Human cerebrovascular and ventilatory CO₂ reactivity to end‐tidal, arterial and internal jugular vein P_CO2

Abstract

This study examined cerebrovascular reactivity and ventilation during step changes in CO 2 in humans. We hypothesized that: (1) end-tidal P CO 2 (P ET,CO 2 ) would overestimate arterial P CO 2 (P a,CO 2 ) during step variations in P ET,CO 2 and thus underestimate cerebrovascular CO 2 reactivity; and (2) sinceP CO 2 from the internal jugular vein (P jv,CO 2 ) better represents brain tissueP CO 2 , cerebrovascular CO 2 reactivity would be higher when expressed against P jv,CO 2 than with P a,CO 2 , and would be related to the degree of ventilatory change during hypercapnia. Incremental hypercapnia was achieved through 4 min administrations of 4% and 8% CO 2 . Incremental hypocapnia involved two 4 min steps of hyperventilation to changeP ET,CO 2 , in an equal and opposite direction, to that incurred during hypercapnia. Arterial and internal jugular venous blood was sampled simultaneously at baseline and during each CO 2 step. Cerebrovascular reactivity to CO 2 was expressed as the percentage change in blood flow velocity in the middle cerebral artery (MCAv) per mmHg change in P a,CO 2 and P jv,CO 2 . During hypercapnia, but not hypocapnia, P ET,CO 2 overestimated P a,CO 2 by +2.4 ± 3.4 mmHg and underestimated MCAv-CO 2 reactivity (P < 0.05). The hypercapnic and hypocapnic MCAv-CO 2 reactivity was higher (∼97% and ∼24%, respectively) when expressed with P jv,CO 2 than P a,CO 2 (P < 0.05). The hypercapnic MCAv-P jv,CO 2 reactivity was inversely related to the increase in ventilatory change (R 2 = 0.43; P < 0.05), indicating that a reduced reactivity results in less central CO 2 washout and greater ventilatory stimulus. Differences in the P ET,CO 2 , P a,CO 2 and P jv,CO 2 -MCAv relationships have implications for the true representation and physiological interpretation of cerebrovascular CO 2 reactivity.

Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training

“…Additional mechanisms potentially contributing to this increased cerebrovascular reactivity include brain-derived neurotrophic factor (Seifert et al 2010) and insulin-like growth factor-1 (Llorens-Martin et al 2010). Furthermore, hypocapnic cerebrovascular reactivity-a response which is not NO mediated (Peebles et al 2007)-was unchanged following training, further supporting the suggestion that the training-induced elevation in hypercapnic reactivity is mediated by NO. Although the role of NO is a possibility based on this information, we acknowledge that this suggestion is purely speculative because we did not measure systemic or cerebrovascular NO.…”

“…Cerebrovascular vasodilatation in response to hypercapnia is, in part, dependent upon NO bioavailability (Peebles et al 2007). Nitric oxide has been reported to increase with exercise training (Green et al 2004;Kingwell et al 1997).…”

“…This fitness-induced reduction in the risk of stroke is due to upregulation of endothelial NO synthase (Endres et al 2003;Gertz et al 2006;Lee and Paffenbarger 1998). Furthermore, it is known that hypercapnia-induced cerebrovascular vasodilatation is, at least in part, NO dependent (Peebles et al 2007). Since systemic NO production/ bioavailability is increased with exercise training (Kingwell et al 1997), it seems possible that increases in aerobic fitness will be associated with increases in cerebrovascular reactivity.…”

Aging blunts hyperventilation-induced hypocapnia and reduction in cerebral blood flow velocity during maximal exercise

“…During exercise and related hypercapnia, P ET CO 2 may slightly overestimate arterial PCO 2 (Jones et al 1979;Peebles et al 2007). Although this is a relevant consideration, we feel that this is unlikely to affect our findings since we used otherwise healthy subjects and we know of no evidence to indicate that end-tidal to arterial PCO 2 gradients may be altered with aging.…”

“…Although this is a relevant consideration, we feel that this is unlikely to affect our findings since we used otherwise healthy subjects and we know of no evidence to indicate that end-tidal to arterial PCO 2 gradients may be altered with aging. Unlike hypercapnia, P ET CO 2 is a better reflection of arterial PCO 2 during hypocapnia (Peebles et al 2007;Thomas et al 2009). Although cerebrovascular response to both hypocapnia and hypercapnia is enhanced during exercise , it is unknown whether this response is altered with aging.…”