The harmful impact, mechanism and potential treatment of exertional and non-exertional hyperthermia

Walter, Edward James (2023) The harmful impact, mechanism and potential treatment of exertional and non-exertional hyperthermia. (PhD thesis), Kingston University, .


This publication-based thesis aims to add to the existing knowledge surrounding three consecutive aspects of hyperthermia: (1) the threats to human health from hyperthermia, (2) the putative mechanisms underlying the systemic damage, and (3) potential treatments. The six primary research papers forming the basis of the thesis have been published in peer-reviewed journals, using a variety of methodologies, including field studies, lab-based studies and systematic reviews. Prolonged exertion, especially if causing hyperthermia, and passive heat illness, for example in heat waves or due to adverse effects of certain medications, are common causes of multi-organ failure and death. Similarities between the various hyperthermic states suggest that the raised temperature rather than the underlying cause in itself is predominant. Two of these effects, acute kidney injury (AKI) and electrolyte disturbancesin exertional heat illness(EHI), are examined further in papers one and two. The deleterious effects of hyperthermia may include the heat rendering the intestinal tract more permeable, allowing bacteria and toxins from the intestinal tract to enter the systemic circulation. Endurance exercise also appears to stimulate a systemic inflammatory response and increase intestinal permeability. Hyperthermia, especially when associated with exertion, is further characterised in papers three and four, which found that the intestinal permeability was higher after exercise-induced hyperthermia than passive hyperthermia or exercise, respectively, alone, suggesting synergistic effects. There may therefore be the possibility of reducing the systemic damage caused by the exertional and non-exertional hyperthermia by reducing the inflammatory response or the bacterial load in the circulation. Papers five and six are systematic reviews suggesting that in animals both drugs appear to be beneficial in reducing the harm and risk of death from hyperthermia. The work presented here allows the possibility for development of future work on reducing the inflammatory response and intestinal toxin absorption, for example with steroids or antibiotics, to reduce the risk of death and disability after heatstroke and hyperthermia.

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