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)

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.

A photostable Si-rhodamine-based near-infrared fluorescent probe for monitoring lysosomal pH during heat stroke.

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H+-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pKa is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.

Controversies in exertional heat stroke diagnosis, prevention, and treatment.

During the past several decades, the incidence of exertional heat stroke (EHS) has increased dramatically. Despite an improved understanding of this syndrome, numerous controversies still exist within the scientific and health professions regarding diagnosis, pathophysiology, risk factors, treatment, and return to physical activity. This review examines the following eight controversies: 1) reliance on core temperature for diagnosing and assessing severity of EHS; 2) hypothalamic damage induces heat stroke and this mediates "thermoregulatory failure" during the immediate recovery period; 3) EHS is a predictable condition primarily resulting from overwhelming heat stress; 4) heat-induced endotoxemia mediates systemic inflammatory response syndrome in all EHS cases; 5) nonsteroidal anti-inflammatory drugs for EHS prevention; 6) EHS shares similar mechanisms with malignant hyperthermia; 7) cooling to a specific body core temperature during treatment for EHS; and 8) return to physical activity based on physiological responses to a single-exercise heat tolerance test. In this review, we present and discuss the origins and the evidence for each controversy and propose next steps to resolve the misconception.

Unique cytokine and chemokine responses to exertional heat stroke in mice.

In heat stroke, cytokines are believed to play important roles in multiorgan dysfunction and recovery of damaged tissue. The time course of the cytokine response is well defined in passive heat stroke (PHS), but little is known about exertional heat stroke (EHS). In this study we used a recently developed mouse EHS model to measure the responses of circulating cytokines/chemokines and cytokine gene expression in muscle. A very rapid increase in circulating IL-6 was observed at maximum core temperature (Tc,max) that peaked at 0.5 h of recovery and disappeared by 3 h. IL-10 was not elevated at any time. This contrasts with PHS where both IL-6 and IL-10 peak at 3 h of recovery. Keratinocyte chemoattractant (KC), granulocyte-colony-stimulating factor (G-CSF), macrophage inflammatory protein (MIP)-2, MIP-1ß, and monocyte chemoattractive factor-1 also demonstrated near peak responses at 0.5 h. Only G-CSF and KC remained elevated at 3 h. Muscle mRNA for innate immune cytokines (IL-6, IL-10, IL-1ß, but not TNF-α) were greatly increased in diaphragm and soleus compared with similar measurements in PHS. We hypothesized that these altered cytokine responses in EHS may be due to a lower Tc,max achieved in EHS or a lower overall heat load. However, when these variables were controlled for, they could not account for the differences between EHS and PHS. We conclude that moderate exercise, superimposed on heat exposure, alters the pattern of circulating cytokine and chemokine production and muscle cytokine expression in EHS. This response may comprise an endocrine reflex to exercise in heat that initiates survival pathways and early onset tissue repair mechanisms. NEW & NOTEWORTHY: Immune modulators called cytokines are released following extreme hyperthermia leading to heat stroke. It is not known whether exercise in hyperthermia, leading to EHS, influences this response. Using a mouse model of EHS, we discovered a rapid accumulation of interleukin-6 and other cytokines involved in immune cell trafficking. This response may comprise a protective mechanism for early induction of cell survival and tissue repair pathways needed for recovery from thermal injury.

Mesenchymal stem cell-based treatments for stroke, neural trauma, and heat stroke.

