Leon LR, Helwig BG. 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: 3.06). 12/2010; 109(6):1980-8. DOI: 10.1152/japplphysiol.00301.2010
Source: PubMed


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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    • "Heat stress (HS) is a major environmental hazard for both humans and animals. Despite advances in the understanding of heat-related illnesses, there is no treatment against specific aspects of their pathophysiology, and protocols are limited to generic cooling and rehydration (Leon and Helwig 1985). Therefore, a better understanding of the biological consequences of HS is critical in order to develop effective treatment protocols and mitigation strategies. "
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    ABSTRACT: Proper insulin homeostasis appears critical for adapting to and surviving a heat load. Further, heat stress (HS) induces phenotypic changes in livestock that suggest an increase in insulin action. The current study objective was to evaluate the effects of HS on whole-body insulin sensitivity. Female pigs (57 ± 4 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 21°C) and were fed ad libitum. During period 2, pigs were exposed to: (i) constant HS conditions (32°C) and fed ad libitum (n = 6), or (ii) TN conditions and pair-fed (PFTN; n = 6) to eliminate the confounding effects of dissimilar feed intake. A hyperinsulinemic euglycemic clamp (HEC) was conducted on d3 of both periods; and skeletal muscle and adipose tissue biopsies were collected prior to and after an insulin tolerance test (ITT) on d5 of period 2. During the HEC, insulin infusion increased circulating insulin and decreased plasma C-peptide and nonesterified fatty acids, similarly between treatments. From period 1 to 2, the rate of glucose infusion in response to the HEC remained similar in HS pigs while it decreased (36%) in PFTN controls. Prior to the ITT, HS increased (41%) skeletal muscle insulin receptor substrate-1 protein abundance, but did not affect protein kinase B or their phosphorylated forms. In adipose tissue, HS did not alter any of the basal or stimulated measured insulin signaling markers. In summary, HS increases whole-body insulin-stimulated glucose uptake. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    08/2015; 3(8). DOI:10.14814/phy2.12478
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    • "It is not uncommon for liver biomarkers to be elevated the days following the event, however, with appropriate treatment these should return to normal values rapidly, usually within a week (Roberts, 2000; Roberts, 2006). In cases where appropriate treatment was not implemented, elevated levels of these biomarkers may be an indicator of possible organ failure that could precipitate death (Leon & Helwig, 2010; O'Connor et al., 2010; Wallace, Kriebel, Punnett, Wegman, & Amoroso, 2007). Because every case of EHS is different, recovery times can vary drastically. "

    12/2014; 12(2). DOI:10.15517/pensarmov.v12i2.15841
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    • "Studies have confirmed the selective vulnerability of cerebellar Purkinje cells to heat-induced injury [3], [13]. A cytotoxic and/or excitotoxic mechanism has been suggested [5], possibly of ischemic nature [3] resulting from hypoperfusion induced by vascular endothelial damage which usually accompanies heat-stroke [14]. Our results are in agreement with previous studies. "
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    ABSTRACT: Objective To assess the role of susceptibility-weighted imaging in the detection of intracranial hemorrhage after heat stroke and in the prognosis. Materials and Methods The study group consisted of eight patients after heat stroke, with a score of 3 to 9 in Glasgow Coma Scale. The MR studies were performed with a 1.5 T scanner. Susceptibility-weighted imaging data were collected within 2–5 days after heat stroke. The study was approved by ethics committee, and written informed consents were obtained from family members of the patients. Results Punctate hemorrhages were detected in brain stem, corona radiata and frontal lobe by susceptibility-weighted imaging for three patients. Among the three cases, two patients came to death in the 5th day and the 25th day after heat stroke respectively. Another patient became a persistent vegetative state and died about 3 months later. Five patients with no hemorrhage detected gradually recovered and cerebellar dysfunction remained to various degrees. Conclusions Heat stroke is a life-threatening condition characterized by hyperthermia and accompanied by various complications such as disseminated intravascular coagulation. Susceptibility-weighted imaging is a very useful tool for detection of intracranial hemorrhage and may probably evaluate the prognosis after heat stroke.
    PLoS ONE 08/2014; 9(8):e105247. DOI:10.1371/journal.pone.0105247 · 3.23 Impact Factor
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