phosphonopentanoic acid (AP5, 0.5-1 mg, i.c.v.) or ketamine (10 mg kg-1), vagal stimulation at low frequencies (5-40 Hz) during the I phase prevented or markedly delayed the spontaneous I termination. In contrast, stimulation of the same vagal afferent at the same intensity but at a higher frequency (100-160 Hz) during the I phase immediately terminated the I phase. 3. In non-vagotomized rabbits, maintaining the tidal volume at end-expiratory levels during the I phase prevented spontaneous I termination and maintained apneusis after NMDA-R blockade with dizocilpine. 4. Brief stimulation of vagal afferents at low frequency (5-40 Hz) during the expiratory (E) phase constantly initiated phrenic I discharge after NMDA-R block. 5. We conclude that low-frequency discharge of vagal pulmonary stretch receptor afferents, as when lung volume is near functional residual capacity, promotes central I activity under NMDA-R blockade. (+info)
Randomised controlled trial of aminophylline for severe acute asthma.
(14/2868)
OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment. (+info)
Prevalence of exercise induced bronchospasm in Kenyan school children: an urban-rural comparison.
(15/2868)
BACKGROUND: Higher rates of exercise induced bronchospasm (EIB) have been reported for urban than for rural African schoolchildren. The change from a traditional to a westernized lifestyle has been implicated. This study was undertaken to examine the impact of various features of urban living on the prevalence of EIB in Kenyan school children. METHODS: A total of 1226 children aged 8-17 years attending grade 4 at five randomly selected schools in Nairobi (urban) and five in Muranga district (rural) underwent an exercise challenge test. A respiratory health and home environment questionnaire was also administered to parents/guardians. This report is limited to 1071 children aged < or = 12 years. Prevalence rates of EIB for the two areas were compared and the differences analysed to model the respective contributions of personal characteristics, host and environmental factors implicated in childhood asthma. RESULTS: A fall in forced expiratory volume in one second (FEV1) after exercise of > or = 10% occurred in 22.9% of urban children and 13.2% of rural children (OR 1.96, 95% CI 1.41 to 2.71). The OR decreased to 1.65 (95% CI 1.10 to 2.47) after accounting for age, sex, and host factors (a family history of asthma and breast feeding for less than six months), and to 1.21 (95% CI 0.69 to 2.11) after further adjustment for environmental factors (parental education, use of biomass fuel and kerosene for cooking, and exposure to motor vehicle fumes). CONCLUSIONS: The EIB rates in this study are higher than any other reported for African children, even using more rigorous criteria for EIB. The study findings support a view which is gaining increasing credence that the increase in prevalence of childhood asthma associated with urbanisation is the consequence of various harmful environmental exposures acting on increasingly susceptible populations. (+info)
External thoracic restriction, respiratory sensation, and ventilation during exercise in men.
(16/2868)
Multiple factors may contribute to the dyspnea associated with restrictive ventilatory disease (RVD). Simple models that examine specific features of this problem are likely to provide insight into the mechanisms. Previous models of RVD utilizing elastic loads may not represent completely the impact on pulmonary and chest wall receptors derived from breathing at low thoracic volumes. The purpose of this study was to investigate the sensory consequences of breathing at low lung volumes induced by external thoracic restriction in an attempt to further elucidate the etiology of dyspnea in this setting. Ten men were studied, with and without an inelastic corset applied at residual volume (restriction resulted in mean reductions in vital capacity, functional residual capacity, residual volume, and forced expired volume in 1 s of 44, 31, 12.5, and 42%, respectively). During 10-min steady-state exercise tests (at a workload set to achieve approximately 65% maximum heart rate), restriction resulted in significant increases, compared with control, in minute ventilation (61 vs. 49 l/min), respiratory frequency (43 vs. 23 breaths/min), and visual analog scale measurements of respiratory discomfort (65 vs. 20 mm). Alveolar hyperventilation (end-tidal PCO2 = 39 vs. 44 Torr for control) and mild O2 desaturation (arterial blood O2 saturation = 93 vs. 95% for control) occurred. Hypoxemia, atelectasis, increased work and effort of breathing, or a decrease in the volume-related feedback from chest wall and/or lungs could be responsible for the increased dyspnea reported. External thoracic restriction provides a useful model to study mechanisms of dyspnea in RVD. (+info)