The existence of a patent foramen ovale (PFO) has been known about for nearly 2,000 years. The prevalence of a PFO has been shown to be 25-40% in the general population. Despite the fact that blood flowing through a PFO acts as a shunt, there has been little research looking at the effect a PFO has on physiology in otherwise healthy humans. In Chapter IV, the effect of a PFO on core temperature (Tcore) prior to, and during exercise, was investigated. The design of this experiment included appropriate controls for a thermoregulatory study (i.e. measuring at same time of day, appropriate hydration and food intake, etc.). Results from this study indicate that subjects with a PFO (PFO+) have a Tcore that is ~0.4°C higher at rest and during exercise than subjects without a PFO (PFO–). Additionally, this study showed that PFO– subjects do not increase Tcore to the same extent breathing cold air as they do breathing ambient air during a 10-minute exercise bout, whereas there was no difference in Tcore increase between these two conditions for PFO+ subjects. These findings suggest that the difference in Tcore between PFO+ and PFO– subjects is potentially due to differences in respiratory heat loss. The studies for Chapter V examined differences in thermoregulatory and ventilatory responses during hot water (40°C) and cold water (20°C) immersion. This study found that compared to PFO– subjects, PFO+ subjects 1) increase Tcore at the same rate during hot water immersion and 2) do not cool off as quickly during cold water immersion. Additionally, in subjects who reached a ventilatory threshold, PFO+ subjects had blunted ventilatory responses to increased Tcore compared to PFO– subjects. Finally, in Chapter VI it was shown that PFO+ subjects have blunted ventilatory responses during acute exposure to hyperoxic and normoxic hypercapnia. However, there were no differences in ventilatory responses between PFO+ and PFO– subjects during exposure to either isocapnic or poikilocapnic hypoxia. These findings suggest that PFO+ subjects have a blunted central chemoreflex. This dissertation contains previously, unpublished co-authored material.

The objective of this research is to analyze the relationship between environ-mental heat exchange and vascular response in the pallid bat wing during systemicheating and to develop a simplied model of heat transfer for theoretical analysis.During heating experiments, metabolic activity, body temperature and alterations invessel diameter and blood ow were monitored. This research is very signicant, asit will correlate thermoregulation and vascular response in a way that has not beenstudied before.The wing of the pallid bat is selected because the microvascular bed performssimilar functions as that of the human skin in terms of thermoregulation; understand-ing vascular response to heat or cold allows to analyze vascular function, or arterialhealth, a response that is altered at early stages of several diseases in humans. Athigh body temperatures, bats can dissipate heat through their wings; the bat wingserves as a thermal window where heat exchange is determined by local blood owand vascular response in the wing.For this study, a lumped mathematical model to calculate body and skin tem-perature alterations in response to changes in environmental conditions has beendeveloped. In order to formulate this model, experiments have been proposed wherethe pallid bat is subjected to dynamic systemic heating with and without the wingextended. By having the wing extended outside a metabolic chamber during heating,the bats were able to maintain an equilibrated body temperature; having the wing enclosed caused body temperature to increase rapidly. The experiments were designedto obtain correlations between systemic and vascular responses and therefore learnabout the thermoregulatory mechanisms of the pallid bat.Results from experiments following Animal Use Protocols 2006-253 and 2007-110indicate that vascular responses to environmental temperature changes (changes inTchamber) maintain or reduce body temperature to basal conditions. Vessel diameter,centerline velocity, blood ow and heat ux increase with Tchamber therefore deliveringa greater volume of blood to the bat wing and increasing heat exchange with theenvironment. The positive responses in the wing to Tchamber signify that the pallidbat is regulating its body temperature as had been expected.

