Decrease In Core Body Temperature Research Articles

The Role of Deep Hypothermia in Cardiac Surgery.

Hypothermia is defined as a decrease in body core temperature to below 35 °C. In cardiac surgery, four stages of hypothermia are distinguished: mild, moderate, deep, and profound. The organ protection offered by deep hypothermia (DH) enables safe circulatory arrest as a prerequisite to carrying out cardiac surgical intervention. In adult cardiac surgery, DH is mainly used in aortic arch surgery, surgical treatment of pulmonary embolism, and acute type-A aortic dissection interventions. In surgery treating congenital defects, DH is used to assist aortic arch reconstructions, hypoplastic left heart syndrome interventions, and for multi-stage treatment of infants with a single heart ventricle during the neonatal period. However, it should be noted that a safe duration of circulatory arrest in DH for the central nervous system is 30 to 40 min at most and should not be exceeded to prevent severe neurological adverse events. Personalized therapy for the patient and adequate blood temperature monitoring, glycemia, hematocrit, pH, and cerebral oxygenation is a prerequisite and indispensable part of DH.

Electronic Nicotine Vapor Exposure Produces Differential Changes in Central Amygdala Neuronal Activity, Thermoregulation and Locomotor Behavior in Male Mice.

Nicotine is an addictive substance historically consumed through smoking and more recently through the use of electronic vapor devices. The increasing prevalence and popularity of vaping prompts the need for preclinical rodent models of nicotine vapor exposure and an improved understanding of the impact of vaping on specific brain regions, bodily functions, and behaviors. We used a rodent model of electronic nicotine vapor exposure to examine the cellular and behavioral consequences of acute and repeated vapor exposure. Adult male C57BL/6J mice were exposed to a single 3-h session (acute exposure) or five daily sessions (repeated exposure) of intermittent vapes of 120 mg/ml nicotine in propylene glycol:vegetable glycerol (PG/VG) or PG/VG control. Acute and repeated nicotine vapor exposure did not alter body weight, and both exposure paradigms produced pharmacologically significant serum nicotine and cotinine levels in the 120 mg/ml nicotine group compared with PG/VG controls. Acute exposure to electronic nicotine vapor increased central amygdala (CeA) activity in individual neuronal firing and in expression of the molecular activity marker, cFos. The changes in neuronal activity following acute exposure were not observed following repeated exposure. Acute and repeated nicotine vapor exposure decreased core body temperature, however acute exposure decreased locomotion while repeated exposure increased locomotion. Collectively, these studies provide validation of a mouse model of nicotine vapor exposure and important evidence for how exposure to electronic nicotine vapor produces differential effects on CeA neuronal activity and on specific body functions and behaviors like thermoregulation and locomotion.

Correlation Knowledge to Hypothermic Handling Practices in Students

Hypothermia is a decrease in core body temperature to <35˚C due to heat loss. Factors causing hypothermia are cold weather, exposure to cold winds at high altitudes, immersion in cold water, and prolonged exposure to cold. Hypothermia is more common in hikers or mapala because they do activities exploring the highlands. The purpose of this study was to determine the relationship between knowledge of hypothermia and the practice of handling hypothermia in Mapala. This study used a correlation study method with a cross-sectional approach. The population in this study were Mapala UNISSULA, UNNES, and USM with a total of 52 students. The sampling technique was purposive sampling, the number of samples of this study was 30 students. The results of the Spearman Rank statistical test obtained a value of ρ value of 0.738 (ρ ≥ 0.05), so it was stated that there was no relationship between knowledge of hypothermia and the practice of handling hypothermia in Nature Lovers Students. Recommendations from research so that mapala members increase their knowledge and practice in handling emergency hypothermia by conducting ongoing training.

Perinatal Infection: A Major Contributor to Efficacy of Cooling in Newborns Following Birth Asphyxia.

Neonatal encephalopathy (NE) is a global burden, as more than 90% of NE occurs in low- and middle-income countries (LMICs). Perinatal infection seems to limit the neuroprotective efficacy of therapeutic hypothermia. Efforts made to use therapeutic hypothermia in LMICs treating NE has led to increased neonatal mortality rates. The heat shock and cold shock protein responses are essential for survival against a wide range of stressors during which organisms raise their core body temperature and temporarily subject themselves to thermal and cold stress in the face of infection. The characteristic increase and decrease in core body temperature activates and utilizes elements of the heat shock and cold shock response pathways to modify cytokine and chemokine gene expression, cellular signaling, and immune cell mobilization to sites of inflammation, infection, and injury. Hypothermia stimulates microglia to secret cold-inducible RNA-binding protein (CIRP), which triggers NF-κB, controlling multiple inflammatory pathways, including nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and cyclooxygenase-2 (COX-2) signaling. Brain responses through changes in heat shock protein and cold shock protein transcription and gene-expression following fever range and hyperthermia may be new promising potential therapeutic targets.

