VENTILATORY RESPONSES TO EXERCISE IN HUMANS LACKING VENTILATORY CHEMOSENSITIVITY

1. In healthy humans during aerobic exercise ventilation increases and mean arterial P(CO2) usually remains constant over a wide range of CO 2 production. 2. Congenital central hypoventilation syndrome (CCHS) is associated with ineffective chemoreceptor regulation of breathing and severe hypoventilation during sleep (requiring mechanical ventilation ) reflecting abnormalities in the brainstem respiratory complex or its chemoreceptor input. Such patients can have adequate spontaneous vent ilation during resting wakefulness and participate in normal activitie s. 3. If children with CCHS have normal ventilatory responses to exerc ise then chemoreceptors are not necessary for this ventilatory respons e or the resultant control of P(a,CO2) during exercise. We studied fiv e children with CCHS (aged 8-17 years) with abnormally low ventilatory responses to steady-state increased end-tidal P(CO2) ( < 9 ml min-1 k g-1 mmHg-1) and five age -matched controls.4. Depth and rate of breath ing, end-tidal P(CO2), end-tidal P(O2), CO2 production, 02 utilization and heart rate were monitored during the following conditions: whilst subjects stood at rest; following the onset of treadmill exercise (4 m.p.h.); during steady-state exercise (4 m.p.h.); during an incrementa l maximal exercise test; and during recovery from exercise. 5. There w ere no significant differences in the ventilatory responses between CC HS subjects and controls during the onset of treadmill exercise, in th e dynamic response in achieving the steady-state exercise, during stea dy-state exercise, in the recovery from steady-state exercise, or duri ng incremental exercise (up to the point of presumed blood lactate acc umulation, as indicated by gas exchange criteria). There was a very sm all mean increase in P(CO2) in both groups during steady-state exercis e (controls 1.4 mmHg; CCHS 2.2 mmHg). 6. The only differences which em erged between groups were (i) slightly more variability in P(CO2) in t he CCHS group during steady-state exercise, and (ii) the OCHS subjects did not hyperventilate, as the controls did, at exercise levels above the point of presumed blood lactate accumulation. 7. Breath-by-breath coefficient of variation of ventilation was significantly reduced in both groups during steady-state exercise compared to rest. There were no differences between groups in either state. 8. We conclude that che moreceptors are not necessary for an appropriate ventilatory response to aerobic exercise. Hence, other stimuli, such as afferent informatio n from the exercising limbs or signals related to activation of the mo tor cortex, can increase alveolar ventilation in close proportion to C O2 production. 9. The lack of hyperventilatory response to blood lacta te accumulation during heavy exercise provides good evidence that thes e CCHS patients have ineffective peripheral chemoreception.