The significant mechanism and treatments of cell death in heatstroke.

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

Heat-related illness.

ABSTRACT: This article concisely overviews heat-related illnesses, emphasizing their significant impact on public health. It explores the pathophysiology of conditions ranging from mild heat cramps to life-threatening heat stroke, highlighting key heat transfer mechanisms and the importance of environmental factors. Differential diagnosis considerations, prevention strategies, and nursing implications are discussed, underscoring the need for prompt recognition and intervention in managing these conditions.

Exertional heat stroke-induced changes in gut microbiota cause cognitive impairment in mice.

BACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent. METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed. RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28. CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.

Thromboinflammation and microcirculation damage in heatstroke.

Rising temperatures associated with climate change have significantly increased the risk of heatstroke. Unfortunately, the trend is anticipated to persist and increasingly threaten vulnerable populations, particularly older adults. According to Japan's environment ministry, over 1000 people died from heatstroke in 2021, and 86% of deaths occurred in those above 65. Since the precise mechanism of heatstroke is not fully understood, we examined the pathophysiology by focusing on the microcirculatory derangement. Online search of published medical literature through MEDLINE and Web of Science using the term "heatstroke," "heat-related illness," "inflammation," "thrombosis," "coagulation," "fibrinolysis," "endothelial cell," and "circulation." Articles were chosen for inclusion based on their relevance to heatstroke, inflammation, and thrombosis. Reference lists were reviewed to identify additional relevant articles. Other than preexisting conditions (genetic background, age, etc.), factors such as hydration status, acclimatization, dysregulated coagulation, and inflammation are the additional major factors that promote tissue malcirculation in heatstroke. The fundamental pathophysiologic mechanisms significantly overlap with those seen in the systemic inflammatory response to sepsis, and as a result, coagulation-predominant coagulopathy develops during heat stress. Although a bleeding tendency is not common, bleeding frequently occurs in the microcirculation, causing additional injury. Sterile inflammation is mediated by proinflammatory cytokines, chemokines, and other humoral mediators in concert with cellular factors, including monocytes, neutrophils, platelets, and endothelial cells. Excess inflammation results in inflammatory cell death, including pyroptosis and necroptosis, and the release of danger signals that further propagate systemic inflammation and coagulopathy. Consequently, thromboinflammation is the critical factor that induces microcirculatory disturbance in heatstroke.

Manifestaciones clínicas, diagnóstico y tratamiento del golpe de calor / Clinical Manifestations, Diagnosis and Management of Heat Stroke

Introducción: El golpe de calor es una enfermedad que fue descrita hace más de 2000 años, sin embargo, los cambios climáticos que se han presentado en las últimas décadas han permitido que su prevalencia esté en aumento. Se considera una entidad compleja en la cual existe un compromiso importante de la termorregulación corporal y, en consecuencia, del resto de sistemas. Objetivos: Orientar al abordaje adecuado y óptimo de conceptos clínicos, epidemiológicos, factores el riesgo, presentación clínica y repercusión sobre los diferentes sistemas. Métodos: Se realizó una revisión de la literatura científica de personas con golpe de calor, en quienes se evaluaron sus factores asociados, métodos diagnósticos y manejos terapéuticos. Se realizó una búsqueda de la literatura en las siguientes bases de datos: Pubmed/Medline, Science Direct, Scopus, DOAJ, Embase, Cochrane, Direme, Redalyc y SciELO. Conclusiones: El golpe de calor es una urgencia médica que implica un manejo rápido y óptimo dado su morbilidad y mortalidad, lo cual puede minimizarse si se cumplen los objetivos de tratamiento. El enfriamiento por inmersión en agua helada, por convección o evaporación son las medias más usadas. Evitar la falla multiorgánica es el segundo objetivo terapéutico(AU)

