Bradycardia, increased cardiac output, and reversal of pulmonary hypertension in altitude natives living at sea level.

Sime, Francisco; Peñaloza, Dante; Ruiz, Luis

doi:10.1136/hrt.33.5.647

Cited by 101 publications

(69 citation statements)

References 7 publications

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“…The main role of the structural changes in the pulmonary vasculature is confirmed by the slow decline of PAP, which becomes normal after 2 years of residence at SL. 18 The recent exciting developments in the cellular and molecular mechanism of chronic hypoxic PH are beyond the scope of this review.…”

Section: Pathogenesis Of Human Chronic Hypoxic Pulmonary Hypertensionmentioning

confidence: 99%

The Heart and Pulmonary Circulation at High Altitudes

2007

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Abstract-More than 140 million people worldwide live Ͼ2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential. Key Words: altitude Ⅲ altitude sickness Ⅲ hypertension, pulmonary P eople native to high altitude (HA) environments live in an environment of hypobaric hypoxia with low ambient partial pressure of oxygen. As a consequence, they develop alveolar hypoxia, hypoxemia, and polycythemia. Despite this, healthy highlanders are able to perform physical activities similar to and often even more strenuous than those of people living at sea level (SL). This phenomenon has been ascribed to adaptive mechanisms that occur at sequential steps of the oxygen transport system with the main purpose of decreasing the total pO 2 gradient from ambient hypoxic air to mixed venous blood at the tissue level.The heart and pulmonary circulation in healthy people living at HA exhibit important physiological and anatomic characteristics, which resemble those that occur in chronic clinical conditions associated with alveolar hypoxia, hypoxemia, and polycythemia. Healthy HA natives have pulmonary hypertension (PH), right ventricular hypertrophy (RVH) and increased amount of smooth muscle cells (SMCs) in the distal pulmonary arterial branches. All these findings become exaggerated when healthy highlanders lose their capacity for adaptation and develop chronic mountain sickness (CMS). The physiological, pathological, pathogenic, and cl...

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Section: Pathogenesis Of Human Chronic Hypoxic Pulmonary Hypertensionmentioning

confidence: 99%

The Heart and Pulmonary Circulation at High Altitudes

2007

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“…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 …”

Section: Pathophysiology Of Acclimatization To Hypoxia Pulmonary Vascmentioning

confidence: 99%

“…51 This augmented rise in PAP with exercise can persist for some time in acclimatized highlanders on descent to sea level, most likely reflecting structural remodeling of the pulmonary vasculature with chronic exposure. 5,8 The increase in PAP may impair gas exchange from interstitial and alveolar edema and reduce maximal cardiac output, leading to a reduction in oxygen transport to exercising muscles. 49 However, definitive data from direct measurements of RV function at altitude are few, and not all are convinced that the improvement in exercise capacity at altitude reported with some pulmonary vasodilators is attributed to a reduction in RV afterload.…”

Section: Exercisementioning

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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“…For example, when HA adult natives descended to sea level for several weeks, their cardiac functions remained unchanged. 79,80 Third, the interethnic difference of brain structure can be large. Brain morphologic differences between populations of different origins have been found in whole-brain and region-specific volume.…”

Section: Limitationsmentioning

confidence: 99%