Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model

AbstractHeat stroke is a life-threatening condition characterized by loss of thermoregulation and severe elevation of core body temperature, which can cause organ failure and damage to the central nervous system. While no definitive test exists to measure heat stroke severity, immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear. In this study, we used a mouse model of classic heat stroke to test the effect of immune challenge on pathology. Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non-uniform in size, suggesting younger, more active platelets. Levels of D-dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases presenting with the highest level of organ damage markers D-dimer levels dropped, indicating potential fibrinolysis-resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up-regulated in kidneys of heat-challenged animals, and these increases correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself. We conclude that heat stroke-induced coagulopathy may be a driving mechanistic force in heat stroke pathology, especially when exacerbated by prior infection, and that coagulation markers may serve as an accessible biomarker for heat stroke severity and therapeutic strategies.Key pointsA signature of pro-coagulation markers predicts circadian core body temperature and levels of organ damage in heat strokeChanges in coagulopathy-related gene expression are evidenced before histopathological organ damage

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A novel mouse model of heatstroke accounting for ambient temperature and relative humidity

Journal of Intensive Care ◽

10.1186/s40560-021-00546-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Kazuyuki Miyamoto ◽

Keisuke Suzuki ◽

Hirokazu Ohtaki ◽

Motoyasu Nakamura ◽

Hiroki Yamaga ◽

...

Keyword(s):

Gene Expression ◽

Body Temperature ◽

Relative Humidity ◽

Ambient Temperature ◽

Core Body Temperature ◽

Heat Exposure ◽

Organ Damage ◽

Core Body ◽

The Impact ◽

Treatment Water

Abstract Background Heatstroke is associated with exposure to high ambient temperature (AT) and relative humidity (RH), and an increased risk of organ damage or death. Previously proposed animal models of heatstroke disregard the impact of RH. Therefore, we aimed to establish and validate an animal model of heatstroke considering RH. To validate our model, we also examined the effect of hydration and investigated gene expression of cotransporter proteins in the intestinal membranes after heat exposure. Methods Mildly dehydrated adult male C57/BL6J mice were subjected to three AT conditions (37 °C, 41 °C, or 43 °C) at RH > 99% and monitored with WetBulb globe temperature (WBGT) for 1 h. The survival rate, body weight, core body temperature, blood parameters, and histologically confirmed tissue damage were evaluated to establish a mouse heatstroke model. Then, the mice received no treatment, water, or oral rehydration solution (ORS) before and after heat exposure; subsequent organ damage was compared using our model. Thereafter, we investigated cotransporter protein gene expressions in the intestinal membranes of mice that received no treatment, water, or ORS. Results The survival rates of mice exposed to ATs of 37 °C, 41 °C, and 43 °C were 100%, 83.3%, and 0%, respectively. From this result, we excluded AT43. Mice in the AT 41 °C group appeared to be more dehydrated than those in the AT 37 °C group. WBGT in the AT 41 °C group was > 44 °C; core body temperature in this group reached 41.3 ± 0.08 °C during heat exposure and decreased to 34.0 ± 0.18 °C, returning to baseline after 8 h which showed a biphasic thermal dysregulation response. The AT 41 °C group presented with greater hepatic, renal, and musculoskeletal damage than did the other groups. The impact of ORS on recovery was greater than that of water or no treatment. The administration of ORS with heat exposure increased cotransporter gene expression in the intestines and reduced heatstroke-related damage. Conclusions We developed a novel mouse heatstroke model that considered AT and RH. We found that ORS administration improved inadequate circulation and reduced tissue injury by increasing cotransporter gene expression in the intestines.

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Hyperthermia

10.1093/med/9780199568741.003.0077 ◽

2018 ◽

Author(s):

Matt Wise ◽

Paul Frost

Keyword(s):

Body Temperature ◽

Neuroleptic Malignant Syndrome ◽

Core Body Temperature ◽

Heat Stroke ◽

Drug Induced ◽

Muscle Cramps ◽

Set Point ◽

Heat Exhaustion ◽

Neurological Signs ◽

Core Body

An elevation in core body temperature due to thermoregulatory failure with a normal thermoregulatory set point is called hyperthermia. Globally, the most common heat illnesses are heat exhaustion and heat stroke, and these are major causes of morbidity and mortality. These illnesses represent a continuum of disease ranging from mild (heat exhaustion) to total (heat stroke) failure of thermoregulation. Heat exhaustion is characterized by sweating, muscle cramps, fatigue, vomiting, headaches, dizziness, and fainting. These symptoms may also occur in heat stroke but, in addition, neurological signs such as confusion, seizures, and coma predominate. While the diagnosis of these conditions may be straightforward, hyperthermia may complicate a variety of rarer illnesses, including neuroleptic malignant syndrome and drug-induced hyperthermia.

