Objective To determine the efficacy of dose-response relationships to inhaled aerosolized prostacyclin (IAP) in sheep with endotoxin-induced acute lung injury(ALI).Method The models of acute lung injury(ALI) were established by intravenous injection of endotoxin with 2μg／kg in 13 sheep with PaO2/FiO2 less than 300mmHg. The ALI animals were randomly assigned to control group(n=5) and IAP group(n=8) with the same ventilatory parameters between the two groups (FiO2=50%,Vt=10～15ml·kg-1, PEEP=5mmHg ). Animals in control group were only mechanically ventilatied, while animals in IAP group received IAP 0,5,10,20,30,50,100 ng·kg-1·min-1 with each dosage for 15 minutes and each interval for 15 minutes. The arterial and mixed venous blood gas，hemodynamic parametres, pulmonary dynamic compliance(Cdyn) were measured or calculated just before and after different IAP dosage. Then all animals were intravenously administrated with endotoxin (0.5 μg／kg) to reach the stage of acute respiratory distresss syndrome(ARDS) with PaO2/FiO2 less than 200mmHg. Animals in control group were still kept on mechanical ventilation. After receiving the same treatment as that in ALI stage, the animals in IAP group were inhaled aerosolized prostacyclin at 50 ng·kg-1·min-1 for one hour. The pulmonary pathology, lung water and branch alveolar lavage (BAL) were assessed at the end of the experiment.Result The arterial blood gas analysis showed that PaO2 increased markedly during IAP from 20 to 100 ng·kg-1·min-1 in the stage of ALI and from 50 to 100 ng·kg-1·min-1 in the stage of ARDS (P<0.05) with the improvement of PaO2 as the increase of IAP dosage, while there was no significant difference of PaO2 (P＞0.05) among these doses. There was also no markedly difference of improvement in PaO2 at the same IAP dose between the stages of ALI and ARDS. The PaCO2 did not appear any<WP=7>significant difference at any IAP dose in or between the two stages (P＞0.05). The Qs/Qt decreased markedly during IAP from 20 to 100 ng·kg-1·min-1 in the stages of ALI and ARDS (P<0.05) with the increase of IAP dosage, while there was no significant difference (P＞0.05) among above doses in the stages of ALI and ARDS except that the improvement of Qs/Qt at IAP 100 ng·kg-1·min-1 was better than that of 20 and 30 ng·kg-1·min-1 in ARDS stage. There was no difference of the effect on Qs/Qt at the same IAP dose between the two stages except that the Qs/Qt at IAP 30 ng·kg-1·min-1 in the stage of ALI decreased more markedly than that in the stage of ARDS. Hemodynamic monitoring did not indicate any significant difference of systemic parameters at any IAP dose in the two stages, including MAP, HR, CVP, PCWP, CO, CI and SVR. And the PAP decreased markedly during IAP from 5 to 100 ng·kg-1·min-1 in the stages of ALI and during IAP from 10 to 100 ng·kg-1·min-1 in the stages of ARDS (P<0.05) with IAP at 50 and 100 ng·kg-1·min-1 being better than that from 5 to 30 ng·kg-1·min-1 in the stage of ALI and IAP at 100 ng·kg-1·min-1 being better than that from 10 to 50 ng·kg-1·min-1 in the stage of ARDS. The PVR decreased significant during IAP from 20 to 100 ng·kg-1·min-1 in the stages of ALI and ARDS (P<0.05) with no difference (P＞0.05) among above doses in the two stages. There was no difference of the effect on PAP at same dose between the stages of ALI and ARDS except for IAP 5ng·kg-1·min-1. There was also no difference of the effect on PVR at the same dose between the stages of ALI and ARDS except for IAP 10 ng·kg-1·min-1. There was no difference in Cdyn at any dose in or between the two stages. Lung water and protein, COP, cell counting in BAL in IAP group were lower than those in control group respectively (P<0.05). The pulmonary inflammatory response in IAP group seemed less significant than that in control group.Conclusion IAP, an efficacious selective pulmonary vasodilator, could markedly improve oxygenation， decrease Qs/Qt, PAP and PVR in a dose-dependence with no significant effect on systemic arterial pressures and pulmonary dyn
↧