Respiration physiology最新文献

Avian intrapulmonary chemoreceptors (IPC) are neurons that sense lung P_CO2 and provide phasic feedback for the control of breathing in birds. To try to understand mechanisms of CO₂ transduction and intracellular pH regulation in IPC, the anion exchange inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) was used to block transmembrane Cl⁻/HCO₃⁻ transport. Single-unit IPC discharge rates were measured at steady intrapulmonary CO₂ levels and during step changes in CO₂ in 15 anesthetized, unidirectionally ventilated adult mallard ducks (Anas platyrhynchos). Measurements were repeated after giving 50, 100 and 200 μmol/kg cumulative i.v. dosages of DIDS. Mean IPC discharge rates at steady (tonic) P_CO2 levels were significantly increased by 100 and 200 μmol/kg DIDS, but not by 50 μmol/kg DIDS. Mean dynamic (phasic) IPC responses to CO₂ steps were not significantly affected by DIDS. Results indicate that the DIDS-sensitive Cl⁻/HCO₃⁻ membrane exchanger is involved with tonic CO₂ signal transduction in IPC. However, because some individual IPC were unaffected by DIDS, yet still altered their discharge rate with CO₂, additional mechanisms besides the Cl⁻/HCO₃⁻ exchange are probably required for CO₂ chemotransduction in IPC.

The present study was aimed at assessing laryngeal dynamics and their consequences during anoxic gasping in ketamine-sedated lambs. We first verified that the glottis was closed between gasps during anoxic gasping in seven chronically instrumented lambs, aged 11–15 days. Recording of glottal constrictor muscle electrical activity, subglottal pressure and lung volume, together with endoscopic observation, confirmed the presence of active glottal closure with maintenance of a high lung volume between gasps. Secondly, we tested whether maintenance of a high lung volume between gasps improved autoresuscitation efficiency. Six sedated lambs aged 8–11 days underwent two anoxic runs, including one with an open tracheostomy to prevent maintenance of a high lung volume. Access back to air was allowed for gasping. No significant difference was found in time to eupnea resumption, hemodynamic parameters or arterial blood gases. We conclude that a high lung volume is actively maintained by glottal closure between anoxic gasps in sedated lambs. Further studies are however needed to define the importance of laryngeal dynamics during gasping.

We determined the effects of chronic hypoxia on end-expiratory lung volume (EELV), end-expiratory diaphragmatic activity (DE) and ventilation ($\text{V}\text{̇}$E) in 27 intact (awake and anesthetized) and six carotid body-denervated (CBD; anesthetized) rats. Twenty-nine control animals were also studied. Recordings were made during hypoxia and normoxia before and after 2 or 3 weeks of hypoxia (+3 days of recovery from chronic hypoxia). In awake rats, 2 weeks of chronic hypoxia increased only normoxic $\text{V}\text{̇}$E, while 3 weeks of chronic hypoxia did not change $\text{V}\text{̇}$E or DE. In anesthetized intact rats, after both exposures, hypoxic and normoxic $\text{V}\text{̇}$E tended to decrease, DE did not change and hypoxic and normoxic EELV were enlarged. In CBD animals, 2 weeks of chronic hypoxia did not affect hypoxic $\text{V}\text{̇}$E but decreased normoxic ventilation and enlarged EELV similar to the intact animals. After 3 days of recovery in normoxia, all parameters except EELV were restored to prehypoxic values. Also, transition from hypoxia to normoxia induced parallel changes in EELV and DE while chronic hypoxia increased only EELV. Therefore, chronic normobaric hypoxia induced, (1) an increase in normoxic ventilation reflecting a process of acclimatization; (2) an enlargement of EELV that did not depend on changes in DE and carotid chemoreceptors.

Repeated hypercapnic exercise augments future exercise ventilatory responses, an effect termed long-term modulation. We hypothesized that serotonin depletion with p-chlorophenylalanine (PCPA, 100 mg  kg⁻¹ i.v.) would attenuate long-term modulation. Ventilation, CO₂ production and arterial blood gases were measured at rest and during exercise (4 km h⁻¹, 5% grade) in goats before and after training (14 hypercapnic exercise trials). Six post-training exercise trials were performed. Trials 1–3 and 4–6 were grouped for analysis (post-training 1 and 2, respectively). Without PCPA, training exaggerated the Pa_CO2 decrease from rest to exercise (pre-training: $\text{1.4±0.3}\text{mmHg}\text{;}$ post-training 1: $\text{3.1±0.3}\text{mmHg}\text{;}$ post-training 2: $\text{2.3±0.3}\text{mmHg}\text{; P<0.05),}$ indicative of long-term modulation. The Pa_CO2 decrease from rest to exercise was unaffected by training following PCPA (pre-training: $\text{1.4±0.1}\text{mmHg}\text{;}$ post-training 1: $\text{1.4±0.3}\text{mmHg}\text{;}$ post-training 2: $\text{1.1±0.5}\text{mmHg}\text{; P>0.05).}$ Thus, PCPA abolishes long-term modulation, implicating serotonin in its underlying mechanism.

