Application of approach speed criteria derived from closed-loop pilot-vehicle systems analyses to an Ogee wing aircraft

Approach speed criteria derived from closed loop pilot-vehicle systems analyses and applied to Ogee wing F-5 aircraf

Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways

Maladaptive changes in the carotid body (CB) induced by chronic intermittent hypoxia (IH) account for the pathogenesis of cardiovascular morbidity in patients with sleep-disordered breathing. We postulated that the proinflammatory cytokines, namely interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and cytokine receptors (IL-1r1, gp130 and TNFr1) locally expressed in the rat CB play a pathophysiological role in IH-induced CB inflammation. Results showed increased levels of oxidative stress (serum 8-isoprostane and nitrotyrosine in the CB) in rats with 7-day IH treatment resembling recurrent apneic conditions when compared with the normoxic control. Local inflammation shown by the amount of ED1-containing cells (macrophage infiltration) and the gene transcripts of NADPH oxidase subunits (gp91phox and p22phox) and chemokines (MCP-1, CCR2, MIP-1α, MIP-1β and ICAM-1) in the CB were significantly more in the hypoxic group than in the control. In addition, the cytokines and receptors were expressed in the lobules of chemosensitive glomus cells containing tyrosine hydroxylase and the levels of expressions were significantly increased in the hypoxic group. Exogenous cytokines elevated the intracellular calcium ([Ca2+]i) response to acute hypoxia in the dissociated glomus cells. The effect of cytokines on the [Ca2+]i response was significantly greater in the hypoxic than in the normoxic group. Moreover, daily treatment of IH rats with anti-inflammatory drugs (dexamethasone or ibuprofen) attenuated the levels of oxidative stress, gp91phox expression and macrophage infiltration in the CB. Collectively, these results suggest that the upregulated expression of proinflammatory cytokine pathways could mediate the local inflammation and functional alteration of the CB under chronic IH conditions

The emerging role of AMPK in the regulation of breathing and oxygen supply

Regulation of breathing is critical to our capacity to accommodate deficits in oxygen availability and demand during, for example, sleep and ascent to altitude. It is generally accepted that a fall in arterial oxygen increases afferent discharge from the carotid bodies to the brainstem and thus delivers increased ventilatory drive, which restores oxygen supply and protects against hypoventilation and apnoea. However, the precise molecular mechanisms involved remain unclear. We recently identified as critical to this process the AMP-activated protein kinase (AMPK), which is key to the cell-autonomous regulation of metabolic homoeostasis. This observation is significant for many reasons, not least because recent studies suggest that the gene for the AMPK-α1 catalytic subunit has been subjected to natural selection in high-altitude populations. It would appear, therefore, that evolutionary pressures have led to AMPK being utilized to regulate oxygen delivery and thus energy supply to the body in the short, medium and longer term. Contrary to current consensus, however, our findings suggest that AMPK regulates ventilation at the level of the caudal brainstem, even when afferent input responses from the carotid body are normal. We therefore hypothesize that AMPK integrates local hypoxic stress at defined loci within the brainstem respiratory network with an index of peripheral hypoxic status, namely afferent chemosensory inputs. Allied to this, AMPK is critical to the control of hypoxic pulmonary vasoconstriction and thus ventilation–perfusion matching at the lungs and may also determine oxygen supply to the foetus by, for example, modulating utero-placental blood flow

Nasal and pharyngeal resistance after topical mucosal vasoconstriction in normal humans.

Phenylephrine, an alpha-adrenergic agonist, increases pharyngeal cross-sectional area when applied topically to the nasal and pharyngeal mucosa, as determined by magnetic resonance imaging. In this study, we examined the possibility that the increase in area results from either a decrease in transmural collapsing pressure, as a result of a decrease in upstream (nasal) resistance, or an increase in upper airway muscle activity. In eight normal, awake men we measured inspiratory pharyngeal and nasal resistance and the electrical activity of the genioglossus (EMGGG) and alae nasi (EMG(AN) before and after pharyngeal and nasal + pharyngeal instillation of 1 ml of either 0.25% phenylephrine or normal saline; phenylephrine and saline were tested on separate days. Under control eucapnic conditions, pharyngeal resistance was 0.43 +/- 0.03 cm H2O/L/s, and nasal resistance was 2.43 +/- 0.14 cm H2O/L/s. Pharyngeal resistance was 0.29 +/- 0.03 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 0.98 +/- 0.13 cm H2O/L/s after saline; nasal resistance was 2.18 +/- 0.13 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 3.15 +/- 0.21 cm H2O/L/s after saline. Thus, phenylephrine decreased both nasal and pharyngeal inspiratory resistance. The change in pharyngeal resistance was not dependent on the change in nasal resistance. Eucapnic EMGGG and EMGAN activities did not change after phenylephrine or saline. We conclude that phenylephrine decreased pharyngeal resistance independent of a change in nasal resistance of upper airway muscle activity, and we believe that the changes in resistance we observed reflect a direct effect of phenylephrine on the pharyngeal mucosa and a consequent enlargement of pharyngeal size.(ABSTRACT TRUNCATED AT 250 WORDS