Previous research has demonstrated that ingesting fluid of different temperatures results in different whole-body sweat losses (WBSL) and transient changes in local sweat rate (LSR) without any parallel differences in core or skin temperatures. The purpose of this thesis was to determine the potential location and relative contribution of gastrointestinal thermoreceptors that modify sudomotor activity. Eight participants cycled for 75 min while cold (1.5°C) and warm (50°C) water was either swilled in the mouth, or delivered directly to the stomach bypassing the mouth using a nasogastric tube, after 15, 30 and 45-min of exercise. Mouth-swilling warm or cold water did not alter sudomotor output, however delivering warm or cold water directly into the stomach led to a temperature-dependent change in sudomotor output, despite similar core and skin temperatures. These data indicate that thermoreceptors independently modulating sudomotor output probably reside within the abdominal area, but not the mouth.

Previous research has demonstrated that ingesting fluid of different temperatures results in different whole-body sweat losses (WBSL) and transient changes in local sweat rate (LSR) without any parallel differences in core or skin temperatures. The purpose of this thesis was to determine the potential location and relative contribution of gastrointestinal thermoreceptors that modify sudomotor activity. Eight participants cycled for 75 min while cold (1.5°C) and warm (50°C) water was either swilled in the mouth, or delivered directly to the stomach bypassing the mouth using a nasogastric tube, after 15, 30 and 45-min of exercise. Mouth-swilling warm or cold water did not alter sudomotor output, however delivering warm or cold water directly into the stomach led to a temperature-dependent change in sudomotor output, despite similar core and skin temperatures. These data indicate that thermoreceptors independently modulating sudomotor output probably reside within the abdominal area, but not the mouth.

Reports indicate that postexercise heat loss is modulated by baroreceptor input; however, the mechanisms remain unknown. We examined the time-dependent involvement of adenosine receptors, noradrenergic transmitters, and nitric oxide (NO) in modulating baroreceptor-mediated changes in postexercise heat loss. Eight males performed two 15-min cycling bouts (85% VO2max) each followed by a 45-min recovery in the heat (35°C). Lower body positive (LBPP), negative (LBNP), or no (Control) pressure was applied in three separate sessions during the final 30-min of each recovery. Four microdialysis fibres in the forearm skin were perfused with: 1) lactated Ringer’s (Ringer’s); 2) 4mM Theophylline (inhibits adenosine receptors); 3) 10mM Bretylium (inhibits noradrenergic transmitter release); or 4) 10mM L-NAME (inhibits NO synthase). We measured cutaneous vascular conductance (CVC; percentage of maximum) calculated as perfusion units divided by mean arterial pressure, and local sweat rate. Compared to Control, LBPP did not influence CVC at L-NAME, Theophylline or Bretylium during either recovery (P>0.07); however, CVC at Ringer’s was increased by ~5-8% throughout 30 min of LBPP during Recovery 1 (all P<0.02). In fact, CVC at Ringer’s was similar to Theophylline and Bretylium during LBPP. Conversely, LBNP reduced CVC at all microdialysis sites by ~7-10% in the last 15 min of Recovery 2 (all P<0.05). Local sweat rate was similar at all treatment sites as a function of pressure condition (P>0.10). We show that baroreceptor input modulates postexercise CVC to some extent via adenosine receptors, noradrenergic vasoconstriction, and NO whereas no influence was observed for postexercise sweating.

Studies show that vasomotor and sudomotor activity is compromised in individuals with Type 1 Diabetes (T1DM) which could lead to altered thermoregulatory function. However, recent work suggests that the impairments may only be evidenced beyond a certain level of heat stress. We therefore examined T1DM-related differences in heat loss responses of sweating and skin blood flow (SkBF) during exercise performed at progressive increases in the requirement for heat loss. Participants were matched for age, sex, body surface area and fitness cycled at fixed rates of metabolic heat production of 200, 250, and 300 W•m-2 of body surface area, each rate being performed sequentially for 30 min. Local sweat rate (LSR), sweat gland activation (SGA), and sweat gland output (SGO) were measured on the upper back, chest and forearm while SkBF (laser-Doppler) was measured on the forearm and upper back only. We found that despite a similar requirement for heat loss, LSR was lower in T1DM on the chest and forearm only, relative to Control and only different at the end of the second and third exercise periods. Differences in chest LSR were due to reduced SGA whereas the decreased forearm LSR was the result of a decrease in SGO. SkBF did not differ between groups. The reduction in the sweating response in the T1DM group was paralleled by a greater increase in core temperature. We show that T1DM impairs heat dissipation as evidenced by reductions in LSR and not SkBF. A compromised thermoregulatory response during and following physical exertion is of considerable concern due to the associated increased risk of post-exertion heat-related injury.

