Research progress on the pathophysiology of cardiovascular dysfunction related to heat stroke

doi:10.3877/cma.j.issn.2095-6568.2026.02.008

Abstract

Abstract:

Heat stroke represents the most severe manifestation of heat-related illnesses, characterized by a core body temperature exceeding 40 ℃, accompanied by central nervous system dysfunction and multiple organ dysfunction syndrome. This condition is highly fatal, and results from exposure to high-temperature environments or strenuous physical activity, which leads to excessive heat production and an imbalance between heat generation and dissipation, culminating in multi-system damage. As global temperatures continue to rise, the incidence of heat stroke is anticipated to increase, with a concomitant rise in mortality rates. The cardiovascular system plays a pivotal role in thermoregulation, and the primary pathological features of myocardial tissue injury in heat stroke include systemic inflammatory responses, endothelial cell damage, ferroptosis, myocardial metabolic disorders, and dysregulation of heat shock proteins. This article provides a comprehensive review of the pathophysiological effects of heat stroke on the cardiovascular system, with the aim of informing future research on the mechanisms underlying cardiac damage induced by heat stroke.

Key words: Heat shock, Heat stroke, Myocardial injury, Pathophysiology, Mechanism, Inflammation

Lele Liu, Jie Xiang, Ling Zhang. Research progress on the pathophysiology of cardiovascular dysfunction related to heat stroke[J]. Chinese Journal of Heart and Heart Rhythm(Electronic Edition), 2026, 14(02): 112-120.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxzyxldzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-6568.2026.02.008