Effects of Pre-cooling and Per-cooling on Neural, Physiological, and Functional Responses in Active Young Girls

Background: Stressful environments, especially air temperature, have significant effects on human physiological responses to physical activity. Objectives: The current study aimed to determine the effects of pre-cooling and per-cooling on neural, physiological, and functional responses in active young girls. Methods: Twelve active girls (age 24.6 ± 1.4, weight 55.46 ± 8.18, height 165.1 ± 5.91) were tested in three separate sessions with intervals of three days between each session. All subjects performed the Balke test in three groups either without an ice vest (control and pre-cooling) or with an ice vest (per-cooling) in each session, randomly. Pre-cooling was applied with an ice vest for 30 min just before the test, while per-cooling was used with an ice vest from the beginning of the test to exhaustion. A Buerer FT-70 digital thermometer, polar-FT60 heart rate monitoring, Microlife blood pressure monitoring, and ELISA technique were used to measure core body temperature, heart rate, blood pressure, dopamine, cortisol, and lactate dehydrogenase, respectively. Two-way repeated-measures ANOVA was applied to analyze the data with a confidence interval of 95%. Results: The heart rate and core body temperature significantly decreased at the end of the test in the pre-cooling and per-cooling groups (P < 0.05). There was an improved performance with an increase in Tmax in the per-cooling group compared to the control group (P < 0.05) although this difference was not significant in the pre-cooling group compared to the control group (P > 0.05). Dopamine, cortisol, and lactate dehydrogenize increased in the groups in comparison with the pretest (P < 0.05) even though these differences were not significant in the comparison between the groups (P > 0.05). Conclusion: The findings suggest that pre-cooling and per-cooling could be used as a beneficial method to improve performance due to not only a decrease in core body temperature and heart rate but also an increase in the level of dopamine and cortisol. Moreover, per-cooling was more effective than pre-cooling to increase performance.

Inhibition of type 4 cAMP-phosphodiesterases (PDE4s) in mice induces hypothermia via effects on behavioral and central autonomous thermoregulation

Inhibitors of Type 4 cAMP-phosphodiesterases (PDE4s) exert a number of promising therapeutic benefits, including potent anti-inflammatory, memory- and cognition-enhancing, metabolic, and antineoplastic effects. We report here that treatment with a number of distinct PDE4 inhibitors, including Rolipram, Piclamilast, Roflumilast and RS25344, but not treatment with the PDE3-selective inhibitor Cilostamide, induces a rapid (10–30 min), substantial (−5 °C) and long-lasting (up to 5 h) decrease in core body temperature of C57BL/6 mice; thus, identifying a critical role of PDE4 also in the regulation of body temperature. As little as 0.04 mg/kg of the archetypal PDE4 inhibitor Rolipram induces hypothermia. As similar or higher doses of Rolipram were used in a majority of published animal studies, most of the reported findings are likely paralleled by, or potentially impacted by hypothermia induced by these drugs. We further show that PDE4 inhibition affects central body temperature regulation and acts by lowering the cold-defense balance point of behavioral (including posture and locomotion) and autonomous (including cutaneous tail vasodilation) cold-defense mechanisms. In line with the idea of an effect on central body temperature regulation, hypothermia is induced by moderate doses of various brain-penetrant PDE4 inhibitors, but not by similar doses of YM976, a PDE4 inhibitor that does not efficiently cross the blood–brain barrier. Finally, to begin delineating the mechanism of drug-induced hypothermia, we show that blockade of D2/3-type dopaminergic, but not β-adrenergic, H1-histaminergic or opiate receptors, can alleviate PDE4 inhibitor-induced hypothermia. We thus propose that increased D2/3-type dopaminergic signaling, triggered by PDE4 inhibitor-induced and cAMP-mediated dopamine release in the thermoregulatory centers of the hypothalamus, is a significant contributor to PDE4 inhibitor-induced hypothermia.

