Richalet Jean-Paul, Gratadour Pierre, Robach Paul, Pham Isabelle, Déchaux Michèle, Joncquiert-Latarjet Aude, Mollard Pascal, Brugniaux Julien, Cornolo Jérémy
Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, Université Paris, Bobigny, France.
Am J Respir Crit Care Med. 2005 Feb 1;171(3):275-81. doi: 10.1164/rccm.200406-804OC. Epub 2004 Oct 29.
Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.
暴露于高海拔会诱发肺动脉高压，这可能导致危及生命的状况。在一项随机、双盲、安慰剂对照研究中，研究了口服西地那非对正常受试者高海拔诱发的肺动脉高压和气体交换的影响。12名受试者（西地那非[SIL]组n = 6；安慰剂[PLA]组n = 6）在4350米的高度暴露6天。从海平面到达高海拔6至8小时后开始治疗（每日3次，每次40毫克），并持续6天。治疗前，高海拔时收缩期肺动脉压（超声心动图）升高（与海平面相比升高29%，p < 0.01），然后西地那非组恢复正常（与海平面相比降低6%，无统计学意义），而安慰剂组仍升高（与海平面相比升高21%，p < 0.05）。安慰剂组肺动脉加速时间下降27%，而西地那非组下降6%（p < 0.01）。高海拔时心输出量和体循环血压升高，然后两组均类似地下降。在静息和运动时，西地那非组的动脉血氧分压（Pa(O₂)）较高，肺泡-动脉氧分压差较低（p < 0.05）。西地那非组中高海拔诱发的最大氧耗量下降幅度小于安慰剂组（p < 0.05）。西地那非可预防高海拔诱发的肺动脉高压的发生，并改善气体交换，限制高海拔诱发的低氧血症和运动能力下降。