BACKGROUND: Mesenchymal stem cell (MSC) transplantation has been reported to improve neurological function following neural injury. Many physiological and molecular mechanisms involving MSC therapy-related neuroprotection have been identified. METHODS: A review is presented of articles that pertain to MSC therapy and diverse brain injuries including stroke, neural trauma, and heat stroke, which were identified using an electronic search (e.g., PubMed), emphasize mechanisms of MSC therapy-related neuroprotection. We aim to discuss neuroprotective mechanisms that underlie the beneficial effects of MSCs in treating stroke, neural trauma, and heatstroke. RESULTS: MSC therapy is promising as a means of augmenting brain repair. Cell incorporation into the injured tissue is not a prerequisite for the beneficial effects exerted by MSCs. Paracrine signaling is believed to be the most important mediator of MSC therapy in brain injury. The multiple mechanisms of action of MSCs include enhanced angiogenesis and neurogenesis, immunomodulation, and anti-inflammatory effects. Microglia are the first source of the inflammatory cascade during brain injury. Cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6, are significantly produced by microglia in the brain after experimental brain injury. The proinflammatory M1 phenotype of microglia is associated with tissue destruction, whereas the anti-inflammatory M2 phenotype of microglia facilitates repair and regeneration. MSC therapy may improve outcomes of ischemic stroke, neural trauma, and heatstroke by inhibiting the activity of M1 phenotype of microglia but augmenting the activity of M2 phenotype of microglia. CONCLUSION: This review offers a testable platform for targeting microglial-mediated cytokines in clinical trials based upon the rational design of MSC therapy in the future. MSCs that are derived from the placenta provide a great choice for stem cell therapy. Although targeting the microglial activation is an important approach to reduce the burden of the injury, it is not the only one. This review focuses on this specific aspect.

[Malignant hyperthermia syndrome in the intensive care unit : Differential diagnosis and acute measures]. / Maligne hypertherme Syndrome auf der Intensivstation : Differenzialdiagnostik und Akutmaßnamen.

Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 °C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems.

Heat shock protein 70 and AMP-activated protein kinase contribute to 17-DMAG-dependent protection against heat stroke.

Heat shock protein 70 (Hsp70) preconditioning induces thermotolerance, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a role in the process of autophagy. Here, we investigated whether 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) protected against heat stroke (HS) in rats by up-regulation of Hsp70 and phosphorylated AMPK (pAMPK). To produce HS, male Sprague-Dawley rats were placed in a chamber with an ambient temperature of 42°C. Physiological function (mean arterial pressure, heart rate and core temperature), hepatic and intestinal injury, inflammatory mediators and levels of Hsp70, pAMPK and light chain 3 (LC3B) in hepatic tissue were measured in HS rats or/and rats pre-treated with 17-DMAG. 17-DMAG pre-treatment significantly attenuated hypotension and organ dysfunction induced by HS in rats. The survival time during HS was also prolonged by 17-DMAG treatment. Hsp70 expression was increased, whereas pAMPK levels in the liver were significantly decreased in HS rats. Following pre-treatment with 17-DMAG, Hsp70 protein levels increased further, and pAMPK levels were enhanced. Treatment with an AMPK activator significantly increased the LC3BII/LC3BI ratio as a marker of autophagy in HS rats. Treatment with quercetin significantly suppressed Hsp70 and pAMPK levels and reduced the protective effects of 17-DMAG in HS rats. Both of Hsp70 and AMPK are involved in the 17-DMAG-mediated protection against HS. 17-DMAG may be a promising candidate drug in the clinical setting.

Mesenteric Lymph Duct Ligation Alleviating Lung Injury in Heatstroke.

To explore the roles of mesenteric lymph on lung injury in heatstroke (HS), HS rat model was prepared in a prewarmed incubator. Vascular endothelium injury biomarkers (circulating endothelial cell [CEC] as well as von Willebrand factor [vWF] and thrombomodulin [TM]), proinflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1ß [IL-1ß], IL-6, and high mobility group box 1), and coagulant markers (activated partial thromboplastin time, prothrombin time, D-Dimer, and platelet count) were tested in HS and HS with mesenteric lymph duct ligation (LDL) rats. In addition, lung histopathology; arterial blood gas; Evans Blue dye (EBD) and protein lung permeability; intralung inflammatory parameters including bronchoalveolar lavage fluid (BALF) TNF-α, IL-1ß, and IL-6 levels; myeloperoxidase (MPO) activity; and vWF immune staining were analyzed. LDL prolonged HS onset time but not HS survival time. LDL significantly attenuated endothelial cell injury for decreased CEC counts as well as plasma vWF and TM concentrations; downregulated systemic inflammation for decreased plasma TNF-α, IL-1ß, IL-6, and high mobility group box 1 levels; and ameliorated coagulant disorders for decreased activated partial thromboplastin time, prothrombin time, and D-Dimer levels as well as increased platelet counts. LDL also significantly reduced acute lung pathological injury; improved lung function indexes including arterial blood PaO2, pH, PaCO2, and lactic acid; decreased BALF TNF-α, IL-1ß, and IL-6 levels and lung MPO activity; improved EBD and protein lung permeability; and inhibited lung vascular endothelium vWF expression. However, all of these parameters were not recovered to the normal states. In summary, LDL developed protection roles systemically and alleviated lung injury in HS rats which indicated that modulating mesenteric lymph flow may have some potential benefits in HS.

