Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Aug 2009
PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models.
Phox2b is a master regulator of visceral reflex circuits. Its role in the control of respiration has been highlighted by the identification of heterozygous PHOX2B mutations as the cause of Central Congenital Hypoventilation Syndrome (CCHS), a rare disease defined by the lack of CO(2) responsiveness and of breathing automaticity in sleep. Phox2b(27Ala/+) mice that bear a frequent CCHS-causing mutation do not respond to hypercapnia and die in the first hour after birth from central apnoea. ⋯ Neurons of the retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG) were found severely depleted in these mice and no other neuronal loss could be identified. Physiological experiments show that RTN/pFRG neurons are crucial to driving proper breathing at birth and are necessary for central chemoreception and the generation of a normal respiratory rhythm. To date, the reason for the selective vulnerability of RTN/pFRG neurons to PHOX2B protein dysfunction remains unexplained.
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Cardiogenic oscillations are small waves produced by heartbeats, which are superimposed on the pressure and flow signals at the airway opening. The aim of this study was to investigate the role of the two main factors believed to generate these oscillations: (1) contact between heart and lungs and (2) pulmonary blood flow. ⋯ Cardiogenic oscillations for pressure and flow were smaller at 50% compared to 100% pulmonary blood flow (0.80+/-0.12 cmH(2)O and 1.56+/-0.34 L min(-1) vs 1.19+/-0.14 cmH(2)O and 2.38+/-0.19 L min(-1)). We conclude that the amount of pulmonary blood flow and not the contact between heart and lungs is the main factor determining the amplitude of cardiogenic oscillations.
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Respir Physiol Neurobiol · Jul 2009
Comparative StudyComparison of the metabolic and ventilatory response to hypoxia and H2S in unsedated mice and rats.
Hypoxia alters the control of breathing and metabolism by increasing ventilation through the arterial chemoreflex, an effect which, in small-sized animals, is offset by a centrally mediated reduction in metabolism and respiration. We tested the hypothesis that hydrogen sulfide (H(2)S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. ⋯ When mice were simultaneously exposed to H(2)S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H(2)S alone. H(2)S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H(2)S in small mammals appears to be dependent upon the ability to decrease metabolism.
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Respir Physiol Neurobiol · Jun 2009
Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury.
Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa O2), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. ⋯ In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa O2. PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain.
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Respir Physiol Neurobiol · May 2009
Editorial ReviewMechanisms of activity-related dyspnea in pulmonary diseases.
Progressive activity-related dyspnea dominates the clinical presentation of patients afflicted by chronic obstructive and restrictive lung diseases. This symptom invariably leads to activity limitation, global skeletal muscle deconditioning and an impoverished quality of life. The effective management of exertional dyspnea remains an elusive goal but our understanding of the nature and mechanisms of this distressing symptom continues to grow. ⋯ Reductionist experimental approaches that attempt to partition, or isolate, the contribution of central and multiple peripheral sensory afferent systems to activity-induced dyspnea have met with limited success. Integrative approaches which explore the possible neurophysiological mechanisms involved in the two dominant qualitative descriptors of activity-related dyspnea in both diseases may prove to be more fruitful. In this review, we present a hypothetical model for exertional dyspnea that is based on current neurophysiological constructs that have been rigorously developed to explain the origins of perceptions of "effort," "air hunger" and the accompanying affective "distress" response.