Glucocorticoids do not protect against the lethal effects of experimental heatstroke in baboons.
The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.
Bouchama
Abderrezak
A
Departments of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. abouchama@kfshrc.edu.sa
Kwaasi
Aaron
A
Dehbi
Mohammed
M
Al Mohanna
Falah
F
Eldali
Abdelmoneim
A
El-Sayed
Raafat
R
Tbakhi
Abdelghani
A
Alzahrani
Ali S
AS
Roberts
And George
AG
D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D018883:Heat Stroke / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D010215:Papio; D011897:Random Allocation; D013696:Temperature; D013997:Time Factors
D003176:Complement C3; D003181:Complement C4; D005938:Glucocorticoids; D015850:Interleukin-6; D019344:Lactic Acid; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D003402:Creatine Kinase; D001663:Bilirubin