Effects of the α-2 Adrenergic Receptor Agonists Lofexidine and Guanfacine on Food-Cocaine Choice in Socially Housed Cynomolgus Monkeys.

Although norepinephrine (NE) does not appear to play a prominent role in mediating the abuse-related effects of cocaine, studies have indicated that NE α-2 receptor agonists can attenuate reinstatement of extinguished cocaine self-administration in rats and monkeys and can decrease cocaine craving in humans. In the present studies, we examined the effects of two α-2 receptor agonists, lofexidine and guanfacine, on choice between food and cocaine (0.0-0.1 mg/kg per injection) in cynomolgus monkeys. Male and female subjects were housed in stable same-sex social groups of four; social rank did not influence the effects of lofexidine and guanfacine. When administered acutely, lofexidine (0.03-3.0 mg/kg, i.v.) significantly decreased cocaine choice in females (n = 7) but not males (n = 8). However, in males, the same lofexidine doses produced dose-dependent decreases in core body temperature (n = 7), and acute guanfacine (0.003-1.0 mg/kg, i.v.) significantly decreased cocaine choice (n = 11). When lofexidine was administered for five consecutive days to a subset of the monkeys in whom lofexidine acutely decreased cocaine choice, tolerance to this effect developed to varying degrees of completeness in three of three males and two of four females. Taken together, these data suggest that α-2 receptor agonists can produce small decreases in the reinforcing strength of cocaine relative to food and that, even when efficacy is observed after acute administration, tolerance to the decreases in cocaine choice are apparent and more likely in males compared with females. SIGNIFICANCE STATEMENT: Cocaine use disorder remains a significant public health problem with no US Food and Drug Administration-approved treatments. Although cocaine elevates dopamine, serotonin, and norepinephrine (NE), the latter target has received less research. The present study noted modest effects of NE agonists on the relative reinforcing strength of cocaine with greater efficacy in female compared with male monkeys.

Insightful Backbone Modifications Preventing Proteolytic Degradation of Neurotensin Analogs Improve NTS1-Induced Protective Hypothermia.

Therapeutic hypothermia represents a brain-protective strategy for multiple emergency situations, such as stroke or traumatic injury. Neurotensin (NT), which exerts its effects through activation of two G protein-coupled receptors, namely NTS1 and NTS2, induces a strong and long-lasting decrease in core body temperature after its central administration. Growing evidence demonstrates that NTS1 is the receptor subtype mediating the hypothermic action of NT. As such, potent NTS1 agonists designed on the basis of the minimal C-terminal NT(8-13) bioactive fragment have been shown to produce mild hypothermia and exert neuroprotective effects under various clinically relevant conditions. The high susceptibility of NT(8-13) to protease degradation (half-life <2 min) represents, however, a serious limitation for its use in pharmacological therapy. In light of this, we report here a structure-activity relationship study in which pairs of NT(8-13) analogs have been developed, based on the incorporation of a reduced Lys8-Lys9 bond. To further stabilize the peptide bonds, a panel of backbone modifications was also inserted along the peptide sequence, including Sip10, D-Trp11, Dmt11, Tle12, and TMSAla13. Our results revealed that the combination of appropriate chemical modifications leads to compounds exhibiting improved resistance to proteolytic cleavages (>24 h; 16). Among them, the NT(8-13) analogs harboring the reduced amine bond combined with the unnatural amino acids TMSAla13 (4) and Sip10 (6) or the di-substitution Lys11 - TMSAla13 (12), D-Trp11-TMSAla13 (14), and Dmt11-Tle12 (16) produced sustained hypothermic effects (−3°C for at least 1 h). Importantly, we observed that hypothermia was mainly driven by the increased stability of the NT(8-13) derivatives, instead of the high binding-affinity at NTS1. Altogether, these results reveal the importance of the reduced amine bond in optimizing the metabolic properties of the NT(8-13) peptide and support the development of stable NTS1 agonists as first drug candidate in neuroprotective hypothermia.

