Key pointsr This study assessed the dynamic response of global cerebral blood flow (CBF) and cerebral fuel utilization during and following incremental supine exercise to exhaustion.r Global CBF increased more during exercise and recovery at high altitude (HA) compared with sea level (SL) such that cerebral oxygen delivery (CD O 2 ) was maintained.r The increase in cerebral metabolic rate of oxygen during maximal exercise at HA was half the increase observed at SL.r Arterial lactate production during exercise at the same absolute intensities was greater at HA compared with SL, but reduced at the same relative intensities.r Cerebral carbohydrate uptake (lactate and glucose) is greater than oxygen uptake at HA compared with SL, indicating a shift towards an increased non-oxidative metabolic utilization.r These results suggest that CBF increases to maintain CD O 2 during exercise at HA while changes in arterial lactate concentration and exercise intensity augment the oxidative and non-oxidative pathways to cerebral metabolism at HA. AbstractWe examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CD O 2 ) in excess of that required by an increasing cerebral metabolic rate of oxygen (CMR O 2 ); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (W max )) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute W max was reduced by ß50%. During submaximal exercise workloads (20-60% W max ), despite an elevated absolute gCBF (ß20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% W max and recovery.

Shear-Mediated Dilation of the Internal Carotid Artery Occurs Independent of Hypercapnia.http://researchonline.ljmu.ac.uk/6418/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription.

Our aim was to quantify the end-tidal-to-arterial gas gradients for O2 (PET-PaO2) and CO2 (Pa-PETCO2) during a CO2 reactivity test to determine their influence on the cerebrovascular (CVR) and ventilatory (HCVR) response in subjects with (PFO+, n = 8) and without (PFO-, n = 7) a patent foramen ovale (PFO). We hypothesized that 1) the Pa-PETCO2 would be greater in hypoxia compared with normoxia, 2) the Pa-PETCO2 would be similar, whereas the PET-PaO2 gradient would be greater in those with a PFO, 3) the HCVR and CVR would be underestimated when plotted against PETCO2 compared with PaCO2, and 4) previously derived prediction algorithms will accurately target PaCO2. PETCO2 was controlled by dynamic end-tidal forcing in steady-state steps of -8, -4, 0, +4, and +8 mmHg from baseline in normoxia and hypoxia. Minute ventilation (V̇E), internal carotid artery blood flow (Q̇ICA), middle cerebral artery blood velocity (MCAv), and temperature corrected end-tidal and arterial blood gases were measured throughout experimentation. HCVR and CVR were calculated using linear regression analysis by indexing V̇E and relative changes in Q̇ICA, and MCAv against PETCO2, predicted PaCO2, and measured PaCO2. The Pa-PETCO2 was similar between hypoxia and normoxia and PFO+ and PFO-. The PET-PaO2 was greater in PFO+ by 2.1 mmHg during normoxia (P = 0.003). HCVR and CVR plotted against PETCO2 underestimated HCVR and CVR indexed against PaCO2 in normoxia and hypoxia. Our PaCO2 prediction equation modestly improved estimates of HCVR and CVR. In summary, care must be taken when indexing reactivity measures to PETCO2 compared with PaCO2.

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We sought to characterize and quantify the performance of a portable dynamic end-tidal forcing (DEF) system in controlling the partial pressure of arterial CO2 (Pa(CO2)) and O2 (Pa(O2)) at low (LA; 344 m) and high altitude (HA; 5,050 m) during an isooxic CO2 test and an isocapnic O2 test, which is commonly used to measure ventilatory and vascular reactivity in humans (n = 9). The isooxic CO2 tests involved step changes in the partial pressure of end-tidal CO2 (PET(CO2)) of -10, -5, 0, +5, and +10 mmHg from baseline. The isocapnic O2 test consisted of a 10-min hypoxic step (PET(O2) = 47 mmHg) from baseline at LA and a 5-min euoxic step (PET(O2) = 100 mmHg) from baseline at HA. At both altitudes, PET(O2) and PET(CO2) were controlled within narrow limits (<1 mmHg from target) during each protocol. During the isooxic CO2 test at LA, PET(CO2) consistently overestimated Pa(CO2) (P < 0.01) at both baseline (2.1 ± 0.5 mmHg) and hypercapnia (+5 mmHg: 2.1 ± 0.7 mmHg; +10 mmHg: 1.9 ± 0.5 mmHg). This P(a)-PET(CO2) gradient was approximately twofold greater at HA (P < 0.05). At baseline at both altitudes, PET(O2) overestimated Pa(O2) by a similar extent (LA: 6.9 ± 2.1 mmHg; HA: 4.5 ± 0.9 mmHg; both P < 0.001). This overestimation persisted during isocapnic hypoxia at LA (6.9 ± 0.6 mmHg) and during isocapnic euoxia at HA (3.8 ± 1.2 mmHg). Step-wise multiple regression analysis, on the basis of the collected data, revealed that it may be possible to predict an individual's arterial blood gases during DEF. Future research is needed to validate these prediction algorithms and determine the implications of end-tidal-to-arterial gradients in the assessment of ventilatory and/or vascular reactivity.

New FindingsGiven that the transient tests exploit the temporal domain of the peripheral chemoreceptors and have minimal cardiovascular and cerebrovascular confounders, we suggest that they may have broader utility than previously appreciated.

We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

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