## 3 Results and Discussion
### Physiological/Mechanistic Interpretation of Thermoregulatory CIVC/CIVD Reactions  
#### 3.2.1 Mechanisms of CIVC/CIVD Reactions during Localised Cooling  
The initial response to cold exposure is a sympathetically mediated peripheral vasoconstriction, resulting in reduced local tissue temperature [11; 15; 39; 40]. With continued cold exposure, this vasoconstriction may be interrupted, resulting in periods of vasodilation, which correspond to an increase in tissue temperature [41]. The local cooling vasoconstrtor response is dependent on intact noradrenergic cutaneous active vasoconstrtor nerves [36; 39; 42]. [PERSON] et al. [36] concluded in their work that local cooling of skin occurs in two phases (biphasic): an initial phase, which lasts for few minutes (in accordance to the aforementioned results) and a prolonged phase. The initial phase is mediated by activation of cold-sensitive afferent neurons that affect the release of norepinephrine from sympathetic cutaneous vasoconstrtor nerves. Norepinephrine then vasoconstrtorts skin vessels (mainly the AVAs, in this case) through post-junctional \(\alpha\)-receptors. On the other hand, the mechanisms for the prolonged phase, which follows an initial CIVD (hunting reaction), are suggested to be non-neurogenic [36], because no manipulations altered the prolonged cutaneous vasoconstriction during prolonged local cooling. However, these mechanisms have not been defined further [36]. Additionally, prolonged local cooling also mediates an initial \"non-neurogenic\" vasodilation (CIVD) that competes with the initial noradrenergically mediated vasoconstriction. Several hypotheses have been postulated on the mechanism of CIVD [15]. The main hypotheses to explain the initial CIVD and prolonged CIVC are depicted in Figure 12. In the case of prolonged localised cooling, and after an initial episode of CIVC (Figure 12A), an initial CIVD might occur. Based on previous research work (e.g., [15; 18; 43; 44]), three different mechanisms are suggested to explain this initial CIVD (Figure 12). The first hypothesized mechanism (_pathway_ 1) states that the smooth muscles in the blood-vessel walls become paralysed, for example, by a decreased concentration of Ca\({}^{2+}\) ions. Consequently, the paralysed smooth muscles will not be able to maintain vasoconstriction, and then vasodilation occurs. The second hypothesized mechanism (_pathway_ 2) states that the smooth muscles become less sensitive to norepinephrine, for example, due to the resorption of the receptors from the cell membrane. The  
Figure 11: Dynamic response of finger skin temperature (upper graph), dissipated heat rate (\(\dot{Q}_{dis}\), middle graph), and first derivative of the dissipated heat rate (\(\frac{dQ_{dis}}{dt}\), lower graph) to localised intermittent cooling obtained from test subject (s5) during the experiment (Exp.2, Phase II). more resorption, the less norepinephrine can interact, the less the increase in intracellular Ca\({}^{2+}\) ion concentration, and the less the constriction. The third and final hypothesized mechanism (_pathway_ 3) states that the adrenergic vasoconstrtor nerves release less norepinephrine. Thereby, the concentration of epinephrine in the synaptic cleft decreases. The bound epinephrine will detach from the receptors due to the concentration difference (diffusion), resulting in vasodilation. The findings of the current study do not support the first hypothesis (_pathway_ 1), since it is clear from the case of intermittent localised cooling that the skin was cooled to the same temperature as in case of continuous cooling and yet no vasodilation evidence is recorded. In agreement with the work of [PERSON] et al. [35], the present study suggests that the triggering of local cooling induced-vasodilation in the finger's skin is dependent on the heat dissipation rate (\(\dot{\mathrm{Q}}_{\mathrm{dis}}\)) or the rate of cooling as termed in [35; 38].