Evidence for direct CO -mediated alterations in cerebral oxidative metabolism in humans.

Aim: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO and CMR, respectively) are affected by alterations in arterial PCO (PaCO) is equivocal and therefore was the primary question of this study.

Methods: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO ranging between 30 and 60 mmHg.

Recent insights into mechanisms of hypoxia-induced vasodilatation in the human brain.

The cerebral vasculature manages oxygen delivery by adjusting arterial blood in-flow in the face of reductions in oxygen availability. Hypoxic cerebral vasodilatation, and the associated hypoxic cerebral blood flow reactivity, involve many vascular, erythrocytic and cerebral tissue mechanisms that mediate elevations in cerebral blood flow via micro- and macrovascular dilatation. This contemporary review focuses on in vivo human work - with reference to seminal preclinical work where necessary - on hypoxic cerebrovascular reactivity, particularly where recent advancements have been made.

The jugular venous-to-arterial difference during rebreathing and end-tidal forcing: Relationship with cerebral perfusion.

We examined two assumptions of the modified rebreathing technique for the assessment of the ventilatory central chemoreflex (CCR) and cerebrovascular CO reactivity (CVR), hypothesizing: (1) that rebreathing abolishes the gradient between the partial pressures of arterial and brain tissue CO [measured via the surrogate jugular venous and arterial difference (P CO )] and (2) rebreathing eliminates the capacity of CVR to influence the P CO difference, and thus affect CCR sensitivity. We also evaluated these variables during two separate dynamic end-tidal forcing (ETF) protocols (termed: ETF-1 and ETF-2), another method of assessing CCR sensitivity and CVR. Healthy participants were included in the rebreathing (n = 9), ETF-1 (n = 11) and ETF-2 (n = 10) protocols and underwent radial artery and internal jugular vein (advanced to jugular bulb) catheterization to collect blood samples.

Cerebral endothelium-dependent function and reactivity to hypercapnia: the role of α-adrenoreceptors.

We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery (ICA) with and without systemic α-adrenoreceptor blockade via Prazosin. We hypothesized that CVR would be reduced, whereas cSMD would remain unchanged, after Prazosin administration when compared with placebo. In 15 healthy adults (3 female, 26 ± 4 years), we conducted ICA duplex ultrasound during CVR [target +10 mmHg partial pressure of end-tidal carbon dioxide ([Formula: see text]) above baseline, 5 min] and cSMD (+9 mmHg [Formula: see text] above baseline, 30 s) using dynamic end-tidal forcing with and without α-adrenergic blockade (Prazosin; 0.

Brachial artery responses to acute hypercapnia: The roles of shear stress and adrenergic tone.

New Findings: What is the central question of this study? What are the contributions of shear stress and adrenergic tone to brachial artery vasodilatation during hypercapnia? What is the main finding and its importance? In healthy young adults, shear-mediated vasodilatation does not occur in the brachial artery during hypercapnia, as elevated α₁-adrenergic activity typically maintains vascular tone and offsets distal vasodilatation controlling flow.

Abstract: We aimed to assess the shear stress dependency of brachial artery (BA) responses to hypercapnia, and the α₁-adrenergic restraint of these responses. We hypothesized that elevated shear stress during hypercapnia would cause BA vasodilatation, but where shear stress was prohibited (via arterial compression), the BA would not vasodilate (study 1); and, in the absence of α₁-adrenergic activity, blood flow, shear stress and BA vasodilatation would increase (study 2).

Nitric oxide contributes to cerebrovascular shear-mediated dilatation but not steady-state cerebrovascular reactivity to carbon dioxide.

Cerebrovascular CO reactivity (CVR) is often considered a bioassay of cerebrovascular endothelial function. We recently introduced a test of cerebral shear-mediated dilatation (cSMD) that may better reflect endothelial function. We aimed to determine the nitric oxide (NO)-dependency of CVR and cSMD.

The stability of cerebrovascular CO reactivity following attainment of physiological steady-state.

New Findings: What is the central question of this study? During a steady-state cerebrovascular CO reactivity test, do different data extraction time points change the outcome for cerebrovascular CO reactivity? What is the main finding and its importance? Once steady-state end-tidal pressure of CO and haemodynamics were achieved, cerebral blood flow was stable, and so cerebrovascular CO reactivity values remained unchanged regardless of data extraction length (30 vs. 60 s) and time point (at 2-5 min).

Abstract: This study assessed cerebrovascular CO reactivity (CVR) and examined data extraction time points and durations with the hypotheses that: (1) there would be no difference in CVR values when calculated with cerebral blood flow (CBF) measures at different time points following the attainment of physiological steady-state, (2) once steady-state was achieved there would be no difference in CVR values derived from 60 to 30 s extracted means, and (3) that changes in would not be associated with any changes in CVR.

Acid-base balance and cerebrovascular regulation.

The regulation and defence of intracellular pH is essential for homeostasis. Indeed, alterations in cerebrovascular acid-base balance directly affect cerebral blood flow (CBF) which has implications for human health and disease. For example, changes in CBF regulation during acid-base disturbances are evident in conditions such as chronic obstructive pulmonary disease and diabetic ketoacidosis.

Alterations in arterial CO rather than pH affect the kinetics of neurovascular coupling in humans.

Key Points: We investigated the influence of arterial ( ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso-oxic alterations in prior to and following intravenous NaHCO to acutely elevate arterial pH and [HCO ]. The NVC response was not altered following NaHCO between stepwise stages; therefore, NVC is acutely mediated by rather than the prevailing arterial [H ]/pH.

Cerebral blood flow, cerebrovascular reactivity and their influence on ventilatory sensitivity.

New Findings: What is the topic of this review? Cerebrovascular reactivity to CO , which is a principal factor in determining ventilatory responses to CO through the role reactivity plays in determining cerebral extra- and intracellular pH. What advances does it highlight? Recent animal evidence suggests central chemoreceptor vasculature may demonstrate regionally heterogeneous cerebrovascular reactivity to CO , potentially as a protective mechanism against excessive CO washout from the central chemoreceptors, thereby allowing ventilation to reflect the systemic acid-base balance needs (respiratory changes in ) rather than solely the cerebral needs. Ventilation per se does not influence cerebrovascular reactivity independent of changes in .

Arterial carbon dioxide and bicarbonate rather than pH regulate cerebral blood flow in the setting of acute experimental metabolic alkalosis.

Key Points: We investigated the influence of arterial ( ) with and without acutely elevated arterial pH and bicarbonate ([HCO ]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso-oxic alterations in (i.e.

Distinct contributions of skin and core temperatures to flow-mediated dilation of the brachial artery following passive heating.

We measured acute vascular responses to heat stress to examine the hypothesis that macrovascular endothelial-dependent dilation is improved in a shear-dependent manner, which is further modified by skin temperature. Twelve healthy males performed whole body heating (+1.3°C esophageal temperature), bilateral forearm heating (∼38°C skin temperature), and a time-matched (∼60 min) control condition on separate days in a counterbalanced order.

Internal carotid and brachial artery shear-dependent vasodilator function in young healthy humans.

Key Points: Brachial artery (BA) shear-mediated dilatation is a widely used assessment of vascular function with links to coronary artery health and cardiovascular risk. Cerebral vascular health is often interrogated using cerebrovascular (middle cerebral artery velocity) reactivity to carbon dioxide. We show that endothelium-dependent diameter (dilator) responses are not significantly related between the internal carotid artery (ICA) and BA; nor are endothelium-independent responses.