Biphasic ventilatory response of adult cats to sustained hypoxia has central origin

Abstract

Hypoxia stimulates ventilation, but when it is sustained, a decrease in the response is often seen. The mechanism of this depression or "roll off" is unclear. In this study we attempted to localize the responsible mechanism at one of three possible sites: the carotid bodies, the central nervous system (CNS), or the ventilatory apparatus. The ventilatory response to sustained hypoxia (PETO2, 40-50 Torr) was tested in 5 awake and 14 anesthetized adult cats. The roll off was found in both anesthetized and awake cats. Isocapnic hypoxia initially increased ventilation as well as phrenic and carotid sinus nerve activity in anesthetized cats (288 +/- 31, 269 +/- 31, 273 +/- 29% of control value, respectively). During the roll off, ventilation and phrenic nerve activity decreased similarly (to 230 +/- 26 and 222 +/- 28%, respectively after the roll off), but in contrast carotid sinus nerve activity remained unchanged (270 +/- 26%). Thus the ventilatory roll off was reflected in phrenic but not in carotid sinus nerve activity. We conclude that the cat represents a useful animal model of the roll off phenomenon and that the mechanism responsible for the secondary decrease in ventilation lays within the CNS.

Task2 potassium channels set central respiratory CO 2 and O 2 sensitivity

“…By contrast, the hypoxia-induced depression of respiration is abolished in Task2 −/− mice. It has been proposed that this phase of the hypoxic response reflects inhibitory mechanisms located in the VMS (8,9,37). Our data suggest that Task2 is a key molecular substrate of hypoxic ventilatory depression.…”

“…The hypoxia-induced ventilatory response is time-dependent, consisting of an immediate increase followed by depression of respiratory drive and further slow recovery upon long-term hypoxic exposure (8,32). In plethysmography, Task2 −/− mice exhibited a normal initial respiratory increase in response to hypoxia.…”

“…The carotid bodies are the major sensors for acute O 2 changes. However, for longer periods of hypoxia, respiratory adaptation is substantially mediated by central mechanisms (8). The ventrolateral medullary surface comprising the RTN and the parafacial respiratory group (pFRG) has been proposed to contain intrinsically CO 2 -and O 2 -sensing neurons (9)(10)(11)(12).…”

The Role of Gamma-Aminobutyric Acid and Glutamate for Hypoxic Ventilatory Response in Anesthetized Rabbits

“…As it is well known, peripheral chemoreceptors are active during normoxia and the facilitatory inputs from peripheral chemoreceptors burst central inspiratory activity (CIA) (Oruç et al 1982;Vizek et al 1987). GABA produces this inhibitor effect by causing hyperpolarization due to an increase in the influx of Cl -into the cardiorespiratory neurons (Anderson et al 1980;Neubauer et al 1990).…”

“…While ventilation increases in acute hypoxia, the ventilatory response to acute sustained hypoxia is biphasic. Initial hyperventilation phase is followed by ventilatory depression which is also called "roll-off " (Bureau et al 1984;Vizek et al 1987;Karaturan et al 1996). Acute sustained hypoxia is belived to change the release and turnover of neurotransmitters such as glutamate, GABA, dopamine, adenosine, and serotonin in the brain (Richter et al 1999).…”