1760-P: Brain Sh2b1 Protects against Obesity and Insulin Resistance through Multiple Hypothalamic Neural Circuits

Sh2b1 is a SH2 and PH domain-containing adaptor protein and enhances signal transduction in response to leptin, insulin, brain-derived neurotrophic factor (BDNF), and other ligands. Leptin, insulin and BDNF are known to activate the hypothalamic neural circuitry that controls energy balance, body weight, and metabolism. Genome-wide studies have identified numerous SH2B1 single nucleotide polymorphisms linked to human obesity and diabetes. SH2B1 nonsense and missense mutations have also been reported to be associated with obesity and type 2 diabetes in humans. We previously reported that global deletion of Sh2b1 results in hyperphagia, obesity, and type 2 diabetes in mice. Here, we attempted to identify Sh2b1 target cells, using conditional Sh2b1 knockout mice. We ablated Sh2b1 in the ventromedial hypothalamus (VMH) of Sh2b1flox/flox mice (Sh2b1ΔVMH) either by transducing the VMH with AAV-Cre vectors or using Sf1-Cre drivers. Both Sh2b1ΔVMH males and females, like global Sh2b1 knockout mice, developed obesity, insulin resistance, and liver steatosis. To further map Sh2b1 neurons, we generated leptin receptor (LepR) neuron-specific Sh2b1 knockout (Sh2b1ΔLepR) mice using LepR-Cre drivers. Sh2b1ΔLepR males and females also developed obesity, insulin resistance, glucose intolerance, and liver steatosis. Brown adipose tissue (BAT) thermogenic programs were severely impaired in Sh2b1ΔLepR mice, leading to decreased core body temperature and cold intolerance. Remarkably, Sh2b1 deficiency completely abrogated the ability of leptin to stimulate sympathetic nerves projecting to BAT in Sh2b1ΔLepR mice, indicating that Sh2b1 mediates leptin actions on sympathetic-controlled energy expenditure and metabolism. Collectively, our data suggest that hypothalamic Sh2b1 influences multiple neural circuits controlling food intake, energy expenditure, and metabolic processes by integrating leptin, insulin, BDNF, and/or other nutritional signals. Disclosure Y. Li: None. M. Kim: None. L. Jiang: None. M.G. Myers: Research Support; Self; AstraZeneca, Novo Nordisk Inc. L. Rui: None.

Inhibition of PDE4 Induces Hypothermia in Mice

Type 4 cyclic nucleotide phosphodiesterases (PDE4s), a group of isoenzymes that hydrolyze and inactivate the second messenger cAMP, are established targets for development of enzyme inhibitors with anti‐inflammatory properties. While testing the anti‐inflammatory effects of a nonselective PDE4 inhibitor in a murine model of bacterial lung infection, we noticed that PDE4 inhibition per se induced significant hypothermia in the animals in the absence of bacterial infection. Because drug‐induced hypothermia may critically impact our animal model, and the role cAMP‐phosphodiesterases play in the regulation of body temperature is poorly understood, we further explored this observation. We found that treatment with a number of structurally distinct PAN‐PDE4 inhibitors, including Rolipram, Roflumilast and RS25344 (all 1 mg/kg, i.p.), but not the PDE3‐selective inhibitor Cilostamide, induced a rapid decrease in core body temperature of C57Bl6 mice as measured with a rectal thermometer at 30 min after drug application, suggesting that hypothermia in mice is a class‐effect of PDE4 inhibitors. PDE4 inhibitor‐induced hypothermia was considerable (~4°C drop), rapid in onset (max effect is reached within 20–30 min), and long lasting (core body temperature remains below controls for up to 5 h). As little as 40 μg/kg of the archetypal PDE4 inhibitor Rolipram induced a hypothermic effect. Similar or higher doses of Rolipram were used in most published animal studies. Thus, the reported findings are likely associated with, or at least paralleled by, drug‐induced hypothermia. The initial decrease in body temperature after PDE4 inhibitor injection is so rapid that it is no different from heat dissipation after euthanasia, suggesting that PDE4 inhibition affects central body temperature regulation so that both heat‐generating (e.g. shivering/non‐shivering thermogenesis) as well as heat‐preserving (e.g. skin vasoconstriction) mechanisms are simultaneously suspended, either by lowering the cold defense set point or by impairing its enforcement. Indeed, PDE4 inhibitor treatment induced a temporary heat‐loss via tail vasodilation as assessed by thermography. Consistent with the idea of an effect on central body temperature regulation, hypothermia was induced by moderate doses (≤1 mg/kg) of various brain‐penetrant PDE4 inhibitors. Conversely, YM976, a PDE4 inhibitor that does not cross the blood‐brain barrier, had no effect. Finally, to begin delineating the mechanism of drug‐induced hypothermia, we show that a blockade of serotonergic‐ and dopaminergic‐, but not β‐adrenergic‐, histaminergic‐ or opiate receptors, can alleviate PDE4 inhibitor‐induced hypothermia.Support or Funding InformationSupported by grants from the Cystic Fibrosis Foundation (SALEH18H0,RICHTE16GO) and the NIH (HL76125, HL141473, HL066299).

