Year

2008

Degree Name

Doctor of Philosophy

Department

School of Health Sciences - Faculty of Health & Behavioural Sciences

Abstract

Regulation of skin blood flow (Qsk) is vital to homeostasis, with adjustments to flow in response to important sympathetic thermal and non-thermal reflexes and by other factors which remain to be fully determined, but include local regulatory mechanisms (i.e. axon reflexes, release of endothelial vasoactive substances etc.). Laser-Doppler flowmetry is a well-known technique, used for assessing microvascular function, with raw Qsk traces displaying marked variability, which is in part due to the above mechanisms, but also results from passive influences (i.e. oscillations in pressure resulting from cardiac frequency (fc) or respiration (fb), alterations to local transmural pressure and turbulences in flow due to vessel structure and or the viscosity of blood). The central focus of this dissertation was an investigation and characterisation of an apparently hidden, novel Qsk phenomenon, which has not been previously reported in the literature, possibly due to traditional data processing techniques. This phenomenon encompasses high-amplitude oscillations in Qsk which were detected using laser-Doppler flowmetry in human and rat Qsk, which have a characteristic frequency of -0.4 Hz, spanning -1000 ms, and consist of high-amplitude peaks, accounting for up to a seven-fold increase of basal Qsk.

Experiments presented within this thesis confirm the biological nature of these oscillations, which are present in both acral and non-acral skin regions. These oscillations, increase significantly with increases in local and mean skin temperature (Tsk; humans and rats Qsk; P<0.05) and may occur independently of core temperature. Further, these oscillations appear to be unaffected by global changes in mean arterial pressure within the normotensive range (P>0.05). Local application of anaesthetic (i.e. to remove vessel tone) attenuated these oscillations in response to whole-body heating. However, propranolol treatment (80mg; orally) produced no significant differences in the characteristics of these oscillations (P>0.05), despite producing a significant reduction in/c (~ 10 b-min-1; P<0.05). Differences in baroreceptor loading between a supine and seated posture (as reflected by a significant increase in fc of - 10 b-min-1 in the seated posture; P<0.05) produced nodifferences in the frequency of the high-amplitude oscillations at the forearm when recorded at heart level (~0.4 Hz). However, measurements at the thigh in the seated posture, displayed a significant decrease in the frequency of these oscillations (reduction of ~0.3 Hz) when compared to the supine position (P<0.05). In addition, alterations to local vessel pressure by movement of the position of the Qsk measurement site above or below heart level significantly increased the frequency of these oscillations (by ~0.2 Hz and -0.1 Hz respectively; P<0.05). Remarkably, additional manipulations of local pressure by means of upper arm occlusion (2 min; to either ~90 or 240mm Hg) , increased the frequency of these oscillations in some subjects, while in others a reduction in frequency was observed (P<0.05). Furthermore, time frequency analysis, shows that these oscillations occur independently of fc and fb.

Taken together, it is likely that sympathetic nervous system has a minimal role in the induction of these oscillations (i.e. not associated with an active vasodilator mechanism, as this system is lacking in acral regions) and the oscillations occurring under conditions where the sympathetic vasoconstrictor tone to the skin would be expected to be minimal (e.g. hyperthermia). Local threshold-dependent thermal mechanisms (i.e. Tsk ~35-36°C) may mediate these oscillations. However, since these oscillations have also been detected under normothermic conditions in the thigh and forearm in human subjects (Tsk ~32-33°C), it is also possible that local temperature may exacerbate or facilitate non-thermal mechanisms, leading to the induction of these oscillations. The other possibilities are that multiple mechanisms may account for the high-amplitude oscillations, or that the threshold skin temperature for the induction of these oscillations varies with experimental conditions. However, if non-thermal factors account for the high-amplitude oscillations, then the results support a local passive mechanism, as these oscillations appear to be unaffected by central changes in vascular pressure (i.e. mean arterial pressure and oscillations in intravascular pressure due to fc and fb), yet are greatly affected by local alterations to pressure and vessel tone. The exact local passive mechanism behind these oscillations remains to be determined, but is likely to be c ommo n across skin regions and species, and the physiological relevance of the high-amplitude oscillations m a y relate to enhanced tissue perfusion, and or heat transfer through the cutaneous circulation.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.