Objective

The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported.

Approach and results

The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p < 0.001). Endotoxin had no significant effect on changes in the response of the receptor after ristocetin stimulation. After stopping endotoxin infusion, a significant restoration of receptor activity was observed for collagen and TRAP, while ASPI and ADP remained partially depressed. Inhaled nitric oxide did not cause additional inhibition of platelet aggregation, either during or after endotoxin challenge.

Conclusions

A profound reduction in platelet aggregation was observed during endotoxic shock. After stopping endotoxin infusion a restoration of platelet receptor activity was seen. The inhibition of platelet aggregation induced by endotoxin infusion was not intensified by nitric oxide, indicating there was no harmful effect of inhaled nitric oxide on platelet aggregation.

中文翻译：

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内毒素休克大型动物模型的血小板功能障碍；吸入一氧化氮和低剂量类固醇的影响

客观的

吸入一氧化氮在休克治疗中的作用仍存在争议，需要进一步的转化研究。使用内毒素诱发休克模型评估吸入一氧化氮对血小板聚集影响的长期观察研究尚未见报道。

方法和结果

这些测试是在休克动物模型中进行的，每个周期为 10 小时。在最初的10小时内，输注内毒素并评价血小板聚集的抑制作用；内毒素输注终止后，评估血小板聚集的恢复情况，持续 10 小时。总共使用了 30 头猪（NO 组，N = 14；对照组，N = 16）。在 NO 组中，在内毒素输注后 3 小时开始吸入一氧化氮 (30 ppm)，并持续到研究结束。与对照相比，在实验的 4 小时（p = 0.002）和 8 小时（p = 0.05），用 NO 治疗选择性地降低了肺动脉压。内毒素显着降低了血小板聚集，如实验期间血小板受体活性降低所表明的：ASPI、ADP、胶原蛋白和 TRAP (p < 0.001)。内毒素对瑞斯托霉素刺激后受体反应的变化没有显着影响。停止内毒素输注后，观察到胶原蛋白和 TRAP 的受体活性显着恢复，而 ASPI 和 ADP 仍然部分抑制。吸入一氧化氮不会在内毒素攻击期间或之后引起血小板聚集的额外抑制。

结论

在内毒素休克期间观察到血小板聚集的显着减少。停止内毒素输注后，血小板受体活性恢复。内毒素输注诱导的血小板聚集抑制作用并未因一氧化氮而增强，说明吸入一氧化氮对血小板聚集无有害影响。