Heat stroke: Role of the systemic inflammatory response

U.S. Army Research Institute of Environmental Medicine, Thermal Mountain Medicine Division, Kansas St., Bldg 42, Natick, MA 01760-5007, USA.
Journal of Applied Physiology (Impact Factor: 3.43). 12/2010; 109(6):1980-8. DOI: 10.1152/japplphysiol.00301.2010
Source: PubMed

ABSTRACT Heat stroke is a life-threatening illness that is characterized clinically by central nervous system dysfunction, including delirium, seizures, or coma and severe hyperthermia. Rapid cooling and support of multi-organ function are the most effective clinical treatments, but many patients experience permanent neurological impairments or death despite these efforts. The highest incidence of heat stroke deaths occurs in very young or elderly individuals during summer heat waves, with ∼ 200 deaths per year in the United States. Young, fit individuals may experience exertional heat stroke while performing strenuous physical activity in temperate or hot climates. Factors that predispose to heat stroke collapse include pre-existing illness, cardiovascular disease, drug use, and poor fitness level. For decades the magnitude of the hyperthermic response in heat stroke patients was considered the primary determinant of morbidity and mortality. However, recent clinical and experimental evidence suggests a complex interplay between heat cytotoxicity, coagulation, and the systemic inflammatory response syndrome (SIRS) that ensues following damage to the gut and other organs. Cytokines are immune modulators that have been implicated as adverse mediators of the SIRS, but recent data suggest a protective role for these proteins in the resolution of inflammation. Multi-organ system failure is the ultimate cause of mortality, and recent experimental data indicate that current clinical markers of heat stroke recovery may not adequately reflect heat stroke recovery in all cases. Currently heat stroke is a more preventable than treatable condition, and novel therapeutics are required to improve patient outcome.

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    ABSTRACT: Heat stress (HS) jeopardizes human and animal health and reduces animal agriculture productivity; however, its pathophysiology is not well understood. Study objectives were to evaluate the direct effects of HS on carbohydrate and lipid metabolism. Female pigs (57 ± 5 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 20°C) and were ad libitum fed. During period 2, pigs were exposed to: (1) constant HS conditions (32°C) and fed ad libitum (n = 7), or (2) TN conditions and pair-fed (PFTN; n = 10) to minimize the confounding effects of dissimilar feed intake. All pigs received an intravenous glucose tolerance test (GTT) and an epinephrine challenge (EC) in period 1, and during the early and late phases of period 2. After 8 days of environmental exposure, all pigs were killed and tissue samples were collected. Despite a similar reduction in feed intake (39%), HS pigs tended to have decreased circulating nonesterified fatty acids (NEFA; 20%) and a blunted NEFA response (71%) to the EC compared to PFTN pigs. During early exposure, HS increased basal circulating C-peptide (55%) and decreased the insulinogenic index (45%) in response to the GTT. Heat-stressed pigs had a reduced T3 to T4 ratio (56%) and hepatic 5'-deiodinase activity (58%). After 8 days, HS decreased or tended to decrease the expression of genes involved in oxidative phosphorylation in liver and skeletal muscle, and ATGL in adipose tissue. In summary, HS markedly alters both lipid and carbohydrate metabolism independently of nutrient intake. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    02/2015; 3(2). DOI:10.14814/phy2.12315
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    ABSTRACT: Climate change may significantly affect human health. The possible effects of high ambient temperature must be better understood, particularly in terms of certain diseases' sensitivity to heat (as reflected in relative risks [RR]) and the consequent disease burden (number or fraction of cases attributable to high temperatures), in order to manage the threat. This study investigated the number of deaths attributable to abnormally high ambient temperatures in Seoul, South Korea, for a wide range of diseases. The relationship between mortality and daily maximum temperature using a generalized linear model was analyzed. The threshold temperature was defined as the 90th percentile of maximum daily temperatures. Deaths were classified according to ICD-10 codes, and for each disease, the RR and attributable fractions were determined. Using these fractions, the total number of deaths attributable to daily maximum temperatures above the threshold value, from 1992 to 2009, was calculated. Data analyses were conducted in 2012-2013. Heat-attributable deaths accounted for 3,177 of the 271,633 deaths from all causes. Neurological (RR 1.07; 95% CI, 1.04-1.11) and mental and behavioral disorders (RR 1.04; 95% CI, 1.01-1.07) had relatively high increases in the RR of mortality. The most heat-sensitive diseases (those with the highest RRs) were not the diseases that caused the largest number of deaths attributable to high temperatures. This study estimated RRs and deaths attributable to high ambient temperature for a wide variety of diseases. Prevention-related policies must account for both particular vulnerabilities (heat-sensitive diseases with high RRs) and the major causes of the heat mortality burden (common conditions less sensitive to high temperatures).
    PLoS ONE 02/2015; 10(2):e0118577. DOI:10.1371/journal.pone.0118577 · 3.53 Impact Factor
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    ABSTRACT: Background The pathogenesis of heatstroke is a multi-factorial process involved with an interplay among subsequent inflammation, endothelial injury and coagulation disturbances, which makes pharmacological therapy of heatstroke a challenging problem. Xuebijing injection (XBJ), a traditional Chinese medicine used to sepsis, has been reported to suppress inflammatory responses and restore coagulation disturbances. However, little is known about the role of XBJ in heatstroke.Methods Mice were treated with indicated dose of XBJ before and/or after the induction of heatstroke. Serum inflammatory cytokines, tumor necrosis factor-¿ (TNF-¿) and interleukin-6 (IL-6), and endothelial markers, von Willebrand Factor (vWF) and E-selectin, were measured by ELISA. Liver, kidney and heart profiles including alanine aminotransferase, aspartic aminotransferase, creatinine, blood urea nitrogen, and lactate dehydrogenase, were evaluated by UniCel DxC 800 Synchron Clinical Systems, and troponin was measured by ELISA. Coagulation profiles, including thrombin time, prothrombin time, activated partial thromboplastin time, international normalized ratio, and fibrinogen were examined by STA Compact® Hemostasis System. Jejunum injury was evaluated with H&E staining. Changes in mitochondrial structure in cardiac tissue were assesed by electron microscopy.ResultsPretreatment with XBJ decreased serum pro-inflammatory cytokines including TNF-¿ and IL-6, as well as endothelial injury markers, vWF and E-selectin, in a dose-dependent manner in heatstroke mice. Similar protective effects were observed when XBJ was administered after, or both before and after heat insult. These protective effects lasted for over 12 h in mice receiving XBJ before and after heat insult. XBJ also improved survival rates in heatstroke mice, ameliorated liver, heart, and kidney injuries, including mitochondrial damage to the heart, and reduced coagulation disturbances.ConclusionsXBJ prevents organ injuries and improves survival in heatstroke mice by attenuating inflammatory responses and endothelial injury. XBJ may be a potentially useful in the prevention and treatment of heatstroke.
    BMC Complementary and Alternative Medicine 02/2015; 15(1):4. DOI:10.1186/s12906-015-0519-5 · 1.88 Impact Factor


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