Elevated Core Body Temperature Research Articles

Characterising core body temperature response of free-moving C57BL/6 mice to 1.95 GHz whole-body radiofrequency-electromagnetic fields.

The present study investigated the core body temperature (CBT) response of free-moving adult male and female C57BL/6 mice, during and following a 2-h exposure to 1.95 GHz RF-EMF within custom-built reverberation chambers, using temperature capsules implanted within the intraperitoneal cavity and data continuously logged and transmitted via radiotelemetry postexposure. Comparing RF-EMF exposures (WBA-SAR of 1.25, 2.5, 3.75, and 5 W/kg) to the sham-exposed condition, we identified a peak in CBT within the first 16 min of RF-EMF exposure (+0.15, +0.31, +0.24, +0.37°C at 1.25, 2.5, 3.75, and 5 W/kg respectively; statistically significant at WBA-SAR ≥ 2.5 W/kg only), which largely dissipated for the remainder of the exposure period. Immediately before the end of exposure, only the CBT of the 5 W/kg condition was statistically differentiable from sham. Based on our findings, it is apparent that mice are able to effectively compensate for the increased thermal load at RF-EMF strengths up to 5 W/kg. In addition, the elevated CBT at the end of the exposure period in the 5 W/kg condition was statistically significantly reduced compared to the sham condition immediately after RF-EMF exposure ceased. This would indicate that measures of CBT following the end of an RF-EMF exposure period may not reflect the actual change in the CBT of mice caused by RF-EMF exposure in mice.

Effect of heat stress on the hypothalamic expression profile of water homeostasis-associated genes in low- and high-water efficient chicken lines.

With climate change, selection for water efficiency and heat resilience are vitally important. We undertook this study to determine the effect of chronic cyclic heat stress (HS) on the hypothalamic expression profile of water homeostasis-associated markers in high (HWE)- and low (LWE)-water efficient chicken lines. HS significantly elevated core body temperatures of both lines. However, the amplitude was higher by 0.5-1°C in HWE compared to their LWE counterparts. HWE line drank significantly less water than LWE during both thermoneutral (TN) and HS conditions, and HS increased water intake in both lines with pronounced magnitude in LWE birds. HWE had better feed conversion ratio (FCR), water conversion ratio (WCR), and water to feed intake ratio. At the molecular level, the overall hypothalamic expression of aquaporins (AQP8 and AQP12), arginine vasopressin (AVP) and its related receptor AVP2R, angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), and calbindin 2 (CALB2) were significantly lower; however, CALB1 mRNA and AQP2 protein levels were higher in HWE compared to LWE line. Compared to TN conditions, HS exposure significantly increased mRNA abundances of AQPs (8,12), AVPR1a, natriuretic peptide A (NPPA), angiotensin I-converting enzyme (ACE), CALB1 and 2, and transient receptor potential cation channel subfamily V member 1 and 4 (TRPV1 and TRPV4) as well as the protein levels of AQP2, however it decreased that of AQP4 gene expression. A significant line by environment interaction was observed in several hypothalamic genes. Heat stress significantly upregulated AQP2 and SCT at mRNA levels and AQP1 and AQP3 at both mRNA and protein levels, but it downregulated that of AQP4 protein only in LWE birds. In HWE broilers, however, HS upregulated the hypothalamic expression of renin (REN) and AVPR1b genes and AQP5 proteins, but it downregulated that of AQP3 protein. The hypothalamic expression of AQP (5, 7, 10, and 11) genes was increased by HS in both chicken lines. In summary, this is the first report showing improvement of growth performances in HWE birds. The hypothalamic expression of several genes was affected in a line- and/or environment-dependent manner, revealing potential molecular signatures for water efficiency and/or heat tolerance in chickens.

Eurycoma longifolia (Tongkat Ali) enhances wakefulness during active periods but facilitates sleep during resting periods in C57BL/6 mice.

