Residence at 3,800-m altitude for 5 mo in growing dogs enhances lung diffusing capacity for oxygen that persists at least 2.5 years

Abstract

Mammals native to high altitude (HA) exhibit larger lung volumes than their lowland counterparts. To test the hypothesis that adaptation induced by HA residence during somatic maturation improves pulmonary gas exchange in adulthood, male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5 mo of age and then returned to SL prior to somatic maturity while their littermates were simultaneously raised at SL. Following return to SL, all animals were trained to run on a treadmill; gas exchange and hemodynamics were measured 2.5 years later at rest and during exercise while breathing 21% and 13% O(2). The multiple inert gas elimination technique was employed to estimate ventilation-perfusion (Va/Q) distributions and lung diffusing capacity for O(2) (Dl(O(2))). There were no significant intergroup differences during exercise breathing 21% O(2). During exercise breathing 13% O(2), peak O(2) uptake and Va/Q distributions were similar between groups but arterial pH, base excess, and O(2) saturation were higher while peak lactate concentration was lower in animals raised at HA than at SL. At a given exercise intensity, alveolar-arterial O(2) tension gradient (A-aDo(2)) attributable to diffusion limitation was lower while Dlo(2) was 12-25% higher in HA-raised animals. Mean systemic arterial blood pressure was also lower in HA-raised animals; mean pulmonary arterial pressures were similar. We conclude that 5 mo of HA residence during maturation enhances long-term gas exchange efficiency and Dl(O(2)) without impacting Va/Q inequality during hypoxic exercise at SL.

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

“…Development or prolonged residence at high altitude can increase pulmonary diffusion capacity by increasing the surface area available for diffusion and by reducing the thickness of the pulmonary blood-gas interface (Hsia et al, 2005;Hsia et al, 2007;Ravikumar et al, 2009). Although relatively little is known about how O 2 levels control lung morphogenesis during development or during adult life stages (Metzger et al, 2008), these induced changes in lung morphology clearly help improve O 2 transport during hypoxia.…”

Why Are High Altitude Natives So Strong at High Altitude? Nature vs. Nurture: Genetic Factors vs. Growth and Development

“…In contrast, long-term exposure of adult dogs to hypoxia (>3 years) does not affect the morphology or physiology of the pulmonary system [ 43 , 49 ]. The recent study by Hsia et al [ 47 ] in fox-hounds raised at 3800 m assessed pulmonary gas exchange during exercise using the multiple inert gas elimination technique. Compared to littermates raised at sea-level, altitude-raised dogs had enhanced gas exchange effi ciency at altitude.…”

Humans In Hypoxia: A Conspiracy Of Maladaptation?!

“…For example, on the adaptive side, substantial hypoxic-induced angiogenesis in the coronary circulation enhances myocardial O 2 transport in a hypoxic environment. Furthermore, in the lung of natives and long-term residents of high altitudes (22) and in young animals exposed to long-term hypoxia (49), alveolarcapillary proliferation occurs, inducing large increases in the pulmonary diffusion surface as manifested in substantial increases in diffusion capacity at both rest and exercise. At the same time, ventilatory chemosensitivity is substantially blunted in the altitude resident both at rest and during exercise.…”