Introduction: Heat stroke is a disease described more than 2000 years ago; however, the climatic changes that have occurred in recent decades have allowed an increase in its prevalence. It is considered a complex entity in which there is an important compromise of body thermoregulation and, consequently, of the rest of the systems. Objectives: To define important concepts concerning heat stroke, risk factors, clinical presentation and repercussions on the different systems, as well as to guide an appropriate and optimal management. Methods: A review of the scientific literature about people with heat stroke was carried out to assess its associated factors, diagnostic methods and therapeutic management. A literature search was performed in the following databases: Pubmed/Medline, Science Direct, Scopus, DOAJ, Embase, Cochrane, Bireme, Redalyc, and SciELO. Conclusions: Heat stroke is a medical emergency that requires rapid and optimal management given its morbidity and mortality, which can be minimized if management goals are met. Cooling by immersion into ice water, convection or evaporation are the most commonly used measures. Avoidance of multiorgan failure is the second therapeutic objective(AU)

Exosomes Derived From Heat Stroke Cases Carry miRNAs Associated With Inflammation and Coagulation Cascade.

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.

NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1ß-mediated neuroinflammation.

BACKGROUND: Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. METHODS: In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1ß neutralizing antibody was injected to test potential therapeutic effect on heat stroke. RESULTS: Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1ß in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1ß production with prior infection condition. Furthermore, IL-1ß neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. CONCLUSIONS: Based on the above results, NLRP3/IL-1ß induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1ß may serve as a biomarker for heat stroke severity and potential therapeutic method.

The Role of Skeletal Muscles in Exertional Heat Stroke Pathophysiology.

The active participation of skeletal muscles is a unique characteristic of exertional heat stroke. Nevertheless, the only well-documented link between skeletal muscle activities and exertional heat stroke pathophysiology is the extensive muscle damage (e. g., rhabdomyolysis) and subsequent leakage of intramuscular content into the circulation of exertional heat stroke victims. Here, we will present and discuss rarely explored roles of skeletal muscles in the context of exertional heat stroke pathophysiology and recovery. This includes an overview of heat production that contributes to severe hyperthermia and the synthesis and secretion of bioactive molecules, such as cytokines, chemokines and acute phase proteins. These molecules can alter the overall inflammatory status from pro- to anti-inflammatory, affecting other organ systems and influencing recovery. The activation of innate immunity can determine whether a victim is ready to return to physical activity or experiences a prolonged convalescence. We also provide a brief discussion on whether heat acclimation can shift skeletal muscle secretory phenotype to prevent or aid recovery from exertional heat stroke. We conclude that skeletal muscles should be considered as a key organ system in exertional heat stroke pathophysiology.

Exertional heat stroke on fertility, erectile function, and testicular morphology in male rats.

The association of exertional heat stroke (EHS) and testicular morphological changes affecting sperm quality, as well as the association of EHS and hypothalamic changes affecting sexual behavior, has yet to be elucidated. This study aimed to elucidate the effects of EHS on fertility, erectile function, and testicular morphology in male rats. Animals were exercised at higher room temperature (36 ℃ relative humidity 50%) to induce EHS, characterized by excessive hyperthermia, neurobehavioral deficits, hypothalamic cell damage, systemic inflammation, coagulopathy, and multiple organ injury. In particular, EHS animals had erectile dysfunction (as determined by measuring the changes of intracavernosal pressure and mean arterial pressure in response to electrical stimulation of cavernous nerves). Rats also displayed testicular temperature disruption, poorly differentiated seminiferous tubules, impaired sperm quality, and atrophy of interstitial Leydig cells, Sertoli cells, and peri-tubular cells in the testicular tissues accompanied by no spermatozoa and broken cells with pyknosis in their seminal vesicle and prostatitis. These EHS effects were still observed after 3 days following EHS onset, at least. Our findings provide a greater understanding of the effect of experimentally induced EHS on masculine sexual behavior, fertility, stress hormones, and morphology of both testis and prostate.

Acute phase response to exertional heat stroke in mice.