The effects of the Eurycoma longifolia (also known as Tongkat Ali [TA]) on sleep and wakefulness was evaluated in C57BL/6 mice. While TA has been used as an aphrodisiac in males, it exhibits various pharmacological effects. The most notable effect observed with TA was wake-enhancement during the second half of the active period, accompanied by significant elevations in core body temperature (CBT). In contrast, sleep was enhanced during the resting period (i.e., increase in rapid eye movement [REM] sleep and delta electroencephalography [EEG] power in non-REM sleep) with significant declines in CBT. The transition of TA's effects between resting and active periods was rapid. The results of the experiments in constant darkness indicate that TA prolongs the circadian tau and that this transition is governed by circadian clock mechanisms rather than light exposure. TA did not demonstrate efficacy in aiding sleep in an acute stress-induced insomnia model; thus, TA may be more suitable as a wake-enhancing agent for daytime sleepiness, as sleep propensity tends to accumulate towards the end of active period. Since TA amplifies the rest-activity pattern, prolongs circadian tau and increases REM sleep, thereby reversing some common symptoms seen in elderly subjects, it may also hold promise as a rejuvenating medicine.

Burn size and environmental conditions modify thermoregulatory responses to exercise in burn survivors.

This project tested the hypothesis that burn survivors can perform mild/moderate-intensity exercise in temperate and hot environments without excessive elevations in core body temperature. Burn survivors with low (23 ± 5%TBSA; N = 11), moderate (40 ± 5%TBSA; N = 9), and high (60 ± 8%TBSA; N = 9) burn injuries performed 60 minutes of cycle ergometry exercise (72 ± 15 watts) in a 25°C and 23% relative humidity environment (ie, temperate) and in a 40°C and 21% relative humidity environment (ie, hot). Absolute gastrointestinal temperatures (TGI) and changes in TGI (ΔTGI) were obtained. Participants with an absolute TGI of >38.5°C and/or a ΔTGI of >1.5°C were categorized as being at risk for hyperthermia. For the temperate environment, exercise increased ΔTGI in all groups (low: 0.72 ± 0.21°C, moderate: 0.42 ± 0.22°C, and high: 0.77 ± 0.25°C; all P < .01 from pre-exercise baselines), resulting in similar absolute end-exercise TGI values (P = .19). Importantly, no participant was categorized as being at risk for hyperthermia, based upon the aforementioned criteria. For the hot environment, ΔTGI at the end of the exercise bout was greater for the high group when compared to the low group (P = .049). Notably, 33% of the moderate cohort and 56% of the high cohort reached or exceeded a core temperature of 38.5°C, while none in the low cohort exceeded this threshold. These data suggest that individuals with a substantial %TBSA burned can perform mild/moderate intensity exercise for 60 minutes in temperate environmental conditions without risk of excessive elevations in TGI. Conversely, the risk of excessive elevations in TGI during mild/moderate intensity exercise in a hot environment increases with the %TBSA burned.

Energy metabolism and thermoregulation during sleep in young and old females

Core body temperature (CBT) shows a diurnal rhythm, and the nocturnal decrease in CBT is blunted in older people. The physiological mechanisms responsible for the blunted nocturnal decrease in CBT in older people remain to be revealed. The aim of this study was to compare heat production and heat dissipation in young and old subjects during sleep, as assessed by indirect calorimetry and the distal–proximal temperature gradient (DPG) of skin temperature. A complete dataset of 9 young (23.3 ± 1.1 years) and 8 old (72.1 ± 2.5 years) females was analyzed. CBT and energy metabolism were monitored during sleep using an ingestible temperature sensor in a metabolic chamber maintained at 25 °C. Skin temperature was measured at proximal and distal parts of the body. CBT, distal skin temperature, and DPG in older subjects were higher than in young subjects. Protein oxidation was similar between the two groups, but fat oxidation was lower and carbohydrate oxidation was higher in old subjects compared to young subjects. On the other hand, energy expenditure was similar between the two age groups. Thus, the elevated CBT in older subjects was not attributed to deteriorated heat dissipation or enhanced heat production, suggesting an alternative explanation such as deteriorated evaporative heat loss in old subjects.

