Biomarkers of multiorgan injury in a preclinical model of exertional heat stroke

J Appl Physiol (1985). 2015 May 15;118(10):1207-20. doi: 10.1152/japplphysiol.01051.2014. Epub 2015 Mar 26.


It is likely that the pathophysiology of exertional heat stroke (EHS) differs from passive heat stroke (PHS), but this has been difficult to verify experimentally. C57Bl/6 mice were instrumented with temperature transponders and underwent 3 wk of training using voluntary and forced running wheels. An EHS group was exposed to environmental temperatures (Tenv) of 37.5, 38.5, or 39.5°C at either 30, 50, or 90% relative humidities (RH) while exercising on a forced running wheel. Results were compared with sham-matched exercise controls (EXC) and naïve controls (NC). In EHS, mice exercised in heat until they reached limiting neurological symptoms (loss of consciousness). The symptom-limited maximum core temperatures achieved were between 42.1 and 42.5°C at 50% RH. All mice that were followed for 4 days survived. Additional groups were killed at 0.5, 3, 24, and 96 h, post-EHS or -EXC. Histopathology revealed extensive damage in all regions of the small intestine, liver, and kidney. Plasma creatine kinase, blood urea nitrogen, alanine transaminase, and intestinal fatty acid binding protein-2 were significantly elevated compared with matched EXC and NC, suggesting multiple organ injury to striated muscle, kidney, liver, and intestine, respectively. EHS mice were hypoglycemic immediately following EHS but exhibited sustained hyperglycemia through 4 days. The results demonstrate unique features of survivable EHS in the mouse that included loss of consciousness, extensive organ injury, and rhabdomyolysis.

Keywords: exercise; hyperthermia; intestinal injury; liver injury; rhabdomyolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Heat Stroke / pathology
  • Heat Stroke / physiopathology*
  • Humidity
  • Intestines / pathology
  • Kidney / pathology
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Multiple Organ Failure / pathology
  • Multiple Organ Failure / physiopathology*
  • Physical Conditioning, Animal
  • Physical Exertion
  • Rhabdomyolysis / pathology
  • Rhabdomyolysis / physiopathology
  • Running / physiology
  • Temperature
  • Unconsciousness / physiopathology


  • Biomarkers
  • Blood Glucose