The role of the hypothalamus in modulation of respiration.

The hypothalamus is a higher center of the autonomic nervous system and maintains essential body homeostasis including respiration. The paraventricular nucleus, perifornical area, dorsomedial hypothalamus, and lateral and posterior hypothalamus are the primary nuclei of the hypothalamus critically involved in respiratory control. These hypothalamic nuclei are interconnected with respiratory nuclei located in the midbrain, pons, medulla and spinal cord. We provide an extensive review of the role of the above hypothalamic nuclei in the maintenance of basal ventilation, and modulation of respiration in hypoxic and hypercapnic conditions, during dynamic exercise, in awake and sleep states, and under stress. Dysfunction of the hypothalamus causes abnormal breathing and hypoventilation. However, the cellular and molecular mechanisms how the hypothalamus integrates and modulates autonomic and respiratory functions remain to be elucidated.

Transdiaphragmatic pressure and neural respiratory drive measured during inspiratory muscle training in stable patients with chronic obstructive pulmonary disease.

PURPOSE: Inspiratory muscle training (IMT) is a rehabilitation therapy for stable patients with COPD. However, its therapeutic effect remains undefined due to the unclear nature of diaphragmatic mobilization during IMT. Diaphragmatic mobilization, represented by transdiaphragmatic pressure (Pdi), and neural respiratory drive, expressed as the corrected root mean square (RMS) of the diaphragmatic electromyogram (EMGdi), both provide vital information to select the proper IMT device and loads in COPD, therefore contributing to the curative effect of IMT. Pdi and RMS of EMGdi (RMSdi%) were measured and compared during inspiratory resistive training and threshold load training in stable patients with COPD. PATIENTS AND METHODS: Pdi and neural respiratory drive were measured continuously during inspiratory resistive training and threshold load training in 12 stable patients with COPD (forced expiratory volume in 1 s ± SD was 26.1%±10.2% predicted). RESULTS: Pdi was significantly higher during high-intensity threshold load training (91.46±17.24 cmH2O) than during inspiratory resistive training (27.24±6.13 cmH2O) in stable patients with COPD, with P<0.01 for each. Significant difference was also found in RMSdi% between high-intensity threshold load training and inspiratory resistive training (69.98%±16.78% vs 17.26%±14.65%, P<0.01). CONCLUSION: We concluded that threshold load training shows greater mobilization of Pdi and neural respiratory drive than inspiratory resistive training in stable patients with COPD.

Thalamic mediation of hypoxic respiratory depression in lambs.

Immaturity of respiratory controllers in preterm infants dispose to recurrent apnea and oxygen deprivation. Accompanying reductions in brain oxygen tensions evoke respiratory depression, potentially exacerbating hypoxemia. Central respiratory depression during moderate hypoxia is revealed in the ventilatory decline following initial augmentation. This study determined whether the thalamic parafascicular nuclear (Pf) complex involved in adult nociception and sensorimotor regulation (Bentivoglio M, Balerecia G, Kruger L. Prog Brain Res 87: 53-80, 1991) also becomes a postnatal controller of hypoxic ventilatory decline. Respiratory responses to moderate isocapnic hypoxia were studied in conscious lambs. Hypoxic ventilatory decline was compared with peak augmentation. Pf and/or adjacent thalamic structures were destroyed by the neuron-specific toxin ibotenic acid (IB). IB lesions involving the thalamic Pf abolished hypoxic ventilatory decline. Lesions of adjacent thalamic nuclei that spared Pf and control injections of vehicle failed to blunt hypoxic respiratory depression. Our findings reveal that the thalamic Pf region is a critical controller of hypoxic ventilatory depression and thus a key target for exploring molecular concomitants of forebrain pathways regulating hypoxic ventilatory depression in early development.

Phrenic nerve stimulation: the Australian experience.