NEW FINDINGS: What is the central question of this study? Exertional heat stroke is accompanied by a marked inflammatory response. In this study, we explored the time course of acute phase proteins during recovery from severe heat stress in mice and the potential role of skeletal muscles as their source. What is the main finding and its importance? Exertional heat stroke transiently increased expression of acute phase proteins in mouse liver and plasma and depleted liver and plasma fibrinogen, a typical response to severe trauma. In contrast, skeletal muscle fibrinogen production was stimulated by heat stroke, which can provide an additional reservoir for fibrinogen supply to maintain the clotting potential throughout the body and locally within the muscle. ABSTRACT: Exertional heat stroke (EHS), the most severe manifestation of heat illness, is accompanied by a marked inflammatory response. The release of acute phase proteins (APPs) is an important component of inflammation, which can assist in tissue survival/repair. The time course of APPs in recovery from EHS is unknown. Furthermore, skeletal muscles produce APPs during infection, but it is unknown whether they can produce APPs after EHS. Our objective was to determine the time course of representative APPs in liver, plasma and skeletal muscle during recovery from EHS. Male C57BL6/J mice ran in a forced running wheel at 37.5°C, 40% relative humidity until symptom limitation. Exercise control (EXC) mice ran for the same duration and intensity at 22.5°C. Samples were collected (n = 6-12 per group) over 14 days of recovery. Protein abundance was quantified using immunoblots. Total and phosphorylated STAT3 (pSTAT3) at Tyr705, responsible for APP activation, increased in liver at 0.5 h after EHS compared with EXC, (P < 0.05 and P < 0.001, respectively). In contrast, in tibialis anterior (TA) muscle, total STAT3 increased at 3 h (P < 0.05) but pSTAT3 (Tyr705) did not. Liver serum amyloid A1 (SAA1) increased at 3 and 24 h after EHS (P < 0.05), whereas plasma SAA1 increased only at 3 h (P < 0.05). SAA1 was not detected in TA muscle. In liver and plasma, fibrinogen decreased at 3 h (P < 0.01) and increased in TA muscle (P < 0.05). Lipocalin-2 was undetectable in liver or TA muscle. Recovery from EHS is characterized by a transient acute phase response in both liver and skeletal muscle. However, APP expression profiles and subtypes differ between skeletal muscle and liver.

Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia.

Background: Hypoxia-inducible factor-1α (HIF-1α), heat shock protein-72 (HSP-72), hemeoxygenase-1 (HO-1), and matrix metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets in the brain for cerebral ischemia. To elucidate their underlying mechanisms, we first aimed to ascertain whether these proteins participate in the pathogenesis of heat-induced ischemic damage to the hypothalamus of rats. Second, we investigated whether hypobaric hypoxia preconditioning (HHP) attenuates heat-induced hypothalamic ischemic/hypoxic injury by modulating these proteins in situ. Methods: Anesthetized rats treated with or without HHP were subjected to heat stress. Hypothalamic ischemic/hypoxic damage was evaluated by measuring hypothalamic levels of cerebral blood flow (CBF), partial oxygen pressure (PO2), and hypothalamic temperature via an implanted probe. Hypothalamic apoptotic neurons were counted by measuring the number of NeuN/caspase-3/DAPI triple-stained cells. Hypothalamic protein expression of HIF-1α, HSP-72, HO-1, and MMP-9 was determined biochemically. Results: Before the start of the thermal experiments, rats were subjected to 5 hours of HHP (0.66 ATA or 18.3% O2) daily for 5 consecutive days per week for 2 weeks, which led to significant loss of body weight, reduced brown adipose tissue (BAT) wet weight and decreased body temperature. The animals were then subjected to thermal studies. Twenty minutes after heat stress, heat-exposed rats not treated with HHP displayed significantly higher core and hypothalamic temperatures, hypothalamic MMP-9 levels, and numbers of hypothalamic apoptotic neurons but significantly lower mean blood pressure, hypothalamic blood flow, and PO2 values than control rats not exposed to heat. In heat-exposed rats, HHP significantly increased the hypothalamic levels of HIF-1α, HSP-72, and HO-1 but significantly alleviated body and hypothalamic hyperthermia, hypotension, hypothalamic ischemia, hypoxia, neuronal apoptosis and degeneration. Conclusions: HHP may protect against hypothalamic ischemic/hypoxic injury and overexpression of MMP-9 by upregulating the hypothalamic expression of HIF-1α, HSP-72, and HO-1 in rats subjected to heatstroke.

[Exertional heat stroke in athletes and soldiers]. / Inspanningsgebonden hitteberoerte bij sporters en militairen.