Impact of rewarming rate on the mortality of patients with accidental hypothermia: analysis of data from the J-Point registry

BackgroundAccidental hypothermia (AH) is defined as an involuntary decrease in core body temperature to < 35 °C. The management of AH has been progressing over the last few decades, and numerous techniques for rewarming have been validated. However, little is known about the association between rewarming rate (RR) and mortality in patients with AH.MethodThis was a multicentre chart review study of patients with AH visiting the emergency department of 12 institutions in Japan from April 2011 to March 2016 (Japanese accidental hypothermia network registry, J-Point registry). We retrospectively registered patients using the International Classification of Diseases, Tenth Revision code T68: ‘hypothermia’. We excluded patients whose body temperatures were unknown or ≥ 35 °C, who could not be rewarmed, whose rewarmed temperature or rewarming time was unknown, those aged < 18 years, or who or whose family members had refused to join the registry. RR was calculated based on the body temperature on arrival at the hospital, time of arrival at the hospital, the documented temperature during rewarming, and time of the temperature documentation. RR was classified into the following five groups: ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h. The primary outcome of this study was in-hospital mortality. The association between RR and in-hospital mortality was evaluated using multivariate logistic regression analysis.ResultDuring the study, 572 patients were registered in the J-Point registry, and 481 patients were included in the analysis. The median body temperature on arrival to the hospital was 30.7 °C (interquartile range [IQR], 28.2 °C–32.4 °C), and the median RR was 0.85 °C/h (IQR, 0.53 °C/h–1.31 °C/h). The in-hospital mortality rates were 19.3% (11/57), 11.1% (4/36), 14.4% (15/104), 20.1% (35/175), and 34.9% (38/109) in the ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h groups, respectively. Multivariate regression analysis revealed that in-hospital mortality rate increased with each 0.5 °C/h decrease in RR (adjusted odds ratio, 1.49; 95% confidence interval, 1.15–1.94; Ptrend < 0.01).ConclusionThis study showed that slower RR is independently associated with in-hospital mortality.

Hypothermia‐induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model

BackgroundHypothermia, either therapeutically induced or accidental (ie, an involuntary decrease in core body temperature to <35°C), results in hemostatic disorders. However, it remains unclear whether hypothermia enhances or inhibits coagulation, especially in severe hypothermia. The present study evaluated the thrombocytic and hemostatic changes in hypothermic mice. MethodsC57Bl/6 mice were placed at an ambient temperature of −20°C under general anesthesia. When the rectal temperature decreased to 15°C, 10 mice were immediately euthanized, while another 10 mice were rewarmed, kept in normal conditions for 24 hours, and then euthanized. These treatments were also performed in 20 splenectomized mice. ResultsThe hypothermic mice had adhesion of CD62P‐positive platelets with high expression of von Willebrand factor (vWF) in their spleens, while the status of the peripheral platelets was unchanged. Furthermore, the plasma levels of platelet factor 4 (PF4) and pro‐platelet basic protein (PPBP), which are biomarkers for platelet degranulation, were significantly higher in hypothermic mice than in control mice, indicating that hypothermia activated the platelets in the splenic pool. Thus, we analyzed these biomarkers in asplenic mice. There was no increase in either PF4 or PPBP in splenectomized hypothermic mice. Additionally, the plasma D‐dimer elevation and microthrombosis were caused in rewarmed mice, but not in asplenic rewarmed mice. ConclusionsOur results indicate that hypothermia leads to platelet activation in the spleen via the upregulation of vWF, and this activation causes hypercoagulability after rewarming.

