Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Oct 2009
Recruitment maneuver: RAMP versus CPAP pressure profile in a model of acute lung injury.
We examined whether recruitment maneuvers (RMs) with gradual increase in airway pressure (RAMP) provide better outcome than continuous positive airway pressure (CPAP) in paraquat-induced acute lung injury (ALI). Wistar rats received saline intraperitoneally (0.5 mL, CTRL) or paraquat (15 mg/kg, ALI). Twenty-four hours later lung mechanics [static elastance, viscoelastic component of elastance, resistive, viscoelastic and total pressures] were determined before and after recruitment with 40cmH2O CPAP for 40s or 40-s-long slow increase in pressure up to 40cmH2O (RAMP) followed by 0 or 5 cmH2O PEEP. ⋯ All mechanical parameters and the fraction area of alveolar collapse were higher in ALI compared to CTRL. Only RAMP-PEEP maneuver significantly improved lung mechanics and decreased PCIII mRNA expression (53%) compared with ALI, while both RMs followed by PEEP decreased alveolar collapse. In conclusion, in the present experimental ALI model, RAMP followed by 5cm H2O PEEP yields a better outcome.
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Respir Physiol Neurobiol · Sep 2009
Chronic hypoxia suppresses the CO2 response of solitary complex (SC) neurons from rats.
We studied the effect of chronic hypobaric hypoxia (CHx; 10-11% O(2)) on the response to hypercapnia (15% CO(2)) of individual solitary complex (SC) neurons from adult rats. We simultaneously measured the intracellular pH and firing rate responses to hypercapnia of SC neurons in superfused medullary slices from control and CHx-adapted adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. ⋯ Further, the magnitudes of the responses of SC neurons from control rats (chemosensitivity index for activated neurons of 166+/-11% and for inhibited neurons of 45+/-15%) were the same in SC neurons from CHx-adapted rats. This plasticity induced in chemosensitive SC neurons by CHx appears to involve intrinsic changes in neuronal properties since they were the same in synaptic blockade medium.
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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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Phox2b-expressing cells in the parafacial region of the ventral medulla are proposed to play a role in central chemoreception and postnatal survival. Recent findings in the adult rat and neonatal mouse suggest that the Phox2b-immunoreactive (ir) cell cluster in the rostral ventrolateral medulla is composed of glutamatergic neurons and expresses neurokinin 1 receptor (NK1R), indicating that the cluster may be identical to the retrotrapezoid nucleus. ⋯ Our findings suggest that Phox2b-expressing pFRG/Pre-I neurons play a role in respiratory rhythm generation as well as central chemoreception and thus are essential for postnatal survival. In this brief review, we focused on these recent findings and discuss the functional role of pFRG/Pre-I neurons.