Body Temperature Manipulation Increases Salivary Cortisol Independent of Exercise

The vast majority of circulating cortisol in the blood is bound and inactivated by binding proteins like corticosteroid-binding globulin (CBG) and albumin. The cortisol that is free of these binding proteins is secreted via saliva and other body fluids. Ex-vivo studies have shown that CBG binding to cortisol is temperature-dependent within the physiological range of human core body temperatures. Exercise is a standard experimental paradigm for inducing cortisol responses. However, these studies rarely consider that exercise-induced changes in core body temperature might increase free cortisol independent of psychological stress or physical exertion. We tested the effect of heat exposure without exertion or other stressors on saliva cortisol. 26 Participants (18 healthy and 8 with Major Depression MDD) sat motionless in a dry infrared sauna set to 65.5 degrees C (150 F). They had their tympanic membrane temperature and salivary cortisol measured as their body temperature increased. Exposure to exogenous heat significantly increased core body temperature from 36.93 C/98.48 F (95% CI 36.79-37.07 C, 98.23-98.73 F) to 38.42 C /101.16 F (95% CI 38.24-38.6 C, 100.83-101.48 F) after 45 minutes of heat exposure, F(15,42.33)=43.509, p<0.001. Concurrently saliva cortisol also increased significantly from 4.00 nmol/l (95%CI 1.89-6.11) to 9.87 nmol/l (95% CI 5.58-14.17), F(1,33.17)=6.64, p=0.015. Elevations in core body temperature can significantly increase free cortisol levels even in the absence of exercise or overt psychological stressors.

Elevated cfDNA after exercise is derived primarily from mature polymorphonuclear neutrophils, with a minor contribution of cardiomyocytes

Strenuous physical exercise causes a massive elevation in the concentration of circulating cell-free DNA (cfDNA), which correlates with effort intensity and duration. The cellular sources and physiological drivers of this phenomenon are unknown. Using methylation patterns of cfDNA and associated histones, we show that cfDNA in exercise originates mostly in extramedullary polymorphonuclear neutrophils. Strikingly, cardiomyocyte cfDNA concentration increases after a marathon, consistent with elevated troponin levels and indicating low-level, delayed cardiac cell death. Physical impact, low oxygen levels, and elevated core body temperature contribute to neutrophil cfDNA release, while muscle contraction, increased heart rate, β-adrenergic signaling, or steroid treatment fail to cause elevation of cfDNA. Physical training reduces neutrophil cfDNA release after a standard exercise, revealing an inverse relationship between exercise-induced cfDNA release and training level. We speculate that the release of cfDNA from neutrophils in exercise relates to the activation of neutrophils in the context of exercise-induced muscle damage.

Changes in sleep profile on exposure to sodium chloride and artificially carbonated springs: a pilot study.

[Purpose] Herein, we aimed to investigate the effects of bathing in a sodium chloride spring and an artificially carbonated spring on core body temperature and electroencephalograms, to assess whether the springs facilitate sleep. [Participants and Methods] This randomized, controlled, crossover study evaluated the effects of a sodium chloride spring, an artificially carbonated spring, a plain hot bath, and no bath on sleep. The subjective evaluations and recording of temperature were performed before/after bathing at 40 °C for 15 min at 22:00 h, before nocturnal sleep (0:00-7:00 h), and after the participants (n=8) woke up in the morning. [Results] Bathing significantly increased the core body temperature, with significant subsequent declines observed until bedtime. Participants in the sodium chloride spring group had the highest average core body temperature, while participants in the no-bath group had the lowest average core body temperature before bedtime (23:00-0:00 h). During bedtime (1:00-2:00 h), the participants in the no bath group had the highest average core body temperature, while participants in the artificially carbonated spring group had the lowest average core body temperature. The amount of delta power/min in the first sleep cycle significantly increased in the bathing groups, with the highest value during bedtime being recorded in the artificially carbonated spring group, followed by the sodium chloride spring, plain hot bath, and no-bath groups. These sleep changes were associated with significant declines in the elevated core body temperature. Increased heat dissipation and decreased core body temperature were observed in the artificially carbonated spring and sodium chloride spring groups, which increased the delta power during the first sleep cycle compared with that observed in the plain hot bath group, followed by the no-bath group. [Conclusion] An artificially carbonated spring would be the most appropriate given each circumstance because it did not cause fatigue, as observed with the sodium chloride spring.

Homeostatic response to sleep deprivation and circadian rhythmicity are intact in older adults with insomnia.