https://zhxzyxldzzz.cma-cmc.com.cn/EN/Y2026/V14/I02/112

Figures/Tables 1

References 101

[1]	Ebi KL, Capon A, Berry P, et al. Hot weather and heat extremes: health risks[J]. Lancet, 2021, 398(10301):698-708.
[2]	Epstein Y, Yanovich R. Heatstroke[J]. New Engl J Med, 2019, 380(25): 2449-2459.
[3]	宋景春, 宋青, 张伟, 等. 中国热射病诊断与治疗指南(2025版)[J]. 解放军医学杂志, 2025, 50(4):367-386.
[4]	Barletta JF, Palmieri TL, Toomey SA, et al. Management of heat-related illness and injury in the ICU: a concise definitive review[J]. Crit Care Med, 2024, 52(3):362-375.
[5]	Bouchama A, Abuyassin B, Lehe C, et al. Classic and exertional heatstroke[J]. Nat Rev Dis Primers, 2022, 8(1):8.
[6]	Shi L, Wang B, Wu Q, et al. Heatstroke: a multicenter study in Southwestern China[J]. Front Public Health, 2024, 12:1349753.
[7]	Leon LR, Bouchama A. Heat stroke[J]. Compr Physiol, 2015, 5(2):611-647.
[8]	Sun Z, Chen C, Yan M, et al. Heat wave characteristics, mortality and effect modification by temperature zones: a time-series study in 130 counties of China[J]. Int J Epidemiol, 2021, 49(6):1813-1822.
[9]	Crandall CG, González-Alonso J. Cardiovascular function in the heat-stressed human[J]. Acta Physiol (Oxf), 2010, 199(4):407-423.
[10]	Nzvere FP, Tariq E, Nishanth K, et al. Long-term cardiovascular diseases of heatstroke: a delayed pathophysiology outcome[J]. Cureus, 2020, 12(8):e9595.
[11]	Marchand M, Gin K. The cardiovascular system in heat stroke[J]. CJC Open, 2022, 4(2):158-163.
[12]	Moghadamnia MT, Ardalan A, Mesdaghinia A, et al. Ambient temperature and cardiovascular mortality: a systematic review and meta-analysis[J]. PeerJ, 2017, 5:e3574.
[13]	Desai Y, Khraishah H, Alahmad B. Heat and the heart[J]. Yale J Biol Med, 2023, 96(2):197-203.
[14]	Peters A, Schneider A. Cardiovascular risks of climate change[J]. Nat Rev Cardiol, 2021, 18(1):1-2.
[15]	Xia R, Sun M, Li Y, et al. The pathogenesis and therapeutic strategies of heat stroke-induced myocardial injury[J]. Front Pharmacol, 2023, 14:1286556.
[16]	Bouchama A, Knochel J P. Heat Stroke[J]. New Engl J Med, 2002, 346(25): 1978-1988.
[17]	Roberts GT, Ghebeh H, Chishti MA, et al. Microvascular injury, thrombosis, inflammation, and apoptosis in the pathogenesis of heatstroke: a study in baboon model[J]. Arterioscler Thromb Vasc Biol, 2008, 28(6):1130-1136.
[18]	Iba T, Helms J, Levi M, et al. Inflammation, coagulation, and cellular injury in heat-induced shock[J]. Inflamm Res, 2023, 72(3):463-473.
[19]	Geng Y, Ma Q, Liu YN, et al. Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis[J]. J Hepatol, 2015, 63(3):622-633.
[20]	Rosenberger K, Dembny P, Derkow K, et al. Intrathecal heat shock protein 60 mediates neurodegeneration and demyelination in the CNS through a TLR4- and MyD88-dependent pathway[J]. Mol Neurodegener, 2015, 10:5.
[21]	Xue L, Guo W, Li L, et al. Metabolomic profiling identifies a novel mechanism for heat stroke-related acute kidney injury[J]. Mol Med Rep, 2021, 23(4):241.
[22]	Li P, Wang G, Zhang XL, et al. MicroRNA-155 promotes heat stress-induced inflammation via targeting liver X receptor α in microglia[J]. Front Cell Neurosci, 2019, 13:12.
[23]	马海欣, 祝艳梨, 李佳妍, 等. 热射病致病机制和治疗策略的研究进展[J]. 中华危重病急救医学, 2024, 36 (5): 546-551.
[24]	Zhang ZT, Gu XL, Zhao X, et al. NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1β-mediated neuroinflammation[J]. J Neuroinflammation, 2021, 18(1):128.
[25]	Leon LR, Blaha MD, DuBose DA. Time course of cytokine, corticosterone, and tissue injury responses in mice during heat strain recovery[J]. J Appl Physiol (1985), 2006, 100(4):1400-1409.
[26]	Liu J, Li Q, Zou Z, et al. The pathogenesis and management of heatstroke and heatstroke-induced lung injury[J]. Burns Trauma, 2025, 13:tkae048.
[27]	Li F, Deng J, He Q, et al. ZBP1 and heatstroke[J]. Front Immunol, 2023, 14:1091766.
[28]	Dörge H, Neumann T, Behrends M, et al. Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation[J]. Am J Physiol Heart Circ Physiol, 2000, 279(6):H2587-H2592.
[29]	Dörge H, Schulz R, Belosjorow S, et al. Coronary microembolization: the role of TNF-alpha in contractile dysfunction[J]. J Mol Cell Cardiol, 2002, 34(1):51-62.
[30]	Lin X, Lin CH, Liu R, et al. Myricetin against myocardial injury in rat heat stroke model[J]. Biomed Pharmacother, 2020, 127:110194.
