AltitudeOmics: effect of reduced barometric pressure on detection of intrapulmonary shunt, pulmonary gas exchange efficiency, and total pulmonary resistance

Abstract

Blood flow through intrapulmonary arteriovenous anastomoses (Q) occurs in healthy humans at rest and during exercise when breathing hypoxic gas mixtures at sea level and may be a source of right-to-left shunt. However, at high altitudes, Q is reduced compared with sea level, as detected using transthoracic saline contrast echocardiography (TTSCE). It remains unknown whether the reduction in Q (i.e., lower bubble scores) at high altitude is due to a reduction in bubble stability resulting from the lower barometric pressure (P) or represents an actual reduction in Q. To this end, Q, pulmonary artery systolic pressure (PASP), cardiac output (Q), and the alveolar-to-arterial oxygen difference (AaDO) were assessed at rest and during exercise (70-190 W) in the field (5,260 m) and in the laboratory (1,668 m) during four conditions: normobaric normoxia (NN; [Formula: see text] = 121 mmHg, P = 625 mmHg; n = 8), normobaric hypoxia (NH; [Formula: see text] = 76 mmHg, P = 625 mmHg; n = 7), hypobaric normoxia (HN; [Formula: see text] = 121 mmHg, P = 410 mmHg; n = 8), and hypobaric hypoxia (HH; [Formula: see text] = 75 mmHg, P = 410 mmHg; n = 7). We hypothesized Q would be reduced during exercise in isooxic hypobaria compared with normobaria and that the AaDO would be reduced in isooxic hypobaria compared with normobaria. Bubble scores were greater in normobaric conditions, but the AaDO was similar in both isooxic hypobaria and normobaria. Total pulmonary resistance (PASP/Q) was elevated in HN and HH. Using mathematical modeling, we found no effect of hypobaria on bubble dissolution time within the pulmonary transit times under consideration (<5 s). Consequently, our data suggest an effect of hypobaria alone on pulmonary blood flow. NEW & NOTEWORTHY Blood flow through intrapulmonary arteriovenous anastomoses, detected by transthoracic saline contrast echocardiography, was reduced during exercise in acute hypobaria compared with normobaria, independent of oxygen tension, whereas pulmonary gas exchange efficiency was unaffected. Modeling the effect(s) of reduced air density on contrast bubble lifetime did not result in a significantly reduced contrast stability. Interestingly, total pulmonary resistance was increased by hypobaria, independent of oxygen tension, suggesting that pulmonary blood flow may be changed by hypobaria.

Specific effect of hypobaria on cerebrovascular hypercapnic responses in hypoxia

“…In hypobaria, the putative increased physiological dead space and altered alveolo‐capillary diffusion in HH compared to NH (Millet et al, ). The present results of E (10.3 vs. 12.1 L/min in HN vs. NN) are in line with previous values in HN versus NN at rest (11.5 vs. 15.6 L/min) (Petrassi et al, ). The lower P ET CO 2 in HN versus NN was observed in the three phases (baseline, hyperventilation, and hypercapnia) without any hyperventilation.…”

“…Decrease in barometric pressure has been reported to also increase pulmonary vascular vasoconstriction pressure due to the lower air density in hypobaria (Conkin, ). More precisely, pulmonary resistance was increased in hypobaria (HN and HH), independent of oxygen tension, suggesting that pulmonary blood flow may be changed in hypobaria (Petrassi et al, ). Moreover, different fluid and acid–base balance responses mediated by augmentation of aldosterone and altered cell‐membrane permeability have been suggested as a consequence of hypobaria (Loeppky et al, ).…”

Impaired pulmonary gas exchange efficiency, but normal pulmonary artery pressure increases, with hypoxia in men and women with a patent foramen ovale

“…However, below a of ∼70 Torr the contribution of a diffusion limitation would increase and the would begin to widen, or would be similar to the under resting normoxia, depending on the level of . This is precisely what the present data and previous work (Eldridge, Braun, Yoneda, & Walby, 2006; Elliott et al., 2015; Farrell et al., 2015; Jonk et al., 2007; Petrassi et al., 2018; Podolsky et al., 1996) demonstrate and is parallel to what was proposed by the modelling work of Farhi and Rahn (1955).…”

No effect of patent foramen ovale on acute mountain sickness and pulmonary pressure in normobaric hypoxia

“…Many studies have examined differences in hypobaric and normobaric hypoxia to determine whether hypoxia per se is causing the physiological changes observed, or whether reductions in barometric pressure combined with hypoxia result in the observed physiological alterations. While there is still considerable debate in this area (Millet et al., 2012; Mounier & Brugniaux, 2012), multiple studies have shown many different responses to hypobaric hypoxia compared to normobaric hypoxia despite identical $${P_{{\rm{I}}{{\rm{O}}_{\rm{2}}}}}$$, $${P_{{\rm{a}}{{\rm{O}}_{\rm{2}}}}}$$ and $${P_{{\rm{A}}{{\rm{O}}_{\rm{2}}}}}$$ between conditions (Aebi et al., 2020; Beidleman et al., 2014; Coppel et al., 2015; Faiss et al., 2013; Loeppky et al., 1997, 2005; Petrassi et al, 2018; Roach et al., 1996; Saugy et al., 2016; Savourey et al., 2003; Takezawa et al., 2021; Woods et al., 2017). For example, $${S_{{\rm{a}}{{\rm{O}}_{\rm{2}}}}}$$ and $${\dot{V}_{\rm{E}}}$$ are lower during short term exposure to hypobaric hypoxia compared to normobaric hypoxia (Loeppky et al., 1997; Savourey et al., 2003).…”