We examined whether homeostatic sleep drive and circadian rhythmicity differ in older adults with insomnia (OAI) compared to older good sleepers (GS). OAI (n = 37) and GS (n = 30) participated in a 60-h in-lab study with sleep deprivation and constant routine paradigms. Homeostatic sleep drive was assessed by examining the effect of sleep deprivation on delta EEG power and theta EEG power, and repeated sleep latency tests. Circadian rhythm was assessed with salivary melatonin (phase and amplitude), core body temperature (phase, amplitude, and mesor), and sleep latency during a constant routine paradigm. Mixed models were used to assess interactions of group (OAS vs GS) with homeostatic sleep and circadian effects. Compared to GS, OAI showed a greater linear increase in waking theta power during sleep deprivation, but the two groups did not show differential responses to sleep deprivation in delta EEG, or in repeated sleep latency tests. The two groups did not differ in circadian phase or amplitude of melatonin or core body temperature rhythms. OAI had a significantly elevated core body temperature mesor compared to GS. Homeostatic response to sleep deprivation was intact in OAI compared to GS; theta EEG power suggested a greater homeostatic response in OAI. Circadian rhythm amplitude and phase were similar in OAI compared to GS. Elevated body temperature mesor in OAI may indicate elevated physiological arousal. These findings suggest that effective treatments for insomnia in older adults may leverage intact sleep and circadian regulatory mechanisms, rather than repair defective sleep and circadian regulation.

Estimating core body temperature using electrocardiogram signals.

Suppressing the elevation in core body temperature is an important factor in preventing heatstroke. However, there is still no non-invasive method to sense core body temperature. This study proposed an algorithm that estimates core body temperature based on electrocardiogram signals. A total of 12 healthy men (mean age ± SD = 39.6 ± 13.4) performed an ergometric exercise load test under two conditions of exercise load in an environmental chamber adjusted to a temperature of 35°C and humidity of 50%. Vital sensing data such as electrocardiograms, core body temperatures, and body surface temperatures were continuously measured, and physical data such as body weight were obtained from participants pre- and post-experiment. According to basic physiological knowledge, heart rate and body temperature are closely related. We analyzed the relationship between core body temperature and several indexes obtained from electrocardiograms and found that the amount of change in core body temperature had a strong relationship with analyzed data from electrocardiograms. Based on these findings, we developed the amount of change in core body temperature estimation model using multiple regression analysis including the Poincaré plot index of the ECG R-R interval. The estimation model showed an average estimation error of -0.007°C (average error rate = -0.02%) and an error range of 0.457–0.445°C. It is suggested that continuous core body temperature change can be estimated using electrocardiogram signals regardless of individual characteristics such as age and physique. Based on this applicable estimation model, we plan to enhance estimation accuracy and further verify efficacy by considering clothing and environmental conditions.

Dive Performance and Aquatic Thermoregulation of the World's Smallest Mammalian Diver, the American Water Shrew (Sorex palustris).

Allometry predicts that the 12-17-g American water shrew (Sorex palustris)-the world's smallest mammalian diver-will have the highest diving metabolic rate coupled with the lowest total body oxygen storage capacity, skeletal muscle buffering capacity, and glycolytic potential of any endothermic diver. Consistent with expectations, and potentially owing to their low thermal inertia, water shrews had a significantly higher diving metabolic rate in 10°C water (8.77 mL O2 g-1 h-1) compared with 30°C water (6.57 mL O2 g-1 h-1). Unlike larger-bodied divers, muscle myoglobin contributed minimally (7.7%-12.4%) to total onboard O2 stores of juvenile and adult water shrews, respectively, but was offset by high blood O2 carrying capacities (26.4%-26.9% v/v). Diving was predominantly aerobic, as only 1.2%-2.3% of dives in 10°C and 30°C water, respectively, exceeded the calculated aerobic dive limits at these temperatures (10.8-14.4 s). The mean voluntary dive time of water shrews during 20-min trials in 3°C-30°C water was s (, ), with a mean maximum dive time of s. However, the average dive duration ( s, ) of radio-telemetered shrews exclusively foraging in a simulated riparian environment (3°C water) for 12-28 h suggests that mean (but not maximum) dive times of water shrews in the wild may be longer. Mean dive duration, duration of the longest dive, and total time in water all decreased significantly as water temperature declined, suggesting that shrews employed behavioral thermoregulation to defend against immersion hypothermia. Additionally, free-diving shrews in the 24-h trials consistently elevated core body temperature by ∼1°C immediately before initiating aquatic foraging bouts and ended these bouts when body temperature was still at or above normal resting levels (∼37.8°C). We suggest that this observed predive hyperthermia aids to heighten the impressive somatosensory physiology, and hence foraging efficiency, of this diminutive predator while submerged.

The Effect of Increasing Levels of Hyperthermia on Autophagy in Peripheral Blood Mononuclear Cells from Young Adults

Exposure to an elevated state of hyperthermia is associated with heat‐induced cytotoxicity, thereby resulting in impaired cellular function. Cellular dysfunction during heat stress leads to the initiation of systemic inflammation and apoptotic cell death, which if left unabated, can cause tissue damage and death. To counter heat‐induced cellular injury, cells employ the vital mechanism of autophagy which acts to prevent the accumulation of toxic protein aggregates and dysfunctional organelles to promote cellular survival. In our recent ex vivomodel, we demonstrated that the process of autophagy is activated during exposure to increased temperatures (37‐41°C) in peripheral blood mononuclear cells (PBMCs) from young adults which acts to suppress heat‐induced apoptotic cell death. Despite this, the dose‐dependent autophagic response to heat stress has yet to be evaluated in an in vivo human model and thus the relationship between elevations in core body temperature (Tcore) and autophagy have yet to be established in humans. Therefore, we sought to extend upon our previous work by assessing if in vivorises in Tcore are associated with greater autophagic activation in healthy young adults. We evaluated the hypothesis that in parallel to elevations in Tcore(indexed by esophageal temperature), greater autophagic initiation would occur in a dose‐dependent manner in young adults during immersion in mild to very warm water. To assess this hypothesis, on separate days 6 young adults (mean [SD] 22 [3] years; 3 women) were immersed (up to the clavicle) in water set at a temperature to clamp Tcore at either thermoneutral (TN, 37°C), 38°C, or 39°C for 60‐min. Autophagy was characterized in PBMCs prior to and immediately post‐water immersion, as well as following 3‐h of seated recovery. Western blot was used to assess autophagy proteins microtubule associated protein 1 light chain 3 beta (LC3)‐II and sequesterome‐1/p62 (p62). All proteins were normalized to β‐actin and reported as fold change relative to baseline. Data were compared via a two‐way repeated measures ANOVA with Fisher’s LSD (α=0.05). No changes in either LC3‐II or p62 were observed during TN, indicating no time‐dependent changes in autophagy (all p≥0.28). Immediately following the 38°C clamp, LC3‐II increased (1.56 [0.32]; p=0.02) and p62 decreased (0.52 [0.30]; p=0.049) from baseline, with both proteins returning to basal levels within 3‐h (both, p≥0.22). Similarly, LC3‐II increased (1.90 [0.70]; p=0.04) and p62 decreased (0.58 [0.21]; p=0.03) immediately after clamping Tcore at 39°C, however LC3‐II remained elevated above baseline at 3‐h (2.54 [1.08]; p=0.03) while p62 did not differ from pre‐immersion levels at the end of recovery (p=0.57). Given LC3‐II accumulation and p62 degradation indicate elevated autophagy, our preliminary findings indicate greater autophagy during increasing levels of hyperthermia in healthy young adults. Further, we showed increased reliance on autophagy to restore cellular homeostasis after exposure to an elevated state of hyperthermia of 39°C, although the mechanism of activation is unclear.

Addition of In-Play Cooling Breaks During Intermittent Exercise While Wearing Lacrosse Uniforms in The Heat Attenuates Increases in Rectal Temperature.

To reduce the risk of heat-related illness, appropriate body cooling strategies are needed during men’s lacrosse competitions in hot-humid environments. The current study investigated whether additional in-play cooling breaks would attenuate the core (rectal) body temperature rise during exercise designed to mimic the activity patterns of a men’s lacrosse match while wearing uniform in hot-humid environments. In randomized and counterbalanced order, ten physically active men completed two experimental trials comprising four quarters of 15-min intermittent cycling exercises separated by a 10-min simulated half-time break and two 2-min quarter breaks in a climate chamber (35°C, 50% relative humidity). The two trials included a regular simulated match condition (REG) and a water break time out condition (WBTO) that included additional 2-min breaks 7.5-min into each quarter. Rectal temperature was significantly lower (p=0.017) in the WBTO condition (38.23±0.23°C) compared with the REG condition (38.50±0.46°C) at the end of the 4th quarter. In addition, ratings of perceived exertion, thermal sensation, heart rate and the physiological strain index were significantly lower (all p<0.05) in the WBTO condition compared with the REG condition. The current results indicated that, even when wearing lacrosse uniforms, the implementation of WBTO attenuated the core body temperature elevation only in the latter stages of an intermittent cycling exercise protocol designed to mimic the exercise pattern of a men’s lacrosse match. Therefore, WBTO may provide a feasible and effective cooling strategy for lacrosse players to reduce the risk of heat-illness.

Comorbidities, Triggers, Management, and Rate of Resolution of Cholinergic Urticaria in 18 Pediatric Patients

Cholinergic urticaria (ChU) represents a subtype of chronic inducible urticaria (CindU) elicited by elevated core body temperature. We examined the triggers, comorbidities, management, and resolution of ChU in a pediatric population.

Unraveling quad fever: Severe hyperthermia after traumatic cervical spinal cord injury

PurposeThere are many infectious and inflammatory causes for elevated core-body temperatures, though they rarely pass 40 ℃ (104 ℉). The term “quad fever” is used for extreme hyperpyrexia in the setting of acute cervical spinal cord injuries (SCIs). The traditional methods of treating hyperpyrexia are often ineffective and reported morbidity and mortality rates approach 100%. This study aims to identify the incidence of elevated temperatures in SCIs at our institution and assess the effectiveness of using a non-invasive dry water temperature management system as a treatment modality with mortality. MethodsA retrospective analysis of acute SCI patients requiring surgical intensive care unit admission who experienced fevers ≥ 40 ℃ (104 ℉) were compared to patients with maximum temperatures < 40 ℃. Patients ≥18 years old who sustained an acute traumatic SCI were included in this study. Patients who expired in the emergency department; had a SCI without radiologic abnormality; had neuropraxia; were admitted to any location other than the surgical intensive care unit; or had positive blood cultures were excluded. SAS 9.4 was used to conduct statistical analysis. ResultsOver the 9-year study period, 35 patients were admitted to the surgical intensive care unit with a verified SCI. Seven patients experienced maximum temperatures of ≥ 40 ℃. Six of those patients were treated with the dry water temperature management system with an overall mortality of 57.1% in this subgroup. The mortality rate for the 28 patients who experienced a maximum temperature of ≤ 40 ℃ was 21.4% (p = 0.16). ConclusionThe diagnosis of quad fever should be considered in patients with cervical SCI in the presence of hyperthermia. In this study, there was no significant difference in mortality between quad fever patients treated with a dry water temperature management system versus SCI patients without quad fever. The early use of a dry water temperature management system appears to decrease the mortality rate of quad fever.

Sufficiently Elevated Core Body Temperature May Be Necessary to Maintain Cerebral Blood Flow Response throughout the Morning

In comparison to a carbohydrate-rich breakfast, a nutritionally balanced breakfast reportedly leads to a higher core body temperature because of diet-induced thermogenesis (DIT) and also results in higher task performance. This study aimed to examine the relationships among the core body temperature, blood glucose level, cerebral blood flow, and cognitive performance when the core body temperature is raised to a similar extent as in DIT in the morning. This crossover study included 18 male participants who performed four sets of cognitive tests in the morning with four different foot baths and glucose intake conditions. In elevated body temperature (EBT) conditions, the core body temperature was increased by a foot bath at 42˚C or 39˚C, while in low body temperature (LBT) conditions, it was maintained at 35˚C by a foot bath; the participants received no glucose or two intakes of 20-g glucose for each thermal condition. In addition to the core body temperature measurement, the cerebral blood flow in the dorsolateral prefrontal cortex (DLPFC) was measured using near-infrared spectroscopy. Three blood collections were performed to measure the changes in blood glucose levels. The results revealed that in the EBT conditions, the core body temperature remained 0.3˚C - 0.5˚C higher than that at wake-up time, while the glucose intake conditions increased blood glucose levels which remained higher than those during fasting. No significant between-treatment difference was observed in the results of cognitive tests. However, the blood flow in the DLPFC increased during the second test period in the EBT/glucose and LBT/glucose conditions, whereas during the fourth test period, it increased solely in the EBT/glucose condition. Thus, in addition to the blood glucose level, an elevated core body temperature within the physiological range may be needed for long-term maintenance of the cerebral blood flow response.

Adolescent Development of Biological Rhythms in Female Rats: Estradiol Dependence and Effects of Combined Contraceptives.

Adolescence is a period of continuous development, including the maturation of endogenous rhythms across systems and timescales. Although, these dynamic changes are well-recognized, their continuous structure and hormonal dependence have not been systematically characterized. Given the well-established link between core body temperature (CBT) and reproductive hormones in adults, we hypothesized that high-resolution CBT can be applied to passively monitor pubertal development and disruption with high fidelity. To examine this possibility, we used signal processing to investigate the trajectory of CBT rhythms at the within-day (ultradian), daily (circadian), and ovulatory timescales, their dependence on estradiol (E2), and the effects of hormonal contraceptives. Puberty onset was marked by a rise in fecal estradiol (fE2), followed by an elevation in CBT and circadian power. This time period marked the commencement of 4-day rhythmicity in fE2, CBT, and ultradian power marking the onset of the estrous cycle. The rise in circadian amplitude was accelerated by E2 treatment, indicating a role for this hormone in rhythmic development. Contraceptive administration in later adolescence reduced CBT and circadian power and resulted in disruption to 4-day cycles that persisted after discontinuation. Our data reveal with precise temporal resolution how biological rhythms change across adolescence and demonstrate a role for E2 in the emergence and preservation of multiscale rhythmicity. These findings also demonstrate how hormones delivered exogenously in a non-rhythmic pattern can disrupt rhythmic development. These data lay the groundwork for a future in which temperature metrics provide an inexpensive, convenient method for monitoring pubertal maturation and support the development of hormone therapies that better mimic and support human chronobiology.

The impact of elevated body core temperature on critical power as determined by a 3-min all-out test.

Critical power (CP) delineates the heavy and severe exercise intensity domains, and sustained work rates above CP result in an inexorable progression of oxygen uptake to a maximal value and, subsequently, the limit of exercise tolerance. The finite work capacity above CP, W', is defined by the curvature constant of the power-duration relationship. Heavy or severe exercise in a hot environment generates additional challenges related to the rise in body core temperature (Tc) that may impact CP and W'. The purpose of this study was to determine the effect of elevated Tc on CP and W'. CP and W' were estimated by end-test power (EP; mean of final 30 s) and work above end-test power (WEP), respectively, from 3-min "all-out" tests performed on a cycle ergometer. Volunteers (n = 8, 4 female) performed the 3-min tests during a familiarization visit and two experimental visits (thermoneutral vs. hot, randomized crossover design). Before experimental 3-min tests, the subjects were immersed in water (thermoneutral: 36°C for 30 min; hot: 40.5°C until Tc was ≥38.5°C). Mean Tc was significantly greater in the hot condition than in the thermoneutral condition (38.5 ± 0.0°C vs. 37.4 ± 0.2°C; means ± SD, P < 0.01). All 3-min tests were performed in an environmental chamber [thermoneutral: 18°C, 45% relative humidity (RH); hot: 38 °C, 40% RH]. EP was similar between thermoneutral (239 ± 57 W) and hot (234 ± 66 W; P = 0.55) conditions. WEP was similar between thermoneutral (10.9 ± 3.0 kJ) and hot conditions (9.3 ± 3.6; P = 0.19). These results suggest that elevated Tc has no significant impact on EP or WEP.NEW & NOTEWORTHY The parameters of the power-duration relationship (critical power and W') estimated by a 3-min all-out test were not altered by elevated body core temperature as compared with a thermoneutral condition.