[31]	Lin X, Lin CH, Zhao T, et al. Quercetin protects against heat stroke-induced myocardial injury in male rats: Antioxidative and antiinflammatory mechanisms[J]. Chem Biol Interact, 2017, 265:47-54.
[32]	Lin X, Zhao T, Lin CH, et al. Melatonin provides protection against heat stroke-induced myocardial injury in male rats[J]. J Pharm Pharmacol, 2018, 70(6):760-767.
[33]	Chen GD, Fan H, Zhu JH. Salidroside pretreatment protects against myocardial injury induced by heat stroke in mice[J]. J Int Med Res, 2019, 47(10):5229-5238.
[34]	Yamakawa K, Matsumoto N, Imamura Y, et al. Electrical vagus nerve stimulation attenuates systemic inflam- mation and improves survival in a rat heatstroke model[J]. PLoS One, 2013, 8(2):e56728.
[35]	Sun M, Li Q, Zou Z, et al. The mechanisms behind heatstroke-induced intestinal damage[J]. Cell Death Discov, 2024, 10(1):455.
[36]	Hraoui G, Grondin M, Breton S, et al. Nrf2 mediates mitochondrial and NADPH oxidase-derived ROS during mild heat stress at 40°C[J]. Biochim Biophys Acta Mol Cell Res, 2025, 1872(3):119897.
[37]	Li H, Liu Y, Gu Z, et al. p38 MAPK-MK2 pathway regulates the heat-stress-induced accumulation of reactive oxygen species that mediates apoptotic cell death in glial cells[J]. Oncol Lett, 2018, 15(1):775-782.
[38]	Tsai HY, Hsu YJ, Lu CY, et al. Pharmacological activation of aldehyde dehydrogenase 2 protects against heatstroke- induced acute lung injury by modulating oxidative stress and endothelial dysfunction[J]. Front Immunol, 2021, 12:740562.
[39]	Tseng CK, Liu TT, Lin TC, et al. Expression of heme oxygenase-1 in type II pneumocytes protects against heatstroke-induced lung damage[J]. Cell Stress Chaperones, 2021, 26(1):67-76.
[40]	Du D, Lv W, Jing X, et al. Camel whey protein alleviates heat stress-induced liver injury by activating the Nrf2/HO-1 signaling pathway and inhibiting HMGB1 release[J]. Cell Stress Chaperones, 2022, 27(4):449-460.
[41]	He S, Guo Y, Zhao J, et al. Ferulic acid protects against heat stress-induced intestinal epithelial barrier dysfunction in IEC-6 cells via the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway[J]. Int J Hyperthermia, 2019, 35(1):112-121.
[42]	Christen F, Desrosiers V, Dupont-Cyr BA, et al. Thermal tolerance and thermal sensitivity of heart mitochondria: mitochondrial integrity and ROS production[J]. Free Radic Biol Med, 2018, 116:11-18.
[43]	Li L, Tan H, Gu Z, et al. Heat stress induces apoptosis through a Ca²⁺-mediated mitochondrial apoptotic pathway in human umbilical vein endothelial cells[J]. PLoS One, 2014, 9(12):e111083.
[44]	De Nicolo B, Cataldi-Stagetti E, Diquigiovanni C, et al. Calcium and reactive oxygen species signaling interplays in cardiac physiology and pathologies[J]. Antioxidants (Basel), 2023, 12(2):353.
[45]	Yang L, Tan GY, Fu YQ, et al. Effects of acute heat stress and subsequent stress removal on function of hepatic mitochondrial respiration, ROS production and lipid peroxidation in broiler chickens[J]. Comp Biochem Physiol C Toxicol Pharmacol, 2010, 151(2):204-208.
[46]	Mujahid A, Akiba Y, Toyomizu M. Olive oil-supplemented diet alleviates acute heat stress-induced mitochondrial ROS production in chicken skeletal muscle[J]. Am J Physiol Regul Integr Comp Physiol, 2009, 297(3):R690-R698.
[47]	Ni XX, Nie J, Xie QY, et al. Protective effects of hyperbaric oxygen therapy on brain injury by regulating the phosphorylation of Drp1 through ROS/PKC pathway in heatstroke rats[J]. Cell Mol Neurobiol, 2020, 40(8):1253-1269.
[48]	Hamilton S, Terentyeva R, Kim TY, et al. Pharmacological modulation of mitochondrial Ca²⁺ content regulates sarcoplasmic reticulum Ca²⁺ release via oxidation of the ryanodine receptor by mitochondria-derived reactive oxygen species[J]. Front Physiol, 2018, 9:1831.
[49]	Wang Z, Zhu J, Zhang D, et al. The significant mechanism and treatments of cell death in heatstroke[J]. Apoptosis, 2024, 29(7-8):967-980.
[50]	Zhao F, Whiting S, Lambourne S, et al. Melatonin alleviates heat stress-induced oxidative stress and apoptosis in human spermatozoa[J]. Free Radic Biol Med, 2021, 164:410-416.
[51]	Zhu J, Chen Y, Ji J, et al. Microglial exosomal miR-466i-5p induces brain injury via promoting hippocampal neuron apoptosis in heatstroke[J]. Front Immunol, 2022, 13:968520.
