Respiration physiology最新文献

Overall inhomogeneity of ventilation distribution, as measured by single-breath vital capacity (VC) washout (SBW) is known to be greater supine vs. standing. To establish the underlying mechanisms 13 healthy males performed VC SBW of 4% SF₆ and He, standing and supine, with or without a 10 sec breathhold (BH). Overall inhomogeneity, as indicated by normalized phase III slopes, was >50% greater supine (SF₆ 13.1×10⁻³; He 10.7×10⁻³ L⁻¹) than standing (SF₆ 8.6×10⁻³; He 6.4×10⁻³ L⁻¹; P<0.001). The (SF₆–He) slope, an index of intraacinar inhomogeneity, did not change with posture. Breathholding, assumed to eliminate convective dependent inhomogeneity within and/or between small lung units, produced twice as great reduction of inhomogeneity when supine vs. standing. After BH inhomogeneity remained significantly greater supine vs. standing. In conclusion, at least two events seem to underlie the increased inhomogeneity when supine: (1) a substantially increased convection dependent non-uniformity between well-separated lung regions; and (2) a somewhat increased convection dependent non-uniformity within and/or between peripherally located lung units.

Nitric oxide (NO) has important functions in the regulation of pulmonary smooth muscle tone. In the human lung, published data on the expression and distribution of neuronal nitric oxide synthase (NOS-I) are contradictory. The aim of this study, therefore, was to determine the predominant cells expressing NOS-I in the human lung. Immunofluorescence double staining techniques were applied to normal human lung tissue using established monospecific antibodies directed against NOS-I. Suprisingly, capillary endothelial cells in the alveolar septa were identified as the major sites of NOS-I expression. Neither alveolar nor bronchiolar epithelium, nor the alveolar macrophages, expressed NOS-I. These results indicate that the predominant sites of NOS-I expression in the human lung are confined to non-neuronal, i.e. capillary endothelial cells and suggest a role for NO in the regulation of pulmonary endothelial cell permeability.

In vivo, the augmenting pattern of integrated phrenic nerve discharge of eupnea is altered to the decrementing pattern of gasping in severe hypoxia or ischaemia. Identical alterations in phrenic discharge are found in perfused in situ preparations of the juvenile rat. In this preparation, gasping was produced by equilibration of the perfusate with various levels of carbon dioxide and oxygen. The duration of the phrenic burst, the interval between bursts and the burst amplitude were not significantly different following equilibration with 21–6%O₂ at 5% CO₂ or with 0–9% CO₂ at 6% O₂, with the exception that the burst amplitude was significantly greater in hypercapnic-hypoxia (9% CO₂ at 6% O₂). It is proposed that hypoxia-induced gasping results from the release of an endogenous pacemaker activity of rostral medullary neurons. This release is caused by cellular mechanisms that change the balance between membrane ionic currents. Moreover, these cellular mechanisms may be explicitly induced by alterations in the ionic and metabolic homeostasis.

A canine model of exercise-induced asthma was used to test the hypothesis that the development of a late phase response to hyperventilation depends on the acute production of pro-inflammatory mediators. Peripheral airway resistance, reactivity to hypocapnia and aerosol histamine, and bronchoalveolar lavage fluid (BALF) cell and eicosanoid content were measured in dogs ∼5 h after dry air challenge (DAC). DAC resulted in late phase obstruction, hyperreactivity to histamine, and neutrophilic inflammation. Both cyclooxygenase and lipoxygenase inhibitors administered in separate experiments attenuated the late phase airway obstruction and hyperreactivity to histamine. Neither drug affected the late phase inflammation nor the concentrations of eicosanoids in the BALF obtained 5 h after DAC. This study confirms that hyperventilation of peripheral airways with unconditioned air causes late phase neutrophilia, airway obstruction, and hyperreactivity. The late phase changes in airway mechanics are related to the hyperventilation-induced release of both prostaglandins and leukotrienes, and appear to be independent of the late phase infiltration of inflammatory cells.

We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne–Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P_CO2 with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P_CO2 over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness changes, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep.

Amphibians and reptiles possess CO₂-sensitive olfactory receptors that cause a dose-dependent decrease in breathing when stimulated by CO₂ concentrations ranging from 0.5 to 8%. In amphibians, it has been shown that inhibition of the enzyme, carbonic anhydrase (CA), attenuates the response of CO₂-sensitive olfactory receptors to transient changes in nasal CO₂. Histology and electrophysiology studies in frogs show that identification of sites of CA activity can serve as markers for locations of CO₂ chemosensitivity in the olfactory epithelium. There is also growing evidence that CO₂ receptors may be present in the olfactory epithelium of mammals. The objectives of this review are to, (1) summarize the current state of knowledge of olfactory CO₂ receptors in amphibians, reptiles, and mammals; (2) present results from an experiment designed to determine the distribution and density of CA activity within the rat nasal cavity; (3) show results from an experiment that recorded the olfactory receptor response to CO₂ in areas of the rat nasal cavity exhibiting the highest densities of CA activity; and (4) discuss the presumed role of the olfactory CO₂ receptors in the control of breathing and in abnormalities of breathing, such as sudden infant death syndrome (SIDS).

The objectives of this paper are: (1) to review advances in our understanding of the mechanisms of respiratory plasticity elicited by episodic versus continuous hypoxia in short to intermediate time domains (min to h); and (2) to present new data suggesting that different patterns of hypercapnia also elicit distinct forms of respiratory plasticity. Episodic, but not continuous hypoxia elicits long-term facilitation (LTF) of respiratory motor output. Phrenic LTF is a serotonin-dependent central neural mechanism that requires: (a) activation of spinal serotonin receptors; and (b) spinal protein synthesis. Continuous and episodic hypercapnia also elicit different mechanisms of plasticity. Continuous, severe hypercapnia (25 min of ∼10% inspired CO₂) elicits long-term depression (LTD) of phrenic motor output (−33±8% at 60 min post-hypercapnia) in anesthetized rats. In contrast, 3, 5 min hypercapnic episodes do not elicit LTD (9±17% at 60 min). We hypothesize that the response of respiratory motoneurons to serotonergic and noradrenergic modulation may contribute to pattern sensitivity to hypoxia and hypercapnia.

The brain is a major energy consumer and dependent on carbohydrate and oxygen supply. Electrical and synaptic activity of neurons can only be sustained given sufficient availability of ATP. Glial cells, which have long been assigned trophic functions, seem to play a pivotal role in meeting the energy requirements of active neurons. Under conditions of high neuronal activity, a number of glial functions, such as the maintenance of ion homeostasis, neurotransmitter clearance from synaptic domains, the supply of energetic compounds and calcium signalling, are challenged. In the vertebrate brain, astrocytes may increase glucose utilization and release lactate, which is taken up and consumed by neurons to generate ATP by oxidative metabolism. The CO₂ produced is processed primarily in astrocytes, which display the major activity of carboanhydrase in the brain. Protons and bicarbonate in turn may contribute to drive acid/base-coupled transporters. In the present article a scenario is discussed which couples the transfer of energy and the conversion of CO₂ with the high-affinity glutamate uptake and other transport processes at glial and neuronal cell membranes. The transporters can be linked to glial signalling and may cooperate with each other at the cellular level. This could save energy, and would render energy exchange processes between glial cells and neurons more effective. Functions implications and physiological responses, in particular in chemosensitive brain areas, are discussed.