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Inflammation, coagulation, and cellular injury in heat-induced shock

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Abstract

Background

The number of heatstroke victims hit record numbers in 2022 as global warming continues. In heat-induced injuries, circulatory shock is the most severe and deadly complication. This review aims to examine the mechanisms and potential approaches to heat-induced shock and the life-threatening complications of heatstroke.

Methods

A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning heatstroke, shock, inflammation, coagulopathy, endothelial cell, cell death, and heat shock proteins.

Results

Dehydration and heat-induced cardiomyopathy were reported as the major causes of heat-induced shock, although other heat-induced injuries are also involved in the pathogenesis of circulatory shock. In addition to dehydration, the blood volume decreases considerably due to the increased vascular permeability as a consequence of endothelial damage. Systemic inflammation is induced by factors that include elevated cytokine and chemokine levels, dysregulated coagulation/fibrinolytic responses, and the release of damage-associated molecular patterns (DAMPs) from necrotic cell death that cause distributive shock. The cytoprotective heat shock proteins can also facilitate circulatory disturbance under excess heat stress.

Conclusions

Multiple mechanisms are involved in the pathogenesis of heat-induced shock. In addition to dehydration, heat stress-induced cardiomyopathy due to the thermal damage of mitochondria, upregulated inflammation via damage-associated molecular patterns released from oncotic cells, unbalanced coagulation/fibrinolysis, and endothelial damage are the major factors that are related to circulatory shock.

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Funding

This work was supported in part by a Grant-in-Aid for Special Research in Subsidies for ordinary expenses of private schools from The Promotion and Mutual Aid Corporation for Private Schools of Japan.

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Authors and Affiliations

  1. Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo, 113-8421, Japan

    Toshiaki Iba

  2. Medical Intensive Care Unit-NHC, Strasbourg University (UNISTRA) Strasbourg University Hospital INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France

    Julie Helms

  3. Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands

    Marcel Levi

  4. Department of Medicine, University College London Hospitals NHS Foundation Trust, and Cardio-Metabolic Programme-NIHR UCLH/UCL BRC, London, UK

    Marcel Levi

  5. Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC, USA

    Jerrold H. Levy

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Contributions

Iba T. and Levy J.H. wrote the main manuscript text and Iba T. prepared figures 1-5. Helms J. and Levi M. revised the manuscript. All authors reviewed the manuscript.

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Correspondence to Toshiaki Iba.

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Conflict of interest

Iba T. has received a research grant from Japan Blood Products Organization and JIMRO. Helms J. has received honoraria from Diagnostica Stago, Pfizer PFE France and Sanofi Aventis France, MSD, Shionogi and Inotrem. Levi M. has received grants and participated in the advisory boards of NovoNordisk, Eli Lilly, Asahi Kasei Pharmaceuticals America, and Johnson & Johnson. Levy JH. serves on the Steering Committees for Instrumentation Laboratories, Merck, and Octapharma.

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Iba, T., Helms, J., Levi, M. et al. Inflammation, coagulation, and cellular injury in heat-induced shock. Inflamm. Res. 72, 463–473 (2023). https://doi.org/10.1007/s00011-022-01687-8

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  • DOI: https://doi.org/10.1007/s00011-022-01687-8

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