Studies show that vasomotor and sudomotor activity is compromised in individuals with Type 1 Diabetes (T1DM) which could lead to altered thermoregulatory function. However, recent work suggests that the impairments may only be evidenced beyond a certain level of heat stress. We therefore examined T1DM-related differences in heat loss responses of sweating and skin blood flow (SkBF) during exercise performed at progressive increases in the requirement for heat loss. Participants were matched for age, sex, body surface area and fitness cycled at fixed rates of metabolic heat production of 200, 250, and 300 W•m-2 of body surface area, each rate being performed sequentially for 30 min. Local sweat rate (LSR), sweat gland activation (SGA), and sweat gland output (SGO) were measured on the upper back, chest and forearm while SkBF (laser-Doppler) was measured on the forearm and upper back only. We found that despite a similar requirement for heat loss, LSR was lower in T1DM on the chest and forearm only, relative to Control and only different at the end of the second and third exercise periods. Differences in chest LSR were due to reduced SGA whereas the decreased forearm LSR was the result of a decrease in SGO. SkBF did not differ between groups. The reduction in the sweating response in the T1DM group was paralleled by a greater increase in core temperature. We show that T1DM impairs heat dissipation as evidenced by reductions in LSR and not SkBF. A compromised thermoregulatory response during and following physical exertion is of considerable concern due to the associated increased risk of post-exertion heat-related injury.

