Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

OBJECTIVES: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). METHODS: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. RESULTS: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042). CONCLUSIONS: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. CLINICAL RELEVANCE STATEMENT: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. KEY POINTS: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

Heat exhaustion.

Heat exhaustion is part of a spectrum of heat-related illnesses that can affect all individuals, although children, older adults, and those with chronic disease are particularly vulnerable due to their impaired ability to dissipate heat. If left uninterrupted, there can be progression of symptoms to heatstroke, a life-threatening emergency. Signs and symptoms of heat exhaustion may develop suddenly or over time. Exposure to a hot environment for a prolonged period and performing exercise or work in the heat can overwhelm the body's ability to cool itself, causing heat exhaustion. Heat exhaustion can be worsened by dehydration due to inadequate access to water or insufficient fluid replacement. Heat exhaustion can be managed by the immediate reduction of heat gain by discontinuing exercise and reducing radiative heat source exposure. The individual should be encouraged to drink cool fluids and remove or loosen clothing to facilitate heat loss. In more extreme situations, more aggressive cooling strategies (e.g., cold shower, application of wet towels) to lower core temperature should be employed. Heat-related illnesses such as heat exhaustion can be prevented by increasing public awareness of the risks associated with exposure to high temperatures and prolonged exercise.

Endoplasmic Reticulum Stress in Heat- and Shake-Induced Injury in the Rat Small Intestine.

We investigated the mechanisms underlying damage to rat small intestine in heat- and shake-induced stress. Eighteen Sprague-Dawley rats were randomly divided into a control group and a 3-day stressed group treated 2 h daily for 3 days on a rotary platform at 35°C and 60 r/min. Hematoxylin and eosin-stained paraffin sections of the jejunum following stress revealed shedding of the villus tip epithelial cells and lamina propria exposure. Apoptosis increased at the villus tip and extended to the basement membrane. Photomicrographs revealed that the microvilli were shorter and sparser; the nuclear envelope invaginated and gaps in the karyolemma increased; and the endoplasmic reticulum (ER) swelled significantly. Gene microarray analysis assessed 93 differentially expressed genes associated with apoptosis, ER stress, and autophagy. Relevant genes were compiled from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Forty-one genes were involved in the regulation of apoptosis, fifteen were related to autophagy, and eleven responded to ER stress. According to KEGG, the apoptosis pathways, mitogen-activated protein kinase(MAPK) signaling pathway, the mammalian target of rapamycin (mTOR) signaling pathway, and regulation of autophagy were involved. Caspase3 (Casp3), caspase12 (Casp12), and microtubule-associate proteins 1 light chain 3(LC3) increased significantly at the villus tip while mTOR decreased; phosphorylated-AKT (P-AKT) decreased. ER stress was involved and induced autophagy and apoptosis in rat intestinal damage following heat and shake stress. Bioinformatic analysis will help determine the underlying mechanisms in stress-induced damage in the small intestine.

Heat illnesses: a hot topic in the setting of global climate change.

BACKGROUND: Heat illnesses affect a large number of people every year and are becoming an increasing cause of pathology as climate change results in increasing global temperatures. OBJECTIVE: This article will review the physiological responses to heat, as well as the pathophysiological processes that result in heat illnesses. The emphasis will be on providing general practitioners (GPs) with an understanding of how to prevent heat illness in their patients and how to predict who is most at risk. DISCUSSION: Heat illnesses may be thought of as minor or major illnesses, any of which may present to the GP. Consideration must be given to identifying those who need more critical intervention and on when to transfer for higher-level of care.

Alteration in circulating metabolites during and after heat stress in the conscious rat: potential biomarkers of exposure and organ-specific injury.

BACKGROUND: Heat illness is a debilitating and potentially life-threatening condition. Limited data are available to identify individuals with heat illness at greatest risk for organ damage. We recently described the transcriptomic and proteomic responses to heat injury and recovery in multiple organs in an in vivo model of conscious rats heated to a maximum core temperature of 41.8°C (Tc,Max). In this study, we examined changes in plasma metabolic networks at Tc,Max, 24, or 48 hours after the heat stress stimulus. RESULTS: Circulating metabolites were identified by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. Bioinformatics analysis of the metabolomic data corroborated proteomics and transcriptomics data in the tissue at the pathway level, supporting modulations in metabolic networks including cell death or catabolism (pyrimidine and purine degradation, acetylation, sulfation, redox alterations and glutathione metabolism, and the urea cycle/creatinine metabolism), energetics (stasis in glycolysis and tricarboxylic acid cycle, ß-oxidation), cholesterol and nitric oxide metabolism, and bile acids. Hierarchical clustering identified 15 biochemicals that differentiated animals with histopathological evidence of cardiac injury at 48 hours from uninjured animals. The metabolic networks perturbed in the plasma corroborated the tissue proteomics and transcriptomics pathway data, supporting a model of irreversible cell death and decrements in energetics as key indicators of cardiac damage in response to heat stress. CONCLUSIONS: Integrating plasma metabolomics with tissue proteomics and transcriptomics supports a diagnostic approach to assessing individual susceptibility to organ injury and predicting recovery after heat stress.

