Ventilatory and pulmonary vascular response to hypoxia and susceptibility to high altitude pulmonary oedema

Abstract

Reduced tolerance to high altitude may be associated with a low ventilatory and an increased pulmonary vascular response to hypoxia. We therefore, examined whether individuals susceptible to acute mountain sickness (AMS) or high altitude pulmonary oedema (HAPE) could be identified by noninvasive measurements of these parameters at low altitude. Ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) at rest and during exercise, as well as hypoxic pulmonary vascular response (HPVR) at rest, were examined in 30 mountaineers whose susceptibility was known from previous identical exposures to high altitude. Isocapnic HVR expressed as difference in minute ventilation related to difference in arterial oxygen saturation (delta V'E/ delta Sa,O2) (L.min-1/%) was significantly lower in subjects susceptible to HAPE (mean +/- SEM 0.8 +/- 0.1; n = 10) compared to nonsusceptible controls (1.5 +/- 0.2; n = 10), but was not significantly different from subjects susceptible to AMS (1.2 +/- 0.2; n = 10). Hypercapnic ventilatory response was not significantly different between the three groups. Discrimination between groups could not be improved by measurements of HVR during exercise (50% maximum oxygen consumption (V'O2,max)), or by assessing ventilation and oxygen saturation during a 15 min steady-state exercise (35% V'O2,max) at fractional inspiratory oxygen (FI,O2) of 0.14. Pulmonary artery pressure (Ppa) estimated by Doppler measurements of tricuspid valve pressure at an FI,O2 of 0.21 and 0.12 (10 min) did not lead to a further discrimination between subjects susceptible to HAPE and AMS with the exception of three subjects susceptible to HAPE who showed an exaggerated HPVR. It is concluded that a low ventilatory response to hypoxia is associated with an increased risk for high altitude pulmonary oedema, whilst susceptibility to acute mountain sickness may be associated with a high or low ventilatory response to hypoxia. A reliable discrimination between subjects susceptible to high altitude pulmonary oedema and acute mountain sickness with a low ventilatory response to hypoxia is not possible by Doppler echocardiographic estimations of hypoxic pulmonary vascular response.

Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude

“…The crucial role of high pulmonary artery pressure is confirmed by elevated pulmonary artery pressures in patients with HAPE [2][3][4], enhanced pulmonary vasoconstrictive response in HAPE-susceptible subjects to acute hypoxia [5][6][7][8] or exercise in normoxia [6,7,9]. It is also confirmed by the fact that interventions decreasing pulmonary artery pressure are effective in the treatment [10,11] and prevention [4] of HAPE.…”

“…Most studies report positive associations [8,12,13], although one study found no relationship between HAPE and HVR [14]. Furthermore, some studies have reported associations between susceptibility to HAPE and lower vital capacity [8,9,15,16] or lower functional residual capacity [16].…”

Acute high-altitude sickness

“…These blood gas changes might be due to a mild interstitial oedema not visible on chest radiographs [8], but suggested by a slight decrease of vital capacity and increase of closing volume [9,10]; however, these are inconsistent findings [11]. Furthermore, a lower ventilatory drive in hypoxia might contribute to more severe hypoxaemia in AMS, at least in some individuals [12,13]. Laboratory investigations of the brain in AMS show that all subjects exposed to altitudes of 4500 m had normal lumbar cerebrospinal fluid pressure and a small increase of brain volume assessed using MRI (<1%, ∼7-10 mL) after 16 h, independent of presence or absence of AMS [14].…”

“…They have lower HVR [12,67] and stronger sympathetic tone [68]. HVR is set largely by the peripheral chemoreceptors, which results in a lower alveolar oxygen tension and higher carbon dioxide tension at the same altitude as HAPE-resistant subjects, and thus leads to a stronger stimulus for HPV [69].…”

“…Increased peripheral hypoxic chemoreceptor sensitivity also appears to reduce the strength of HPV, independent of differences in alveolar ventilation [70]. HAPE-susceptible individuals have slightly lower lung volumes and reduced diffusion capacity [12,71,72].…”