Two long‐lasting central respiratory responses following acute hypoxia in glomectomized cats.

Abstract

SUMMARY1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats.2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired 02 fraction, FI°2 = 0-06-0-15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial 02 pressure, Pa,°< 26 Torr) to 'mild' (Pa, 02 > 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100 % oxygen.3. The results confirmed the finding of prolonged ( > 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting ( > 60 min) facilitation of respiration following exposure to less severe (Pa, 02 > 35 Torr) hypoxia.4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the longlasting facilitation observed following mild hypoxia.5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon.6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia.7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild hypoxia. Inhibition is more likely following severe hypoxia. However, both mechanisms appear to be triggered simultaneously and the output of the central respiratory controller reflects the influence of each.

Comparison of Respiratory and Circulatory Human Responses to Progressive Hypoxia and Hypercapnia

“…sensi tive to C()2. are thought to be responsible for the initial fast phase of the response. With their denervation, the re sponse occurs at later time periods and has a more inert pattern [3], The removal of the glomus carotid results in complete disappearance of the response to hypoxia, al though this dogma is argued [25]. The response to hyper capnia in such a situation was found to be preserved, albeit of slowed magnitudes [26], In our investigations, the hemodynamic responses to the hypoxic challenge developed without any delay, in par allel to the respiratory responses.…”

Chemoreceptor Responsiveness at Sea Level Does Not Predict the Pulmonary Pressure Response to High Altitude

“…Changes in peripheral chemoreceptor responsiveness 19,36,37 , central processing 18,20,38 , and the consequent efferent output 18 all effect the ventilatory response to hypoxia at altitude 16,17 . The further effect of changes in acid-base balance, as well as the complex nature of breathing at HA have been reviewed in detail 15 .…”

“…Due to the myriad of physiologic changes at HA related to the HVR [18][19][20] and HPV 21 , we hypothesized that resting SpO 2 at HA would correlate better than variability in HVR at SL to PASP at HA (i.e., by virtue of SpO 2 reflecting alveolar PO 2 and hence HPV). We also reasoned that chronic adaptation to HA, as seen in the Sherpa, would result in higher resting SpO 2 and lower PASP than that of lowlanders at HA.…”

Mesencephalic stimulation elicits inhibition of phrenic nerve activity in cat.

“…The motivation for this study was to locate the region of the mesencephalon responsible for the post-hypoxic inhibition of respiration which we have previously reported (Gallman & Millhorn, 1988). If hypoxia were acting directly upon neurones of the mesencephalon, it could, theoretically, operate in at least two manners.…”

“…This inhibition lasts up to 1 h or more following cessation of the hypoxic insult. Further investigation revealed that the mesencephalon is required, but that structures further rostral are not necessary, for expression of this long-lasting post-hypoxic inhibition (Gallman & Millhorn, 1988). Other investigators have similarly concluded that a suprapontine mechanism is involved in depression of respiration, particularly in fetal and neonatal animals (Dawes, Gardner, Johnston & Walker, 1983;Martin-Body & Johnston, 1988;Martin-Body, 1988).…”