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.

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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 transfer-function 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 ( approximately 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 approximately 50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.

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In experienced hands, ultrasound provides at least as good success rates as other methods of peripheral nerve location. Individual studies have demonstrated that ultrasound may reduce complication rates and improve quality, performance time, and time to onset of blocks. Due to wide variations in study outcomes we chose not to combine the studies in our analysis.

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% CO 2), hypocapnia (voluntary hyperventilation), and hypoxia (12 and 10% O 2). 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 Ϯ 18 and 150 Ϯ 36 mol/l at 4% and 8% CO 2, respectively (both P Ͻ 0.05). Release of cerebral CNP was also observed during changes in CO 2 (hypercapnia vs. hypocapnia, P Ͻ 0.05). During hypoxia, there was a net cerebral uptake of nitrite, which was reflected by a decreased venous-arterial difference for nitrite: Ϫ96 Ϯ 14 mol/l at 10% O 2 (P Ͻ 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 CO 2-induced CBF changes. cerebral circulation; nitric oxide; endothelium RESPIRATORY-INDUCED CHANGES in arterial PCO 2 (Pa CO 2 ) and, to a lesser extent, PO 2 (Pa O 2 ) play a major role in cerebral blood flow (CBF) regulation (9). Elevations in Pa CO 2 (hypercapnia) lead to vasodilation of cerebral arterioles in the downstream bed and a subsequent increase in CBF, whereas a reduction in Pa CO 2 (hypocapnia) leads to vasoconstriction and a subsequent decrease in CBF (28, 65). A fall in Pa O 2 (hypoxia) below a certain threshold (Ͻ40 Torr) also produces cerebral vasodilation (19). These arterial blood gas-induced changes in CBF are mediated through changes in cerebrovascular resistance via alterations in vascular smooth muscle diameter in response to changes in the level of intracellular calcium and/or calcium sensitivity (for review see Ref. 22). Cerebrovascular tone is influenced by several chemical substances, including nitric oxide (NO). NO, synthesized from the terminal guanidino nitrogen atom(s) of L-arginine in a two-step reaction that is catalyzed by the enzyme NO synthase (NOS) (48), is an important vasoactive factor that dilates the cerebral vasculature. Under normal conditions, two isoforms of NOS are expressed in the brain, endothelium-derived NOS (eNOS) and neuronal-derived NOS (nNOS) (61), although evidence for the role of eNOS vs. nNOS in the control of CBF is controversial (3). Vasodilation evoked by NO is initiated by an increase in cGMP (7).Pharmac...

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