Dynamic cerebral autoregulation and baroreflex sensitivity during modest and severe step changes in arterial PCO₂

Changes in the partial pressure of arterial CO₂ (PaCO₂) regulates cerebrovascular tone and dynamic cerebral autoregulation (CA). Elevations in PaCO₂ also increases autonomic neural activity and may alter the arterial baroreflex. We hypothesized that hypercapnia would impair, and hypocapnia would improve, dynamic CA and that these changes would occur independently of any change in baroreflex sensitivity (BRS). In 10 healthy male subjects, incremental hypercapnia was achieved through 4-min administrations of 4% and 8% CO₂. Incremental hypocapnia involved two 4-min steps of hyperventilation to change end-tidal PCO₂, in an equal and opposite direction, to that incurred during hypercapnia. End-tidal, arterial and internal jugular vein PCO₂ were sampled simultaneously at baseline and during each CO₂ step. Dynamic CA and BRS was assessed at baseline and during each step change in PaCO₂ using spectral and transfer-function analysis of beat-by-beat changes in mean arterial blood pressure (MAP), heart rate and flow velocity in the middle cerebral arterial (MCAv). Critical closing pressure (CCP), an estimate of cerebrovascular tone, was estimated from extrapolation of the MAP-MCAv waveforms. Hypercapnia caused a progressive increase in PaCO₂ and MCAv whereas hypocapnia caused the opposite effect. Despite marked changes in CPP, there were no evident change in transfer-function gain, coherence, MAP variability or BRS; however, both MCAv variability and phase in the very-low frequency range was reduced during the most severe level of hyper- and hypocapnia (P < 0.05), and were related to elevations in ventilation (R²=0.42-0.52, respectively; P<0.001). It seems that hyperventilation, rather than PaCO₂, has an important influence on dynamic CA.10 page(s

Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases

Cerebral blood flow (CBF) is highly regulated by changes in arterial PCO₂ and arterial PO₂. Evidence from animal studies indicates that various vasoactive factors, including release of norepinephrine, endothelin, adrenomedullin, C-natriuretic peptide (CNP), and nitric oxide (NO), may play a role in arterial blood gas-induced alterations in CBF. For the first time, we directly quantified exchange of these vasoactive factors across the human brain. Using the Fick principle and transcranial Doppler ultrasonography, we measured CBF in 12 healthy humans at rest and during hypercapnia (4 and 8% CO₂), hypocapnia (voluntary hyperventilation), and hypoxia (12 and 10% O₂). At each level, blood was sampled simultaneously from the internal jugular vein and radial artery. With the exception of CNP and NO, the simultaneous quantification of norepinephrine, endothelin, or adrenomedullin showed no cerebral uptake or release during changes in arterial blood gases. Hypercapnia, but not hypocapnia, increased CBF and caused a net cerebral release of nitrite (a marker of NO), which was reflected by an increase in the venous-arterial difference for nitrite: 57 ± 18 and 150 ± 36 μmol/l at 4% and 8% CO₂, respectively (both P < 0.05). Release of cerebral CNP was also observed during changes in CO₂ (hypercapnia vs. hypocapnia, P < 0.05). During hypoxia, there was a net cerebral uptake of nitrite, which was reflected by a decreased venous-arterial difference for nitrite: -96 ± 14 μmol/l at 10% O2 (P < 0.05). These data indicate that there is a differential exchange of NO across the brain during hypercapnia and hypoxia and that CNP may play a complementary role in CO₂-induced CBF changes.9 page(s

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation : alterations with hyperoxia

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O₂ fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O₂ fraction, 1.0; n = 12). Dynamic CA was assessed using transferfunction gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA (~5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 ± 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 ± 3 vs. -5 ± 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by ~50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.9 page(s

Human cerebrovascular and ventilatory CO2 reactivity to end-tidal, arterial and internal jugular vein PCO2

This study examined cerebrovascular reactivity and ventilation during step changes in CO2 in humans. We hypothesized that: (1) end-tidal PCO2 (PET,CO2) would overestimate arterial PCO2 (Pa,CO2) during step variations in PET,CO2 and thus underestimate cerebrovascular CO2 reactivity; and (2) since PCO2 from the internal jugular vein (Pjv,CO2) better represents brain tissue PCO2, cerebrovascular CO2 reactivity would be higher when expressed against Pjv,CO2 than with Pa,CO2, and would be related to the degree of ventilatory change during hypercapnia. Incremental hypercapnia was achieved through 4 min administrations of 4% and 8% CO2. Incremental hypocapnia involved two 4 min steps of hyperventilation to change PET,CO2, 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 CO2 step. Cerebrovascular reactivity to CO2 was expressed as the percentage change in blood flow velocity in the middle cerebral artery (MCAv) per mmHg change in Pa,CO2 and Pjv,CO2. During hypercapnia, but not hypocapnia, PET,CO2 overestimated Pa,CO2 by +2.4 ± 3.4 mmHg and underestimated MCAv-CO2 reactivity (P < 0.05). The hypercapnic and hypocapnic MCAv-CO2 reactivity was higher (∼97% and ∼24%, respectively) when expressed with Pjv,CO2 than Pa,CO2 (P < 0.05). The hypercapnic MCAv–Pjv,CO2 reactivity was inversely related to the increase in ventilatory change (R2= 0.43; P < 0.05), indicating that a reduced reactivity results in less central CO2 washout and greater ventilatory stimulus. Differences in the PET,CO2, Pa,CO2 and Pjv,CO2–MCAv relationships have implications for the true representation and physiological interpretation of cerebrovascular CO2 reactivity