Roberts George T, Ghebeh Hazem, Chishti Muhammad A, Al-Mohanna Falah, El-Sayed Rafaat, Al-Mohanna Futwan, Bouchama Abderrezak
Department of Pathology & Laboratory Medicine, King Faisal Specialist Hospital & Research Center, Riyadh 11211, Saudi Arabia.
Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1130-6. doi: 10.1161/ATVBAHA.107.158709. Epub 2008 Apr 3.
Severe heatstroke is a leading cause of morbidity and mortality during heat waves. The pathogenesis of tissue injury, organ failure, and death in heatstroke is not well understood.
We investigated the pathways of heatstroke-induced tissue injury and cell death in anesthetized baboons (Papio hamadyras) subjected to environmental heat stress until core temperature attained 42.5 degrees C (moderate heatstroke; n = 3) or onset of severe heatstroke (n = 4) signaled by a fall in systolic blood pressure to < 90 mm Hg and rise in core temperature to 43.1+/-0.1 degrees C. Three sham-heated animals served as controls. Light and electron microscopy revealed widespread hemorrhage and thrombosis, transmural migration of leukocytes, and microvascular endothelium injury in severe heatstroke. Immunohistology and ultrastructural analysis demonstrated increased staining of endothelial von Willebrand factor (vWF), tissue factor (TF), and endothelial leukocyte-platelet interaction. Extensive apoptosis was noted in spleen, gut, and lung, and in hematopoeitic cells populating these organs. Double-labeling studies colocalized active caspase-3 and TF with apoptotic cells. Findings in sham-heated animals were unremarkable.
These data suggested that microvascular injury, thrombosis, inflammation, and apoptosis may play an important role in the pathogenesis of heatstroke injury.
严重中暑是热浪期间发病和死亡的主要原因。中暑时组织损伤、器官衰竭及死亡的发病机制尚不清楚。
我们研究了环境热应激下麻醉的狒狒（阿拉伯狒狒）中暑诱导的组织损伤和细胞死亡途径，直至核心体温达到42.5℃（中度中暑；n = 3）或出现严重中暑（n = 4），严重中暑的标志是收缩压降至<90 mmHg且核心体温升至43.1±0.1℃。三只假加热动物作为对照。光镜和电镜显示严重中暑时广泛出血和血栓形成、白细胞跨壁迁移及微血管内皮损伤。免疫组织学和超微结构分析表明内皮血管性血友病因子（vWF）、组织因子（TF）染色增加以及内皮白细胞 - 血小板相互作用增强。在脾脏、肠道和肺以及这些器官中的造血细胞中发现广泛凋亡。双标记研究显示活化的半胱天冬酶 - 3和TF与凋亡细胞共定位。假加热动物的结果无明显异常。
这些数据表明微血管损伤、血栓形成、炎症和凋亡可能在中暑损伤的发病机制中起重要作用。
