The Mechanisms of Platelet Hyporeactivity Induced by Heatstroke in Rats

• Main Authors: CHEN, JYE-HANN, 陳頡翰
• Other Authors: SHIH, CHIH-CHIN
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/e9fj7w

碩士 === 國防醫學院 === 藥理學研究所 === 106 === Heatstroke is a life-threatening illness resulting from dysregulated body heat accumulation. Clinically, coagulopathy is one of the most common complications observed in patients with heatstroke. Epidemiological studies have shown that severe coagulopathy usually causes hypotensive shock and dramatically increases the mortality in heatstroke patients. The over-activation of coagulation cascade is thought to be the main mechanism of heatstroke-induced coagulopathy, leading to systemic thrombosis and the consumption of both coagulation factors and platelets. However, the role of platelets in the coagulopathy of heatstroke remains unclear. Thus, the functional changes of platelets in heatstroke rats were evaluated and the mechanisms of heatstroke-induced platelet dysfunction were investigated. In the present study, adult male Wistar rats were anesthetized and placed into a heating chamber at 42 ℃ (or 25 ℃ as normothermic controls) until the core temperature reached 44 ℃. The changes of rectal temperature, hemodynamic parameters, platelet count, and biochemical variables were recorded during the 6-h observation. At the end of the experiment, blood was collected for the preparation of platelet-rich plasma (PRP), platelet-poor plasma (PPP), and washed platelets (WP). An aliquot of PRP was diluted with autologous PPP to acquire normalized PRP (300×〖10〗^3/μL). The reactivities of PRP, WP, and normalized PRP to adenosine diphosphate (ADP), protease-activated receptor-4 agonist (PAR4-amide), collagen, and arachidonic acid (AA) were determined through the optical density method. Our results showed that platelet reactivities to endogenous agonists were strongly inhibited by circulatory substances in heatstroke rats. Platelet aggregation induced by ADP and collagen were partially reversed by ODQ and istradefylline. Istradefylline also enhanced platelet response to PAR4-amide, and SQ-22,536 only improved platelet response to collagen. Moreover, platelets showed greater responses to all agonists after apyrase treatment. However, the pH levels of PRP in heatstroke rats were not different from control rats. Taken together, the attenuation of platelet response to different agonists in heatstroke rats was independent of blood acidification and could be attributed to the over-activation of soluble guanylate cyclase and adenosine/adenylate cyclase pathway as well as purinergic receptors desensitization. It is reasonable to speculate that platelet hyporeactivity contributes to heatstroke-induced coagulopathy, and this issue is worth more attention in heatstroke treatment.