Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Nov 2013
ReviewRespiration following spinal cord injury: evidence for human neuroplasticity.
Respiratory dysfunction is one of the most devastating consequences of cervical spinal cord injury (SCI) with impaired breathing being a leading cause of morbidity and mortality in this population. However, there is mounting experimental and clinical evidence for moderate spontaneous respiratory recovery, or "plasticity", after some spinal cord injuries. ⋯ While the extent of spontaneous recovery remains limited, it is possible that enhancing or facilitating neuroplastic mechanisms may have significant therapeutic potential. The next generation of treatment strategies for SCI and related respiratory dysfunction should aim to optimize these recovery processes of the injured spinal cord for lasting functional restoration.
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Respir Physiol Neurobiol · Nov 2013
ReviewActivation of inspiratory muscles via spinal cord stimulation.
Diaphragm pacing is a clinically useful modality providing artificial ventilatory support in patients with ventilator dependent spinal cord injury. Since this technique is successful in providing full-time ventilatory support in only ~50% of patients, better methods are needed. In this paper, we review a novel method of inspiratory muscle activation involving the application of electrical stimulation applied to the ventral surface of the upper thoracic spinal cord at high stimulus frequencies (300 Hz). ⋯ Since this method results in an asynchronous pattern of EMG activity and mean peak firing frequencies similar to those observed during spontaneous breathing, HF-SCS is a more physiologic form of inspiratory muscle activation. Further, ventilation can be maintained on a long-term basis with repetitive stimulation at low stimulus amplitudes (<1 mA). These preliminary results suggest that HF-SCS holds promise as a more successful method of inspiratory muscle pacing.
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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.