Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · May 2009
Editorial ReviewPathophysiology of dyspnea evaluated by breath-holding test: studies of furosemide treatment.
Breath-holding is one of the most powerful methods to induce the dyspneic sensation, and the breath-holding test gives us much information on the onset and endurance of dyspnea. In conscious subjects, immediately after the start of breath-holding at functional residual capacity (FRC), there is a certain period of no particular respiratory sensation lasting for 20-30s, which is designated "no respiratory sensation period". This period is terminated by the onset of dyspnea and followed by a progressive increase in the intensity of dyspnea until the breaking point of breath-holding. ⋯ Alleviation of dyspnea with inhaled furosemide in conscious subjects is also consistent with the result of animal studies in which inhaled furosemide suppresses the escape behavior in the lightly anesthetized condition. The purpose of this article is to emphasize the usefulness of breath-holding test as a tool for evaluation of dyspnea. Furthermore, the possible mechanisms of alleviation of dyspnea with inhaled furosemide are highlighted.
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Respir Physiol Neurobiol · Dec 2008
ReviewPharmacology of vagal afferent influences on disordered breathing during sleep.
Sleep-related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of approximately 2% of women and approximately 4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. ⋯ Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep-related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved.
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The transcription factor PHOX2B is essential for the development of the autonomic nervous system. In humans, polyalanine expansion mutations in PHOX2B cause Congenital Central Hypoventilation Syndrome (CCHS), a rare life-threatening disorder characterized by hypoventilation during sleep and impaired chemosensitivity. CCHS is combined with comparatively less severe impairments of autonomic functions including thermoregulation, cardiac rhythm, and digestive motility. ⋯ However, these impairments resolved rapidly, whereas the CCHS phenotype is irreversible. Heterozygous Phox2b(27Ala/+) pups exhibited a lack of responsiveness to hypercapnia and unstable breathing; they died within the first few postnatal hours. The generation of mouse models of CCHS provides tools for evaluating treatments aimed at alleviating both the respiratory symptoms and all other autonomic symptoms of CCHS.
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Acute lung injury (ALI) is a common, frequently hospital-acquired condition with a high morbidity and mortality. The stress associated with invasive mechanical ventilation represents a potentially harmful exposure, and attempts to minimize deforming stress through low tidal ventilation have proven efficacious. Lung cells are both sensors and transducers of deforming stress, and are frequently wounded in the setting of mechanical ventilation. ⋯ These downstream effects of mechanotransduction have been referred to collectively as "Biotrauma". Our review will focus on cellular stress failure, that is cell wounding, and the mechanisms mediating subsequent plasma membrane repair, we hold that a better mechanistic understanding of cell plasticity, deformation associated remodeling and repair will reveal candidate approaches for lung protective interventions in mechanically ventilated patients. We will detail one such intervention, lung conditioning with hypertonic solutions as an example of ongoing research in this arena.
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Respir Physiol Neurobiol · Aug 2008
ReviewImplication of receptor for advanced glycation end product (RAGE) in pulmonary health and pathophysiology.
Receptor for advanced glycation end products (RAGE) is a membrane bound receptor and member of the immunoglobulin super family and is normally present in a highly abundant basal level expression in lung. This high expression of RAGE in lung alveolar epithelial type I (ATI) cells is presumably involved in the proliferation and differentiation of pulmonary epithelial cells. ⋯ Recently, a soluble form of RAGE (sRAGE) produced by recombinant gene technology was shown to exhibit a therapeutic potential in experimental animal models. Detailed study of RAGE in the pulmonary tissues will facilitate the understanding of the importance of RAGE signaling in the pulmonary health and pathophysiology.