Amide proton transfer imaging in rats after heatstroke.

Metabolic acidosis is the most common acid-base change following heatstroke. This study aimed to evaluate the internal environment changes caused by heatstroke using amide proton transfer (APT) imaging. Nineteen male Sprague-Dawley rats were randomly divided into the control group (CTRL, n  = 7) and the heatstroke group (HS, n  = 12). All the rats underwent a 7.0-T MRI, which included T2-weighted imaging (T2WI) and APT imaging. Subsequently, the surviving HS group rats repeated the same magnetic resonance scanning after 25 days and were designated as the follow-up group (FU, n  = 7). APT values were measured in the hippocampus, thalamus, and corpus callosum. The APT values of the three groups were statistically analyzed and found in the hippocampus (CTRL vs. HS, P  = 0.011; CTRL vs. FU, P  = 0.078; HS vs. FU, P  = 0.484; η ² = 0.276), left thalamus (CTRL vs. HS, P  = 0.004; CTRL vs. FU, P  = 0.014; HS vs. FU, P  = 0.822; η ² = 0.331), right thalamus (CTRL vs. HS, P  = 0.003; CTRL vs. FU, P  = 0.015; HS vs. FU P  = 0.769; η ² = 0.336), and corpus callosum (CTRL vs. HS, P  < 0.001; CTRL vs. FU, P  = 0.005; HS vs. FU, P  = 0.523; η ² = 0.437). APT imaging can be a viable and practical tool for diagnosing heatstroke and monitoring its progression.

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).

Application of diffusion tensor imaging and functional alterations in evaluating brain alterations related to heatstroke in a rat model.

OBJECTIVES: To assess the alterations in resting-state functions and neural structures in the brain of a heatstroke rat model and explore the underlying relationship. METHODS: In total, 17 male Sprague Dawley rats were randomly divided into a control group (CTRL, n = 7) and a heatstroke group (HS, n = 10). All rats underwent 7.0 T magnetic resonance imaging (MRI). T2-weighted imaging, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were obtained. On day 25, the surviving HS group rats (the follow-up group, FU, n = 7) were scanned again. RESULTS: Heatstroke resulted in functional alterations and structural damage in the cerebellar molecular layer (CML), right perirhinal area (PA), pretectal region (PR), right dentate gyrus, and external cortex of the inferior colliculus (ECIC). Further functional changes occur in the right temporal associative cortex (TAC), left retrosplenial cortex (RC), and CML during convalescence. The fractional anisotropy values were significantly positively correlated with the amplitude of low-frequency fluctuation (ALFF) (HS-CML: r = 0.746, p = 0.034; right PR: r = 0.648, p = 0.049; FU-right PA: r = 0.817, p = 0.025)/regional homogeneity (ReHo) ratio (HS-CML: r = 0.833, p = 0.008; ECIC: r = 0.678, p = 0.045) and negatively correlated with the ALFF (FU-left RC: r = -0.818, p = 0.024; right TAC: r = -0.813, p = 0.049). CONCLUSION: DTI and rs-fMRI allow meticulous monitoring of the progression of neurological and functional alterations in the brain after heatstroke.

Bone Scanning Findings in a Patient with Heat Stroke-Induced Rhabdomyolysis.

We present a case that caused a diagnostic dilemma on a bone scan. We also review the broad spectrum of nonmalignant findings that can impact the interpretation of a bone scan and the value of correlative imaging using SPECT/CT for exact localization and characterization of lesions. The imaging features of important benign pathologies-that is, metastatic mimics-are elaborated so that the reader can avoid misinterpretations when reporting them. We elucidate 4 uncommon benign findings on a bone scan. Rhabdomyolysis is a result of lysis of skeletal muscle with release of cell contents, such as myoglobin and muscle enzymes, and is diagnosed mostly through a combination of clinical appearance and laboratory values. Myositis ossificans is the most common form of heterotopic ossification, usually occurring within large muscles. Its importance stems largely from its ability to mimic more aggressive pathologic processes. Myositis ossificans is one of the skeletal "do not touch" lesions. Such bone lesions are defined by characteristic imaging features, the identification of which precludes the need for additional diagnostic tests or biopsies, thereby avoiding unnecessary interventions. Acute tubular necrosis is kidney injury caused by damage to the kidney tubule cells (kidney cells that reabsorb fluid and minerals from urine as it forms). Common causes are low blood flow to the kidneys, drugs that damage the kidneys, or a severe underlying infection.