Exertional Heat Stroke and Susceptibility to Malignant Hyperthermia in an Athlete: Evidence for a Link?

OBJECTIVE: To describe the possible association (pathophysiologic and clinical features) between exertional heat stroke (EHS) and malignant hyperthermia (MH). BACKGROUND: Both EHS and MH are acute and life-threatening disorders. It has repeatedly been shown that EHS can occur in well-trained patients with known MH-associated mutation in the RYR1 gene in the absence of any extreme environmental conditions or extreme physical activity, thereby supporting a possible link between EHS and MH. In this case, a highly trained 30-year-old male athlete suddenly collapsed while running. He had initial hyperthermia (40.2°C) and progressive multiple organ failure requiring medical management in an intensive care unit. After he recovered completely, a maximal exercise test was performed and showed an obvious abnormality of oxidative metabolism in muscle; genetic analysis of the RYR1 gene identified a heterozygous missense variation p.K1393R. Consequently, the athlete was given appropriate information and allowed to progressively return to sport competition. DIFFERENTIAL DIAGNOSIS: Doping, use of drugs and toxic agents, exercise-associated hyponatremia, exertional heat illness. TREATMENT: Initial management started with the basic resuscitative guidelines of airway, breathing, and circulation (intubation). Cooling, administration of fresh frozen plasma, and intensive rehydration resulted in improvement. UNIQUENESS: To our knowledge, ours is the first description of this MH mutation (p.K1393R) in the RYR1 gene that was associated with exertional rhabdomyolysis involving a dramatic impairment of oxidative metabolism in muscle. CONCLUSIONS: Common features are shared by EHS and MH. Careful attention must therefore be paid to athletes who experience EHS, especially in temperate climates or when there are no other predisposing factors.

Is there a link between exertional heat stroke and susceptibility to malignant hyperthermia?

OBJECTIVE: The identification of a predisposition toward malignant hyperthermia (MH) as a risk factor for exertional heat stroke (EHS) remains a matter of debate. Such a predisposition indicates a causal role for MH susceptibility (MHS) after EHS in certain national recommendations and has led to the use of an in vitro contracture test (IVCT) to identify the MHS trait in selected or unselected EHS patients. The aim of this study was to determine whether the MHS trait is associated with EHS. METHODS: EHS subjects in the French Armed Forces were routinely examined for MHS after experiencing an EHS episode. This retrospective study compared the features of IVCT-diagnosed MHS (iMHS) EHS subjects with those of MH-normal EHS patients and MH patients during the 2004-2010 period. MHS status was assessed using the European protocol. RESULTS: During the study period, 466 subjects (median age 25 years; 31 women) underwent MHS status investigation following an EHS episode. None of the subjects reported previous MH events. An IVCT was performed in 454 cases and was diagnostic of MHS in 45.6% of the study population, of MH susceptibility to halothane in 18.5%, of MH susceptibility to caffeine in 9.9%, and of MH susceptibility to halothane and caffeine in 17.2%. There were no differences in the clinical features, biological features or outcomes of iMHS EHS subjects compared with those of MH-normal or caffeine or halothane MHS subjects without known prior EHS episode. The recurrence rate was 12.7% and was not associated with MH status or any clinical or biological features. iMHS EHS patients exhibited a significantly less informative IVCT response than MH patients. CONCLUSIONS: The unexpected high prevalence of the MHS trait after EHS suggested a latent disturbance of calcium homeostasis that accounted for the positive IVCT results. This study did not determine whether EHS patients have an increased risk of MH, and it could not determine whether MH susceptibility is a risk factor for EHS.

[Changes in blood gas parameters of heatstroke rats in dry-heat environment of desert].

