Lack of Smooth Muscle in the Small Pulmonary Arteries of the Native Ladakhi: Is the Himalayan Highlander Adapted?

Gupta, Mohini; Rao, K. S.; Anand, Inder; Banerjee, Amal; Boparai, M. S.

doi:10.1164/ajrccm/145.5.1201

Cited by 62 publications

(36 citation statements)

References 8 publications

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“…However, this does not imply that the reverse proposal (intermittent hypoxaemia could lead to pulmonary hypertension) is true. In fact, it is now recognized that the development of pulmonary hypertension due to chronic alveolar hypoxia requires a certain threshold of severity and duration [28]. It is likely that this threshold was not reached during the episodes of nocturnal hypoxia in this study9s desaturator patients.…”

Section: Discussionmentioning

confidence: 68%

Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation

Chaouat¹,

Weitzenblum²,

Kessler³

et al. 2001

Eur Respir J

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The aim of the present study was to compare the evolution of pulmonary haemodynamics and of arterial blood gases in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate hypoxaemia, with or without sleep-related oxygen desaturation.COPD patients with daytime arterial oxygen partial pressure in the range 56-69 mmHg were included prospectively. Sleep-related oxygen desaturation was defined as spending ¢30% of the nocturnal recording time with arterial oxygen saturation v90%.From the 64 patients included, 35 were desaturators (group 1) and 29 were nondesaturators (group 2). At baseline (t0), patients with sleep-related desaturation had a significantly higher daytime (mean¡SD) arterial carbon dioxide partial pressure (Pa,CO 2 ) (44.9¡4.9 mmHg versus 41.0¡4.1 mmHg, p~0.001) whereas mean pulmonary artery pressure (mPAP) was similar in the two groups. After 2 yrs (t2) of followup, 22 desaturators and 14 nondesaturators could be re-evaluated, including pulmonary haemodynamic measurements. None of the nondesaturator patients became desaturators at t2. The difference between the two groups in terms of daytime Pa,CO 2 was still present at t2. The mean changes in mPAP from t0 to t2 were similar between the two groups, as were the rates of death or requirement for long-term oxygen therapy (American Thoracic Society criteria) during follow-up of up to 6 yrs.The presence of sleep-related oxygen desaturation is not a transitional state before the worsening of daytime arterial blood gases, but is a characteristic of some chronic obstructive pulmonary disease patients who have a higher daytime arterial carbon dioxide partial pressure. Such isolated nocturnal hypoxaemia or sleep-related worsening of moderate daytime hypoxaemia does not appear to favour the development of pulmonary hypertension, nor to lead to worsening of daytime blood gases. Eur Respir J 2001; 17: 848-855.

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Section: Discussionmentioning

confidence: 68%

Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation

Chaouat¹,

Weitzenblum²,

Kessler³

et al. 2001

Eur Respir J

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“…18,19 An identical lack of medial wall in the cerebral resistance vessels might explain in part the diminished CA capacity in the Sherpas. However, because Sherpas have a cerebral CO 2 reactivity similar to that for sea-level standards, 8 a lack of medial wall in the cerebral vessels probably does not play a major role in explaining the impaired CA in the Sherpas.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Autoregulation in Subjects Adapted and Not Adapted to High Altitude

Jansen

Krins

Basnyat

et al. 2000

Stroke

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Background and Purpose-Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude. Methods-We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP. Results-In the sea-level group, at a relative MABP increase of 23Ϯ4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2Ϯ7%, Pϭ0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29Ϯ7%, there was a uniform and significant increase of Vmca of 24Ϯ9% (PϽ0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21Ϯ6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%. Conclusions-All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.

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“…Data are few, but PAP measurements in ethnic Tibetans living over 3600 m are in the range typical of healthy adults at sea level, 77,78 and postmortem studies show little vascular remodeling. 78,80 A blunted pulmonary vascular pressor response to acute and sustained hypoxia is retained by Tibetans at sea level.…”

Section: Insights From Humans Adapted To Hypoxia Variation In Susceptmentioning

confidence: 99%

Pathophysiology and Treatment of High-Altitude Pulmonary Vascular Disease

et al. 2015

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582I t is estimated that >140 million people live above 2500 m in various regions of the world.1 There are many challenges to living at high altitude, but chronic exposure to alveolar hypoxia is prominent among them. Inspired Po 2 falls from ≈150 mm Hg at sea level to ≈100 mm Hg at 3000 m and 43 mm Hg on the summit of Everest (8400 m). 2,3 The body responds by hyperventilating, increasing resting heart rate, and stimulating red cell production in an attempt to maintain the oxygen content of arterial blood at or above sea level values.2 However, hypoxic pulmonary vasoconstriction (HPV) and vascular remodeling, together with increased erythropoiesis, place an increased pressure load on the right ventricle (RV). How well healthy humans adapt to hypoxia depends on their rate of ascent to altitude, the severity and duration of their exposure, and their genetic background. Pathophysiology of Acclimatization to Hypoxia Pulmonary Vascular Response to HypoxiaFor most mammals, including humans, a rise in pulmonary artery pressure (PAP) is an early and inevitable consequence of ascent to high altitude. Resting mean PAP increases along a parabolic curve from 15 mm Hg at 2000 m to ≈30 mm Hg at 4500 m. 4 The exceptions and interindividual variation in the magnitude of response offer a natural experiment that might provide insight into fundamental underlying mechanisms (vide infra).The initial rise in PAP on exposure to hypoxia is attributed to HPV. With chronic hypoxia, other mechanisms that likely drive vascular remodeling soon contribute to the elevated pressure ( Figure 1A). After 2 or 3 weeks of hypoxia, there is little response to rebreathing 100% oxygen, indicating a structural resistance to pulmonary blood flow rather than one based solely on increased vasomotor tone. 6 A fall in PAP on re-exposure to a normal oxygen environment is evident in rats monitored by telemetry over days after removal from a hypoxic chamber 7 ( Figure 1B) and is also documented in humans. 4,8 Pulmonary Arteriolar Vasoconstriction Dominates the Acute Pulmonary Vascular Response to HypoxiaOxygen tension is a major regulator of pulmonary vascular tone and a physiological mechanism for matching perfusion with ventilation. A fall in alveolar Po 2 is the main stimulus for HPV, but a reduction in mixed venous and bronchial arterial Po 2 may also contribute. 9 Ventilation of intact lungs with a hypoxic gaseous mixture (eg, fraction of inspired oxygen=0.10) leads to acute pulmonary vasoconstriction throughout the pulmonary vascular bed, including nonmuscular arterioles, capillaries, and veins, but is most pronounced in small pulmonary arterioles. [10][11][12][13] That said, HPV is not distributed evenly throughout the lung and lung perfusion is inhomogeneous during hypoxia.14 HPV has at least 2 phases ( Figure 1A). An initial constrictor response that starts within seconds and reaches a maximum within minutes is followed by a sustained phase, which develops after 30 to 120 minutes. 9 A transient phase of vasodilation may be observed linking the two, an...

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Lack of Smooth Muscle in the Small Pulmonary Arteries of the Native Ladakhi: Is the Himalayan Highlander Adapted?

Cited by 62 publications

References 8 publications

Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation

Outcome of COPD patients with mild daytime hypoxaemia with or without sleep-related oxygen desaturation

Cerebral Autoregulation in Subjects Adapted and Not Adapted to High Altitude

Pathophysiology and Treatment of High-Altitude Pulmonary Vascular Disease

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