Danaparoid sodium attenuates the effects of heat stress.

BACKGROUND: Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke. MATERIALS AND METHODS: Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples. RESULTS: In rats pretreated with DA, induction of cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation. CONCLUSION: Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.

[Inhalation heat shock]. / Untersuchungen zum Inhalations-Hitzeschock.

Using the example of a recent case, we examine the possibilities of trace analysis and fire protection techniques in the investigation of fire deaths. The effective cooperation between forensic pathologists and fire inspectors is presented and we discuss the mathematical-physical uses of fire simulation calculations. We review the trace analysis results and discuss the variety of technical possibilities of modern engineering techniques for fire protection.

[Fatalities caused by exposure to heat]. / Todesfälle bei Hitzeeinwirkung.

Between 1978 and 1987 52 cases of death by burning or in connection with fire (13 females and 39 males) were examined at the Institute of Legal Medicine of the Medical School of Hannover. The causes were fires in flats (25), cars (15) and buildings(4), clothes set on fire (3) and explosions (3). In two cases death was caused by scalding. These cases could be divided into accidents (30), over 1/3 caused by smoking (11)), suicides (9) and homicides (6). The other seven cases could not be clarified definitively. Evidence of CO-elevation (38), soot inhalation (33), petechiae (11) and "crow's feet" (6) were noted. However, isolated findings cannot lead to a satisfactory assessment after death by burning. The reconstruction of events requires a comprehensive evaluation of the case history, the scene of death and the autopsy as well as complementary analyses. Therefore intensive cooperation between criminal investigators and forensic physicians is absolutely necessary.

Dopamine depletion protects striatal neurons from heatstroke-induced ischemia and cell death in rats.

To explore the importance of brain dopamine in the heatstroke-induced striatal ischemia and neuronal injury, we compared the temporal profile of the heatstroke-induced striatal extracellular dopamine release, striatal blood flow, and striatal neuronal loss in rats with or without striatal dopamine depletion produced by 6-hydroxydopamine. In vivo voltammetry was used in rats to measure changes in extracellular concentrations of dopamine in the corpus striatum. Striatal neuronal damage was rated on a scale from zero to three (0, no damage; 3, maximum cell loss). The autoradiographic diffusible tracer technique was used for the measurement of striatal blood flow. After the onset of heatstroke, the heatstroke rats without brain dopamine depletion displayed hyperthermia, decreased mean arterial pressure, increased intracranial pressure, decreased cerebral perfusion pressure, decreased striatal blood flow, increased striatal dopamine release, and increased score of striatal neuronal damage as compared with those of normothermic controls. However, when the striatal dopamine system was destroyed by 6-hydroxydopamine, the heatstroke-induced arterial hypotension, intracranial hypertension, ischemic damage to the striatum, and elevated striatal dopamine release were reduced. In addition, the survival time of the heatstroke rats was prolonged after depleting striatal dopamine. Thus it appears that dopamine depletion protects striatal neurons from heatstroke-induced ischemia and cell death.

Fatal classic and exertional heat stroke--report of four cases.

Heat stroke is the outcome of impaired heat dissipation which is aggravated by hot and humid environmental conditions. The very young and debilitated on the one hand and healthy individuals under considerable physical stress on the other are vulnerable to heat stroke. Post-mortem findings will depend on the time lapse between the stroke event and death. We report on the deaths resulting from heat stroke in a 12-month-old baby and three 19-year-old soldiers. Reconstruction of the environmental conditions enables elucidation of the circumstances that precipitated exogenous hyperpyrexia. The Discomfort Index presents reliable criteria for the assessment of heat load: values above 28 units are considered as severe heat load and are life threatening. Awareness of the hazards related to severe heat load on the body is helpful in preventing avoidable calamities.

Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the young rat.

The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21 degrees C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.

An autopsy case of infant death due to heat stroke.

We report an autopsy case of infant death due to heat stroke. On a winter day, a 52-day-old female baby was placed under a Japanese electric foot warmer with a coverlet (kotatsu) on an electric carpet warmer in a heated room at home. After about 5 h, the mother noticed that the baby was unconscious and took her to a hospital. Spontaneous respiration, however, was already absent, and the pupils were dilated. The trunk was hot; body temperature was 41.3 degrees C. The skin of the whole body was dry. Autopsy revealed second-degree burn injuries on the left side of the face and the dorsum of the left hand. Numerous marked petechiae and ecchymoses were found in the thymus (capsule and parenchyma), pleurae (visceral and parietal), pericardial cavity (internal and external surfaces), epicardium, and beneath the serosa at the origin of the aorta. In addition, there was congestion in various organs, edema in the brain and lungs, and hemorrhage in the lungs. Histopathologically, macrophages without hemosiderin granules were present in the alveoli. When the heating conditions at the accident were reproduced experimentally, the temperature in the electric kotatsu warmer rose to 50-60 degrees C. Thus, we concluded that misuse of the electric kotatsu caused heat stroke in this infant.