OBJECTIVE: To investigate the changes in characteristics of blood gas analysis of heatstroke rats residing in dry-heat environment of desert, and to provide a theoretical reference for its treatment in clinic. METHODS: Forty-eight male Sprague-Dawley ( SD ) adult rats under anesthesia were divided into six groups by random number table, with 8 rats in each group: namely mild, moderate, severe heatstroke groups and their corresponding control groups. The rats were placed in an artificial chamber with simulated desert dry-heat environment ( temperature 41 centigrade, humidity 10% ) for about 70, 110, 145 minutes, respectively, to reproduce mild, moderate, severe heatstroke models. The rats in control groups were placed in a normothermic environment for corresponding duration. Abdominal aorta blood of each group was collected for blood gas analysis, and electrolytes were determined by a portable blood gas analyzer. RESULTS: (1) Arterial partial pressure of carbon dioxide ( PaCO(2) ) in mild heatstroke group was increased to ( 45.64±8.19 ) mmHg ( 1 mmHg = 0.133 kPa ), arterial oxygen saturation ( SaO(2) ) was decreased to 0.84±0.08, pH value was lowered to 7.36±0.11, showing that respiratory acid-base imbalance was resulted. Base excess of extracellular fluid ( BEecf ) in moderate heatstroke group was decreased to ( -3.00±0.76 ) mmol/L, HCO(3)(-) was decreased to ( 19.39±1.89 ) mmol/L, and pH value was lowered to 7.21±0.07, indicating that metabolic acid-base imbalance was aggravated gradually. The changes in parameters in severe heatstroke group gradually became more serious, and a significant difference was found as compared with those of mild and moderate heatstroke groups ( PaCO(2): F = 6.537, P = 0.006; SaO(2): F = 5.174, P = 0.015; pH value: F = 10.736, P = 0.001; BEecf: F = 67.136, P = 0.000; HCO(3)(-): F = 5.612, P = 0.011 ), manifesting an obvious combination of respiratory acidosis and metabolic acidosis, and a serious mixed acid-base disturbance was produced. (2) Compared with corresponding control groups, hemoglobin ( Hb ) was significantly increased in moderate heatstroke group ( g/L: 15.31±1.84 vs. 13.28±0.94, t = 2.791, P = 0.014 ), Hb and hematocrit ( HCT ) in severe heatstroke group were significantly increased [ Hb ( g/L ): 16.59±2.52 vs. 13.42±1.15, t = 3.224, P = 0.006; HCT: ( 53.50±6.63 )% vs. ( 45.50±4.47 )%, t = 2.828, P = 0.013 ], showing that the degree of dehydration was aggravated gradually from mild to serious degree. (3) Serum sodium content in mild heatstroke group was normal ( t = 0.665, P = 0.517 ), serum potassium content was lowered significantly ( t = -2.526, P = 0.024 ); serum sodium content in moderate heatstroke group was increased significantly ( t = 2.162, P = 0.048 ), serum potassium content was lowered significantly ( t = -5.458, P = 0.000 ); and serum sodium content in severe heatstroke group rose obviously ( U = 12.500, P = 0.038 ), and most of the rats showed hypokalemia, with a small proportion of rats showed obvious hyperkalemia ( U = 19.500, P = 0.195 ). CONCLUSIONS: Acidosis, electrolyte disturbance, respiratory failure and dehydration in heatstroke occurred in dry-heat environment of desert. It indicates that resuscitation should focus on correction of respiratory acidosis, with simultaneous correction of metabolic acidosis, and one should be alert to correct dehydration and electrolyte disturbance. During the moderate phase and the serious phase, correction of aggravated metabolic acidosis should be reinforced, and the prevention and treatment of the severe dehydration and electrolyte disturbance should be undertaken actively.

TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches.

We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x10(6)) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.

Combination treatment with Gua Sha and Blood-letting causes attenuation of systemic inflammation, activated coagulation, tissue ischemia and injury during heatstroke in rats.