Metabolomic profiling identifies a novel mechanism for heat stroke­related acute kidney injury.

Heat stroke can induce a systemic inflammatory response, which may lead to multi­organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)­related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41˚C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro­positron emission tomography­computed tomography (micro­PET/CT), H&E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis­inducing factor mitochondria­associated 2 (Aifm2), high­mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography­mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro­PET/CT revealed active metabolism in the whole body of HS mice. H&E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the 'biosynthesis of unsaturated fatty acids' pathway was detected. HS­associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS­related AKI.

An AIE probe for imaging mitochondrial SO2-induced stress and SO2 levels during heat stroke.

A probe, MITO-TPE, was developed for imaging mitochondrial SO2 with good selectivity, high sensitivity, and a fast response time. Cell imaging indicated that SO2-induced oxidative stress may cause damage to cells through O2˙- bursting. MITO-TPE has here been used to image the misregulation of SO2 levels in mitochondria during heat stroke for the first time.

Exertional heat stroke in an amateur runner - Challenges in diagnostics and the role of unhealthy competition.

Exertional heat stroke (EHS) is a potentially life-threatening condition with a variety of symptoms and abnormal laboratory findings. Nevertheless, data evaluating the course of making an EHS diagnosis in real-life practice, as well as the role of predisposing psychological components are limited. Thus, the aim of our study was to present a multi-faceted differentiation process and show the role of unhealthy competition in the development of EHS. We describe a case of a young amateur runner, admitted to the hospital due to loss of consciousness, further mental confusion, and increased body temperature above 40°C. Head scans excluded brain haemorrhage and stroke. Elevated troponin I levels suggested an acute coronary syndrome (ACS) or myocarditis. An increase of procalcitonin levels, signs of rhabdomyolysis and severe liver injury resulted in evaluation for infection and acute hepatic damage. Subsequently, the patient's negative results pointed us to a diagnosis of EHS. In-depth anamnesis revealed that the patient's excessive effort during the race was linked to the male-female competition. EHS can present diagnostic challenges, as it mimics various diseases, such as stroke, myocarditis, ACS, infection, or liver dysfunction. In addition, the role of psychological components, such as unhealthy competition, in the development of EHS should be considered.

Analysis of Clinical Symptoms and Brain MRI of Heat Stroke: 2 Case Reports and a Literature Review.

INTRODUCTION: Heat stroke is defined as high body temperature causing multiple organ failure, psychological change, seizure, and consciousness disturbance, which lead to its high mortality rate. However, the involvement of brain injury is rare, and heat-stroke has only been reported in a few case reports or case series. The purpose of this case study was to evaluate the clinical symptoms and radiological features of heat stroke. METHODS: We reviewed our hospital records and previously published reports to find cases of heat stroke. We excluded those with unknown clinical features or radiological findings. RESULTS: We retrieved 2 cases of heat stroke from our hospital, which presented as extensive lesions on brain imaging that led to disseminated intravascular coagulation and death within a few days. In 21 previously reported cases of heat stroke, similar brain lesions were noted. These were classified as infarction/posterior reversible encephalopathy syndrome (PRES)-like lesions. The patients who developed PRES-like lesions and survived often developed cerebellar sequelae. CONCLUSION: The mechanism of heat stroke is presumed to be multifactorial. Ischemic-like lesions result from hypovolemia and unusual coagulation, whereas PRES-like lesions are caused by direct heat and vasogenic edema due to hypercytokinemia. We need to consider the above mentioned conditions when evaluating heat stroke.

Magnetic resonance imaging and magnetic resonance venography features in heat stroke: a case report.