Exertional heat stroke (EHS) is a medical emergency characterized by life-threatening hyperthermia and central nerve system dysfunction during or directly after exercise. Early recognition and aggressive cooling reduces morbidity and mortality of patients with EHS. Therefore, all health care professionals involved in acute care should immediately recognise EHS and start cooling with cold water immersion as soon as possible. Most EHS occur in young and healthy individuals without a medical history, such as athletes or soldiers. We report the case of EHS in a 26-year-old man without a medical history. He suffered from EHS during a military admission test. A few years later he had a second EHS during military training. This time, the EHS was complicated by compartment syndrome, rhabdomyolysis, acute kidney injury and epilepsy. He fully recovered from both EHS episodes. Muscle histology, whole exome sequencing and heat tolerance tests did not show any abnormalities.

The efficacy of steroids in reducing morbidity and mortality from extreme hyperthermia and heatstroke-A systematic review.

Severe hyperthermia from classical or exertional heatstroke, or from drug ingestion or other noninfective pyrogens, is associated with a high mortality and morbidity. A systemic pro-inflammatory response occurs during heatstroke, characterized by elevated cytokines with endotoxemia from elevated lipopolysaccharide (LPS) levels. Corticosteroids reduce LPS and cytokine levels, suggesting that they may improve outcome. A systematic review searching Embase, MEDLINE, and PubMed from the earliest date available until September 2019 was conducted, according to the PRISMA guidelines, with five papers identified. In four studies, systemic steroids administered before or at the onset of heat stress improved mortality or reduced organ dysfunction. Survival time was greatest when steroid administration preceded heat stress. In one study, a nonsignificant increase in mortality was seen. A dose response was observed, with higher doses extending survival time. Animal studies suggest that steroids improve mortality and/or organ dysfunction after an episode of heat stress or extreme hyperthermia.

Effective intranasal cooling in an 80 year old patient with heatstroke.

Intranasal cooling by the evaporation of perflourcarbon is almost exclusively used for the induction of therapeutic hypothermia in post-resuscitation care. This method has proven to be effective and safe. This case presents a successful application to a patient with external heatstroke. The 80 year old male patient was found in deep coma (GCS 4) by emergency medical services (EMS) showing a core temperature around 42 °C. Despite of preclinical physical cooling, the patient showed a persistent temperature of 41.5 °C upon reaching the emergency department. After endotracheal intubation intranasal evaporation cooling was performed and the patient's core temperature was reduced efficiently. We recorded an excellent cooling rate of 2.8 °C per hour. 16 h later the patient was successfully extubated with a good neurological outcome. This case shows that although intranasal cooling is mostly known for post-resuscitation care, there is a sensible application in heatstroke with imminent cerebral oedema.

Systematic review of gender differences in the epidemiology and risk factors of exertional heat illness and heat tolerance in the armed forces.

OBJECTIVES: This review aimed to describe the epidemiology of all heat-related illnesses in women compared with men in the armed forces and to identify gender-specific risk factors and differences in heat tolerance. DESIGN: A systematic review of multiple databases (MEDLINE, Emcare, CINAHL, PsycINFO, Informit and Scopus) was conducted from the inception of the databases to 1 April 2019 using the preferred reporting items for systematic review and meta-analysis guidelines. ELIGIBILITY CRITERIA: All relevant studies investigating and comparing heat illness and heat tolerance in women and men in the armed forces were included in the review. RESULTS: Twenty-four studies were included in the systematic review. The incidence of heat stroke in women ranged from 0.10 to 0.26 per 1000 person-years, while the incidence of heat stroke ranged from 0.22 to 0.48 per 1000 person-years in men. The incidence of other heat illnesses in women compared with men ranged from 1.30 to 2.89 per 1000 person-years versus 0.98 to 1.98 per 1000 person-years. The limited evidence suggests that women had a greater risk of exertional heat illness compared with men. Other gender-specific risk factors were slower run times and body mass index. Although there was a higher proportion of women who were heat intolerant compared with men, this finding needs to be interpreted with caution due to the limited evidence. CONCLUSION: The findings of this review suggest that men experienced a slightly higher incidence of heat stroke than women in the armed forces. In addition, the limited available evidence suggests that a higher proportion of women were heat intolerant and being a female was associated with a greater risk of exertional heat illnesses. Given the limited evidence available, further research is required to investigate the influence of gender differences on heat intolerance and heat illness.