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Exercise activates compensatory thermoregulatory reaction in rats: a modeling study

Journal of Applied Physiology ◽

10.1152/japplphysiol.00392.2015 ◽

2015 ◽

Vol 119 (12) ◽

pp. 1400-1410 ◽

Cited By ~ 8

Author(s):

Yeonjoo Yoo ◽

Michelle LaPradd ◽

Hannah Kline ◽

Maria V. Zaretskaia ◽

Abolhassan Behrouzvaziri ◽

...

Keyword(s):

Body Temperature ◽

Heat Generation ◽

Heat Production ◽

Core Body Temperature ◽

Heat Stroke ◽

The Body ◽

Model Parameters ◽

The Core ◽

Treadmill Speed ◽

Core Body

The importance of exercise is increasingly emphasized for maintaining health. However, exercise itself can pose threats to health such as the development of exertional heat shock in warm environments. Therefore, it is important to understand how the thermoregulation system adjusts during exercise and how alterations of this can contribute to heat stroke. To explore this we measured the core body temperature of rats ( Tc) running for 15 min on a treadmill at various speeds in two ambient temperatures ( Ta = 25°C and 32°C). We assimilated the experimental data into a mathematical model that describes temperature changes in two compartments of the body, representing the muscles and the core. In our model the core body generates heat to maintain normal body temperature, and dissipates it into the environment. The muscles produce additional heat during exercise. According to the estimation of model parameters, at Ta = 25°C, the heat generation in the core was progressively reduced with the increase of the treadmill speed to compensate for a progressive increase in heat production by the muscles. This compensation was ineffective at Ta = 32°C, which resulted in an increased rate of heat accumulation with increasing speed, as opposed to the Ta = 25°C case. Interestingly, placing an animal on a treadmill increased heat production in the muscles even when the treadmill speed was zero. Quantitatively, this “ready-to-run” phenomenon accounted for over half of the heat generation in the muscles observed at maximal treadmill speed. We speculate that this anticipatory response utilizes stress-related circuitry.

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The Human Penguin Project: Climate, Social Integration, and Core Body Temperature

10.31234/osf.io/6b7ne ◽

2016 ◽

Cited By ~ 1

Author(s):

Hans IJzerman ◽

Siegwart Lindenberg ◽

İlker Dalğar ◽

Sophia Christin Weissgerber ◽

Rodrigo Clemente Vergara ◽

...

Keyword(s):

Body Temperature ◽

Social Integration ◽

Social Factors ◽

Cross Validation ◽

Core Body Temperature ◽

Modern Human ◽

Supervised Machine Learning ◽

Data Driven ◽

Human Relationships ◽

Core Body

Social thermoregulation theory posits that modern human relationships are pleisiomorphically organized around body temperature regulation. In two studies (N=1755) designed to test the principles from this theory, we used supervised machine learning to identify social and non-social factors that relate to core body temperature. This data-driven analysis found that complex social integration (CSI), defined as the number of high contact roles one engages in, is a critical predictor of core body temperature. We further used a cross-validation approach to show that colder climates relate to higher levels of CSI, which in turn relates to higher CBT (when climates get colder). These results suggest that despite modern affordances for regulating body temperature, people still rely on social warmth to buffer their bodies against the cold.

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Accuracy of Tympanic Temperature Measurement in Firefighters Completing a Simulated Structural Firefighting Task

Prehospital and Disaster Medicine ◽

10.1017/s1049023x15005038 ◽

2015 ◽

Vol 30 (5) ◽

pp. 461-465 ◽

Cited By ~ 5

Author(s):

Toby Keene ◽

Matt Brearley ◽

Beth Bowen ◽

Anthony Walker

Keyword(s):

