The Effects of Acute Hypobaric Hypoxia on Arterial Stiffness and Endothelial Function and its Relationship to Changes in Pulmonary Artery Pressure and Left Ventricular Diastolic Function

Abstract

This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.

Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia

“…In agreement with our results, Boos et al, who employed a similar protocol, did not find changes in arterial stiffness in response to acute HH [11]. On contrary, biochemical markers of endothelial function were markedly modified by HH.…”

“…Therefore, the increment in endothelin-1 levels observed would not be enough to cause a significant vasoconstriction. Other possible explanations for these findings would be that the increase in endothelin-1 had differentially affected particular arterial beds [11,35] increasing cardiac output by the increase of cardiac contractility.…”

“…Moreover, HAPE patients featured lower nitric oxide concentration in comparison with healthy controls [10]. However, inconsistent results have been obtained when vascular reactivity was assessed in subjects exposed to acute HH [11][12][13].…”

The Effects of Sex on Cardiopulmonary Responses to Acute Normobaric Hypoxia

“…Our sample size of 14 subjects was based on previously published work which demonstrated significant changes in cardiac function and hemodynamic indices with acute hypobaric hypoxia with a sample size of 10-14 subjects (Boos et al, 2012(Boos et al, , 2103.…”

The Impact of Repetitive Long-duration Water Immersion on Vascular Function

“…Previous studies have documented changes in arterial stiffness following both acute and chronic interventions, and acute changes have been detected in response to many stimuli other than diving or immersion [57,58,59,60,61]. Acute aerobic exercise (rowing) caused stiffness to decrease [62], and acute sprint interval exercise caused increased compliance but no change in brachial artery stiffness [63].…”