Human Skin Hypoxia Modulates Cerebrovascular and Autonomic Functions

<div><p>Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.</p> </div

Middle cerebral artery flow velocities recorded in the field from the left artery in one Tibetan age 28 and one sea level Caucasian of the same age at 5000 m. in the Himalayas.

<p>Acute altitude exposure for the Caucasian one day after arrival at the Everest base camp on the Tibetan side of the mountain. Note the differences in heart rate and flow velocities in these healthy young subjects. (from reference #3, with permission).</p

Mandelbrot set under skin normoxia (air) and hypoxia (N₂) derived from the low power spectrum on the X-axis and the high power spectrum on the Y-axis of heart rate variability in one subject.

<p>(Mandelbrot.ovh.org). Note the width of the fractal illustration from the same individual under skin hypoxic condition is much reduced.</p

Predicted responses to carbon dioxide of the middle cerebral blood flow velocities under the two experimental conditions.

<p>The slopes of the fitted lines in all subjects were significantly different and the response was significantly enhanced in the left middle cerebral artery as compared to the right. (P<0.001, left and right upper panels). The responses of the cerebral circulation to increasing CO₂ levels during skin hypoxia and skin normoxia were significantly enhanced on the left compared to the right (P<0.001, left and right lower panels). Additionally, both were significant compared to the baseline (P<0.001).</p

Power spectra of heart rate variability under two experimental conditions (skin normoxia = blue line; skin hypoxia = red line) during baseline (segment 2) and rebreathing (segment 4).

<p>A statistically significant difference in power of the low power segment (between 0.06–0.27 Hz, P<0.001^***) was present. The frequency band selection was based on statistical considerations and not on International standards that define the low frequency bands for purposes of ANS control of cardiovascular function. Y-axis = Spectral power; X-axis = Frequency/2π.</p

Bilateral middle cerebral artery blood flow velocities (Y-axis) against time in seconds (X-axis) in one subject.

<p>All subjects followed similar trends. The records were divided into 4 segments; we analyzed segment 2 considered as baseline (taken before the CO₂ induced hyperventilation phase) and segment 4 taken as the response of the cerebral circulation to increasing blood CO₂ levels during Duffin’s hypoxic ventilatory response test (orange, TCD 1 = left MCA flow velocities; green, TCD 2 = right MCA flow velocities.</p

Cross correlation function (normoxia = blue; hypoxia = red).

<p>Under baseline conditions, with <u>air</u> in the bag, SBP followed heart rate with lag = 1, left panel, whereas during <u>rebreathing</u> (segment 4) SBP followed heart rate with a longer lag of 2, right panel. With the skin hypoxic these relationships of blood pressure and heart rate were further disrupted.</p

Effects of skin hypoxia on systolic blood pressure (SBP) and heart rate (HR) (blue = normoxia, red = skin hypoxia; left = baseline, right = during rebreathing).

<p>Note that there were statistically significant increases (P<0.0001) in systolic blood pressure with skin hypoxia (1) at baseline but this was converted to a statistically significant decrease (P<0.0001) during rebreathing (2), left panel. The changes were similar for heart rate during the two condition of the experiment, right panel (analysis of records from surface recording devices such as ear oximeter).</p