Body Temperature ◽

Temperature Measurement ◽

Fire Suppression ◽

Core Body Temperature ◽

Heat Stroke ◽

Fire Service ◽

Tympanic Temperature ◽

Publication Type ◽

Heat Chamber ◽

Core Body

AbstractIntroductionIn the course of their duties, firefighters risk heat stroke and other medical conditions due to exertion in high-temperature environments. Infrared tympanic temperature measurement (TTym) is often used by Emergency Medical Services (EMS) to assess the core body temperature of firefighters. The accuracy of TTym in this setting has been called into question.Hypothesis/ProblemThis study aimed to examine the accuracy of TTym for core body temperature assessment at emergency firefighting events compared with gastrointestinal temperature measurement (TGI) as measured by ingestible thermometers.MethodsForty-five (42 male, three female) professional urban firefighters from an Australian fire service completed two 20-minute work periods in a 100°C (± 5°C) heat chamber while wearing personal protective clothing (PPC) and breathing apparatus (weighing approximately 22 kg). Measurements were taken immediately before entering, and on exiting, the heat chamber. Tympanic temperature was assessed by an infrared tympanic thermometer and TGI was measured by ingestible sensor and radio receiver.ResultsComplete data were available for 37 participants. Participant temperatures were higher on exiting the heat chamber than at baseline (TTym: 35.9°C (SD=0.7) vs 37.5°C (SD=0.8); TGI: 37.2°C (SD=0.4) vs 38.6°C (SD=0.5)). Tympanic temperature underestimated TGI on average by 1.3°C (SD=0.5) before entering the chamber and by 1.0°C (SD=0.8) following the exercise. Using pooled data, the average underestimation was 1.2°C (SD=0.7).ConclusionTympanic thermometers cause an unreliable measure of core body temperature for firefighters engaged in fire suppression activities. Accurate and practical measures of core body temperature are required urgently.KeeneT, BrearleyM, BowenB, WalkerA. Accuracy of tympanic temperature measurement in firefighters completing a simulated structural firefighting task. Prehosp Disaster Med. 2015;30(5):461–465.

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The Human Penguin Project: Climate, Social Integration, and Core Body Temperature

Collabra Psychology ◽

10.1525/collabra.165 ◽

2018 ◽

Vol 4 (1) ◽

Cited By ~ 7

Author(s):

Hans IJzerman ◽

Siegwart Lindenberg ◽

İlker Dalğar ◽

Sophia S. C. Weissgerber ◽

Rodrigo C. Vergara ◽

...

Keyword(s):

Body Temperature ◽

Social Integration ◽

Social Factors ◽

Cross Validation ◽

Core Body Temperature ◽

Modern Human ◽

Supervised Machine Learning ◽

Data Driven ◽

Human Relationships ◽

Core Body

Social thermoregulation theory posits that modern human relationships are pleisiomorphically organized around body temperature regulation. In two studies (N = 1755) designed to test the principles from this theory, we used supervised machine learning to identify social and non-social factors that relate to core body temperature. This data-driven analysis found that complex social integration (CSI), defined as the number of high-contact roles one engages in, is a critical predictor of core body temperature. We further used a cross-validation approach to show that colder climates relate to higher levels of CSI, which in turn relates to higher CBT (when climates get colder). These results suggest that despite modern affordances for regulating body temperature, people still rely on social warmth to buffer their bodies against the cold.

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Reliability and Validity of the CORE Sensor to Assess Core Body Temperature during Cycling Exercise

Sensors ◽

10.3390/s21175932 ◽

2021 ◽

Vol 21 (17) ◽

pp. 5932

Author(s):

Nina Verdel ◽

Tim Podlogar ◽

Urša Ciuha ◽

Hans-Christer Holmberg ◽

Tadej Debevec ◽

...

Keyword(s):

Body Temperature ◽

Relative Humidity ◽

Heat Load ◽

Core Body Temperature ◽

Heat Stroke ◽

Reliability And Validity ◽

The Body ◽

Validity And Reliability ◽

The Core ◽

Core Body

Monitoring core body temperature (Tc) during training and competitions, especially in a hot environment, can help enhance an athlete’s performance, as well as lower the risk for heat stroke. Accordingly, a noninvasive sensor that allows reliable monitoring of Tc would be highly beneficial in this context. One such novel non-invasive sensor was recently introduced onto the market (CORE, greenTEG, Rümlang, Switzerland), but, to our knowledge, a validation study of this device has not yet been reported. Therefore, the purpose of this study was to evaluate the validity and reliability of the CORE sensor. In Study I, 12 males were subjected to a low-to-moderate heat load by performing, on two separate occasions several days apart, two identical 60-min bouts of steady-state cycling in the laboratory at 19 °C and 30% relative humidity. In Study II, 13 males were subjected to moderate-to-high heat load by performing 90 min of cycling in the laboratory at 31 °C and 39% relative humidity. In both cases the core body temperatures indicated by the CORE sensor were compared to the corresponding values obtained using a rectal sensor (Trec). The first major finding was that the reliability of the CORE sensor is acceptable, since the mean bias between the two identical trials of exercise (0.02 °C) was not statistically significant. However, under both levels of heat load, the body temperature indicated by the CORE sensor did not agree well with Trec, with approximately 50% of all paired measurements differing by more than the predefined threshold for validity of ≤0.3 °C. In conclusion, the results obtained do not support the manufacturer’s claim that the CORE sensor provides a valid measure of core body temperature.

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