[52]	Li H, Liu Y, Wen M, et al. Hydroxysafflor yellow A (HSYA) alleviates apoptosis and autophagy of neural stem cells induced by heat stress via p38 MAPK/MK2/Hsp27-78 signaling pathway[J]. Biomed Pharmacother, 2019, 114:108815.
[53]	Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death[J]. Cell Mol Immunol, 2021, 18(5):1106-1121.
[54]	Yuan F, Cai J, Wu J, et al. Z-DNA binding protein 1 promotes heatstroke-induced cell death[J]. Science, 2022, 376(6593):609-615.
[55]	Luan Y, Huang E, Huang J, et al. Serum myoglobin modulates kidney injury via inducing ferroptosis after exertional heatstroke[J]. J Transl Int Med, 2023, 11(2):178-188.
[56]	He S, Li R, Peng Y, et al. ACSL4 contributes to ferroptosis-mediated rhabdomyolysis in exertional heat stroke[J]. J Cachexia Sarcopenia Muscle, 2022, 13(3):1717-1730.
[57]	Dong Z, Zhou J, Zhang Y, et al. Astragaloside-IV alleviates heat-induced inflammation by inhibiting endoplasmic reticulum stress and autophagy[J]. Cell Physiol Biochem, 2017, 42(2):824-837.
[58]	Wang L, Ye B, Liu Y, et al. Xuebijing injection attenuates heat stroke-induced brain injury through oxidative stress blockage and parthanatos modulation via PARP-1/AIF signaling[J]. ACS Omega, 2023, 8(37):33392-33402.
[59]	Yang Y, Li C, Xiang X, et al. Ursolic acid prevents endoplasmic reticulum stress-mediated apoptosis induced by heat stress in mouse cardiac myocytes[J]. J Mol Cell Cardiol, 2014, 67:103-111.
[60]	Chen Y, Jiang W, Liu X, et al. Curcumin supplementation improves heat-stress-induced cardiac injury of mice: physiological and molecular mechanisms[J]. J Nutr Biochem, 2020, 78:108331.
[61]	Tang S, Buriro R, Liu Z, et al. Localization and expression of Hsp27 and αB-crystallin in rat primary myocardial cells during heat stress in vitro[J]. PLoS One, 2013, 8(7):e69066.
[62]	Tang S, Chen H, Cheng Y, et al. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress[J]. Int J Mol Med, 2016, 37(1):56-62.
[63]	Kregel KC. Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance[J]. J Appl Physiol (1985), 2002, 92(5): 2177-2186.
[64]	Hsu SF, Chao CM, Huang WT, et al. Attenuating heat-induced cellular autophagy, apoptosis and damage in H9c2 cardiomyocytes by pre-inducing HSP70 with heat shock preconditioning[J]. Int J Hyperthermia, 2013, 29(3):239-247.
[65]	Hsu SF, Chao CM, Chang CP, et al. Heat shock protein 72 may improve hypotension by increasing cardiac mechanical efficiency and arterial elastance in heatstroke rats[J]. Int J Cardiol, 2016, 219:63-69.
[66]	Proctor EA, Dineen SM, Van Nostrand SC, et al. Coagulopathy signature precedes and predicts severity of end-organ heat stroke pathology in a mouse model[J]. J Thromb Haemost, 2020, 18(8):1900-1910.
[67]	Gómez Ramos MJ, Miguel González Valverde F, Sánchez Álvarez C, et al. Fatal heat stroke in a schizophrenic patient[J]. Case Rep Crit Care, 2012, 2012:924328.
[68]	Iba T, Maier CL, Levi M, et al. Thromboinflammation and microcirculation damage in heatstroke[J]. Minerva Med, 2024, 115(2):191-202.
[69]	Stern A. Canine environmental hyperthermia: a case series[J]. J Vet Med Sci, 2019, 81(2):190-192.
[70]	Quinn CM, Duran RM, Audet GN, et al. Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model[J]. J Appl Physiol (1985), 2014, 117(9):971-978.
[71]	Laitano O, Garcia CK, Mattingly AJ, et al. Delayed metabolic dysfunction in myocardium following exer- tional heat stroke in mice[J]. J Physiol, 2020, 598(5):967-985.
[72]	Deng CC, Zhang JP, Huo YN, et al. Melatonin alleviates the heat stress-induced impairment of Sertoli cells by reprogramming glucose metabolism[J]. J Pineal Res, 2022, 73(3):e12819.
[73]	Qian L, Song X, Ren H, et al. Mitochondrial mechanism of heat stress-induced injury in rat cardiomyocyte[J]. Cell Stress Chaperones, 2004, 9(3):281-293.
[74]	Fang W, Yin B, Fang Z, et al. Heat stroke-induced cerebral cortex nerve injury by mitochondrial dysfunction: a comprehensive multi-omics profiling analysis[J]. Sci Total Environ, 2024, 919:170869.
[75]	Chen D, Geng Y, Deng Z, et al. Inhibition of TLR4 alleviates heat stroke-induced cardiomyocyte injury by down- regulating inflammation and ferroptosis[J]. Molecules, 2023, 28(5):2297.
[76]	Roths M, Freestone AD, Rudolph TE, et al. Environment-induced heat stress causes structural and biochemical changes in the heart[J]. J Therm Biol, 2023, 113:103492.
