Skin blood flow in adult human thermoregulation: how it works, when it does not, and why.

SINCE the sympathetic nervous system has such a central place in homeostasis in general, and in circulatory adaptation in particular, it is paradoxical that so little is known about the possible contribution of disturbed sympathetic nervous function to the development of human diseases. Clinical tests of sympathetic nervous system activity have, by and large, been routinely applied in one setting only: the detection of sympathetic nervous failure, from autonomic insufficiency syndromes, in patients with postural hypotension. A list of \"candidate\" diseases for sympathetic nervous system dysfunction might include, for example, essential hypertension, cardiac failure, coronary artery spasm, cirrhosis, mitral valve prolapse, and Raynaud's syndrome. Until very recently, the picture of sympathetic nervous pathophysiology for conditions such as these was particularly sketchy, mainly because of the rudimentary nature of the tests of sympathetic nervous system function available to investigative clinical medicine. Pertinent questions have gone incompletely answered at best — questions such as: Is the sympathetic nervous system directly involved in the early pathogenesis of essential hypertension? Is increased renal sympathetic activity a common cause of sodium retention in edematous states? Is increased cardiac sympathetic nerve firing an important element in the development of cardiac arrhythmias in humans?

Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover.

Sympathetic activity was recorded from human skin nerves during the execution of a variety of different manoeuvres. The neural activity (composed of vasoconstrictor and sudomotor impulses) was regularly affected by emotional, thermal and respiratory stimuli. Mental stress, body cooling and increased respiratory movements all increased the sympathetic outflow, whereas the activity decreased during moderate body warming and when the. subject was calm and relaxed. Manoeuvres known to cause changes in baroreceptor activity usually did not affect the sympathetic outflow to the skin. When comparing neural and effector organ responses during the different manoeuvres the changes in sympathetic activity correlated well with changes in skin vascular resistance (either measured simultaneously or as reported in the literature). A comparison of the sympathetic responses recorded from human skin- and muscle nerves was also made. It was concluded that most manoeuvres had different effects in the two nerve types, thereby confirming earlier indirect evidence for selective regional control of the sympathetic outflow.

Manoeuvres affecting sympathetic outflow in human skin nerves.

Electrodermal activity (EDA) is a sensitive index of sympathetic nervous system activity. Due to the lack of sensors that can be worn comfortably during normal daily activity and over extensive periods of time, research in this area is limited to laboratory settings or artificial clinical environments. We developed a novel, unobtrusive, nonstigmatizing, wrist-worn integrated sensor, and present, for the very first time, a demonstration of long-term, continuous assessment of EDA outside of a laboratory setting. We evaluated the performance of our device against a Food and Drug Administration (FDA) approved system for the measurement of EDA during physical, cognitive, as well as emotional stressors at both palmar and distal forearm sites, and found high correlations across all the tests. We also evaluated the choice of electrode material by comparing conductive fabric with Ag/AgCl electrodes and discuss the limitations found. An important result presented in this paper is evidence that the distal forearm is a viable alternative to the traditional palmar sites for EDA measurements. Our device offers the unprecedented ability to perform comfortable, long-term, and in situ assessment of EDA. This paper opens up opportunities for future investigations that were previously not feasible, and could have far-reaching implications for diagnosis and understanding of psychological or neurological conditions.

/pdf/a-wearable-sensor-for-unobtrusive-long-term-assessment-of-wiov6ehz7n.pdf

A Wearable Sensor for Unobtrusive, Long-Term Assessment of Electrodermal Activity

A review of the literature illustrates the many questions about hot flashes that remain unanswered. My survey addresses some of these questions. The prospective and retrospective descriptions of hot flashes provide a more detailed profile of the hot flash than has previously been available. Further, data from this survey demonstrate that while the patterns of hot flashes may be varied, there are commonalities in hot flash physiology and subjective manifestation. The data indicate that hot flashes may start much earlier and continue far longer than is commonly recognized by physicians or acknowledged in textbooks of gynecology. Studies of hot flash duration must control for age or age at hot flash onset, since the older the subjects, the more potential years of hot flashes and the greater the probability of encompassing the entire period of hot flashes. Hot flashes are not static; patterns may change with time. For some women, hot flashes become less frequent and less intense; for others, hot flashes may continue at hourly intervals well into old age. How common these experiences are for women of all ages still needs to be discovered. As expounded by Kaufert, McKinlay, Goodman, and many others, a greater effort must be made to standardize definitions and question formats as well as to improve methodology in epidemiologic investigations to facilitate comparability between studies and insure that proffered conclusions indeed reflect the questions being asked. Physiological studies are critical counterparts to the epidemiology; yet such studies have been too few. My work, by examining the physiology and psychophysiology of hot flashes, has raised additional questions about central and peripheral inputs that may affect the subjective experience of hot flashes. A more complete understanding of the thermoregulatory, cardiovascular, and psychophysiology of women with hot flashes are compared to women without will facilitate the prediction of who is most likely to be affected and the identification of additional approaches to the management of hot flashes.