Phrenic nerve stimulation is a technique whereby a nerve stimulator provides electrical stimulation of the phrenic nerve to cause diaphragmatic contraction. The most common indications for this procedure are central alveolar hypoventilation and high quadriplegia. This paper reviews the available data on the 19 patients treated with phrenic nerve stimulation in Australia to date. Of the 19 patients, 14 required pacing due to quadriplegia, one had congenital central hypoventilation syndrome and one had brainstem encephalitis. Information was unavailable for the remaining three patients. Currently, 11 of the pacers are known to be actively implanted, with the total pacing duration ranging from 1 to 21 years (mean 13 years). Eight of the 19 patients had revision surgeries. Four of these were to replace the original I-107 system (which had a 3-5-year life expectancy) with the current I-110 system, which is expected to perform electrically for the patient's lifetime. Three patients had revisions due to mechanical failure. The remaining patients' notes were incomplete. These data suggest that phrenic nerve stimulation can be used instead of mechanical ventilators for long-term ongoing respiratory support.

Vienna phrenic pacemaker--experience with diaphragm pacing in children.

Eight children, five boys and three girls, aging from 2 to 13 years (M = 9 +/- 3) were treated with the "Vienna phrenic pacemaker". Indication for implantation was central alveolar hypoventilation syndrome (CAH) in one case and total ventilatory insufficiency due to high cervical cord or brain stem lesion (SCI) in seven cases. Four electrodes were applied to each phrenic nerve via sternotomy. Both hemidiaphragms were paced synchronously with increasing duty cycles to condition the diaphragms for continuous electrophrenic respiration (EPR). EPR could be performed successfully in all children but one. Four children could achieve chronical EPR, one is in conditioning period. Two patients could not be discharged from hospital due to parental neglect and died after two and three years of intermittent stimulation. Six children could be discharged from hospital, two of them died after one and four years of chronic pacing. In one case tracheotomy could be closed definitively. Ventilatory insufficiency due to CAH and SCI can be treated even in children with diaphragm pacing, provided the indication for implantation, containing medical and social aspects, was made correctly. Diaphragm pacing probably will not lengthen life of severely injured children but it can increase the quality of their life and therefore should be preferred to positive pressure mechanical ventilation.

[The role of the limbic cortex in regulating the neuronal impulse activity of the respiratory center in the medulla oblongata under conditions of oxygen deficiency]. / Rol' limbicheskoi kory v reguliatsii impul'snoi aktivnosti neironov dykhatel'nogo tsentra prodolgovatogo mozga v usloviiakh kislorodnoi nedostatochnosti.

Complex action of hypoxia and electrostimulation of the limbic cortex on unit activity of bulbar respiratory neurons was studied. Under normal barometric pressure the influence of the limbic electrostimulation on activity of bulbar respiratory neurons was ambiguous, i.e., both activation and inhibition were observed, but inhibitory influences prevailed. In initial phase (4000-5000 m) at the background of hypoxic activation the influence of electrostimulation of the limbic cortex on activity of respiratory neurons was predominantly inhibitory, as under conditions of normoxia. In the phase of severe hypoxia (7500-8000 m) at the background of expressed hypoxic suppression of activity of respiratory neurons stimulation of the limbic cortex did not induce reactions characteristic of these neurons. Reaction of the respiratory neurons on the electrical stimulation of the limbic cortex in different phases of hypoxic action depended on relatively high sensitivity to hypoxia of the limbic cortex and the functional state of the bulbar respiratory center.

[Hypothalamic mechanisms regulating the activity of the respiratory neurons of the medulla oblongata in hypoxia]. / Issledovanie gipotalamicheskikh mekhanizmov reguliatsii aktivnosti dykhatel'nykh neironov prodolgovatogo mozga v usloviiakh gipoksii.

Under normal conditions of atmosphere pressure the electrical stimulation of hypothalamus induced activating influence on the medullary respiratory and reticular neurons. At the initial stage of the hypoxia (the altitude 4500-5000 m), against the background of hypoxic activation of firing rate, facilitating influence of tetanic stimulation of hypothalamus was lesser though it prevailed over its inhibiting action. At the maximal altitude (8000-9000 m), against the background of hypoxic depression of unit activity, the stimulation of hypothalamus exerted mainly a stimulating effect. That response was particularly obvious in the neurons with low spontaneous activity.