The objective of this research is to analyze the relationship between environ-mental heat exchange and vascular response in the pallid bat wing during systemicheating and to develop a simplied model of heat transfer for theoretical analysis.During heating experiments, metabolic activity, body temperature and alterations invessel diameter and blood ow were monitored. This research is very signicant, asit will correlate thermoregulation and vascular response in a way that has not beenstudied before.The wing of the pallid bat is selected because the microvascular bed performssimilar functions as that of the human skin in terms of thermoregulation; understand-ing vascular response to heat or cold allows to analyze vascular function, or arterialhealth, a response that is altered at early stages of several diseases in humans. Athigh body temperatures, bats can dissipate heat through their wings; the bat wingserves as a thermal window where heat exchange is determined by local blood owand vascular response in the wing.For this study, a lumped mathematical model to calculate body and skin tem-perature alterations in response to changes in environmental conditions has beendeveloped. In order to formulate this model, experiments have been proposed wherethe pallid bat is subjected to dynamic systemic heating with and without the wingextended. By having the wing extended outside a metabolic chamber during heating,the bats were able to maintain an equilibrated body temperature; having the wing enclosed caused body temperature to increase rapidly. The experiments were designedto obtain correlations between systemic and vascular responses and therefore learnabout the thermoregulatory mechanisms of the pallid bat.Results from experiments following Animal Use Protocols 2006-253 and 2007-110indicate that vascular responses to environmental temperature changes (changes inTchamber) maintain or reduce body temperature to basal conditions. Vessel diameter,centerline velocity, blood ow and heat ux increase with Tchamber therefore deliveringa greater volume of blood to the bat wing and increasing heat exchange with theenvironment. The positive responses in the wing to Tchamber signify that the pallidbat is regulating its body temperature as had been expected.

Lübeck, Med. Universität, Thesis (doctoral), 2000.

Streptococcus pyogenes is a re-emerging pathogen that produces superficial and life threatening invasive diseases. One important virulence factor in S. pyogenes is hyaluronic acid capsule which has been shown to increase expression at sub-body temperatures in certain strains. This study showed that thermoregulation is common in invasive clinical isolates. Regulation was shown to occur independent of the CovRS two-component regulator in a post transcription manner and before protein level regulation. The endoribonuclease, CvfA, was also confirmed to be required for capsule thermoregulation. The search for a regulator lead to the discovery of the 1st antisense RNAs in S. pyogenes found opposite the capsule synthesis genes. Its role if any in capsule has not been discovered. Finally, a group of sRNAs were characterized adding to the knowledge of this layer of regulation in S. pyogenes.

Currently no previous study has isolated the independent influence of body fat (BF) on thermoregulatory responses from the confounding biophysical factors of body mass and metabolic heat production (Hprod). Therefore, seven lean (L, BF:10.7 ± 4.1%) and seven non-lean (NL, BF:32.2 ± 6.4%) males matched for total body mass (TBM, L: 87.8 ± 8.5 kg, NL: 89.4 ± 7.8 kg; P= 0.73), cycled for 60 min in a 28.2 ±0.2˚C and 27 ± 10% RH room at i) a Hprod of 546 W; and ii) a Hprod of 7.5 W·kg lean body mass (LBM). Rectal (Tre) and esophageal (Tes) temperatures, and local sweat rate (LSR) were measured continuously; while whole body sweat loss (WBSL) was measured from 0-60 mins. At 546 W, changes in Tre (L: 0.74 ± 0.16ºC, NL: 0.83 ± 0.14ºC), mean local sweat rate (MLSR) based on an average of upper-back and forearm local sweat rates (L: 0.65 ± 0.25, NL: 0.59±0.12 mgcm-2min-1) and WBSL (L: 568 ± 28 mL, NL: 567 ± 29 mL) were similar (P>0.58). At 7.5 W·kg LBM, the L group had greater changes in Tre (L: 0.87 ± 0.16ºC, NL: 0.55 ± 0.11ºC), MLSR (L: 0.83 ±0 .38, NL: 0.41 ± 0.13 mgcm-2min-1) and WBSL (L: 638 ± 19 mL, NL: 399 ± 17 mL) (P<0.05). In conclusion, i) body fat does not independently alter thermoregulatory responses during exercise; ii) core temperature comparisons between groups differing in BF should be performed using a Hprod normalized for TBM, not LBM.