Introduction : La chimiothérapie cytotoxique constitue une modalité thérapeutique de nombreux cancers. L’amélioration de la durée de survie des patients a fait apparaître des complications de ces traitements notamment sur le nerf périphérique. Il s’agit d’une complication fréquente et potentiellement sévère qui peut avoir un impact durable. Pourtant, bien que les chimiothérapies neurotoxiques soient connues, il n’existe pas de données précises permettant de prédire la tolérance individuelle. La détection précoce des polyneuropathies chimio-induites (PNCI) est donc capitale pour évaluer les facteurs favorisants. L’utilisation du TNSc (Total Neuropathy Score clinical version) et le Sudoscan® peut notamment permettre la détection de ces PNCI. En effet, le TNSc (Total Neuropathy Score clinical version), un score composite évaluant les petites et grosses fibres nerveuses. Celui-ci a été validé pour déterminer la sévérité de la PNCI. Selon le traitement, l’atteinte concerne les grosses fibres myélinisées ou les fibres fines amyéliniques (FFA). L’examen des grosses fibres est bien standardisé au moyen de l’EMG. Cependant il n’en est pas de même pour le diagnostic d’atteinte des FFA. Le Sudoscan® mesure la conductance cutanée (mesure chronoampérométrique) après une exposition à un courant continu inférieur à 100µA/6V permet d’apprécier la fonction sudomotrice. Des études dans le diabète ont montré que la fonction sudomotrice est directement liée à l’état des FFA, car ces fibres contrôlent les glandes sudoripares. Le Sudoscan® pourrait donc être utilisé pour la détection de PNCI.Objectifs i) Evaluer l’incidence des PNCI par le TNSc selon la dose et évaluer l’atteinte des FFA chez des patients au cours de traitement par Sels de platines ou Taxanes ou Alcaloïdes de pervenche; ii) étudier l’évolution dans le temps des PNCI par le TNSc et par Sudoscan® au cours de la chimiothérapie et à distance de son arrêt; iii) caractériser des facteurs de risque de PNCI; iv) comparer les TNSc et mesures chronoampérométriques selon les traitements reçus v) évaluer l’intérêt des conductances par rapport au TNSc.Résultats Une attention particulière a été portée aux patients sous Oxaliplatine (n=65) et Taxanes (n=28). Nous avons retrouvé une augmentation du TNSc chez tous les patients sous chimiothérapie neurotoxique. Pendant le suivi, 57% des patients sous Oxaliplatine et 58% des patients sous Taxanes atteignaient un TNSc correspondant à une neuropathie clinique. Aucune différence du TNSc entre les patients symptomatiques et asymptomatiques n’a été observée à distance de traitement par Oxaliplatine (≥4mois). De même, on ne retrouvait pas de différences du TNSc entre les patients symptomatiques et asymptomatiques à distance de traitement par Taxanes. D’autre part, l’étude des conductances n’a pas révélé d’évolution en fonction de la dose reçue pour les patients sous Oxaliplatine. En revanche, chez les patients sous Taxanes on retrouvait des différences significatives des conductances en fonction des doses reçues. La mesure la plus basse des pieds pendant le suivi est observée en moyenne 23 jours avant que le TNSc le plus élevé ne soit atteint (p=0,03). On ne retrouve pas de différences des conductances pendant le suivi entres les patients symptomatiques et asymptomatiques à distance de traitement par Oxaliplatine. Toutefois, les patients symptomatiques à distance de traitement par Taxanes avaient des conductances des pieds plus basses que les patients asymptomatiques à distance (p=0.004). Le TNSc est plus élevé selon la dose reçue chez les patients diabétiques que chez les patients non diabétiques. Les conductances des mains et des pieds des patients diabétiques étaient significativement plus basses (p=0.003) chez les patients diabétiques que chez les patients non diabétiques.Conclusion Ces résultats suggèrent que les mesures chronoampérométriques permettent de détecter et quantifier l’atteinte des FFA chez les patients recevant des Taxanes. / Introduction : Cytotoxic chemotherapy is a treatment modality for many cancers. The improved survival time of patients showed some complications of these cytotoxic treatments including chemotherapy-induced peripheral neuropathy (CIPN). This is a common and potentially severe complication that can have a lasting impact on the quality of life. Although neurotoxic chemotherapies are known, there is no accurate data to predict individual tolerance. Early detection of CIPN is therefore essential to assess the contributing factors. To this end, the use of the TNSc (Total Neuropathy Score clinical view) and the Sudoscan® can improve the detection CIPN.Indeed, the TNSc (Total Neuropathy Score clinical view), a composite score assessing small and large nerve fibers, has been validated to evaluate the severity of CIPN. The nerve impairment concerns the large myelinated fibers or small fibers, depending on the treatment. The objective assessment of large fibers is standardized by means of the EMG (Electromyography), but it is not the same for the diagnosis of the small fibers impairment.On the other hand, the Sudoscan® measures skin conductance (chronoamperometric measurement) after exposure to a direct current of less than 100μA and 6V, and can assess the sudomotor function. Interestingly, studies in diabetes have shown that sudomotor function is directly related to the status of the small fibers that control the sweat glands. The Sudoscan® could thus be used for the detection of CIPN.Objectives: i) to evaluate the impact, depending on the dose received of chemotherapy, of CIPN by TNSc and assess the impairment of small fibers in patients during treatment with Platinum compounds or Taxanes or vinca alkaloids; ii) to study the evolution of the peripheral neurologic impairment by TNSC and skin conductance measurements during chemotherapy and after the end of the treatment; iii) to characterize risk factors for CIPN; iv) to assess the usefulness of conductance measurements compared to TNSc.Results: Particular attention has been given to patients treated with Oxaliplatin (n= 65) and Taxanes (n= 28), known to damage small fibers. We found an increased TNSc in all patients receiving neurotoxic chemotherapy. During follow-up, 57% of patients receiving Oxaliplatin and 58% of patients receiving Taxanes reach a TNSc corresponding to a clinical neuropathy. However, there was no difference of TNSc during the follow-up between symptomatic and asymptomatic patients, 4 months after the end of the treatment by Oxaliplatin. Similarly, we did not find differences of TNSc during the follow-up between symptomatic and asymptomatic patients, 4 months after the end of the treatment by Taxanes.Regarding conductance values, we didn’t observe changes depending on the dose received for patients treated by Oxaliplatin. However, in patients receiving Taxanes we found significant differences, based on the cumulative dose, for the hands and feet. Indeed, the lowest measure of the feet during the tracking is observed within an average of 23 days before the TNSc reached its highest value (p = 0.03). We didn’t find differences in conductance values during follow-up among symptomatic and asymptomatic patients 4 months after the end of their treatment. However, 4 months after the end of the chemotherapy, symptomatic patients treated with Taxanes had feet conductance values lower than asymptomatic patients (p= 0.004). The TNSc was higher in diabetic patients than in non-diabetic patients depending on the dose received during the follow-up. During the follow-up, the conductance values of the hands and feet were significantly lower (p= 0.003) for these patients than in nondiabetic ones.Conclusion: These results suggest that the chronoamperometric measurements can be useful in the detection and quantification of small fibers impairment in patients receiving Taxanes.