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Updated: Jul 5, 2025

A Preclinical Model of Exertional Heat Stroke in Mice
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Thromboinflammation and microcirculation damage in heatstroke.

Toshiaki Iba1, Cheryl L Maier2, Marcel Levi3,4

  • 1Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan - toshiiba@juntendo.ac.jp.

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Heatstroke risk increases with rising temperatures, particularly for older adults. This study reveals that heatstroke pathophysiology involves microcirculatory derangement driven by inflammation and thrombosis, termed thromboinflammation.

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Area of Science:

  • Environmental Health
  • Physiology
  • Pathology

Background:

  • Climate change is increasing global temperatures, elevating heatstroke risk, especially among the elderly.
  • Heatstroke mortality is high, with over 1000 deaths in Japan in 2021, predominantly in individuals over 65.
  • The precise mechanisms underlying heatstroke pathophysiology remain incompletely understood.

Purpose of the Study:

  • To investigate the pathophysiology of heatstroke, focusing on microcirculatory derangements.
  • To elucidate the roles of inflammation and coagulation in heatstroke-induced tissue injury.

Main Methods:

  • A comprehensive literature search was conducted using MEDLINE and Web of Science.
  • Keywords included "heatstroke," "heat-related illness," "inflammation," "thrombosis," "coagulation," "fibrinolysis," "endothelial cell," and "circulation."
  • Articles were selected based on relevance to heatstroke, inflammation, and thrombosis; reference lists were also reviewed.

Main Results:

  • Heatstroke pathophysiology involves microcirculatory dysfunction exacerbated by factors like hydration status, acclimatization, dysregulated coagulation, and inflammation.
  • The mechanisms share similarities with sepsis, leading to coagulation-predominant coagulopathy during heat stress.
  • Sterile inflammation, mediated by cytokines and cellular factors, contributes to cell death and propagates systemic inflammation and coagulopathy.

Conclusions:

  • Thromboinflammation is identified as the critical factor inducing microcirculatory disturbance in heatstroke.
  • Understanding these mechanisms is crucial for developing targeted interventions for heatstroke prevention and treatment.
  • Further research into the interplay of inflammation and coagulation in heatstroke is warranted.