Heat stroke alters hippocampal and cerebellar transmitter metabonomics

BACKGROUND:The mechanisms underlying heat stroke(HS)-induced hippocampal injury remain unclear.This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters.METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42℃ at a humidity of(55.0±5.0)%.The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography–mass spectrometry(UPLC-MS/MS).The primary transmitters and metabolites were identified by principal component analysis(PCA)and orthogonal partial least square-discriminant analysis(OPLS-DA).The major metabolic pathways for HS were selected after enrichment.The brain injury was evaluated by histological tests.RESULTS:HS induced hippocampal and cerebellar injuries in rats.HS upregulated the protein levels of hippocampal glutamate,glutamine,gamma-aminobutyric acid,L-tryptophan(Trp),5-hydroxy-indoleacetic acid,and kynurenine;however,it downregulated asparagine,tryptamine,5-hydroxytryptophan,melatonin,3,4-dihydroxyphenylalanine(L-DOPA),and vanillylmandelic acid.HS also sharply elevated the protein levels of cerebellar methionine and Trp,and decreased the levels of serotonin,L-alanine,L-asparagine,L-aspartate,cysteine,norepinephrine,spermine,spermidine,and tyrosine.Hippocampal glutamate,monoamine transmitters,cerebellar aspartate acid,and catecholamine transmitters’metabolic pathways were identified as the main metablic pathways in HS.CONCLUSION:The hippocampus and cerebellum were injured in rats with HS,possibly induced the disorder of hippocampal glutamate and serotonin metabolism,cerebellar aspartate acid and catecholamine transmitter metabolism,and related metabolic pathways.

Full neurological recovery from severe nonexertional heat stroke with multiple organ dysfunction:A case report

BACKGROUND We report a rare case of full neurological recovery from severe nonexertional heat stroke in a 67-year-old woman with an initial Glasgow Coma Scale of 3.This report raises awareness among doctors that when heatstroke is diagnosed,comprehensive treatment should be implemented as soon as possible.Moreover,targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.CASE SUMMARY A previously healthy 67-year-old woman with an initial Glasgow Coma Scale of 3 was found lying prone on the road at noon on a summer day.Laboratory tests revealed multiorgan failure.As soon as heatstroke was diagnosed,comprehensive treatment was implemented.On hospital Day 3,the patient was extubated.Her initial Sequential Organ Failure Assessment score at hospitalization was 14 and decreased to 2 on hospital Day 4.On the seventh day following hospital admission,as the patient’s general condition improved,the levels of laboratory test findings decreased rapidly.Finally,the patient gradually recovered with no other neurological symptoms(the Glasgow Coma Scale at discharge was 15,and her ability to walk independently was restored).CONCLUSION This case demonstrated that targeted temperature management,combination therapy with hemodialysis and hemoperfusion,and hyperbaric oxygen therapy may alleviate multiorgan failure and prevent neurological sequelae caused by heatstroke.

Expert consensus on the diagnosis and treatment of heat stroke in China

Heat stroke(HS)is a fatal disease caused by thermal damage in the body,and it has a very high mortality rate.In 2015,the People’s Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China,Expert consensus on standardized diagnosis and treatment for heat stroke.With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years,the 2015 consensus no longer meet the requirements for HS prevention and treatment.It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage,is more practical and is more in line with China’s national conditions.This new expert consensus includes new concept of HS,recommendations for laboratory tests and auxiliary examinations,new understanding of diagnosis and differential diagnosis,On-site emergency treatment and In-hospital treatment,translocation of HS patients and prevention of HS.

Research progress of heat stroke during 1989–2019: A bibliometric analysis

Background: Heat stroke(HS) is an acute physical disorder that is associated with a high risk of organ dysfunction and even death. HS patients are usually treated symptomatically and conservatively;however, there remains a lack of specific and effective drugs in clinical practice. An analysis of publication contributions from institutions, journals and authors in different countries/regions was used to study research progress and trends regarding HS.Methods: We extracted all relevant publications on HS between 1989 and 2019 from Web of Science. Using the Statistical Package for Social Science(SPSS, version 24) and the software GraphPad Prism 8, graphs were generated and statistical analyses were performed, while VOSviewer software was employed to visualize the research trends in HS from the perspectives of co-occurring keywords.Results: As of April 14, 2020, we identified 1443 publications with a citation frequency of 5216. The United States accounted for the largest number of publications(36.2%) and the highest number of citations(14,410), as well as the highest H-index at 74. Although the sum of publications from China ranked second, there was a contradiction between the quantity and quality of publications. Furthermore, Medicine & Science in Sports & Exercise published the most papers related to HS, with Lin MT publishing the most papers in this field(112), while the review by Knochel JP received the highest citation frequency at 969. The keyword heat-stress appeared most recently, with an average appearing year of 2015.5. In the clinical research cluster, exertional heat-stroke was determined to be the hotspot, while ambient-temperature and heat waves were the new trends in the epidemiological research cluster.Conclusions: Corresponding to this important field, while the contributions of the publications from the United States were significant, the mismatch between the quantity and quality of publications from China must be examined. Moreover, it is hypothesized that clinical and epidemiological studies may become hotspots in the near future.

Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

While cardiopulmonary symptoms are common in patients undergoing dassical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio （INR）. No other causes for liver failure could be identified but physical exhaustion and hyperthermia.

Acute liver failure is frequent during heat stroke

Acute liver failure （ALF） is relatively frequent during heat stroke （HS）. This risk must be emphasized, because its inddence is higher than is usually thought. In a recent study by Weigand et al, two cases were reported in which liver failure was the leading symptom. We have confirmed their conclusion in a study of 25 cases of HS with ALF, compared with 25 other cases without ALE Moreover, we observed that hypophosphatemia on admission could predict occurrence of ALF during HS. As for clinical and other biological parameters, phosphatemia should be monitored for at least 3 d in all cases of HS, even when it is thought to be mild.

Interpretations and comments for expert consensus on the diagnosis and treatment of heat stroke in China

Heat stroke is the most severe type of heat illness,it is often accompanied by severe multiorgan damage and has a high fatality rate.In January 2020,based on new research evidence and the experiences of Chinese experts in heat stroke,the Expert Group of Heat Stroke Prevention and Treatment of the Chinese People’s Liberation Army(PLA)and the Professional Committee of Critical Care Medicine of the Chinese PLA jointly issued a new Expert Consensus on the Diagnosis and Treatment of Heat Stroke in China.This article aims to interpret and supplement the major updates to the new consensus.

A bibliometric analysis of exertional heat stroke research in Web of Science

Background:Exertional heat stroke is a fatal condition and remains a health problem.This paper evaluates the publication trend regarding exertional heat stroke research between 1996 and 2015 using a bibliometric method.Methods:Articles regarding exertional heat stroke research published between 1996 and December 2015 were searched for in the SCI-EXPANDED database of Web of Science.The search results were analyzed with regard to publication year;publication quantity regarding countries/regions;authors;citation frequency;and journal distribution.Cite Space(v3.6) was used for a document co-citation visualization analysis.Results:In total,289 publications on heat stroke were located.After selection,209 original articles conducted across 28 countries/regions and published in 83 journals were included in the analysis.The USA,Isreal,and France were the most common locations for exertional heat stroke studies.The Cite Space visualization cluster analysis showed that exertional heat stroke-related mortality and protective measures were constant concerns of research.Conclusion:Research related to exertional heat stroke has been continuous concerned.USA is still the leading country in this field.

Establishment and effectiveness evaluation of a scoring system for exertional heat stroke by retrospective analysis

Background: Heat stroke(HS) is a serious, life-threatening disease. However, there is no scoring system for HS so far. This research is to establish a scoring system that can quantitatively assess the severity of exertional heat stroke(EHS).Methods: Data were collected from a total of 170 exertional heat stroke(EHS) patients between 2005 and 2016 from 52 hospitals in China. Univariate statistical methods and comparison of the area under the receiver operating characteristic(ROC) curve(AUC) were used to screen exertional heat stroke score(EHSS) parameters, including but not limited body temperature(T), Glasgow Coma Scale(GCS) and others. By comparing the sizes of the AUCs of the APACHE II, SOFA and EHSS assessments, the effectiveness of EHSS in evaluating the prognosis of EHS patients was verified.Results: Through screening with a series of methods, as described above, the present study determined 12 parameters – body temperature(T), GCS, p H, lactate(Lac), platelet count(PLT), prothrombin time(PT), fibrinogen(Fib), troponin I(Tn I), aspartate aminotransferase(AST), total bilirubin(TBIL), creatinine(Cr) and acute gastrointestinal injury(AGI) classification – as EHSS parameters. It is a 0–47 point system designed to reflect increasing severity of heat stroke. Low(EHSS<20) and high scores(EHSS>35) showed 100% survival and 100% mortality, respectively. We found that AUCEHSS>AUCSOFA>AUCAPACHE II.Conclusions: A total of 12 parameters – T, GCS, p H, Lac, PLT, PT, Fib, Tn I, AST, TBIL, Cr and gastrointestinal AGI classification – are the EHSS parameters with the best effectiveness in evaluating the prognosis of EHS patients. As EHSS score increases, the mortality rate of EHS patients gradually increases.

Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study

BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.

Severe liver injury by heat stroke: analysis of 10 cases

Objective: To analyse the clinical features and prognosisof liver injury caused by heat stroke.Methods: The clinical data of 10 patients with severe liverinjury caused by heat stroke were analysed retrospective-ly.Results: In 4 patients the level of ALT was over 1000 U/L, in 3 patients ranged from 300 to 1000 U/L, and in 3patients 50-300 U/L. The level of TBIL in 2 patientswas over 400 μmol/L and in 5 varied from 20 to 75μmol/L. Two patients showed jaundice and petechia on

Heat stroke induced cerebellar dysfunction:A “forgotten syndrome”

We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature.

Exertional rhabdomyolysis and heat stroke: Beware of volatile anesthetic sedation

In view of the enormous popularity of mass sporting events such as half-marathons, the number of patients with exertional rhabdomyolysis or exercise-induced heat stroke admitted to intensive care units(ICUs) has increased over the last decade. Because these patients have been reported to be at risk for malignant hyperthermia during general anesthesia, the intensive care community should bear in mind that the same risk of life-threatening rhabdomyolysis is present when these patients are admitted to an ICU, and volatile anesthetic sedation is chosen as the sedative technique. As illustrated by the three case studies we elaborate upon, a thorough diagnostic work-up is needed to clarify the subsequent risk of strenuous exercise, and the anesthetic exposure to volatile agents in these patients and their families. Other contraindications for the use of volatile intensive care sedation consist of known malignant hyperthermia susceptibility, congenital myopathies, Duchenne muscular dystrophy, and intracranial hypertension.

Rodent models for experimental heat stroke research

Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.

Exertional heat stroke in a young military trainee:is it preventable?

Background: Heat stroke is a life-threatening condition with exertional heat stroke occurring frequently among soldiers and athletes. Because of its common occurrence, many military trainees practice preventive measures prior to any activity requiring severe exertion. Although it is said to be common in practice, different presentations of heat stroke are scarcely described in literature.Case Presentation: We describe a case of an exertional heat stroke in a 23-year-old male Sinhalese soldier who developed early changes of renal failure, liver failure and rhabdomyolysis. The patient initially presented with convulsions, delirium and loss of consciousness to an outside health care facility before being transferred to our institution.Conclusion: It is clear that heat stroke does occur in military trainees while preventive strategies are being practiced. It is important for those who provide healthcare to soldiers to provide proper advice on how to identify impending heat stroke prior to any exercises resulting in severe physical exertion. Further, treating physicians should educate all military trainees about preventive strategies.

The relation between ambulance transports due to heat stroke and air temperature using daily data in Okayama prefecture, Japan

The aim of this study was to investigate the link between ambulance transports due to heat stroke and air temperature by using daily data of ambulance transports in Okayama prefecture, Japan. Daily observations for ambulance transports due to heat stroke from July to September in 2010 in Okayama prefecture, Japan were obtained from Fire and Disaster Management Agency in Japan. Data of meteorological parameters in Okayama prefecture, Japan were also obtained from Japan Meteorological Agency. Effect of meteorological parameters on ambulance transports due to heat stroke was analyzed. A total of 1133 ambulance transports due to heat stroke were observed in from July to September of 2010 in Okayama prefecture, Japan. Ambulance transports due to heat stroke was significantly correlated with air temperature. In addition, number of subjects with ambulance transports due to heat stroke over 34°C in the highest air temperature was 21.2 ± 9.8 per day. Higher air temperature was closely associated with higher ambulance transports due to heat stroke by using daily data in Okayama, prefecture, Japan.