BACKGROUND: Heat stroke (HS) is a critical illness that can cause multiple organ dysfunction, including damage to the central nervous system (CNS), which can be life-threatening in severe cases. Brain lesions in patients with HS who present with CNS damage have been rarely reported before, and they usually vary in different cases, hence, patients with such lesions may present a clinical challenge in terms of diagnosis and management. Cerebral venous thrombosis (CVT) is a rare cause of stroke that mostly affects young individuals and children. The pathogenesis of brain damage caused by HS is complex, and CVT may be involved in the pathogenesis of HS with CNS damage. In this manuscript, we have reported a case of a patient with HS having CVT with symmetrical lesions in the bilateral putamen, posterior limb of the internal capsule, external capsule, insular lobe, and subcortical white matter in the brain. CASE PRESENTATION: We encountered a 48-year-old man who presented with HS in the summer season. During admission, he had a high body temperature and was in coma and shock. Then, he developed rhabdomyolysis syndrome, acute kidney and liver damage, electrolyte imbalance, and acid-base balance disorders, and his D-dimer level was elevated. After several days of anti-shock treatment, the patient's level of consciousness improved. However, he experienced a decline in vision. Cerebral magnetic resonance imaging (MRI) showed symmetrical lesions in the bilateral posterior limb of the internal capsule, putamen, external capsule, insula, and subcortical white matter, and cerebral magnetic resonance venography (MRV) showed the development of CVT. Therefore, anti-coagulation treatment was provided. After timely clinical intervention, the symptoms of the patient gradually improved. CONCLUSIONS: This case showed that HS can cause CVT. Therefore, cerebral MRI findings in HS must be assessed; in addition, early MRV can help in the diagnosis of the disease, which can effectively improve prognosis.

Dopamine overload visualized in the basal ganglia of rabbit brain during heatstroke can be suppressed by hypothermia.

The present study assesses the changes of dopamine levels in the basal ganglia (BG) of rabbit brain during heatstroke with or without hypothermia therapy. The dopamine levels were determined by using 6(F18) fluoro-L-dopa (FDOPA) positron emission tomography (PET) scan. Heatstroke was induced by exposing the anesthetized rabbits to a high blanket temperature (T(blanket)) of 45 degrees C. Hypothermia therapy was accomplished by decreasing T(blanket) from 45 to 16 degrees C. Regions-of-interest were carefully selected on the BG and cerebellum (C). The uptake ratio of FDOPA was defined as the mean counts per pixel from BG divided by the mean counts from C. BG/C ratios represent the dopamine levels of BG. The results showed that the values of mean arterial pressure (MAP) in heatstroke rabbits without hypothermia therapy were significantly lower than those in normothermic controls. However, BG/C FDOPA ratios were greater. Both the arterial hypotension and the increased BG/C FDOPA ratios observed during heatstroke were all reduced after hypothermia therapy. Our data demonstrate that the dopamine overload visualized in the BG of rabbit brain during heatstroke can be suppressed by hypothermia therapy.

Gray-white matter discrimination--a possible marker for brain damage in heat stroke?

INTRODUCTION/OBJECTIVE: Heat stroke (HS) is a common medical emergency which carries high morbidity and morality. This study was designed to describe the pattern of central nervous system (CNS) changes as detected by brain CT scan in a case series of six patients suffering from classical and exertional HS. METHODS AND PATIENTS: All the patients were admitted in critical condition during the heat wave in the summer of 1999 in Israel. Each was in deep coma with a measured core temperature of over 40 degrees C upon admission to the emergency department. RESULTS: Aggressive cooling measures decreased the core temperature to <38 degrees C within 30 min following admission. Two patients (33.3%) died. One of the survivors remained in a vegetative state. Brain CT studies carried out within 4 days of admission in all the patients revealed severe loss of gray-white matter discrimination (GWMD) without signs of acute bleed or significant focal lesion, findings that persisted in repeated brain CTs in one patient who remained in a vegetative state. DISCUSSION AND CONCLUSIONS: Loss of GWMD may represent an early and sensitive indication of severe brain damage in patients with severe HS. Further studies in larger groups of patients are warranted in order to determine whether the appearance of GWMD in brain CTs of patients with HS has prognostic value.

Echocardiographic and Doppler study of patients with heatstroke and heat exhaustion.

This is a two-dimensional and Doppler echocardiographic study of the hemodynamic changes in patients with heatstroke and heat exhaustion. It demonstrates that the hemodynamic changes in severe heat exposure reflect a hyperdynamic circulation with tachycardia and high cardiac output states. Relative hypovolemia was more pronounced in patients with heatstroke compared to patients with heat exhaustion. Signs of peripheral vasoconstriction were more often present in patients with heatstroke, while patients with heat exhaustion more often demonstrated peripheral vasodilatation.