Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization

Hilty, Matthias P.; Müller, Andreas Michael; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

doi:10.1089/ham.2016.0004

Cited by 22 publications

(35 citation statements)

References 43 publications

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“…In support of our finding of preservation in responsiveness of the pulmonary circulation, Hilty et al (2016) studied healthy volunteers by right heart catheterization after 3 weeks at 3600 m. They found that while PA pressures were mildly elevated, when the pulmonary circulation was challenged with a brief 2.5 l min −1 increase in cardiac output by transient thigh-cuff occlusion there was no increase in PA pressure. In this regard, our findings of maintained responsiveness to changes in inspired oxygen are similar and indicate that the pulmonary vascular pressures, although greater over this time, do not become permanently fixed at a higher resistance.…”

Section: Circulating Biomarker Concentrations At Different Testingmentioning

confidence: 54%

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m)

Luks

Levett

Goss

et al. 2017

Experimental Physiology

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What is the central question of this study? Do the pulmonary vascular responses to hypoxia change during progressive exposure to high altitude and can alterations in these responses be related to changes in concentrations of circulating biomarkers that affect the pulmonary circulation? What is the main finding and its importance? In our field study with healthy volunteers, we demonstrate changes in pulmonary artery pressure suggestive of remodelling in the pulmonary circulation, but find no changes in the acute responsiveness of the pulmonary circulation to changes in oxygenation during 2 weeks of exposure to progressive hypoxia. Pulmonary artery pressure changes were associated with changes in erythropoietin, 8-isoprostane, nitrite and guanosine 3',5'-cyclic monophosphate. We sought to determine whether changes in pulmonary artery pressure responses to hypoxia suggestive of vascular remodelling occur during progressive exposure to high altitude and whether such alterations are related to changes in concentrations of circulating biomarkers with known or suspected actions on the pulmonary vasculature during ascent. We measured tricuspid valve transvalvular pressure gradients (TVPG) in healthy volunteers breathing air at sea level (London, UK) and in hypoxic conditions simulating the inspired O partial pressures at two locations in Nepal, Namche Bazaar (NB, elevation 3500 m) and Everest Base Camp (EBC, elevation 5300 m). During a subsequent 13 day trek, TVPG was measured at NB and EBC while volunteers breathed air and hyperoxic or hypoxic mixtures simulating the inspired O partial pressures at the other locations. For each location, we determined the slope of the relationship between TVPG and arterial oxygen saturation (SaO2) to estimate the pulmonary vascular response to hypoxia. Mean TVPG breathing air was higher at any SaO2 at EBC than at sea level or NB, but there was no change in the slope of the relationship between SaO2 and TVPG between locations. Nitric oxide availability remained unchanged despite increases in oxidative stress (elevated 8-isoprostane). Erythropoietin, pro-atrial natriuretic peptide and interleukin-18 levels progressively increased on ascent. Associations with TVPG were observed only with erythropoietin, 8-isoprostane, nitrite and guanosine 3',5'-cyclic monophosphate. Although the increased TVPG for any given SaO2 at EBC suggests that pulmonary vascular remodelling might occur during 2 weeks of progressive hypoxia, the lack of change in the slope of the relationship between TVPG and SaO2 indicates that the acute pulmonary vascular responsiveness to changes in oxygenation does not vary within this time frame.

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Section: Circulating Biomarker Concentrations At Different Testingmentioning

confidence: 54%

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m)

Luks

Levett

Goss

et al. 2017

Experimental Physiology

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“…In humans, remodelling of the pulmonary arterioles has been indirectly demonstrated during constant exposure to a high altitude environment over several weeks (Hilty et al . ). However, remodelling of pulmonary arterioles and systemic capillary angiogenesis are not necessarily regulated by the same mechanisms, and the timeframe of such processes in animal and human models may diverge.…”

Section: Discussionmentioning

confidence: 97%

“…Cardiac output at rest is expected to decrease towards SL values after an initial increase in well‐acclimatized lowlanders at moderate altitude (Hilty et al . ), as well as at extreme altitude (Reeves et al . ), whereas, in expedition settings, several previous studies have reported a decrease in cardiac output compared to baseline after 10–15 days (Wolfel et al .…”

