Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Department of Cardiovascular Surgery, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Eur J Cardiothorac Surg. 2022 Feb 18;61(3):666-674. doi: 10.1093/ejcts/ezab381.
The surgical treatment for diseases of the descending aorta is related to a high mortality rate because of the activation of a systemic inflammatory process due to ischaemia and reperfusion (I/R) injury. Activation of coagulation can contribute to the inflammatory process, resulting in microcirculatory damage and multiple organ failure. Our goal was to evaluate the role of prophylactic intravenous 17β-oestradiol (E2) in coagulation, the inflammatory response and hepatic injury after occlusion of the descendent proximal aorta in male rats.
Wistar male rats were randomized and allocated to 3 groups (n = 8 per group): sham, surgically manipulated; IR, animals subjected to I/R; and E2, animals treated with E2 (280 µg/kg, intravenously) before I/R. I/R was induced by insertion of a 2-Fr Fogarty arterial embolectomy catheter in the descending aorta, which was occluded for 20 min, followed by a reperfusion period of 2 h. Serological markers, platelet aggregation, hepatic vascular flow, systemic and liver inflammatory response and apoptosis were analysed. The coagulation process was evaluated by thromboelastometry.
The aortic occlusion led to a reduction in plasma fibrinogen concentration in parallel with increased clotting time, greater clot firmness and reduced lysis. E2 treatment was able to increase fibrinogen, prevent the increase in clotting time and normalize clot firmness, but it exerted only a mild effect on clot lysis. Platelet aggregation was increased by IR, and E2 treatment was able to reduce it. There was a reduction in flow percentage in the IR group that was not prevented by E2. In parallel, higher aggregate formation was observed in the vessels of the IR group of animals. There was increased systemic release of interleukin-1-β, interleukin-6 and interleukin-10 in the IR group, which was reduced in the treated animals.
The current results suggest that pretreatment with E2 before an ischaemic period induced by occlusion of the proximal descending aorta is effective in preventing alterations in coagulation and systemic inflammation due to I/R injury.
由于缺血再灌注(I/R)损伤引起的全身炎症反应,降主动脉疾病的手术治疗相关死亡率较高。凝血的激活可能会导致炎症反应,从而导致微循环损伤和多器官衰竭。我们的目标是评估预防性静脉内给予 17β-雌二醇(E2)在凝血、炎症反应和雄性大鼠降主动脉近端闭塞后的肝损伤中的作用。
雄性 Wistar 大鼠随机分为 3 组(每组 n = 8):假手术组;手术组;E2 组,E2(280µg/kg,静脉内)治疗后再进行 I/R。通过将 2-Fr Fogarty 动脉取栓导管插入降主动脉来诱导 I/R,将其闭塞 20 分钟,然后再进行 2 小时的再灌注期。分析血清学标志物、血小板聚集、肝血管血流、全身和肝脏炎症反应和细胞凋亡。通过血栓弹力图评估凝血过程。
主动脉闭塞导致血浆纤维蛋白原浓度降低,同时凝血时间延长,凝块硬度增加,溶解减少。E2 治疗能够增加纤维蛋白原,防止凝血时间延长并使凝块硬度正常化,但对凝块溶解仅发挥轻度作用。IR 导致血小板聚集增加,E2 治疗能够降低其聚集。IR 组的血流百分比降低,E2 治疗不能预防。与此平行的是,IR 组动物的血管中观察到更多的聚集物形成。IR 组中观察到全身白细胞介素-1β、白细胞介素-6 和白细胞介素-10 的释放增加,而在接受治疗的动物中则减少。
目前的结果表明,在降主动脉近端闭塞引起的缺血期前给予 E2 预处理可有效预防 I/R 损伤引起的凝血和全身炎症反应的改变。