[77]	Zhang Z, Wu X, Zou Z, et al. Heat stroke: pathogenesis, diagnosis, and current treatment[J]. Ageing Res Rev, 2024, 100:102409.
[78]	Hausfater P, Doumenc B, Chopin S, et al. Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave[J]. Crit Care, 2010, 14(3):R99.
[79]	Pease S, Bouadma L, Kermarrec N, et al. Early organ dysfunction course, cooling time and outcome in classic heatstroke[J]. Intensive Care Med, 2009, 35(8):1454-1458.
[80]	Feng L, Yin JY, Liu YH, et al. N-terminal pro-brain natriuretic peptide - a significant biomarker of disease development and adverse prognosis in patients with exertional heat stroke[J]. Mil Med Res, 2024, 11(1):26.
[81]	Chen WT, Lin CH, Hsieh MH, et al. Stress-induced cardiomyopathy caused by heat stroke[J]. Ann Emerg Med, 2012, 60(1):63-66.
[82]	Sohal RS, Sun SC, Colcolough HL, et al. Heat stroke. an electron microscopic study of endothelial cell damage and disseminated intravascular coagulation[J]. Arch Intern Med, 1968, 122(1):43-47.
[83]	Yao X, Zhu J, Li L, et al. Hsp90 protected chicken primary myocardial cells from heat-stress injury by inhibiting oxidative stress and calcium overload in mitochondria[J]. Biochem Pharmacol, 2023, 209:115434.
[84]	Shen HH, Tseng YS, Kuo NC, et al. Alpha-lipoic acid protects cardiomyocytes against heat stroke-induced apoptosis and inflammatory responses associated with the induction of Hsp70 and activation of autophagy[J]. Mediators Inflamm, 2019, 2019:8187529.
[85]	Zhang X, Chen B, Wu J, et al. Aspirin enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways[J]. Cells, 2020, 9(1):243.
[86]	Zanobetti A, Coull BA, Kloog I, et al. Fine-scale spatial and temporal variation in temperature and arrhythmia episodes in the VA normative aging study[J]. J Air Waste Manag Assoc, 2017, 67(1):96-104.
[87]	Akhtar MJ, al-Nozha M, al-Harthi S, et al. Electrocardio- graphic abnormalities in patients with heat stroke[J]. Chest, 1993, 104(2):411-414.
[88]	Paul A, Alex R, Jacob JR, et al. Effects of heat stroke on surface ECG: a study on clinical outcomes[J]. Heart Asia, 2019, 11(2):e011221.
[89]	Mimish L. Electrocardiographic findings in heat stroke and exhaustion: a study on Makkah pilgrims[J]. J Saudi Heart Assoc, 2012, 24(1):35-39.
[90]	Bathini T, Thongprayoon C, Petnak T, et al. Circulatory failure among hospitalizations for heatstroke in the United States[J]. Medicines (Basel), 2020, 7(6):32.
[91]	Plummer C, Driessen C, Szabo Z, et al. Management of cardiovascular risk in patients with multiple myeloma[J]. Blood Cancer J, 2019, 9(3):26.
[92]	龚霄雷, 朱丽敏, 姜燕, 等. 急性右心室功能障碍的诊疗进展[J]. 中华心脏与心律电子杂志, 2024, 12(3):161-168.
[93]	Liu S, Xing L, Wang J, et al. The relationship between 24-hour indicators and mortality in patients with exertional heat stroke[J]. Endocr Metab Immune Disord Drug Targets, 2022, 22(2):241-246.
[94]	Alahmad B, Khraishah H, Royé D, et al. Associations between extreme temperatures and cardiovascular cause-specific mortality: results from 27 countries[J]. Circulation, 2023, 147(1):35-46.
[95]	Khraishah H, Alahmad B, Ostergard RL, et al. Climate change and cardiovascular disease: implications for global health[J]. Nat Rev Cardiol, 2022, 19(12):798-812.
[96]	Sprung CL. Hemodynamic alterations of heat stroke in the elderly[J]. Chest, 1979, 75(3):362-366.
[97]	Lian H, Ruan Y, Liang R, et al. Short-term effect of ambient temperature and the risk of stroke: a systematic review and meta-analysis[J]. Int J Environ Res Public Health, 2015, 12(8):9068-9088.
[98]	Zhou L, Chen K, Chen X, et al. Heat and mortality for ischemic and hemorrhagic stroke in 12 cities of Jiangsu Province, China[J]. Sci Total Environ, 2017, 601-602:271-277.
[99]	Wang X, Cao Y, Hong D, et al. Ambient temperature and stroke occurrence: a systematic review and meta-analysis[J]. Int J Environ Res Public Health, 2016, 13(7):698.
[100]	KNOCHEL JP, BEISEL WR, HERNDON EG, et al. The renal, cardiovascular, hematologic and serum electrolyte abnormalities of heat stroke[J]. Am J Med, 1961, 30:299-309.
[101]	Chauhan NR, Kapoor M, Prabha Singh L, et al. Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation[J]. Neuroscience, 2017, 358:79-92.

Please choose a citation manager

Content to export