Mechanism of pulmonary vascular injury in high altitude pulmonary edema.

为了验证高原肺水肿可能是减压时血管内气泡形成所致的假说，本研究采用清醒的慢性肺淋巴瘘绵羊进行了两项实验：1）血栓素合酶抑制剂对绵羊气栓性肺损伤的影响。我们测试了血栓素合酶抑制剂OKY-046对由肺动脉中肺空气输注2小时引起的肺损伤的影响。空气灌注引起持续性肺动脉高压和肺血管通透性增加。输<TxB_2>注空气后，血浆和肺淋巴液中6-酮-PGF_（1（α））水平均显著升高。<TxB_2>在空气注入15分钟时，从左心房获得的血浆中的浓度高于从肺动脉获得的。当绵羊在输注空气之前用OKY-046（10 mg/kg，iv）预处理时，阻止了增加<TxB_2>。肺动脉压升高， ...更多信息 类似于未处理的绵羊。肺淋巴流量的增加在空气注入期间被显著抑制。这些数据表明，在空气栓塞过程中观察到的肺动脉高压不是由<TxA_2>。2）低气压对6600 m模拟高原暴露绵羊肺液体平衡的影响。我们观察到在6600米模拟低氧低气压（气压326 mmHg，<FIO_2>0.21）和6600米模拟常氧低气压（气压326 mmHg，<FIO_2>0.65）下，肺淋巴流量显著增加。但吸入纯氧2 h后暴露于6600 m模拟的常氧低气压（气压326 mmHg，<FIO_2>0.65）对肺淋巴流量无影响。这些结果表明，快速暴露于低气压导致肺血管通透性增加，血管内气泡的形成可能是这种通透性变化的原因。少

To examine the hypothesis that high altitude pulmonary edema might be caused by intravascular air bubble formation during decompression, two experiments were performed by using awake sheep with chronic lung lymph fistula.1) Effects of thromboxane synthase inhibition on air emboli lung injury in sheep. We tested the effects of OKY-046, a thromboxane synthase inhibitor, on lung injury induced by 2 hour of pulmonary air infusion in the pulmonary artery. Air infusion caused sustained pulmonary hypertension and an increase in pulmonary vascular permeability. The levels of <TxB_2> and 6-keto- <PGF_(1(alpha))> in both plasma and lung lymph were significantly elevated during the air infusion. <TxB_2> concentration in plasma obtained from the left atrium was higher than that from the pulmonary artery at 15 min of air infusion. When sheep were pretreated with OKY-046(10mg/kg, iv) prior to the air infusion, increases in <TxB_2> were prevented. The pulmonary arterial pressure, however, increased s … More imilarly to that of untreated sheep. The increase in lung lymph flow was significantly supressed during the air infusion. These data suggest that the pulmonary hypertension observed during air embolism is not caused by <TxA_2> . We also tested the effects of dibutyryl cyclic AMP on air emboli lung injury in awake sheep.2) Effects of hypobaria on lung fluid balance in awake sheep during rapid exposure to 6600m-simulated high altitude. We observed that under both 6600m-simulated hypoxic hypobaria (barometric pressure 326mmHg, <FIO_2> 0.21) and 6600m-simulated normoxic hypobaria (barometric pressure 326mmHg, <FIO_2> 0.65), lung lymph flow significantly increased. But exposure to 6600m-simulated normoxic hypobaria (barometric pressure 326mmHg, <FIO_2> 0.65) after pretreatment with a 2 hour-pure oxygen inhalation caused no changes in lung lymph flow. These results suggest that rapid exposure to hypobaria causes an increase in pulmonary vascular permeability and that intravascular air bubble formation might account for this permeability change. Less