The higher air temperature was closely associated with higher ambulance transports due to heat stroke in elderly Japanese

To investigate the link between higher air temperature and ambulance transports due to heat stroke, especially in elderly subjects, using daily data in Sai-tama prefecture in August, 2010, Japan. We obtained daily data of air temperature in Saitama prefecture in August, 2010, Japan from Japan Meteorological Agency. Number of ambulance transports due to heat stroke was also used by Saitama prefecture official website. The effect of high air temperature on am-bulance transports due to heat stroke was evaluated. A total of 1688 ambulance transports due to heat stroke was observed in Saitama prefecture in August, 2010, Japan. Seven hundred and twenty one subjects (42.7%) were over the age of 65. Mean air temperature, the highest air temperature and day light hours were significantly associated with ambulance transports due to heat stroke in total subjects (mean air temperature: r = 0.749, p < 0.0001) and the over the age of 7. In addition, by separate analysis as classified by age groups, the correlation coefficient between ambulance transports due to heat stroke and mean air temperature was the highest in subjects with over 65. However, the lowest air temperature was not cor-related with ambulance transports due to heat stroke. Higher air temperature was closely associated with higher ambulance transports due to heat stroke using daily data in Saitama prefecture in August, 2010, Ja-pan, especially in elderly subjects.

Whether Increases in Ambulance Transports is Stratified by Heat Stroke in Fukushima Prefecture, Japan in 2011?

We investigated the link between heat stroke and high air temperature from July to September in 2010 in Fukushima prefecture, Japan. Daily data of ambulance transports stratified by heat stroke and the highest air temperature were obtained. Heat stroke was significantly correlated with the highest temperature. The 9.0 magnitude earthquake and following tsunami on March 11, 2011, destroyed many cities in the northwestern part of Japan. Taken together, heat stroke may dramatically increase in Fukushima prefecture, Japan in 2011.

Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

With the escalating prevalence of global heat waves,heat stroke has become a prominent health concern,leading to substantial liver damage.Unlike other forms of liver injury,heat strokeinduced damage is characterized by heat cytotoxicity and heightened inflammation,directly contributing to elevated mortality rates.While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction,their specific correlation with heat stroke liver injury remains unclear.Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke,initiating IL-1bmediated inflammation.Using single-cell RNA sequencing of murine macrophages,a distinct and highly susceptible Kupffer cell subtype,Clec4Ft/CD206t,emerged,with heme oxygenase 1(HMOX-1)playing a pivotal role.Mechanistically,heat-induced HMOX-1,regulated by early growth response factor 1,mediated ferroptosis in Kupffer cells,specifically in the Clec4F t/CD206 t subtype(KC2),activating phosphatidylinositol 4-kinase beta and promoting PI4P production.This cascade triggered NLRP3 inflammasome activation and maturation of IL-1b.These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells,particularly in Clec4F t/CD206 t KCs.Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke,offering a promising avenue for future therapeutic interventions.

Study on the Correlation between IL-6,SAA,CRP and Exertional Heat Stroke in Rats

Objective:To investigate the correlation between interleukin-6(IL-6),serum amyloid A(SAA),C-reactive protein(CRP)and exertional heat stroke in rats.Methods:A total of 90 adult Sprague-Dawley rats without specific pathogens were randomly divided into three groups:control group,classical group and exertion group,with 30 rats in each group.The control group was maintained at a temperature of(26±1)℃and humidity of(60±5)%,while the classical and exertion groups were exposed to a temperature of(40±0.5)℃and humidity of(70±5)%.Additionally,the exertion group underwent treadmill running under these conditions.The levels of IL-6,SAA,and CRP in the three groups were assessed and compared at various time points:before modeling,immediately after onset,and at 2,4,and 8 h after onset.Furthermore,Spearman correlation analysis was employed to examine.Results:The findings from the repeated measures analysis of variance indicated significant variations in the levels of IL-6,SAA,and CRP across the three groups(P<0.05).Both the classic and exertion groups exhibited higher levels of IL-6,SAA,and CRP compared to the control group,with the exertion group demonstrating even higher levels than the classic group(P<0.05).Additionally,Spearman correlation analysis revealed a positive correlation between the onset of heat stroke and the levels of IL-6,SAA,and CRP at the onset,as well as at 2,4,and 8 h post-onset(P<0.05).Furthermore,the types of heat stroke were found to be positively correlated with the levels of IL-6,SAA and CRP(P<0.05).Conclusion:The initiation and nature of heat stroke in rats are significantly associated with the concentrations of IL-6,SAA,and CRP.The concentrations of IL-6,SAA,and CRP within 8 h of onset can reliably forecast the occurrence of heat stroke in rats,serving as a basis for distinguishing classical heat stroke from exertional heat stroke.Nevertheless,the predictive and differentiating efficacy may diminish as the onset time prolongs.