Prevention of Intraoperative Hypothermia in Laparoscopy by the Use of Body-Temperature and Humidified CO2: a Pilot Study

Introduction Hypothermia is defined as a decrease in body core temperature to below 36 °C. If intraoperative heat-preserving measures are omitted, a patientʼs temperature will fall by 1 – 2 °C. Even mild forms of intraoperative hypothermia can lead to a marked increase in morbidity and mortality. The temperature of the insufflation gas is usually disregarded in the treatment and prevention of hypothermia. This study was conducted to investigate the effect of body-temperature and humidified CO 2 on the intraoperative temperature profile and avoidance of hypothermia in laparoscopic surgery. Material and Methods In this retrospective, non-randomised case control study, 110 patients whose planned operation lasted at least 60 minutes were identified from 376 patients by means of an algorithm. Dry (20% humidity) CO 2 at room temperature was insufflated in 51 patients (control group). 59 patients were insufflated with humidified (98% humidity) CO 2 at body temperature (37 °C) (study group). These conditions were achieved with the HumiGard MR860 Surgical Humidification System (Fisher & Paykel Healthcare Limited, Auckland, New Zealand). The intraoperative temperature profile was evaluated by measurements every 10 minutes. Statistical analysis was performed with IBM ® SPSS ® Statistics 23.0.0. Results The intraoperative temperature in the control group fell steadily, while a continuous rise in temperature was observed in the study group. Warming was demonstrated in the study group with a start-end temperature difference of 0.09 °C, which differed significantly from the control group, in which it was − 0.09 °C (p = 0.011). The middle-end difference of 0.11 °C showed even higher significance in favour of the warmed gas (p = 0.003). The rate of hypothermia at the start of the operation fell from 50 to 36% in the study group and increased from 36 to 42% in the control group. Conclusion These results show that the use of body-temperature and humidified insufflation gas for laparoscopy can help to prevent intraoperative hypothermia.

Select panicogenic drugs and stimuli induce consistent increases in tail skin flushes and decreases in core body temperature.

Panic attacks (PAs) are episodes of intense fear or discomfort that are accompanied by a variety of both psychological and somatic symptoms. Panic induction in preclinical models (e.g. rats) has largely been assayed through flight and avoidance behavioral tests and cardiorespiratory activity. Yet, the literature pertaining to PAs shows that thermal sensations (hot flushes/heat sensations and chills) are also a common symptom during PAs in humans. Considering that temperature alterations are objectively measurable in rodents, we hypothesized that select panicogenic drugs and stimuli induce consistent changes in thermoregulation related to hot flushes and chills. Specifically, we challenged male rats with intraperitoneal injections of the GABAergic inverse agonist FG-7142; the α2 adrenoceptor antagonist yohimbine; the serotonin agonist D-fenfluramine, and 20% CO2 (an interoceptive homeostatic challenge). We assayed core body temperature and tail skin temperature using implanted radiotelemetry probes and tail thermistors/thermal imaging camera, respectively, and found that all challenges elicited rapid, high-amplitude (~7-9°C) increase in tail skin temperature and delayed decreases (~1-3°C) in core body temperature. We propose that thermal sensations such as these may be an additional indicator of a panic response in rodents and humans, as these panicogenic compounds or stimuli are known to precipitate PAs in persons with panic disorder.

Oral gavage of capsaicin causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity in the mouse

Capsaicin (CAP), the pungent ingredient of hot red pepper, is a selective ligand for the heat-sensitive transient receptor potential V1 cation channel 1 (TRPV1). Although CAP has been traditionally used as the ingredient of spices for various foods in the world, the effect of oral intake of CAP on thermoregulation and locomotor activity, and CAP-induced activation of brain neural circuits are not well understood. In this study, therefore, we examined the effects of oral gavage of CAP on core body and tail surface temperature, locomotor activity, and Fos expression in thermoregulation- and sensory information-associated hypothalamic and medullary brain regions using freely moving mice. Oral gavage of CAP acutely decreased core body temperature and alternatively increased tail surface temperature of wild type (WT) mice, whereas such acute temperature changes were not observed in TRPV1 knockout (KO) animals. Moreover, a long-lasting increase of locomotor activity was observed in both WT and TRPV1 KO mice after oral gavage of CAP, but increase in core body temperature was seen only in TRPV1 KO animals. Oral gavage of CAP induced neuronal Fos expression in the circumventricular organs, median and medial preoptic area, arcuate nucleus, and nucleus of the solitary tract, whereas neuronal Fos expression was scarcely observed in TRPV1 KO mice. Thus, the present study demonstrates in the mice that oral intake of CAP causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity, and moreover activates the brain circuits controlling thermoregulation and metabolism.

