Acute hypoxaemia and vascular function in healthy humans

Abstract

What is the central question of this study? Endothelium-dependent flow-mediated dilatation (FMD) is impaired during acute (60 min) exposure to moderate hypoxia. We examined whether FMD is impaired to the same degree during exposure to milder hypoxia. Additionally, we assessed whether smooth muscle vasodilatory capacity [glyceryl trinitrate (GTN)-induced dilatation] is impaired during acute hypoxic exposure. What is the main finding and its importance? A graded impairment in FMD and GTN-induced dilatation was evident during acute (≤60 min) exposure to mild and moderate hypoxia. This study is the first to document these graded impairments, and provides rationale to examine the relationship between graded increases in sympathetic nerve activity with hypoxia on FMD and GTN-induced dilatation. Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation [induced with glyceryl trinitrate (GTN)] are impaired at high altitude (5050 m), and FMD is impaired after acute exposure (<60 min) to normobaric hypoxia equivalent to ∼5050 m (inspired oxygen fraction ∼0.11). Whether GTN-induced dilatation is impaired acutely and whether FMD is impaired during milder hypoxia are unknown. Therefore, we assessed brachial FMD at baseline and after 30 min of mild (end-tidal PO2 74 ± 2 mmHg) and moderate (end-tidal PO2 50 ± 3 mmHg) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-induced dilatation after the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared with the normoxic baseline, reductions during mild and moderate hypoxic exposure were evident in FMD (mild versus moderate, -1.2 ± 1.1 versus -3.1 ± 1.7%; P = 0.01) and GTN-induced dilatation (-2.1 ± 1.0 versus -4.2 ± 2.0%; P = 0.01); the declines in FMD and GTN-induced dilatation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve, FMD was attenuated in both conditions (mild versus moderate, 0.6 ± 0.9 versus 0.8 ± 0.7%; P ≤ 0.01). After 30 min of normoxic time control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental decline in smooth muscle vasodilator capacity (impaired GTN-induced dilatation). Our findings from the normoxic control study suggest the decline in FMD in acute hypoxia also appears to be influenced by 30 min of supine rest/inactivity.

UBC-Nepal expedition: upper and lower limb conduit artery shear stress and flow-mediated dilation on ascent to 5,050 m in lowlanders and Sherpa

“…We advance the emerging evidence that hypoxia evokes a shear stress profile associated with vascular dysfunction/impairment (47,90) These putative mechanisms have also been implicated in hypoxia-associated reductions in FMD, however the discussion will concentrate on the observed findings on shear stress and FMD.…”

“…Recently, both acute and sustained hypoxia have been shown to increase brachial artery retrograde and decrease mean shear stress (47,90), which may contribute to the observed reductions in brachial artery flow-mediated dilation (FMD). Indeed, during the process of acclimatization to hypobaric hypoxia (3800m), there appears to be a window wherein the endothelium is more susceptible to oscillatory shear stress (low time-averaged mean, high retrograde)induced dysfunction compared to sea level (91).…”

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…increases in retrograde shear stress; Thijssen et al 2009). Acute and sustained hypoxic exposure has been shown to increase retrograde shear stress (Iwamoto et al 2015;Katayama et al 2016;Lewis et al 2017;Tremblay et al 2018a,b), and decrease mean shear stress (Lewis et al 2017;Tremblay et al 2018a,b). These pro-atherogenic alterations in shear stress have a well-established deleterious impact on endothelial function (Padilla et al 2009;Thijssen et al 2009;Tremblay et al 2019a), and thus, alterations in baseline shear stress magnitude and pattern may contribute to the observed reductions in endothelial function.…”

“…Following a 30 min exposure to moderate (end‐tidal partial pressure of oxygen = 75 mmHg; equivalent to ∼2000 m) or severe (end‐tidal partial pressure of oxygen = 50 mmHg; equivalent to ∼4600 m) isocapnic hypoxia, endothelial function was reduced even after accounting for reduced shear stress stimulus (Lewis et al . ). Although the mechanism(s) responsible for the observed decline in shear stress during acute hypoxia remain unknown, these authors attributed it to heightened sympathetic vascular constraint (Weisbrod et al .…”

“…Similarly, in more recent studies using a slightly more severe degree of hypoxia (F IO 2 = 0.11; equivalent to ß5000 m), it was found that endothelial function decreased following 20 min (Tremblay et al 2018b), and after 1, 3.5, and 5.5 h of exposure (Lewis et al 2014). Following a 30 min exposure to moderate (end-tidal partial pressure of oxygen = 75 mmHg; equivalent to ß2000 m) or severe (end-tidal partial pressure of oxygen = 50 mmHg; equivalent to ß4600 m) isocapnic hypoxia, endothelial function was reduced even after accounting for reduced shear stress stimulus (Lewis et al 2017). Although the mechanism(s) responsible for the observed decline in shear stress during acute hypoxia remain unknown, these authors attributed it to heightened sympathetic vascular constraint (Weisbrod et al 2001).…”