Section: Discussionmentioning

confidence: 99%

Recruitment of non‐perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m

Hilty

Merz

Hefti

et al. 2019

The Journal of Physiology

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Key pointsr A physiological response to increase microcirculatory oxygen extraction capacity at high altitude is to recruit capillaries. r In the present study, we report that high altitude-induced sublingual capillary recruitment is an intrinsic mechanism of the sublingual microcirculation that is independent of changes in cardiac output, arterial blood pressure or systemic vascular hindrance.r Using a topical nitroglycerin challenge to the sublingual microcirculation, we show that high altitude-related capillary recruitment is a functional response of the sublingual microcirculation as opposed to an anatomical response associated with angiogenesis.r The concurrent presence of a low capillary density and high microvascular reactivity to topical nitroglycerin at sea level was found to be associated with a failure to reach the summit, whereas the presence of a high baseline capillary density with the ability to further increase maximum recruitable capillary density upon ascent to an extreme altitude was associated with summit success.Abstract A high altitude (HA) stay is associated with an increase in sublingual capillary total vessel density (TVD), suggesting microvascular recruitment. We hypothesized that microvascular recruitment occurs independent of cardiac output changes, that it relies on haemodynamic changes within the microcirculation as opposed to structural changes and that microcirculatory function is related to individual performance at HA. In 41 healthy subjects, sublingual handheld vital microscopy and echocardiography were performed at sea level (SL), as well as at 6022 m Matthias Peter Hilty has found that, during his education and throughout his board certification in General Internal Medicine and Intensive Care Medicine, his main interests lie in the foundations of human physiology, in addition to their application in clinical practice. Studies of the response of the macro-and microcirculation to critical illness and high altitude environments have lead to his high appreciation of the contrast between witnessing cardiovascular pathophysiology during field studies, in laboratory settings and at the bedside. Hoping to support the upcoming challenge to translate these findings to clinical use, Dr Hilty is applying advanced computational techniques for the objective assessment of a patient's microcirculation. M. P. Hilty and othersJ Physiol 597.10 (C2) and 7042 m (C3), during ascent to 7126 m within 21 days. Sublingual topical nitroglycerin was applied to measure microvascular reactivity and maximum recruitable TVD (TVD NG ). HA exposure decreased resting cardiac output, whereas TVD (mean ± SD) increased from 18.81 ± 3.92 to 20.92 ± 3.66 and 21.25 ± 2.27 mm mm −2 (P < 0.01). The difference between TVD and TVD NG was 2.28 ± 4.59 mm mm −2 at SL (P < 0.01) but remained undetectable at HA. Maximal TVD NG was observed at C3. Those who reached the summit (n = 15) demonstrated higher TVD at SL (P < 0.01), comparable to TVD NG in non-summiters (n = 21) at SL and in both groups at C2. Recruitment of sublingu...

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“…The appropriate water loss and blood concentration is conducive to increase the efficiency of red blood cells carrying oxygen, improving the ability of acclimatization, which may be very important for the early migratory population (Yang F. et al, 2016). In contrast, excessive suppression of thirst, can also cause more serious water metabolic disorders, such as dehydration and abnormal water distribution, which is related to deep vein thrombosis (Gupta and Ashraf, 2012; Hull et al, 2016) and high altitude pulmonary edema (Sawka et al, 2015; Hilty et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats

Yang

Zhou

et al. 2017

Front. Mol. Neurosci.

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Water intake reduction (anti-dipsogenic effects) under hypoxia has been well established, but the underlying reason remains unknown. Our previous report indicated that activated TRPV4 neurons in SFO are associated with anti-dipsogenic effects under hypoxia. Although low partial pressure of blood oxygen directly activates TRPV4, humoral factors could also be involved. In the present study, we hypothesize that adropin, a new endogenous peptide hormone, was rapidly increased (serum and brain) concomitant with reduced water intake in early hypoxia. Also, the nuclear expression of c-Fos, a marker for neuronal activation, related to water-consumption (SFO and MnPO) was inhibited. These effects were mitigated by a scavenger, rat adropin neutralizing antibody, which effectively neutralized adropin under hypoxia. Interestingly, injection of recombinant adropin in the third ventricle of the rats also triggered anti-dipsogenic effects and reduced c-Fos positive cells in SFO, but these effects were absent when TRPV4 was knocked down by shRNA. Moreover, adropin-activated CamKK-AMPK signaling related to TRPV4 calcium channel in SFO in normoxia. These results revealed that dissociative adropin was elevated in acute hypoxia, which was responsible for anti-dipsogenic effects by altering TRPV4-CamKK-AMPK signaling in SFO.

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Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization

Cited by 22 publications

References 43 publications

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m)

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300 m)

Recruitment of non‐perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m

Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats

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