[The mechanism of death in whole-body overheating]. / Mekhanizm smerti pri obshchem peregrevanii organizma.

Data on anatomo-clinical analysis of 36 cases of death due to general overheating of a body are presented. On the basis of these data can be stated that in most cases the effect of high ambient temperature combined with great physical exercise and prolonged exposure to the caused death within short (up to 3 days) periods of time as a result of cessation of CNS functioning. Without physical exercise and direct insolation death usually occurred later (on the average of 5-9 days) from acute renal and renal-hepatic failure. Morphologic changes were unspecific.

Medico-legal problems of ischaemic heart disease and myocardial infarction.

The medicolegal importance of ischaemic heart disease and myocardial infarction is summarized and discussed. Some theories of pathogenesis and aetiology of ischaemic heart disease, specially those which are more important and relevant to the medicolegal practice, are discussed. Results of the study of 33 cases of coronary artery atherosclerosis and myocardial infarction at different stages of development are presented. The condition of the coronary arteries and the myocardium is examined on gross and microscopical levels. Pathological findings are correlated with the clinical data obtained from the case histories and the summaries of the necropsy requests. No good correlation exists between the observed pathological changes and the clinical age of the infarction and, in most instances, the latter appears younger than the age estimated on the pathological ground alone. As far as the age of the infarction is concerned, most special histochemical staining methods are not preferable to the routine haematoxylin and eosin method. However, the former are efficient in demonstrating and confirming certain aspects of the infarction which cannot be ascertained by the latter method of staining. Pathological alterations associated with myocardial infarction at successive ages are explained and various methods of estimating the time of the infarction are discussed. Thus, gross and microscopical appearances of the acute, organizing and healed myocardial infarction are illustrated by photographs and the forensic applications of these morphological changes are discussed. Lastly, a rare case of an acute myocardial infarction associated with a heat stroke is presented and the medicolegal problems resulting from this case are discussed.

[The differential diagnosis of sudden infant death or child abuse--a case of fatal hyperthermia]. / Zur Differentialdiagnose plötzlicher Säuglingstod oder Misshandlung--ein Fall von tödlicher Hyperthermie.

During summer-like outdoor temperature, a seven-month old female infant was put into a sleeping bag, wrapped up with a blanket and tied up by her mother and a friend of hers because of unrest and continuous screaming. Prior to that, between 0.30 a.m. and 0.45 a.m., occurred the rectal measurement of temperature: 37.5 degrees C. The infant died one to two hours later. At 10.00 a.m., about 8 hours after death, in the criminal investigations of the police measurements of temperature were made: rectal 38.1 degrees C; in the pharyngeal cavity 29.5 degrees C; surrounding temperature 22.2 degrees C. In the forensic autopsy, symptoms of maltreatment were noticed: hematoma of the skin at buttock and legs, no essential change of organs. The histological investigation showed an interstitial pulmonary oedema, an acute catarrhal tracheobronchitis and hyperaemic inner organs. Concerning the complete investigation results, an acute cardiac insufficiency and circulatory failure due to hyperthermy after wrapping up and immobilisation of the child were assumed to be the cause of death. In consequence of the avowal of the maltreater they were accused of murder and convicted for bodily injury with death. The difficulties of the differential diagnosis SIDS by hyperthermy and mortal hyperthermy due to maltreatment will be discussed. The necessity of a close cooperation between police and forensic physicians is emphasized as prerequisite to clarify such events.

[Relation between energy metabolism, Na+ and K+ levels, and Na,K-ATPase activity in erythrocytes and their volume and shape during overheating]. / Sootnoshenie énergeticheskogo obmena, soderzhaniia Na+ i K+, aktivnosti Na,K-ATFazy v éritrotsitakh s ikh ob''emom i formoi v usloviiakh peregrevaniia organizma.

Development of heat stroke led to a decrease in main reactions of energy production and energy potential in erythrocytes, to a decrease in activity of Na+, K+-ATPase and in content of sodium and potassium as well as to alterations in forms and to decrease in volume of these cells.

Morphological alterations in the nasal mucosa in heat stroke.

A preliminary histomorphological examination of the nasal mucosa of 8 heatstroke patients who presented without epistaxis, showed stromal vascular damage and degenerative changes in the basal lamina of the overlying epithelium, severe enough in two cases to indicate impending epistaxis, even in the absence of disseminated intravascular coagulation (DIC). It is suggested that direct damage by the extreme heat to mucosal structures, especially the prominent, thin-walled blood vessels, plays an important role in the genesis of epistaxis in heatstroke even in the absence of DIC.