Naeije R, Leeman M, Lejeune P
Bull Eur Physiopathol Respir. 1986 Jan-Feb;22(1):75-80.
Evidence has recently been accumulated that leukotrienes might be involved in the still unknown biochemical mechanism of hypoxic pulmonary vasoconstriction. We therefore investigated the effects of i.v. cromolyn sodium, which prevents the release of leukotrienes from mast cells by a membrane stabilizing effect, and of i.v. diethylcarbamazine citrate (DEC), a leukotriene synthesis inhibitor, in 13 dogs challenged with the inhalation of 10% O2 in nitrogen (FIO2 0.1) during 10 min. The dogs were anaesthetized with pentobarbital, paralysed with pancuronium, ventilated with a FIO2 of 0.4 and equipped with catheters for the purpose of pulmonary and systemic vascular pressure measurements and thermodilution cardiac output determinations. Thirty minute infusions of DEC at respectively 100 mg, 400 mg, 2 g, 5 g, 10 g and 15 g (one dosage per dog) did not alter the hypoxic pulmonary pressor response. Dosages of 10 g and 15 g DEC were associated with systemic hypotension, and one additional dog given 20 g died in refractory shock. A continuous infusion of cromolyn sodium inhibited hypoxic pulmonary vasoconstriction, partially at 3 and 4.5 mg X kg-1 X min-1 (2 dogs) and completely at 6 mg X kg-1 X min-1 (3 dogs). A lower dosage of 1 mg X kg-1 X min-1 cromolyn sodium (one dog) had no circulatory effect. These results do not support the hypothesis that hypoxic pulmonary vasoconstriction is mediated by vasoconstricting leukotrienes in the dog. The mechanisms accounting for the inhibition of the pulmonary hypoxic pressor response by cromolyn sodium are uncertain.
最近有证据表明，白三烯可能参与了低氧性肺血管收缩这一仍不清楚的生化机制。因此，我们研究了静脉注射色甘酸钠和枸橼酸乙胺嗪（DEC）的作用。色甘酸钠通过膜稳定作用阻止白三烯从肥大细胞释放，DEC是一种白三烯合成抑制剂。对13只狗进行实验，让它们在10分钟内吸入含10%氧气的氮气（吸入氧分数FIO2为0.1）。狗用戊巴比妥麻醉，泮库溴铵使其麻痹，吸入氧分数为0.4进行通气，并配备导管用于测量肺血管和体循环血管压力以及热稀释法测定心输出量。分别以100毫克、400毫克、2克、5克、10克和15克的剂量静脉输注DEC（每只狗一个剂量），并未改变低氧性肺血管加压反应。10克和15克剂量的DEC会导致体循环低血压，另外一只给予20克DEC的狗死于难治性休克。持续输注色甘酸钠可抑制低氧性肺血管收缩，在3毫克·千克⁻¹·分钟⁻¹和4.5毫克·千克⁻¹·分钟⁻¹时部分抑制（2只狗），在6毫克·千克⁻¹·分钟⁻¹时完全抑制（3只狗）。较低剂量1毫克·千克⁻¹·分钟⁻¹的色甘酸钠（1只狗）对循环没有影响。这些结果不支持低氧性肺血管收缩是由血管收缩性白三烯介导的这一假说。色甘酸钠抑制肺低氧加压反应的机制尚不确定。