Hot Flashes: Epidemiology and Physiologya

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1959.sp006312

Excitation of cholinergic vasodilator nerves to human skeletal muscles during emotional stress.

During body heating there is a large increase in hand and forearm blood flow owing to vasodilatation mediated by sympathetic nerves. In the forearm the vasodilatation is confined to the vessels of the skin (Barcroft, Bock, Hensel & Kitchin, 1955; Edholm, Fox & Macpherson, 1956; Roddie, Shepherd & Whelan, 1956), and there is some evidence that this is also the case in the hand (Harris, Martin & Williams, 1952). The vessels of the forearm skin are supplied with both vasodilator fibres (Grant & Holling, 1938; Edholm et al. 1956; Roddie, Shepherd & Whelan, 1957) and vasoconstrictor fibres (Roddie et al., 1957). Present evidence indicates that the blood vessels of the hands of normal subjects are supplied only with vasoconstrictor fibres (Arnott & Macfie, 1948; Gaskell, 1956), although the experiments of Lewis & Pickering (1931) suggest that there are vasodilator fibres to the hands of patients with Raynaud's disease. The object of the present experiments was to determine the contribution of vasodilator and vasoconstrictor fibres to the skin dilatation in the upper limb during body heating.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1957.sp005775

The contribution of constrictor and dilator nerves to the skin vasodilatation during body heating

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1956.sp005656

Evidence from venous oxygen saturation measurements that the increase in forearm blood flow during body heating is confined to the skin.

The experiments were carried out on healthy adults aged 19-36 years in a room about 260 C. Changes in posture were brought about by passively raising the legs or the legs and lower trunk of the recumbent subject. Forearm, hand and calf blood flow was measured by venous occlusion plethysmography (Greenfield, 1954). Pressure measurements were made by a capacitance manometer; arterial pressure from a needle in the brachial artery and central venous pressure from a catheter in the right atrium or great thoracic veins. Deep nerve block was performed by iniltrating around the ulnar, median and radial nerves with 3-5 ml. lignocaine with adrenaline 1:50,000 (Whelan, 1952; Roddie, Shepherd & Whelan, 1957a). In one experiment venous blood samples from the forearm muscles were withdrawn through nylon catheters (Roddie, Shepherd & Whelan, 1956) and the oxygen saturation determined using a spectrophotometric technique (Roddie, Shepherd & Whelan, 1957b).

Reflex changes in vasoconstrictor tone in human skeletal muscle in response to stimulation of receptors in a low-pressure area of the intrathoracic vascular bed.

1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses

2. After the pre-treatment of subjects with atropine or hexamethonium, I.C.I. 50172 produced a significant reduction in an isoprenaline tachycardia. This reduction was not competitive and did not exceed 50%.

3. The intravenous injection of 4 mg I.C.I. 50172 reduced an exercise tachycardia; its effect was less than that of 4 mg propranolol. This difference became greater as the doses of the two drugs were increased. The dextro isomer of propranolol had no effect on the exercise tachycardia; I.C.I. 45763 reduced it to the same extent as propranolol.

4. The intravenous injection of I.C.I. 50172 reduced the increase in heart rate produced by tilting a normal subject from the supine to 80° head-up position. After the administration of atropine, I.C.I. 50172 almost abolished the response. In the presence of atropine, I.C.I. 50172 was as active as propranolol in reducing the increase in heart rate on tilting.

5. The reason for the differences in the effects of I.C.I. 50172 on the increases in heart rate brought about by the three procedures is not clear.

6. The increase in forearm blood flow produced by the infusion of isoprenaline into the brachial artery was not reduced by the intra-arterial administration of I.C.I. 50172.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1968.tb07956.x

I. C. Roddie

Papers

Excitation of cholinergic vasodilator nerves to human skeletal muscles during emotional stress.

The contribution of constrictor and dilator nerves to the skin vasodilatation during body heating

Evidence from venous oxygen saturation measurements that the increase in forearm blood flow during body heating is confined to the skin.

Reflex changes in vasoconstrictor tone in human skeletal muscle in response to stimulation of receptors in a low-pressure area of the intrathoracic vascular bed.

Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise.