Reduction In Core Body Temperature Research Articles

The impact and management of symptoms experienced at midlife: a community‐based study of women in northeast Scotland

To determine the frequency and management of menopausal symptoms among community-dwelling women. Cross-sectional study. Northeast Scotland. Women aged 45-54 years registered with 16 general practices. In 2009, a self-completed questionnaire enquiring about the frequency, associated level of bothersomeness and management of 23 symptoms experienced during the previous month was sent to 8206 women. The proportion (95% CI) of women reporting each symptom and management strategy. Hot flushes, night sweats and vaginal dryness were reported by 46.7% (95% CI 45.2-48.2), 46.4% (95% CI 44.9-47.9) and 28.2% (95% CI 26.9-29.6) of women, respectively. Two-fifths of women rated these symptoms as quite bothersome or extremely bothersome. More than 60% managed menopausal symptoms using social support by talking to friends and family. Avoidance or alleviating options were common. Herbal remedies were more commonly used than prescription drugs. Current hormone replacement therapy use was highest among surgically menopausal women (21%); 8% of postmenopausal and <2% of perimenopausal women with symptoms were using hormone replacement therapy. Many women had sought information about symptom management. More than one-third of women wanted more support about menopausal symptoms from their general practitioner or practice nurse. Following the publication of the Women's Health Initiative trial results, menopausal symptoms remain common and are often bothersome. Many women seek information about menopausal symptoms from healthcare professionals. Future studies should look beyond frequently researched management strategies, to consider other commonly used options, such as social support, strategies to reduce core body temperature and information about managing menopausal symptoms.

Therapeutic hypothermia for acute neurological injuries.

Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.

Induction of Mild Hypothermia by Noninvasive Body Cooling in Healthy, Unanesthetized Subjects

The induction of mild hypothermia has been considered as an important means to provide protection against cerebral ischemia. Yet, to date, the relative clinical efficacies of different noninvasive methods for reducing core body temperature have not been thoroughly studied. The aim of the current investigation was to compare the relative effectiveness of several noninvasive cooling techniques for reducing core temperatures in healthy volunteers. Cooling methods included convective/conductive and evaporative/conductive combinations, as well as evaporative cooling alone. Additionally, focal facial warming was employed as a means to suppress involuntary motor activity and thus better enable noninvasive cooling. Core temperatures were measured so to monitor the relative efficiencies of these induced cooling methodologies. With each employed methodology, rectal temperature reductions were induced, with combined evaporative/conductive (n=4, 1.44°C±0.99°C) and convective/conductive (n=4, 1.51°C±0.89°C) approaches yielding the largest decreases: note, that evaporative cooling alone was not as efficient in lowering core body temperature (n=10, 0.56°C±0.20°C; n=16, 0.58°C±0.27°C). In this study on healthy volunteers, the evaporative/conductive and convective/conductive combination methods were more effective in reducing core temperatures as compared with an evaporative approach alone. These therapeutic approaches for the induction of mild hypothermia (including the use of facial warming) could be employed in warranted clinical cases, importantly without the need for administration of anesthetics or paralytics.

Effect of shearing on water turnover and thermobiological variables in German Blackhead mutton sheep1

Current equations for estimating water requirements in sheep do not differentiate between shorn and unshorn sheep. Furthermore, the effect of shearing on thermoregulative responses in sheep has not been adequately studied under temperate environmental conditions. Therefore, the present study was conducted to investigate the effect of wool coverage on water turnover in relation to thermoregulation in sheep by using the deuterium dilution technique to predict total water intake before and after shearing. Physiological responses, such as water turnover, surface temperature, and rectal temperature, as well as drinking behavior of sheep were also evaluated. Fourteen nonlactating German Blackhead mutton ewes were randomly allocated into 2 groups: a control group (n = 7) that was already shorn, and a treatment group (n = 7) that was left unshorn (wool length: 10.6 ± 1.2 cm). Individual feed and water intakes were recorded throughout the experiment (d 1 to 71). Two weeks after measurements commenced (d 15), treatment sheep were shorn. Water intake was estimated twice for 2 consecutive weeks by using deuterium dilution techniques (d 1 to 15 and d 57 to 71). Ambient temperature (T(a)), relative humidity, and respiratory rate were measured daily, whereas BW, rectal and animal surface temperatures (using infrared thermography), and wool length were measured weekly. In the first 2 wk, when treatment sheep were unshorn, treatment and control ewes differed (P < 0.05) in DMI (52 ± 4 vs. 59 ± 4 g·kg(-0.75)·d(-1)), water intake (165 ± 17 vs. 134 ± 18 g·kg(-0.75)·d(-1)), respiratory rate (66 ± 5 vs. 31 ± 4 breath/min), rectal temperature (39.3 ± 0.2 vs. 38.8 ± 0.1°C), and surface temperatures (body side: 19.3 ± 0.3 vs. 24.5 ± 0.6°C; leg: 25.8 ± 2.4 vs. 27.4 ± 1.6°C). However, after shearing, these differences partly disappeared. The same trend in water intake between groups was confirmed using the isotope dilution technique. We found a significant relationship between T(a) and water intake, respiratory rate, and body surface temperatures. Even under temperate conditions (T(a) < 28°C), shearing significantly reduced core body temperature, water intake, and respiratory rate in German Blackhead mutton sheep, thus indicating heat stress in fleeced animals, which should be considered when determining the optimal shearing time in sheep as well as when estimating water requirements.

Core body temperature in obesity

A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI ≥30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.

Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans

Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7 ± 9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769 ± 348 kcal/d) than in the WD (2302 ± 668 kcal/d) and EX (2798 ± 760 kcal/d) groups (P < 0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P ≤ 0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging.

Carbohydrate ingestion and pre-cooling improves exercise capacity following soccer-specific intermittent exercise performed in the heat

Ingestion of carbohydrate and reducing core body temperature pre-exercise, either separately or combined, may have ergogenic effects during prolonged intermittent exercise in hot conditions. The aim of this investigation was to examine the effect of carbohydrate ingestion and pre-cooling on the physiological responses to soccer-specific intermittent exercise and the impact on subsequent high-intensity exercise performance in the heat. Twelve male soccer players performed a soccer-specific intermittent protocol for 90 min in the heat (30.5°C and 42.2% r.h.) on four occasions. On two occasions, the participants underwent a pre-cooling manoeuvre. During these sessions either a carbohydrate-electrolyte solution (CHOc) or a placebo was consumed at (PLAc). During the remaining sessions either the carbohydrate-electrolyte solution (CHO) or placebo (PLA) was consumed. At 15-min intervals throughout the protocol participants performed a mental concentration test. Following the soccer-specific protocol participants performed a self-chosen pace test and a test of high-intensity exercise capacity. The period of pre-cooling significantly reduced core temperature, muscle temperature and thermal sensation (P < 0.05). Self-chosen pace was greater with CHOc (12.5 ± 0.5 km h(-1)) compared with CHO (11.3 ± 0.4 km h(-1)), PLA (11.3 ± 0.4 km h(-1)) and PLAc (11.6 ± 0.5 km h(-1)) (P < 0.05). High-intensity exercise capacity was improved with CHOc and CHO when compared with PLA (CHOc; 79.8 ± 7 s, CHO; 72.1 ± 5 s, PLAc; 70.1 ± 8 s, PLA; 57.1 ± 5 s; P < 0.05). Mental concentration during the protocol was also enhanced during CHOc compared with PLA (P < 0.05). These results suggest pre-cooling in conjunction with the ingestion of carbohydrate during exercise enhances exercise capacity and helps maintain mental performance during intermittent exercise in hot conditions.

Metabolic Depression and Increased Reactive Oxygen Species Production by Isolated Mitochondria at Moderately Lower Temperatures

Temperature (T) reduction increases lifespan, but the mechanisms are not understood. Because reactive oxygen species (ROS) contribute to aging, we hypothesized that lowering T might decrease mitochondrial ROS production. We measured respiratory response and ROS production in isolated mitochondria at 32, 35, and 37 °C. Lowering T decreased the rates of resting (state 4) and phosphorylating (state 3) respiration phases. Surprisingly, this respiratory slowdown was associated with an increase of ROS production and hydrogen peroxide release and with elevation of the mitochondrial membrane potential, ΔΨ(m). We also found that at lower T mitochondria produced more carbon-centered lipid radicals, a species known to activate uncoupling proteins. These data indicate that reduced mitochondrial ROS production is not one of the mechanisms mediating lifespan extension at lower T. They suggest instead that increased ROS leakage may mediate mitochondrial responses to hypothermia.

Hypothermia Is Associated With Improved Outcomes in a Porcine Model of Hemorrhagic Shock

: Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized. : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock. In a prospective survival study, we anesthetized 19 juvenile male pigs (Yorkshire-Landrace, 15-25 kg) and caused them to hemorrhage until their systolic blood pressure was 45 mm Hg to 55 mm Hg for a duration of 45 minutes. Then, we randomized them into three groups (all of which underwent an 8-hour limited resuscitation period) as follows: normothermic (39 degrees C), mildly hypothermic (36 degrees C), and severely hypothermic (33 degrees C). We used ice packs to achieve surface cooling that mimicked environmental hypothermia. After 8 hours, we rewarmed the pigs and fully resuscitated them for 16 hours. We extubated the survivors and observed them for an additional 24 hours, before killing them. : Surface cooling resulted in significant reduction in core body temperature. The mortality rate was significantly higher in the normothermic group (60%) than in the two hypothermic groups combined (7%) (p = 0.015) or in the severely hypothermic group (0%) (p = 0.023). Hypothermic animals had significantly lower levels of creatinine kinase, lactate dehydrogenase, and lactate in addition to a lower base deficit after shock. However, severely hypothermic animals required greater volumes of colloid infusion and whole blood transfusion to maintain our target systolic blood pressure and hemoglobin levels when compared with normothermic animals. We saw a strong trend toward decreased oxygen consumption with hypothermia. : In our porcine model, we found that simulating mild and severe levels of environmental hypothermia during early resuscitation after hemorrhage was associated with a significantly decreased mortality rate. Furthermore, markers of cellular stress and organ dysfunction, including lactate levels and the base deficit, were lower in hypothermic animals. Decreasing oxygen consumption with hypothermia may, in part, explain the protective effects observed with hypothermia.

Influence of two perfusion strategies on oxygen metabolism in paediatric cardiac surgery. Evaluation of the high-flow, low-resistance technique☆

Paediatric cardiac surgery is often performed under hypothermic conditions, that is, with a reduced core body temperature. Certain interventions even require the circulation to be stopped. This can only be done at a body temperature of 18 degrees C, with no risk of neurological damage and harm to the brain and other organs. Vasoconstriction is a natural reaction of the body to cold, causing the blood vessels to contract. Such a reaction would lead to a clear rise in blood pressure on cardiopulmonary bypass (CPB). Since the blood pressure is regulated in the arteriolar loop of the capillary system, there is a marked increase in blood pressure and a suppression of free water into the surrounding tissue, which, in turn, may lead to the intra-operative development of oedemas. This study aimed to investigate whether the high-flow, low-resistance (HFLR) technique offers any benefits over conventional methods. This open, prospective, randomised study was to recruit 48 children scheduled to undergo surgery for congenital heart disease. To investigate the two different perfusion strategies, we have measured intestinal perfusion as well as skin perfusion with laser Doppler spectroscopy. To identify the effects on the immune system, selected immunologic parameters of systemic inflammation were additionally measured. Laser Doppler spectroscopy is a method that uses a glass fibre probe to determine the parameters of oxygen saturation of haemoglobin and relative haemoglobin quantity in an illuminated tissue volume, as well as the perfusion parameters of relative blood flow and blood flow velocity in the sample volume of the probe. During the study period, the change in oxygen saturation over time was comparable in both groups. At the end of surgery, the patients of the high-flow group had significantly higher saturation levels in the intestinal mucosa (p<0.05). Over the course of intensive care, the groups did not differ in terms of fluid supply, administration of packed red blood cells, platelet concentrates or fresh frozen plasma. Analysis of urinary output revealed significant group differences. It was higher in the patients of the high-flow group than the normal-flow group (p<0.03), without differences in diuretic administration. Laser Doppler spectroscopy is highly suited to the detection even of the slightest changes in flow characteristics and oxygenation of the skin, musculature and intestinal mucosa during surgery with extracorporeal circulation using CPB. At the same time, the technique of HFLR perfusion was found to have benefits over conventional bypass methods.

High-dose diazepam facilitates core cooling during cold saline infusion in healthy volunteers

Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, cardiac arrest, or exertional heat illness. While infusion of cold normal saline is a simple and inexpensive method for reducing core temperature, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesized that intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and reduce core body temperature more than the administration of cold saline alone. Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline. Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH), 10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin temperature, and oxygen consumption. Data for the main outcomes were analyzed with generalized estimating equations to identify differences in group, time, or a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/- 0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3 (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x time interaction was observed for core temperature and oxygen consumption (p < 0.001). Administration of high-dose diazepam resulted in decreased oxygen consumption during cold saline infusion, suggesting that 20 mg of intravenous diazepam may reduce the shivering threshold without compromising respiratory or cardiovascular function.

Influence of postexercise cooling techniques on heart rate variability in men

The reduction of core body temperature (T(C)) is vitally important in the treatment of hyperthermia; however, little is known regarding the impact of cooling treatments on the autonomic control of heart rate (HR). The aim of the present study was to examine the influence of three field-based hyperthermia treatments on the neural control of HR via heart rate variability (HRV). Following exercise-induced hyperthermia (T(C) approximately 40.0 degrees C) in a warm environment (34.2 +/- 0.5 degrees C), nine healthy, active men were treated during recovery, in a randomized order, with intravenous cold saline infusion (IV) or ice packs (ICE) or fan cooling with intermittent water spray (FAN) for 40 min. During each treatment, HR dynamics via power spectral (VLF, LF, HF), Poincare plot (SD1, SD2), approximate entropy (ApEn) and short- (alpha(1)) and long-term (alpha(2)) fractal scaling analyses were determined every 10 min. At recovery onset, HR and T(C) were similar between treatments and were significantly reduced over the 40 min recovery period. During recovery, HR and alpha(2) were significantly reduced from initial levels but were significantly greater for IV compared with ICE and FAN. In contrast, VLF, LF, HF, SD1, SD2 and ApEn increased during recovery, with all being significantly lower for IV compared with ICE and/or FAN. The present results demonstrated that IV, compared with ICE and FAN, resulted in significantly greater HR, reduced spectral and geometrical HRV, lower HR complexity and reduced long-term HR control, indicative of reduced vagal and/or increased sympathetic modulation. Specific treatments for exercise-induced hyperthermia may result in an altered sympathovagal balance that requires further examination.

Exertional Heatstroke: Early Recognition and Outcome With Aggressive Combined Cooling—a 12-Year Experience

To determine the clinical outcomes of an aggressive combined cooling technique for exertional heatstroke in Thailand. We analyzed patients who were diagnosed with exertional heatstroke between 1995 and 2007. Outcomes were assessed both in hospital and at 3 months follow-up. Twenty-eight cases of exertional heatstroke presented to Phramongkutklao Army Hospital over 12 years. All patients developed multiorgan dysfunction and encephalopathy. Twenty-four cases had acute renal failure, 7 of whom required dialysis. Disseminated intravascular coagulation (DIC) was detected in 9 patients (32.1%). In-hospital mortality was 7.1%. Most survivors recovered with nearly normal organ function. However, 9 exhibited prolonged neurologic dysfunction and 2 had chronic renal dysfunction requiring hemodialysis. At 3-month follow-up, neurologic and renal dysfunction in those patients persisted. Higher serum prothrombin time and DIC correlated to fatality. The patients whose core body temperature achieved 38 degrees C within 3 hours revealed a significantly lower DIC and twice as low in the frequency of poor outcome than the patients cooled longer than 3 hours to reduce core body temperature to 38 degrees C. Despite early recognition and aggressive combined cooling, exertional heatstroke remains associated with multiorgan dysfunction. However, our 7.1% in-hospital mortality rate was low compared to previous studies. Early diagnosis and prompt treatment are critical.

5′‐AMP and its Role in Fasting‐Induced Torpor and Hypothermia in Ecto‐nucleotidase Knockout (CD73 ‐/‐) Mice

Fasting of mice induces a state called torpor that is accompanied by a reduction of core body temperature (CBT) at ambient temperatures (Ta) lower than thermoneutrality. It was recently shown that fasting raises 5′‐AMP (AMP) levels in plasma and an injection of AMP induces reversible profound hypothermia in mice. To assess whether AMP itself or its breakdown product adenosine is responsible for AMP‐induced hypothermia we compared the effect of AMP in wild type (WT) and CD73‐/‐ mice subjected to 48 h of fasting at a Ta of 22 °C while recording CBT by radiotelemetry. Both genotypes exhibited two hypothermic bouts with nadirs at 12 (WT: 31.9 ± 0.8 °C, CD 73 ‐/‐: 29.7 ± 1.4 °C; n=7) and 36 h (WT: 31.1 ± 0.6 °C, CD 73 ‐/‐: 28.2 ± 1.5 °C; n=7) after the start of fasting. The trend of a more profound torpor bout in CD73 ‐/‐ was also seen when data were expressed as area under curve (WT 8260 ± 1124 °C·min, CD 73 ‐/‐ 12683 ± 3425 °C·min; n=7). Similarly, injection of AMP (550 mg/kg BW) produced a significantly lower nadir of CBT in CD73 ‐/‐ than WT mice (26.9 ± 0.5 °C vs. 28.7 ± 0.4 °C; p &lt; 0.05). Since plasma adenosine was not significantly altered by AMP in CD73‐/‐ mice (311 ± 21 pmol/ml vs. 295 ± 67 pmol/ml) whereas it increased to 1345 ± 287 pmol/ml in WT, it appears unlikely that hypothermia is caused by adenosine. In conclusion, hypothermia following fasting or AMP administration is caused likely by AMP itself and not by its extracellular conversion to adenosine.

Differentiation of CB1 cannabinoid agonists in rats

Results from GTPγS binding and other in vitro assays suggest that cannabinoid (CB) receptor agonists range in efficacy from partial to full agonists. The present studies compared the in vivo effects of a proposed CB1 full agonist, AM4054, and three potential CB1 partial agonists, BAY 59‐3074, an aminoalkylindole (AAI3), and Δ9‐tetrahydrocannabinol (Δ9THC) in female rats. During 6 hr sessions post‐injection AM4054 and BAY 59‐3074 reduced core body temperature by more than 40C and doses required to decrease temperature by 3oC were 0.13 and 6.7 mg/kg, respectively; neither Δ9THC nor AAI3 decreased temperature by more than 2oC. In a rat tail‐flick assay, AM4054, Δ9THC and BAY 59‐3074 all had antinociceptive effects over 6 hr sessions, with respective ED50 values of 0.13, 6.0, and 7.7 mg/kg; AAI3 produced small, but significant, increases in tail flick latency. Similarly, AM4054, Δ9THC and BAY 59‐3074 all had diuretic effects, and the average doses required to yield 15 g/kg urine within 2 hrs were 0.05, 5.3, and 4.9 mg/kg, respectively; AAI3 did not have diuretic effects. All four drugs tested decreased operant responding for sweetened milk at 1‐3 hrs after injection; the respective ED50 values for AM4054, Δ9THC, BAY 59‐3074, and AAI3 were: 0.04, 6.4, 3.8, and 10.2 mg/kg. These data indicate that CB1 agonists may be differentiated according to their profile of behavioral effects in rats. (Supported by PHS Grants DA19205, 15723)

Processed Aconite Root Prevents Cold-Stress-Induced Hypothermia and Immuno-Suppression in Mice

Processed aconite root (PA) is a crude drug used in traditional Chinese or Japanese medicine to generate heat in interior body and dispel cold. We evaluated the effects of PA on hypothermia and reduction in the activity of natural killer (NK) cells in mice exposed to chronic cold stress. Male mice were reared at 4 degrees C, and powdered PA was administered for 10 d as a food additive. Core body temperature of mice significantly decreased by approximately 1 degrees C after rearing in a cold environment, and PA administration significantly restored the reduction in core body temperature in a dose-dependent manner. After 10 d, splenic NK-cell activity of cold-stressed mice was significantly reduced, and the reduction was dose-dependently recovered by PA administration. An aconitine-type alkaloid fraction prepared from PA was ineffective when administered to cold-stressed mice, and the thermogenic effect on hypothermic mice was present in the fraction containing low-molecular-weight compounds without alkaloids. In cold-stressed mice, the weight of brown adipose tissue (BAT) and uncoupling protein (UCP)-1 level in BAT increased, whereas the weight of white adipose tissue decreased. The increase in UCP-1 level in BAT of cold-stressed mice was further augmented by PA treatment. These results indicate that PA exhibited a thermogenic effect on hypothermia induced by cold stress in mice by additional upregulation of UCP-1 level in BAT, which was already enhanced by hypothermia, and that the active ingredients present in PA are non-alkaloidal low-molecular-weight compounds.

Disturbances in core body temperature in RIP140-null mice

1. RIP140-null mice have reduced core body temperature ( T c), but exhibit normal temperature increase in response to stress, and normal upregulation of UCP1 mRNA in brown adipose tissue (BAT) after β3-AR agonist treatment. 2. Expression levels of some genes key to BAT function are altered in RIP140-null mice, including PGC1α. 3. Newborn RIP140-null mice have reduced BAT mass, altered BAT gene expression and a high death rate. 4. Differences in anxiety behavior and activity also exist in RIP140-null mice. 5. Our observations suggest that RIP140 is involved in a broad range of systems critical to energy balance, thermoregulation, BAT development and behavior.

Drowning Survival in Icy Water: A Review

We conducted an extensive literature review using the search terms of “drowning” and “hypothermia” to discover the major factors related to differences in survival rate especially associated with hypothermic effects. Studies indicated that some differences in drowning survival could be identified associated with age, sex, length of submersion, reduced core body temperature, and quality of cardiopulmonary respiratory care. The variability of results associated with the large number of studies prevented us from making any recommendations about whether hypothermia can improve survival among either children or adults.

When administered to rats in a cold environment, 3,4-methylenedioxymethamphetamine reduces brown adipose tissue thermogenesis and increases tail blood flow: Effects of pretreatment with 5-HT1A and dopamine D2 antagonists

When given in a warm environment MDMA (3,4-methylenedioxymethamphetamine, ecstasy) causes hyperthermia by increasing interscapular brown adipose tissue (iBAT) heat production and decreasing heat loss via cutaneous vasoconstriction. When given in a cold environment, however, MDMA causes hypothermia by an unknown mechanism. This paper addresses these mechanisms and in addition examines whether antagonists at 5-HT1A and D2 receptors reduce the hypothermic action of MDMA. Male Sprague–Dawley rats instrumented with a Doppler probe for measuring tail blood flow, and probes for measuring core and iBAT temperatures, were placed in a temperature-controlled chamber. The chamber temperature was reduced to 10 °C and vehicle (0.5 ml Ringer), the 5-HT1A antagonist WAY 100635 (0.5 mg/kg), the D2 antagonist spiperone (20 μg/kg), or the combination of Way 100635 and spiperone were injected s.c. Thirty minutes later the antagonists were injected again along with MDMA (10 mg/kg) or vehicle. MDMA reduced core body temperature by preventing cold-elicited iBAT thermogenesis and by transiently reversing cold-elicited cutaneous vasoconstriction. Pretreatment with WAY 100635 prevented MDMA induced increases in tail blood flow, and briefly attenuated MDMA's effects on iBAT and core temperature. While spiperone alone failed to affect any of the parameters, the combination of spiperone and WAY 100635 decreased MDMA-mediated hypothermia by attenuating both the effects on tail blood flow and iBAT thermogenesis. MDMA's prevention of cold-induced iBAT thermogenesis appears to have a central origin as it rapidly reverses cold-induced increases in iBAT sympathetic nerve discharge in anesthetized rats. Our results demonstrate that MDMA in a cold environment reduces core body temperature by inhibiting iBAT thermogenesis and tail artery vasoconstriction and suggest that mechanisms by which this occurs include the activation of 5-HT1A and dopamine D2 receptors.

Core Temperature Cooling in Healthy Volunteers After Rapid Intravenous Infusion of Cold and Room Temperature Saline Solution

Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, traumatic hemorrhage, and cardiac arrest. Although infusion of cold normal saline solution is a simple and inexpensive method for initiating hypothermia, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesize that rapid infusion of 30 mL/kg of cold (4 degrees C, 39.2 degrees F) 0.9% saline solution during 30 minutes to healthy subjects (aged 27 [standard deviation (SD) 4] years) will reduce core body temperature to the therapeutic range of 33 degrees C to 35 degrees C (91.4 degrees F to 95 degrees F). Sixteen subjects were randomly assigned to receive either cold (4 degrees C, 39.2 degrees F) or room temperature (23 degrees C, 73.4 degrees F) normal saline solution. Subjects were not informed of their assignment, but blinding was not possible after initiation of the infusion. Core temperature, skin temperature, and vital signs were recorded every 2 minutes. Subjects indicated global discomfort during the infusion on a 100-mm visual analog scale at 5-minute intervals. Core temperature decreased in both the cold saline solution (1.0 degrees C [SD 0.4 degrees C]/1.8 degrees F [0.7 degrees F]) and room temperature saline solution (0.5 degrees C [SD 0.1 degrees C]/0.9 degrees F [0.2 degrees F]) groups, whereas skin temperature was unchanged. Slopes calculated from the core temperature cooling curves indicate that the majority of cooling occurred during the first half of the infusion. Examination of the core temperature cooling curves revealed a 2-phase temporal pattern in 30-minute cooling curves. The early phase, spanning 0 to 14 minutes, demonstrated rapid cooling in both groups, with a larger effect observed in subjects receiving cold saline solution. In this pilot study of healthy volunteers, rapid administration of cold saline solution to awake normothermic volunteers resulted in 1 degrees C (1.8 degrees F) cooling but did not induce a therapeutic plane of hypothermia. This change in core temperature was not accompanied by significant changes in skin temperature. These data suggest that a reduction in core temperature of about 1 degrees C (1.8 degrees F) can be achieved in healthy humans before a thermoregulatory response is triggered and that rapid infusion of cold intravenous fluids is insufficient by itself to overcome this response. The clinically relevant control arm of room temperature saline solution also resulted in mild core cooling.