Delayed elevation of plasma endothelin-1 during unilateral alveolar hypoxia without systemic hypoxemia in humans

The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. We investigated whether endothelin-1 (ET-1) could be detected in plasma during pulmonary alveolar hypoxia without systemic hypoxemia (one-lung hypoxia) and whether the levels could be related to hemodynamic status in humans.

Thirteen adult patients with primary lung carcinoma were studied prior to surgery. Anesthesia was induced with fentanyl, diazepam, and pancuronium iv. Differential lung ventilation was performed for 40 min. The right lung was ventilated with a mixture of 6% O2, 5% CO2, and 89% N2 and the left lung ventilated with 100% O2. Blood gas values, hemodynamic parameters, and plasma ET-1 levels were measured.

Mean pulmonary artery pressure increased from 13.0 +/- 3.5 to 17.2 +/- 3.2 mm Hg (P < 0.01) after 20 min of one-lung hypoxia. The plasma ET-1 levels in arterial blood and wedged right pulmonary arterial blood increased from 1.69 +/- 0.61 to 2.13 +/- 0.48 pg/ml (P < 0.01) and from 1.75 +/- 0.47 to 2.26 +/- 0.40 pg/ml (P < 0.001), respectively, after 40 min of one-lung hypoxia. At baseline and after 40 min of one-lung hypoxia, there was a significant correlation between the mean pulmonary artery pressure and arterial plasma ET-1 levels (r = 0.650, P < 0.01) in the wedged pulmonary arterial plasma levels (r = 0.484, P < 0.05). The increase in plasma ET-1 levels in arterial blood and in the wedged pulmonary arterial blood of the hypoxic lung occurred slowly.

We concluded that ET-1 may a supporting, but not a primary, role in human hypoxic pulmonary vasoconstriction.