Sidenafil Pre-Treatment Promotes Decompression Sickness in Rats
Sidenafil Pre-Treatment Promotes Decompression Sickness in Rats
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DOI：
10.1371/journal.pone.0060639
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发表时间：
2013-04-08
期刊：
影响因子：
3.7
通讯作者：
Vallee, Nicolas
中科院分区：
文献类型：
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作者：
Blatteau, Jean-Eric;Brubakk, Alf O.;Vallee, Nicolas
减压后血管气泡的形成会导致内皮损伤，从而形成减压病（DCS）的基础。一氧化氮 (NO) 是一种强大的血管扩张剂，有助于血管稳态。研究表明，NO 释放剂可以减少气泡的形成并预防严重的减压病。西地那非是一种众所周知的磷酸二酯酶 5 阻滞剂，通过增强平滑肌松弛的血管舒张作用而发挥作用，但从未在 DCS 中进行过研究。本研究的目的是评估西地那非预处理对大鼠 DCS 模型的临床效果。在分阶段减压之前，67 只大鼠在 90 msw 下进行了 45 分钟的模拟潜水。实验组在暴露前一小时接受 10 mg/kg 的西地那非 (n = 35)，而对照组则不接受治疗 (n = 32)。临床评估在浮出水面后 30 分钟内进行。最后，收集血样进行血细胞计数，并对右侧腔内的循环气泡水平进行量化。西地那非组的 DCS 表现明显多于对照组（分别为 34.3% 和 6.25%，p = 0.012）。治疗组大鼠的血小板计数比对照组减少更多（分别为 -21.7% 和 -7%，p = 0.029），而气泡等级在各组之间没有差异。我们得出的结论是，西地那非预处理会促进神经性 DCS 的发生和严重程度。当考虑在潜水中使用磷酸二酯酶 5 阻滞剂时，建议与医生仔细讨论。
Vascular bubble formation after decompression contributes to endothelial injuries which form the basis for the development of decompression sickness (DCS). Nitric oxide (NO) is a powerful vasodilator that contributes to vessel homeostasis. It has been shown that NO-releasing agent may reduce bubble formation and prevent serious decompression sickness. The use of sildenafil, a well-known, phosphodiesterase-5 blocker, which act by potentiating the vasodilatory effect on smooth muscle relaxation, has never been studied in DCS. The purpose of the present study was to evaluate the clinical effects of sildenafil pre-treatment on DCS in a rat model. 67 rats were subjected to a simulated dive at 90 msw for 45 min before staged decompression. The experimental group received 10 mg/kg of sildenafil one hour before exposure (n = 35) while controls were not treated (n = 32). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and the level of circulating bubbles in the right cavities was quantified. There were significantly more manifestations of DCS in the sildenafil group than in the controls (34.3% vs 6.25%, respectively, p = 0.012). Platelet count was more reduced in treated rats than in controls (-21.7% vs -7%, respectively, p = 0.029), whereas bubble grades did not differ between groups. We concluded that pre-treatment with sildenafil promotes the onset and severity of neurological DCS. When considering the use of phosphodiesterase-5 blockers in the context of diving, careful discussion with physician should be recommended.