Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon

Abstract

Background Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance. Methods Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100β) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only). Results Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066). Conclusions As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period.

CO2-Breathing Prior to Simulated Diving Increases Decompression Sickness Risk in a Mouse Model: The Microbiota Trail Is Not Forgotten

“…Neuron-specific enolase (NSE) and the glial-derived peptide S100 calcium-binding protein B (S100B) are commonly described to assess the presence and severity of neurological injury. S100B is known to rise in the peripheral circulation in association with both oxidative [61] and heat stress [62], and a relationship is described with core body temperature (Tc) response [63]. NSE is a glycolytic enzyme found in brain neurons and peripheral nervous tissue that is elevated during cerebral inflammation or ischemia.…”

Biomarkers of heatstroke‐induced organ injury and repair

“…EHS more often occurs in younger, physically active, healthy adults, such as military personnel and competitive or recreational athletes, and is characterized by the inability to adequately dissipate heat sufficient to offset the heat load caused by physical exertion (i.e., elevations in metabolic heat production) (Bouchama et al., 2022). As a result, EHS can occur across a comparatively wide range of environmental conditions (Rae et al., 2008; Stacey et al., 2022). Therefore, the threat of heatstroke can impact the health and well‐being of millions of people around the globe, and this risk will likely continue to increase in the coming decades (IPCC, 2021).…”

“…In the interest of conciseness, we will not provide an in‐depth overview of the aetiology of heatstroke, except where it is relevant to understanding injury biomarkers. Likewise, we will not be addressing risk predictive or diagnostic biomarkers of heatstroke, but we invite the interested reader to explore studies on these topics (e.g., Alele et al., 2021; Lu, Wang et al., 2004; Stacey et al., 2022).…”