Ventilated capsules (i.e. hygrometry) are widely used to measure time dependent changes in local sweat rate. Despite this, understanding of the reliability (consistency) of local sweat rate is limited to the forearm during mild hyperthermia. Further, extensive regional heterogeneity in sweating may render some regions more reliable than others. Knowledge of reliability has important implications for experimental design, statistical analysis and interpretation, yet it is relatively unknown. The purpose of this study was to determine local sweat rate across various regions of the body and the reliability of these responses, during increasing levels of hyperthermia. On three separate instances, fourteen young men (age: 24 [SD 5] years) donned a whole-body water perfusion suit to raise and clamp esopogheal temperature at elicit low (+0.6°C), moderate (+1.2°C) and high (+1.8°C) levels of heat strain. Local sweat rate was measured at the forehead, chest, abdomen, bicep, forearm, hand, quadriceps, calf, and foot via ventilated capsules (3.8 cm2). Absolute reliability was assessed using coefficient of variation (CV%) which quantifies the amount of error in a given measurement. Relative reliability was evaluated via the intraclass correlation coefficient (ICC); the consistency of an individual’s rank within a group during repeated measurements. At low heat strain, most sites demonstrated acceptable relative (ICC ≥0.70), and moderate absolute reliability (CV <25%). At moderate-heat strain, the abdomen, hand, quadriceps, calf and foot had acceptable relative reliability while the forehead, abdomen, forearm, hand and quadriceps had moderate absolute reliability. At high-heat strain, relative reliability was acceptable at the abdomen, quadriceps, calf, foot and absolute reliability was moderate at the chest, abdomen, forearm, hand, quadriceps, calf and foot. Our findings indicate that reliability of local sweat rate is dependent on both measurement site and level of hyperthermia. Researchers should consider this in their experimental design to increase the likelihood of detecting an effect of an intervention if one exists.

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.

No description available.

Up to 80% of menopausal women suffer from hot flushes, consisting of a coordinated activation of heat loss mechanisms (sweating, cutaneous vasodilatation, etc.). Ovarian steroid withdrawal also leads to hypersecretion of gonadotropins (LH and FSH) and changes in body fat distribution. Because gonadotropin release, thermoregulation, and energy balance are hierarchically controlled by the hypothalamus, it is likely that changes in response to estrogen withdrawal are occurring at the level of the hypothalamus. The infundibular (arcuate) nucleus of the hypothalamus contains an estrogen-sensitive population of cells that co-express kisspeptin, neurokin B (NKB), and dynorphin ("KNDy neurons"). KNDy neurons have been proposed to be a site of estrogen negative feedback on gonadotropin release in multiple species because they are estrogen sensitive and respond to estrogen withdrawal with somatic hypertrophy and significant changes in gene expression. Because KNDy neurons project to known thermoregulatory centers in the hypothalamus (such as the median preoptic nucleus, MnPO), we also hypothesized that changes in thermoregulation were also a due to changes in KNDy neurons. Ovariectomized (OVX) rats also show disorders of thermoregulation, increased serum LH and FSH, and altered weight gain. Furthermore, OVX rats exhibit KNDy gene expression changes similar to changes seen in the human, making this model ideal to study the effects of estrogen withdrawal. We used a novel neurotoxin conjugate NK₃-SAP to ablate KNDy neurons in OVX female rats. We then observed core and tail skin temperatures, serum gonadotropin levels, and weight changes before and after replacement with 17β-estradiol. Next, we ablated NK3R-expressing neurons in the MnPO and monitored the thermoregulatory axis. Rats with KNDy-ablation did not exhibit the rise in LH and profound weight gain associated with ovariectomy. Furthermore, KNDy-ablated animals did not exhibit the chronic vasodilatation observed in OVX rats, providing the first evidence that KNDy neurons play a role in vasomotion. Rats with NK₃R cell-specific MnPO lesions also exhibited decreased activation of heat loss effectors. Together, these data demonstrate an important role for arcuate KNDy neurons in estrogen modulation of LH release and body weight, and demonstrate that NKB signaling is critical for activation of heat dissipation effectors.