Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Nov 2013
ReviewCommon mechanisms of compensatory respiratory plasticity in spinal neurological disorders.
In many neurological disorders that disrupt spinal function and compromise breathing (e.g. ALS, cervical spinal injury, MS), patients often maintain ventilatory capacity well after the onset of severe CNS pathology. In progressive neurodegenerative diseases, patients ultimately reach a point where compensation is no longer possible, leading to catastrophic ventilatory failure. ⋯ We propose that a suite of mechanisms, operating at distinct sites in the respiratory control system, underlies compensatory respiratory plasticity, including: (1) increased (descending) central respiratory drive, (2) motor neuron plasticity, (3) plasticity at the neuromuscular junction or spared respiratory motor neurons, and (4) shifts in the balance from more to less severely compromised respiratory muscles. To establish this framework, we contrast three rodent models of neural dysfunction, each posing unique problems for the generation of adequate inspiratory motor output: (1) respiratory motor neuron death, (2) de- or dysmyelination of cervical spinal pathways, and (3) cervical spinal cord injury, a neuropathology with components of demyelination and motor neuron death. Through this contrast, we hope to understand the multilayered strategies used to "fight" for adequate breathing in the face of mounting pathology.
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Respir Physiol Neurobiol · Nov 2013
ReviewMechanical ventilation, diaphragm weakness and weaning: a rehabilitation perspective.
Most patients are easily liberated from mechanical ventilation (MV) following resolution of respiratory failure and a successful trial of spontaneous breathing, but about 25% of patients experience difficult weaning. MV use leads to cellular changes and weakness, which has been linked to weaning difficulties and has been labeled ventilator induced diaphragm dysfunction (VIDD). Aggravating factors in human studies with prolonged weaning include malnutrition, chronic electrolyte abnormalities, hyperglycemia, excessive resistive and elastic loads, corticosteroids, muscle relaxant exposure, sepsis and compromised cardiac function. ⋯ Molecular and functional studies on the effects of MV on the human diaphragm have largely confirmed the animal results and identified potential treatment strategies. Only recently potential VIDD treatments have been tested in humans, including pharmacologic interventions and diaphragm "training". A limited number of human studies have found that specific diaphragm training can increase respiratory muscle strength in FTW patients and facilitate weaning, but larger, multicenter trials are needed.
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Congenital central hypoventilation syndrome (CCHS) is characterized by hypoventilation during sleep and impaired ventilatory responses to hypercapnia and hypoxemia. Most cases are sporadic and caused by de novo PHOX2B gene mutations, which are usually polyalanine repeat expansions. ⋯ Conditional mouse mutants in which Phox2b(27Ala) was targeted to the RTN also lacked the ventilatory response to hypercapnia at birth but survived to adulthood and developed a partial hypercapnia response. The therapeutic effects of desogestrel are being evaluated in clinical trials, and recent analyses of cellular responses to polyAla Phox2b aggregates have suggested new pharmacological approaches designed to counteract the toxic effects of mutated Phox2b.
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Respir Physiol Neurobiol · Oct 2013
High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats.
The impact of mechanical ventilation with high V(T)-low PEEP in infant rats with preinjured lungs is unknown. After tracheal instillation of saline or acid, two week old rats were ventilated with V(T) 7 mL/kg and PEEP 5 cm H₂O or V(T) 21 mL/kg and PEEP 1cm H₂O for 4 h. Airway resistance and the coefficient of tissue elastance, measured via low-frequency forced-oscillation technique, and quasi-static pressure-volume curves deteriorated less with high V(T)-low PEEP when compared with low V(T)-high PEEP. ⋯ Moreover, differences in BALF protein concentration and histological lung injury scores were independent of applied ventilation strategies. In contrast to experimental studies with adult rats, short-term mechanical ventilation with high V(T)-low PEEP is not deleterious when compared to low V(T)-high PEEP in both healthy and pre-injured infant rat lungs. Our results call for caution when extrapolating data from adult studies and highlight the need for age-specific animal models.
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Respir Physiol Neurobiol · Oct 2013
Corrections of Enghoff's dead space formula for shunt effects still overestimate Bohr's dead space.
Dead space ratio is determined using Enghoff's modification (VD(B-E)/VT) of Bohr's formula (VD(Bohr)/VT) in which arterial is used as a surrogate of alveolar PCO₂. In presence of intrapulmonary shunt Enghoff's approach overestimates dead space. In 40 lung-lavaged pigs we evaluated the Kuwabara's and Niklason's algorithms to correct for shunt effects and hypothesized that corrected VD(B-E)/VT should provide similar values as VD(Bohr)/VT. ⋯ Uncorrected VD(B-E)/VT (mean ± SD of 0.70 ± 0.10) overestimated VD(Bohr)/VT (0.59 ± 0.12) (p < 0.05), over the entire range of shunts. Mean (K) VD(B-E)/VT was significantly higher than VD(Bohr)/VT (0.67 ± 0.08, bias -0.085, limits of agreement -0.232 to 0.085; p < 0.05) whereas (N)VD(B-E)/VT showed a better correction for shunt effects (0.64 ± 0.09, bias 0.048, limits of agreement -0.168 to 0.072; p < 0.05). Neither Kuwabara's nor Niklason's algorithms were able to correct Enghoff's dead space formula for shunt effects.