Bouchama Abderrezak, Kwaasi Aaron, Dehbi Mohammed, Al Mohanna Falah, Eldali Abdelmoneim, El-Sayed Raafat, Tbakhi Abdelghani, Alzahrani Ali S, Roberts And George
Departments of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Shock. 2007 May;27(5):578-83. doi: 10.1097/01.shk.0000246903.40142.aa.
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.
中暑的死亡率和神经功能障碍被认为是宿主对热应激的炎症反应所致，这表明抗炎治疗可能会改善预后。我们检验了一个假设，即高剂量地塞米松可保护狒狒免受中暑的致命影响。将10只麻醉的狒狒（阿拉伯狒狒）随机分为地塞米松组（n = 5）和对照组（n = 5）。在热应激前即刻开始，每6小时分4次静脉注射地塞米松（2 mg/kg），并在降温过程中持续给药。所有动物在预热至44℃至47℃的新生儿培养箱中进行热应激，直到收缩压降至90 mmHg以下，然后在环境温度下被动降温。记录死亡率和神经功能障碍情况，并测定组织损伤/器官功能障碍的生化标志物。依次测量循环白细胞介素（IL）-6和补体成分（C3和C4）。所有热应激动物均出现全身炎症，表现为血浆IL-6升高、C3和C4水平降低。地塞米松减弱了补体系统的激活，并维持了较高的血浆IL-6浓度，同时动脉血压显著升高。地塞米松未能预防严重中暑的发生，但出人意料地显著加重了组织损伤和多器官系统功能障碍。对照组有2只动物（40%）存活，类固醇组有1只动物存活（P > 0.05）。地塞米松未能保护狒狒免受中暑的致命影响。这些结果不支持将皮质类固醇用于人类中暑预防或治疗策略的临床试验。
