Regulation of cerebral blood flow by arterial PCO independent of metabolic acidosis at 5050 m.

Key Points: We investigated the influence of arterial PCO (PaCO ) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m. At sea level and high altitude, we assessed stepwise alterations in PaCO following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO ). Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO ] (i.

UBC-Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude.

New Findings: What is the central question of the study? Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)? What is the main finding and its importance? This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m).

Abstract: Hypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae.

Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial CO was recently demonstrated in humans during sustained elevations in CO (hypercapnia); however, the relative contributions of CO and shear stress to this response remains unclear. We examined the hypothesis that, after a 30-s transient increase in arterial CO tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants, partial pressures of end-tidal O and CO, ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), internal carotid artery flow, diameter, and shear stress (high-resolution duplex ultrasound), and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-min steady-state and transient 30-s hypercapnic tests (both +9 mmHg CO).

Impact of sympathetic nervous system activity on post-exercise flow-mediated dilatation in humans.

Transient reduction in vascular function following systemic large muscle group exercise has previously been reported in humans. The mechanisms responsible are currently unknown. We hypothesised that sympathetic nervous system activation, induced by cycle ergometer exercise, would contribute to post-exercise reductions in flow-mediated dilatation (FMD).

Technical recommendations for the use of carotid duplex ultrasound for the assessment of extracranial blood flow.

Duplex ultrasound is an evolving technology that allows the assessment of volumetric blood flow in the carotid and vertebral arteries during a range of interventions along the spectrum of health and chronic disease. Duplex ultrasound can provide high-resolution diameter and velocity information in real-time and is noninvasive with minimal risks or contraindications. However, this ultrasound approach is a specialized technique requiring intensive training and stringent control of multiple complex settings; results are highly operator-dependent, and analysis approaches are inconsistent.

Impact of transient hypotension on regional cerebral blood flow in humans.

We examined the impact of progressive hypotension with and without hypocapnia on regional extracranial cerebral blood flow (CBF) and intracranial velocities. Participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope to inflict hypotension. End-tidal carbon dioxide was clamped at baseline levels (isocapnic trial) or uncontrolled (poikilocapnic trial).

Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses.

Key Points: Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms. Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change. Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and PCO2.

Impact of hypocapnia and cerebral perfusion on orthostatic tolerance.

We examined two novel hypotheses: (1) that orthostatic tolerance (OT) would be prolonged when hyperventilatory-induced hypocapnia (and hence cerebral hypoperfusion) was prevented; and (2) that pharmacological reductions in cerebral blood flow (CBF) at baseline would lower the 'CBF reserve', and ultimately reduce OT. In study 1 (n = 24; aged 25 ± 4 years) participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope; end-tidal carbon dioxide (P ET , CO 2) was clamped at baseline levels (isocapnic trial) or uncontrolled. In study 2 (n = 10; aged 25 ± 4 years), CBF was pharmacologically reduced by administration of indomethacin (INDO; 1.

Effect of acute hypoxia on regional cerebral blood flow: effect of sympathetic nerve activity.

We examined 1) whether global cerebral blood flow (CBF) would increase across a 6-h bout of normobaric poikilocapnic hypoxia and be mediated by a larger increase in blood flow in the vertebral artery (VA) than in the internal carotid artery (ICA); and 2) whether additional increases in global CBF would be evident following an α1-adrenergic blockade via further dilation of the ICA and VA. In 11 young normotensive individuals, ultrasound measures of ICA and VA flow were obtained in normoxia (baseline) and following 60, 210, and 330 min of hypoxia (FiO2 = 0.11).

Resting pulmonary haemodynamics and shunting: a comparison of sea-level inhabitants to high altitude Sherpas.

The incidence of blood flow through intracardiac shunt and intrapulmonary arteriovenous anastomoses (IPAVA) may differ between Sherpas permanently residing at high altitude (HA) and sea-level (SL) inhabitants as a result of evolutionary pressure to improve gas exchange and/or resting pulmonary haemodynamics. To test this hypothesis we compared sea-level inhabitants at SL (SL-SL; n = 17), during acute isocapnic hypoxia (SL-HX; n = 7) and following 3 weeks at 5050 m (SL-HA; n = 8 non-PFO subjects) to Sherpas at 5050 m (n = 14). SpO2, heart rate, pulmonary artery systolic pressure (PASP) and cardiac index (Qi) were measured during 5 min of room air breathing at SL and HA, during 20 min of isocapnic hypoxia (SL-HX; PETO2 = 47 mmHg) and during 5 min of hyperoxia (FIO2 = 1.

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation.

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g., chronic mountain sickness) and methodological issues.

Cerebral pressure-flow relationship in lowlanders and natives at high altitude.

We investigated if dynamic cerebral pressure-flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO2 normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m.

Slow breathing as a means to improve orthostatic tolerance: a randomized sham-controlled trial.

Endogenous oscillations in blood pressure (BP) and cerebral blood flow have been associated with improved orthostatic tolerance. Although slow breathing induces such responses, it has not been tested as a therapeutic strategy to improve orthostatic tolerance. With the use of a randomized, crossover sham-controlled design, we tested the hypothesis that breathing at six breaths/min (vs.

Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity.

We examined the hypothesis that α(1)-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal Pco(2) were obtained.

Diurnal variation in vascular function: role of sleep.

Although vascular function is lower in the morning than afternoon, previous studies have not assessed the influence of prior sleep on this diurnal variation. The authors employed a semiconstant routine protocol to study the contribution of prior nocturnal sleep to the previously observed impairment in vascular function in the morning. Brachial artery vascular function was assessed using the flow-mediated dilation technique (FMD) in 9 healthy, physically active males (mean ± SD: 27 ± 9 yrs of age), at 08:00 and 16:00 h following, respectively, 3.

α1-Adrenoreceptor activity does not explain lower morning endothelial-dependent, flow-mediated dilation in humans.

Early morning reduction in endothelium-dependent, flow-mediated dilation (FMD) may contribute to the high incidence of sudden cardiac death at this time of day. The mechanisms underpinning diurnal variation in FMD are unclear, but potentially relate to a circadian rhythm in sympathetic nerve activity. We hypothesized that blockade of α(1)-mediated sympathetic nerve activity would act to attenuate the diurnal variation in FMD.

Post-exercise blood pressure reduction is greater following intermittent than continuous exercise and is influenced less by diurnal variation.

Recently, we reported that circadian variation exists in the response of blood pressure (BP) following a bout of uninterrupted exercise. The usual phenomenon of post-exercise hypotension was absent or reversed when such exercise was performed between 04:00-08:00 h. Nevertheless, research examining BP changes following bouts of intermittent exercise at different times of the day is scarce, even though this type of activity is probably more popular.