Effect of vasodilators on the hypoxic pulmonary vasoconstriction

1. 采用分离通气左下肺模型，观察硝酸甘油（TNG）和前列腺素（PGI_2）等血管扩张剂对狗缺氧性肺血管建设（HPV）的影响。结果表明，TNG和PGI_2可能通过TNG非特异性血管舒张而增加肺通气灌注不均匀性或PGI_2以剂量相关的方式抑制HPV而引起低氧血症。为了更精确地评估肺血管张力，在犬体内建立了测量左下叶血管压力-流量曲线的新模型，并研究了异氟醚和氟烷等吸入麻醉剂对HPV的影响。结果表明，异氟醚和氟烷的临床剂量（1-2MAC）对人乳头状瘤病毒（HPV）的抑制作用不大，但直接吸入缺氧叶时，两者均有剂量相关的抑制作用。采用相同的犬压流曲线模型，前列腺素E_1的剂量可使全身血压降低30%，通过抑制hpv导致低氧血症。用相同的压力-流量曲线模型研究了HPV在ARDS等肺损伤中的调节作用。低剂量内毒素完全抑制HPV，并伴有前列环素，6-酮- pgf_1 α的稳定代谢降低。内毒素对HPV的抑制作用可以通过环氧化酶抑制剂预防，布洛芬和6-酮- pgf_1 α没有降低。这些结果表明，肺内皮细胞释放或产生前列环素的增加与内毒素抑制HPV有关。

1. Using the separatedly ventilated left lower lung model, effects of vasodilators such as nitoroglycerine (TNG) and prostacyclin (PGI_2) on the hypoxic pulumonary vasoconstfiction (HPV) were investigated in the dogs. The results showed that the both TNG and PGI_2 were considered to cause hypoxemia either by increasing pulmonary ventilation-perfusion unevennes because of non-specific vasodilation with TNG or by inhibiting HPV in a dose-related manner with PGI_2.2. For more precise evaluation of pulmonary vascular tone the new model to measure the vascular pressure-flow curve of the left lower lobe was developed in the dogs in vivo and the effects of inhalation anesthetics such as isofulurane and halothane on HPV were investigated. As the results there were little inhibitory effect of HPV with clinical dose (1-2MAC) of isoflurane and halothane, although both of them inhibited HPV in a dose-related manner when directly inhaled to the hypoxic lobe.3. Using the same pressure-flow cureve model in the dogs, a dosage of prostagiandin E_1 which decrease systemic blood pressure by 30% was showed to result hypoxemia by inhibiting HPV.4. Modulation of HPV in the injured lung such as ARDS was investigated with the same pressure-flow curve model in the dogs. Low dose of endotoxin completely depressed HPV and accompanied with a decrese in stable metabolyte of prostacyclin, 6-keto-PGF_1alpha. This depression of HPV with endotoxin was prevented by pretreating with cyclooxgenase inhibitor, ibuprofen and 6-keto-PGF_1alpha did not decreased. These results indicated that incresed release or production of prostacyclin from the pulmonary endothelial cells were involved with the inhibition of HPV by endotoxin.