Dexamethasone Improves Heat Stroke-Induced Multiorgan Dysfunction and Damage in Rats

Abstract

Dexamethasone (DXM) is known as an immunosuppressive drug used for inflammation control. In the present study, we attempted to examine whether DXM administration could attenuate the hypercoagulable state and the overproduction of pro-inflammatory cytokines, improve arterial hypotension, cerebral ischemia and damage, and vital organ failure in a rat model of heat stroke. The results indicated that all the rats suffering from heat stroke showed high serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), accompanied with increased prothrombin time, activated partial thromboplastin time and D-D dimer, and decreased protein C. During the induction period of heat stroke, plasma levels of blood urea nitrogen (BUN), creatinine, glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP), were consistently increased. High striatal levels of glycerol, glutamate, and lactate/pyruvate were simultaneously detected. On the contrary, the mean arterial pressure, plasma levels of interleukin-10 (IL-10), and local cerebral blood flow at the striatum were all decreased. Importantly, intravenous administration of DXM substantially ameliorated the circulatory dysfunction, systematic inflammation, hypercoagulable state, cerebral ischemia and damage during the induction period of heat stroke. These findings demonstrated that DXM may be an alternative therapy that can ameliorate heat stroke victims by attenuating activated coagulation, systemic inflammation, and vital organ ischemia/injury during heat stroke.

Sex-dependent responses to exertional heat stroke in mice

“…The possible therapeutic impact of glucocorticoid supplementation on prevention and recovery from heat stroke has been explored, but there is no consensus on whether it improves outcomes. In a model of passive heat stroke in anesthetized rats, administration of dexamethasone, a common pharmaceutical corticosteroid, has been shown to be effective in increasing survival, and reducing arterial hypotension, cerebral ischemia, and organ damage (39). However, in the baboon model of passive heat stroke, administration of dexamethasone during recovery had no influence on survival and resulted in the presence of significantly elevated and prolonged plasma biomarkers of organ injury during the recovery phase (8).…”

The efficacy of steroids in reducing morbidity and mortality from extreme hyperthermia and heatstroke—A systematic review

“…50 In three studies, the steroid was given after the onset of heat stress. [53][54][55] With the exception of one study, 56 all studies reported improved survival (three reaching statistical significance) and markers of organ dysfunction.…”

“…Of the five studies, three used rats [53][54][55] and two used primates. 50,56 No human studies were found.…”

“…50,56 No human studies were found. Four of the studies used dexamethasone [53][54][55][56] and one methylprednisolone. 50 In three studies, the steroid was given after the onset of heat stress.…”

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures

“…In recent years, several studies have confirmed these findings in comparable rodent models of CHS (peak T core =~43.5 • C). For example, prior corticosteroid injection was shown to inhibit GI MT and improve survival [53][54][55], whereas indomethacin injection enhanced gross morphological GI hemorrhage and worsened survival [56]. Similarly, direct intravenous endotoxin injection prior to sub-lethal CHS in rodents (peak T core =~42-43 • C) unexpectedly led to fatalities in 40% of animals (versus 0% in controls; [57]), or best-case increased symptoms of multiple-organ injury [58].…”