Liver necrosis during severe heat stroke recovery is associated with activation of the complement system (1104.14)

Abstract

Severe heat stroke (HS) is associated with core temperature disturbances, coagulopathy and a systemic inflammatory response syndrome (SIRS) that often leads to organ damage and death. The mechanisms mediating these adverse responses remain unidentified. We hypothesized that severe HS induces coagulation and liver necrosis through activation of the complement system (CS). Male Fischer 344 rats displayed hypothermia (34.8±0.3°C; a marker of HS severity), and increased liver gene expression of fibrinogen (3.0‐fold; a marker of coagulopathy) and C5ar1 (3.6‐fold; a marker of CS activation) at 24 hours of severe HS recovery (N=4) compared to non‐heated controls (CON; N=10; P<0.05). Liver IL‐6 gene expression showed a tendency to be higher in severe HS than CON rats, although this did not reach statistical significance (P=0.091). High C5ar1 gene expression was associated with high plasma alanine aminotransferase (HS:1213.8±474.4 U/L; CON: 76.0±2.3 U/L; a marker of liver damage; P<0.05) with moderate to severe multifocal necrosis of the liver (H&E staining). Liver C5ar1 protein expression (Western blot) was decreased at 24 hours of severe HS recovery suggesting internalization and degradation of the receptor. These data suggest that the CS may mediate coagulopathy and liver necrosis during severe HS recovery in the rat, while IL‐6 may not be involved in these responses. Author views not official US Army or DoD policy.Grant Funding Source: US Army Medical Research and Materiel Command