Immune challenge is known to increase heat stroke risk, although the mechanism of this increased risk is unclear.
Using a mouse model of classic heat stroke, we examined the impact of prior viral or bacterial infection on hematological aspects of recovery. Mice were exposed to heat either 48 or 72 hours following polyinosinic:polycytidylic acid (poly I:C) or lipopolysaccharide injection, time points when symptoms of illness (fever, lethargy, anorexia) were minimized or completely absent.
Employing multivariate supervised machine learning to identify patterns of molecular and cellular markers associated with heat stroke, we found that prior viral infection simulated with poly I:C injection resulted in heat stroke presenting with high levels of factors indicating coagulopathy. Despite a decreased number of platelets in the blood, platelets are large and non‐uniform in size, suggesting younger, more active platelets. Levels of D‐dimer and soluble thrombomodulin were increased in more severe heat stroke, and in cases of the highest level of organ damage markers D‐dimer levels dropped, indicating potential fibrinolysis‐resistant thrombosis. Genes corresponding to immune response, coagulation, hypoxia, and vessel repair were up‐regulated in kidneys of heat‐challenged animals; these correlated with both viral treatment and distal organ damage while appearing before discernible tissue damage to the kidney itself.