Increased ventilatory response to carbon dioxide in COPD patients following vitamin C administration

Abstract

Patients with chronic obstructive pulmonary disease (COPD) have decreased ventilatory and cerebrovascular responses to hypercapnia. Antioxidants increase the ventilatory response to hypercapnia in healthy humans. Cerebral blood flow is an important determinant of carbon dioxide/hydrogen ion concentration at the central chemoreceptors and may be affected by antioxidants. It is unknown whether antioxidants can improve the ventilatory and cerebral blood flow response in individuals in whom these are diminished. Thus, we aimed to determine the effect of vitamin C administration on the ventilatory and cerebrovascular responses to hypercapnia during healthy ageing and in COPD. Using transcranial Doppler ultrasound, we measured the ventilatory and cerebral blood flow responses to hyperoxic hypercapnia before and after an intravenous vitamin C infusion in healthy young (Younger) and older (Older) subjects and in moderate COPD. Vitamin C increased the ventilatory response in COPD patients (mean (95% CI) 1.1 (0.9-1.1) versus 1.5 (1.1-2.0) L·min^-1·mmHg^-1, p<0.05) but not in Younger (2.5 (1.9-3.1) versus 2.4 (1.9-2.9) L·min^-1·mmHg^-1, p>0.05) or Older (1.3 (1.0-1.7) versus 1.3 (1.0-1.7) L·min^-1·mmHg^-1, p>0.05) healthy subjects. Vitamin C did not affect the cerebral blood flow response in the young or older healthy subjects or COPD subjects (p>0.05). Vitamin C increases the ventilatory but not cerebrovascular response to hyperoxic hypercapnia in patients with moderate COPD.

FIGURE 1

Ventilatory and cerebrovascular responses to hyperoxic hypercapnia. Individual (solid lines) and mean values (symbols) for the a) ventilatory (circles) and b) cerebrovascular (squares) responses to hyperoxic hypercapnia in young healthy subjects (Younger), older healthy subjects (Older) and chronic obstructive pulmonary disease (COPD) patients, at baseline (closed symbols) and with vitamin C (open symbols). Note the increased ventilatory response in COPD patients following vitamin C infusion. Symbols represent group means and whiskers represent 95% confidence intervals. *: p≤0.05 for baseline versus vitamin C.

FIGURE 2

Relationship between the change in a) ventilatory and b) cerebrovascular responses in older healthy subjects (Older) and chronic obstructive pulmonary disease (COPD) patients during hyperoxic hypercapnia following vitamin C administration, according to lung function. Note the significant relationship between increasing disease severity (forced expiratory volume in 1 s (FEV₁)) and a larger change in ventilatory, but not cerebrovascular, sensitivity after vitamin C infusion.