From the Lboratory of Zoophysiology, Vniversity of Copenhagen.

Studies on the Regulrttion of Respiration i i i

Acute Hypoxia. Preliminary report.

By

MARIUS NIELSEN a n d HELGE SMITH.

The purpose of the experiments which shall be presented here is to study the effect of CO, on the pulmonary ventilation at various degrees of acute hypoxia. Since both CO, and low oxygen act as stimuli on the respiration it is necessary in order t o olltain clear results, to keep one of these stimuli constant, while the other is varied. I n the present experiments the alveolar carboii dioxide pressure and the alveolar oxygen pressure are used as indicators for the two stimuli, and for a giveii degree of hypoxia the alveolar carbon dioxide pressure has been varied. The oxygen pressure in the inspired air has consequently been adjusted j i i

w c h a way, that the alveolar oxygen pressure remained a t the same level in spite of the changes taking place in the pulmonary ventilation due to the variation in alveolar pC0,.

The experiments were performed under basal conditions on two nornial human subjects who were selected because they showed a very pronounced respiratory response towards low oxy- gen. Both of them had for a long time previous to these experi- ments been trained in respiratioii experiments.

In the experiments the subjects breathed mixtures of oxygen. carbon dioxide and nitrogen from a Ilouglas hag which n-aq continuously filled from cylinders containing the proper air mixture. All determinations were made in the steady state, that is after an equilibrium between the pulnionary ventilation and the alveolar gas pressures in question had been established or nearly established.

STUDIES ON THE REGULATION OF RESPIRATION I N ACUTE HYPOXIA. 45

The experiments showed that the pulmonary ventilation (plotted against the alveolar pC0,) in the normal condition in- creased linearly with increasing alveolar CO, pressures. In the hypoxic state (and no CO, in the inspired air) the pulmonary ventilation was increased and the alveolar CO, pressure decreased very considerably. With increasing alveolar CO, pressures, pro- duced by adding CO, to the inspired air the pulmonary ventilation, however, remained practically unchanged until a definite value of pCO,, the threshold value of CO, was reached. From this definite point the pulmonary ventilation increased linearly with increas- ing alveolar CO, pressures, but the curve was much steeper than in the normal condition. I n one of the subjects (alveolar PO, maintained a t about 37 mm) an increase in the alveolar PO, of 3 mm above the threshold value produced an increase in the pul- monary vent lation of nearly 30 liters per minute, whereas in the normal condition the same increase in pC0, only produced an increase in the ventilation of about 6 liters per minute. In other words: The sensitivity of the respiratory apparatus towards CO, was greatly increased in the hypoxic condition as compared to the sensitivity under normal conditions.

The threshold value of CO, in the normal conditions was deter- mined as the point of intersection between the normal curve and the zero line. It may be slightly lower, but cannot very well be higher than the value found by this extrapolating of the curve back to the zero line. The experiments showed, that the threshold value of CO, for both subjects was practically the same in the normal condition and in the various degrees of hypoxia studied. For one of the subjects i t was found to be 30-31.5 mm Hg and for the other 31.5-33 mm Hg.

It is now a firmly established fact, that the increase in pul- monary ventilation in acute hypoxia is due entirely or mainly t o reflexes from the peripheral chemoreceptors. The results from the present experiments harmonize very well with this. Due to the reflex1 y evoked hyperventilation the alveolar GO, pressure is decreased. and the threshold value of CO, found in these experi- ments corresponds to the CO, pressure a t which CO, begins to stimulate the respiratory center.

I t is obvious that there is no depressant or “devitalizing” effect of {,he hypoxia on the respiratory center itself as far as its response GO CO, is concerned. On the contrary: for CO, pressures above the threshold value the respiratory center responds even

46 MARIUS NIELSEN AND IIELGE SMITH.

more powerfully to CO, than in normal conditions. How this increased sensitivity towards CO, is brought, about cannot be said from these experiments. It may be evoked reflexly from the chemoreceptors or it may be caused by the effect of lack of oxygen on the respiratory center itself. The increased sensitivity plays no part in the calling forth of the hypoxic hyperventilation, because the CO, pressure in the hypoxic state actually is far below the threshold value. The biological importance of this mechanism, however, will appear in conditions where lack of oxygen is combined with accumulation of carbon dioxide.

The stimulus for the increase in ventilation in acute hypoxia is by many investigators thought to be an increased aciditv in the chemoreceptors, caused by a local increase in acid formation. I n the present experiments with hypoxia the alveolar $0, could be increased over a wide range before the threshold value of CO, was reached. In one subject, for instance, the alveolar pC0, could in the hypoxic state be increased by 13 mm Hg Fithout any effect on the pulmonary ventilation although the increase in the CO, pressure of the arterial blood irrigating the chemorecep- tors &-as of the same magnitude. If the stimulus for the hypoxic hyperventilation is an increased acidity in the chemoreceptors, i t seems therefore to be a question of very large increases in acidity.