OBJECTIVE: Gua Sha and Blood-letting at the acupoints were Chinese traditional therapies for heatstroke. The purpose of present study was to assess the therapeutic effect of Gua Sha on the DU Meridian and Bladder Meridian combined with Blood-letting acupoints at Shixuan (EX-UE 11) and Weizhong (BL 40) on heatstroke. METHODS: Anesthetized rats, immediately after the onset of heatstroke, were divided into four major groups: Gua Sha group, Blood-letting group, Gua Sha combined with Blood-letting group and model group. They were exposed to ambient temperature of 43 °C to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normal control group. Their survival times were measured. In addition, their physiological and biochemical parameters were continuously monitored. RESULTS: When rats underwent heatstroke, their survival time values were found to be 21-25 min. Treatment of Gua Sha combined with Bloodletting greatly improved the survival time (230±22 min) during heatstroke. All heatstoke animals displayed and activated coagulation evidenced by increased prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, and decreased platelet count, protein C. Furthermore, the animals displayed systemic inflammation evidenced by increased the serum levels of cytokines interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and malondialdehyde (MDA). Biochemical markers evidenced by cellular ischemia and injury/dysfunction included increased plasma levels of blood urea nitrogen (BUN), creatinine, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP) were all elevated during heatstroke. Core temperatures (Tco) were also increased during heatstroke. In contrast, the values of mean arterial pressure were signifificantly lower during heatstroke. These heatstroke reactions were all signifificantly suppressed by treatment of Gua Sha and Blood-letting, especially the combination therapy. CONCLUSION: Gua Sha combined with Blood-letting after heatstroke may improve survival by ameliorating systemic inflflammation, hypercoagulable state, and tissue ischemia and injury in multiple organs.

Dexamethasone improves heat stroke-induced multiorgan dysfunction and damage in rats.

Dexamethasone (DXM) is known as an immunosuppressive drug used for inflammation control. In the present study, we attempted to examine whether DXM administration could attenuate the hypercoagulable state and the overproduction of pro-inflammatory cytokines, improve arterial hypotension, cerebral ischemia and damage, and vital organ failure in a rat model of heat stroke. The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C. During the induction period of heat stroke, plasma levels of blood urea nitrogen (BUN), creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP), were consistently increased. High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected. On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased. Importantly, intravenous administration of DXM substantially ameliorated the circulatory dysfunction, systematic inflammation, hypercoagulable state, cerebral ischemia and damage during the induction period of heat stroke. These findings demonstrated that DXM may be an alternative therapy that can ameliorate heat stroke victims by attenuating activated coagulation, systemic inflammation, and vital organ ischemia/injury during heat stroke.

[Heatstroke in dogs in southern Germany. A retrospective study over a 5.5-year period]. / Hitzschlag bei Hunden in Süddeutschland. Eine retrospektive Studie über 5,5 Jahre.

OBJECTIVE: Heatstroke is a life-threating emergency in dogs. The aim of this retrospective study was to analyse the sources of heat stroke in dogs, predisposing and prognostic factors, results of physical examination and clinical pathology as well as the course of this condition and appropriate treatment. MATERIAL AND METHODS: Patient histories of 12 dogs diagnosed with heat stroke over a 5.5-year period were analysed retrospectively. Normality was tested using the Kolmogrow-Smirnow Test and analysed using T-tests, the Chi-square test and the Mann-Whitney U-test. P-values < 0.05 were considered significant. RESULTS: Heat stroke occurred most frequently during summer, particularly in the afternoon. The most common cause of heat stroke was heat exposition in a car. Brachycephalic breeds were overrepresented. The most common clinical signs were polypnoea, tachycardia, hyperthermia and depression to prostration as well as gastrointestinal and neurological symptoms. Clinical pathology results included haemoconcentration, thrombocytopenia, hyperkalemia, prolonged activated partial thromboplastin time and azotemia. Therapies employed included oxygen application, cooling, fluid therapy and administration of gastrointestinal protectants, antiemetics and antibiotics. Duration of hospitalization was 1-6 days. The overall mortality rate was 50%. Most of the non-survivors died or were euthanized within 24-48 hours after presentation. All animals remaining alive after 3 days survived and could be discharged from hospital. CLINICAL RELEVANCE: Heat stroke is a life-threating condition, which can lead to shock, sepsis, coagulation disorders and multiorgan failure. Early recognition and appropriate treatment are important factors for a positive outcome. Furthermore, intensive monitoring and rapid therapy adaption as required are pivotal.

Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage.

Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1ß, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage) in mice.