Пирексия и антипиретическая терапия у больных при критических состояниях

Повышение температуры ядра тела является одним из наиболее часто встречающихся аномальных признаков у пациентов, поступивших в ОИТ, и это связано с увеличением смертности среди некоторых групп пациентов с тяжелыми заболеваниями. Повышенная температура тела обнаруживается примерно у 50 % взрослых пациентов, поступивших в отделение интенсивной терапии (ОИТ). Повышенная температура тела классифицируется как пирексия или гипертермия. Пирексия (также ее называют лихорадкой) рассматривается как адаптивный ответ на физиологический стресс, который регулируется через эндогенные пирогенные и антипиретические пути и связан с увеличением гипоталамического заданного значения. Гипертермические синдромы включают: гипертермию окружающей среды, в том числе тепловой удар; гипертермию, вызванную лекарственными средствами; нейролептический злокачественный синдром; синдром серотонина и эндокринные причины, включая тиреотоксикоз, феохромоцитому и надпочечниковый криз. Многие эпизоды пирексии вызваны инфекциями. Наиболее распространенными источниками инфекции являются нижние дыхательные пути, внутрибрюшные инфекции, инфекции мочевых путей и другие, которые включают инфекцию кожи и мягких тканей, костей или суставов, центральной нервной системы, этмоидных и верхнечелюстных пазух. Пирексия из-за неинфекционной этиологии также является распространенной причиной лихорадки у пациентов в ОИТ. Для борьбы с пирексией могут использоваться антипиретики, главным образом парацетамол и нестероидные противовоспалительные препараты, а также физические методы охлаждения. Лечение с помощью жаропонижающих препаратов распространено в ОИТ. Было показано, что исследования жаропонижающей терапии, которые включали как септических, так и несептических пациентов, не обнаружили значительного улучшения 28-дневной госпитальной летальности у взрослых критических пациентов с сепсисом или без него. Дополнительные исследования улучшат понимание патофизиологии пирексии и будут способствовать развитию данного направления.

UTILITY OF DANTROLENE FOR HYPERPYREXIA IN THE MANAGEMENT SARS-COV-2 INFECTION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus Disease 2019 (COVID-19) continues to be a global pandemic with its management evolving as research continues to unveil innovative therapies. Dantrolene, approved in malignant hyperthermia, may have utility for hyperpyrexia in COVID-19 patients, given its cytoprotective effects (1). Here we present a COVID-19 case with persistent hyperpyrexia despite conventional antipyretic measures that abated after dantrolene administration. CASE PRESENTATION: A 57-year-old Hispanic male with no past medical history, presented with fever, palpitations, myalgias and worsening dyspnea. He denied other symptoms. His admission vitals were Temp 101.3F, BP 155/81, Pulse 106, Resp 22, SpO2 88% on RA and 98% on 50% Venturi Mask. Lung examination revealed decreased air entry throughout with scattered crackles. Laboratory investigations showed WBC of 5.61 with normal electrolytes. ABG showed pH 7.45, pCO2 36, pO2 59 with FiO2 0.35 which improved with increased oxygenation. CXR showed hallmark features for COVID-19 pneumonia. COVID-19 PCR was positive. Antibiotics and prophylactic anticoagulation were initiated. He was later admitted to the medical floor. His hospital course was unremarkable until day three when he developed acute hypoxic respiratory failure requiring high flow nasal cannula and intensive care transfer. Despite optimal oxygenation, PF ratio was 105F. Besides multiple positive COVID-19 tests, all other infectious investigations were negative. Antibiotics, antivirals and antifungals were started but pyrexia persisted. Intravenous dantrolene (2.5mg/kg then 1mg/kg) was given after which temperature abated. De-escalation of care ensued, with removal of antimicrobials, intubation and ECMO. Patient had an uneventful transfer from MICU and discharge from the hospital. DISCUSSION: Hyperpyrexia is an extreme elevation of core body temperature usually >106.7 °F due to an elevated hypothalamic thermo-regulatory threshold. It has been reported in COVID-19 patients and portends a poor outcome with up to 100% mortality. Proposed mechanisms include immune dysfunction, direct brain injury from SARS-CoV-2 and vascular thrombosis (2). Dantrolene has been shown to inhibit multiple cell damage induced by SARS-CoV-2 infection (1). In our index case, all conventional antipyretic measures failed, while dantrolene achieved normothermia. CONCLUSIONS: Our case had a favorable outcome juxtaposing those previously reported (1,2). The proposition that dantrolene can be repurposed in COVID-19 patients with hyperpyrexia is novel and hopefully will stimulate and unearth more research. REFERENCE #1: Jiang, B., Liang, S., Liang, G., & Wei, H. (2020). Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?. European review for medical and pharmacological sciences, 24(19), 10228–10238. https://doi.org/10.26355/eurrev_202010_23247 REFERENCE #2: Suwanwongse, K., & Shabarek, N. (2020). Hyperpyrexia in patients with COVID-19. Journal of medical virology, 92(11), 2857–2862. https://doi.org/10.1002/jmv.26154 DISCLOSURES: No relevant relationships by Sneha Adidam, source=Web Response No relevant relationships by Sahai Donaldson, source=Web Response No relevant relationships by Lorenzo Leys, source=Web Response No relevant relationships by Alicia Thomas, source=Web Response