Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated H₂O₂-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.

即使在自主循环成功恢复后，由于缺血/再灌注 (I/R) 损伤导致多器官损伤，心脏骤停后的死亡率和发病率仍然很高。我们之前生成了 H ₂ O ₂- 可激活的抗氧化纳米粒子由含有香草醇 (PVAX) 的共聚草酸酯配制，以防止 I/R 损伤。在这项研究中，我们检查了 PVAX 是否可以有效减少全身缺血/再灌注损伤 (WBIR) 大鼠模型中的器官损伤。为了诱发心脏骤停，通过颈静脉导管给予 70μl/100 g 体重的 1 mmol/l 氯化钾。媒介物和 PVAX 治疗组中的动物具有相似的基线血压。心脏骤停 5.5 分钟后，通过静脉注射肾上腺素和胸外按压使动物复苏。在注意到血压自然恢复后注射 PVAX 或载体，然后在 10 分钟后再次注射相同剂量的药物。24 小时后，摘取多个器官进行病理、生化、分子分析。赋形剂组和 PVAX 组之间在恢复自主循环方面没有观察到显着差异。手术后 24 小时采集的器官分析表明，全身 I/R 显着增加了多个器官（心脏、大脑和肾脏）的活性氧 (ROS) 生成、炎症标志物和细胞凋亡。PVAX 治疗有效地阻止了 ROS 的产生，降低了促炎细胞因子的升高，并减少了这些器官的细胞凋亡。总之，我们的结果表明 PVAX 对 WBIR 诱导的多器官损伤具有有效的保护作用，可能是通过阻断 ROS 介导的细胞损伤。手术后 24 小时采集的器官分析表明，全身 I/R 显着增加了多个器官（心脏、大脑和肾脏）的活性氧 (ROS) 生成、炎症标志物和细胞凋亡。PVAX 治疗有效地阻止了 ROS 的产生，降低了促炎细胞因子的升高，并减少了这些器官的细胞凋亡。总之，我们的结果表明 PVAX 对 WBIR 诱导的多器官损伤具有有效的保护作用，可能是通过阻断 ROS 介导的细胞损伤。手术后 24 小时采集的器官分析表明，全身 I/R 显着增加了多个器官（心脏、大脑和肾脏）的活性氧 (ROS) 生成、炎症标志物和细胞凋亡。PVAX 治疗有效地阻止了 ROS 的产生，降低了促炎细胞因子的升高，并减少了这些器官的细胞凋亡。总之，我们的结果表明 PVAX 对 WBIR 诱导的多器官损伤具有有效的保护作用，可能是通过阻断 ROS 介导的细胞损伤。