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

ABSTRACT: 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. Testing sessions involved resting spontaneous and driven (squat-stand maneuvers at very low (VLF, 0.05?Hz) and low (LF, 0.10?Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure-flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure-flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure-flow relationship (in both frequency and time domains) is unaltered at 5,050?m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP.

SUBMITTER: Smirl JD

PROVIDER: S-EPMC3915197 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

Smirl Jonathan D JD Lucas Samuel J E SJ Lewis Nia C S NC duManoir Gregory R GR Smith Kurt J KJ Bakker Akke A Basnyat Aperna S AS Ainslie Philip N PN

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20131030 2

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. Testing sessions involved resting spontaneous and driven (squat-stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.1 ...[more]

PMID: 24169852

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Project description:New findingsWhat is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de-acclimatized Sherpa both demonstrated pulmonary vascular responsiveness to supplemental oxygen that was maintained for 12 days' exposure to progressively increasing altitude. An additional 2 weeks' acclimatization at 5050 m altitude rendered the pulmonary vasculature minimally responsive to oxygen similar to the fully acclimatized non-ascent Sherpa. Additional hypoxic exposure at that time point did not augment hypoxic pulmonary vasoconstriction.AbstractProlonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n = 20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n = 11) left altitude and after de-acclimatization in Kathmandu for ∼7 days re-ascended with the lowlanders over 8-10 days to 5050 m. The second Sherpa group (non-ascent Sherpa, n = 12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P = 0.02) and PVR (P = 0.02). After ∼14 days at 5050 m, PASP decreased with supplemental oxygen (mean decrease: 3.9 mmHg, 95% CI 2.1-5.7 mmHg, P < 0.001); however, PVR was unchanged (P = 0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14 days at 5050 m altitude, there was no change in PVR to hypoxia or O2 supplementation in lowlanders or either Sherpa group. These data show that both duration of exposure and residential altitude influence the pulmonary vascular responses to hypoxia.

Project description:BackgroundPrevious literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA.MethodsA total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay.FindingsTwelve and three subjects, developed venous (incidence: 5,926/105 person-years) and arterial (incidence: 1,482/105 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001).InterpretationThe incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis.FundingResearch grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.

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

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

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