Respiratory diseases are a frequent reason for using health care. In 1995–1996, diseases of the respiratory tract (ICD 460–519) contributed seven of the top 15 reasons for visits to physician offices among children under 15 years of age in the United States. Environmental tobacco smoke (ETS) is a wide-spread environmental pollutant that has been long linked with respiratory problems. This paper will review the available literature on the role ETS plays in respiratory diseases, including asthma. This review focuses not only on the respiratory problems caused by ETS, but also examines the influence of age at exposure on the consequences of ETS and the importance of the differing sources of ETS exposure. As ETS is a completely preventable form of environmental pollution, the success or failure of various types of interventions will also be reviewed.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality throughout a large part of the western world. Although personal tobacco use has been implicated in a large number of these cases, it is also true that only a fraction of smokers ever develop respiratory problems. Therefore, the question of host susceptibility and other environmental factors should be considered. This paper will briefly review evidence for host susceptibility to COPD, review evidence for additional environmental risk factors for the development of COPD, and give an example of environmental interactions with a known genetic risk factor that further increase the risk of COPD.

Stress stimulates the hypothalamic–pituitary–adrenal axis and leads to elevated glucocorticoid hormones (GCs). GCs reduce inflammation and suppress responses mediated by cytokines, including fever and pulmonary inflammation. Besides cyclooxygenases and lipoxygenases, cytochrome P-450 enzymes (CYP), referred to as epoxygenases, are also involved in the metabolism of arachidonic acid, implicating epoxygenases in regulating inflammation and the generation of fever. Intraperitoneal injection of lipopolysaccharide (LPS) triggers fever in rats and mice, and administration of compounds known to induce CYP reduces LPS-induced fever, while inhibitors of CYP suppress fever. Consistent with these findings, inhibitors of CYP augment the elevation of LPS-induced prostaglandin E2 levels, an endogenous pyrogen, and administration of epoxygenase metabolites results in antipyresis. CYP inducers also reduce lung inflammation, the resulting mucous cell metaplasia, and the percentage of Bcl-2-positive mucous cells in rat airways after intratracheal instillation of LPS. Together, these observations indicate that CYP modulators may have therapeutic anti-inflammatory effects, and this pathway may be involved in stress-induced reduction of inflammation.

Viral infection of the respiratory tract induces a complex series of cellular and molecular events leading to immunological responses designed to terminate viral replication. Anti-viral immunity involves natural resistance mechanisms that overlap and modulate the development of the subsequent adaptive immune responses. An experimental murine infection with influenza A/PR8 virus was used to examine the effects of stress-induced activation of the nervous and endocrine systems on components of innate immunity. Proinflammatory cytokine responses (IL-1α, IL-6 and TNFα) were measured in the lungs during an influenza A/PR8 viral infection. For activation of the nervous and endocrine systems, restraint stress (RST) was applied prior to and during infection. Following infection, IL-1α increased transiently, while elevated IL-6 persisted; TNFα was not detected. RST suppressed virally-induced IL-1α, while IL-6 was unaffected. These data demonstrate differential regulation of proinflammatory cytokines by stress. The mechanism underlying suppression of the lung IL-1α in stressed mice is currently unknown; its downregulation may contribute to increased viral pathogenesis in stressed individuals.

Patients with acute pancreatitis may develop acute lung injury, manifest clinically as the adult respiratory distress syndrome. Most patients who die during the early stages of severe acute pancreatitis die either with or as a result of this lung injury. To explore the events which couple acute pancreatitis to lung injury, a number of recent studies have been performed in the author's laboratory using a variety of experimental models and interventions including gene-targeted deletion of chemokines, cytokines, specific receptors, and adhesion molecules. These studies have indicated that adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), neutrophils, platelet activating factor (PAF), substance P, and chemokines acting via the CCR-1 chemokine receptor play a pro-inflammatory role while complement factor C5a plays an anti-inflammatory role in pancreatitis and lung injury. Future studies will build on these observations to expand the list of pro- and anti-inflammatory coupling factors and explore the mechanisms by which they act to cause or prevent lung injury in acute pancreatitis.

The purpose of this paper is to review the application of mathematical models of inhaled particle deposition to people of various ages. The basic considerations of aerosol physics, biological characteristics and model structure are presented along with limitations inherent in modern modeling techniques. Application of the models to children and senescent adults has been largely based on extrapolating anatomical and physiological data from young adults to match the changes observed during growth and aging. Sample results are included for total particle deposition and deposition in the bronchial and pulmonary regions. The models proposed provide particle deposition predictions that are consistent with the scant measurements available. The models discussed appear to be on firm theoretical grounds, but they are largely limited in application to simple aerosols and average individuals. Also, additional validation of the computational predictions is needed.