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures.

Exertional heat stroke (EHS) is a life-threatening medical condition involving thermoregulatory failure and is the most severe condition along a continuum of heat-related illnesses. Current EHS policy guidance principally advocates a thermoregulatory management approach, despite growing recognition that gastrointestinal (GI) microbial translocation contributes to disease pathophysiology. Contemporary research has focused to understand the relevance of GI barrier integrity and strategies to maintain it during periods of exertional-heat stress. GI barrier integrity can be assessed non-invasively using a variety of in vivo techniques, including active inert mixed-weight molecular probe recovery tests and passive biomarkers indicative of GI structural integrity loss or microbial translocation. Strenuous exercise is strongly characterised to disrupt GI barrier integrity, and aspects of this response correlate with the corresponding magnitude of thermal strain. The aetiology of GI barrier integrity loss following exertional-heat stress is poorly understood, though may directly relate to localised hyperthermia, splanchnic hypoperfusion-mediated ischemic injury, and neuroendocrine-immune alterations. Nutritional countermeasures to maintain GI barrier integrity following exertional-heat stress provide a promising approach to mitigate EHS. The focus of this review is to evaluate: (1) the GI paradigm of exertional heat stroke; (2) techniques to assess GI barrier integrity; (3) typical GI barrier integrity responses to exertional-heat stress; (4) the aetiology of GI barrier integrity loss following exertional-heat stress; and (5) nutritional countermeasures to maintain GI barrier integrity in response to exertional-heat stress.

When Should a Heat-Tolerance Test Be Scheduled After Clinical Recovery From an Exertional Heat Illness?

OBJECTIVE: Researchers have produced a hypothesis of transient heat intolerance (HI) after exertional heat stroke (EHS). Based on this hypothesis, heat-tolerance testing (HTT) has been postponed until weeks 6 to 8 after EHS and other types of exertional heat illness (EHI). We compared the HTT results of participants after either EHS or other EHI who were tested earlier (≤6-week group) versus those who were tested later (>6-week group) to verify the hypothesis. DESIGN: Cohort study. SETTING: Data obtained from records of military athletes who experienced EHS or EHI. PATIENTS OR OTHER PARTICIPANTS: All participants who underwent HTT after EHI or EHS experienced between 2014 and 2018 and for whom complete data regarding the severity of the event (rectal temperature, neurologic symptoms, and laboratory results) and HTT results were available were included. Participants with suspected EHS and those with other EHIs were evaluated separately. MAIN OUTCOME MEASURE(S): The percentages of participants with HI and mean probability of heat tolerance were compared between those tested within 6 weeks of the event and those tested later. RESULTS: A total of 186 participants were included in this study (EHS: 12 in the <6-week group, 9 in the >6-week group; EHI: 94 in the <6-week group, 71 in the >6-week group). In the EHS group, the percentages with HI (33% versus 44%, P = .67) and mean probability of heat tolerance (0.82 versus 0.82, P = .98) did not differ. In the EHI group, participants who were tested after 6 weeks had a greater chance of being diagnosed with HI (38% versus 21.3%, P < .02). CONCLUSIONS: The HTT results were similar between participants with EHS who were tested early (<6 weeks) and those tested late (>6 weeks). Further investigation of heat-tolerance changes in larger cohorts of patients after EHS is required to verify the theory of transient HI.

Exertional Heatstroke in a Marathon Runner Complicated by Concurrent Use of an Antipsychotic Medication Affecting Thermoregulation.

We report the case of a half-marathon runner who presented with exertional heatstroke (EHS), whose management was confounded by concurrent treatment of his bipolar disorder with olanzapine. Antipsychotics can have a profound effect on thermoregulation and can cause athletes to present with features of neuroleptic malignant syndrome in the setting of EHS. It is vital for medical providers to consider the thermoregulatory effects of all medications, including antipsychotics, when providing care during sporting events.