Gonadal hormones influence core body temperature during calorie restriction

ABSTRACTDuring calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (Tb) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring Tb of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of Tb during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of Tb and energy expenditure when nutrient availability is scarce.Abbreviations: AL: ad libitum; ANOVA: analysis of variance; CR: calorie restriction; E2: 17-ß estradiol; GNX: gonadectomy or gonadectomized; IGF-1R: insulin-like growth factor 1 receptor; POA: preoptic area; P4: progesterone; RM: repeated measures; SD: standard deviation; SEM: standard error of mean; Tb: core body temperature; WT: wildtype; 5-α DHT: 5-α dihydrotestosterone.

Hypothermia prevention in long‐standing equine dental procedures

SummaryHypothermia is a common, detrimental post‐operative complication in man and veterinary medicine. Active warming strategies are paramount for prevention and treatment. Duration of operations, administered drugs and their adverse effects put horses undergoing procedures requiring long‐standing sedation in danger of hypothermia. The aim of this study was to investigate whether an air warming device would be helpful to avoid severe hypothermia in adult horses. Twenty client‐owned horses undergoing dental/sinusoidal procedures were divided into two equal groups. The treatment group was covered with a warming blanket connected to the warming device with the temperature set to 43°C. Horses in the control group were not blanketed. Temperature was measured at the time of first sedation (T0) and every hour throughout the length of the procedure. Use of the warming blanket was straightforward and caused no adverse reactions. The mean decrease in body core temperature in the treatment group was significantly less than the mean temperature decrease in the control group, beginning at the second hour of the procedure. No horse in the treatment group reached a body temperature below 36°C. Overall loss of temperature in the control group was more than double when compared with the treatment group (1.5°C and 0.7°C respectively). The use of an active air warming blanket in horses is an easy technique to prevent hypothermia in horses undergoing long‐standing sedation procedures.

Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats.

The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03-0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V1a receptors. Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly reduced activity and caused hypothermia but only the latter was attenuated by the V1a receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1 mg/kg, which did not alter activity and had little effect on temperature, significantly attenuated phencyclidine-induced hyperactivity and increased social interaction between unfamiliar rats without altering the number or pattern of ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex, without influencing serotonin efflux. Systemic oxytocin administration attenuated phencyclidine-induced hyperactivity and increased pro-social behavior without decreasing core body temperature and selectively enhanced nucleus accumbens dopamine release, consistent with activation of mesocorticolimbic circuits regulating associative/reward behavior being involved. This highlights the therapeutic potential of oxytocin to treat social behavioral deficits seen in psychiatric disorders such as schizophrenia.

The Bile Sequestrant Cholestyramine Increases Survival in a Rabbit Model of Brodifacoum Poisoning.

Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anticoagulant effects. Although VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 g/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

Effect of compound heat preservation in middle and late operation on hypothermia and adverse reaction of patients undergoing craniocerebral operation

Objective To explore the effect of compound heat preservation in late operation on intraoperative hypothermia and postoperative adverse reaction of patients undergoing craniocerebral operation. Methods From June 2014 to January 2016, 150 patients undergoing general anesthesia and craniocerebral operation in a Class Ⅲ Grade A hospital in Beijing were selected as the research object. They were divided into control group and observation group by the random method of region group, with 75 cases in each group. Patients in the control group received routine heat preservation during the operation, and patients in the observation group received compound heat preservation in the middle and late period of operation on the basis of routine method. The incidence of postoperative hypothermia and adverse reactions (chill, restlessness and heart rate expedited) were compared between the two groups. Results The two groups of patients showed a decrease in core body temperature during the operation, reaching a mild hypothermia state (35-36 ℃) . After the implementation of compound heat preservation, tracheal extubation time and total wakefulness time in the observation group were (22.24±6.23) and (42.58±9.84) min, and the number of chills, restlessness and heart rate increased were 4, 5 and 8 cases respectively. The time of tracheal extubation and full wakefulness in the control group were (37.45±5.89) and (72.24±8.92) min, and the number of chills, restlessness and heart rate increased were 30, 35, 25 cases respectively. The differences were statistically significant (t/χ2=3.897, 4.546, 25.710, 30.682, 11.228; P<0.01) . Conclusions Compound heat preservation measures during operation in patients with craniocerebral operation can improve postoperative hypothermia and reduce adverse reactions in postoperative recovery. Key words: Neurosurgical procedures; Craniocerebral operation; Hypothermia; Adverse reaction; Compound heat preservation