Therapeutic effect of inhaled aerosolized versus intravenous milrinone on oleic acid-induced acute lung injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To compare the therapeutic effect of inhaled aerosolized and intravenous milrinone,a phosphodiesterase-3 inhibitor in rats with oleic acid-induced acute lung injury (ALI) .Methods Forty male SD rats weighing 300-350 g were randomly divided into 4 groups (n=10 each) group Ⅰ normal control group Ⅱ ALI; group Ⅲ milfinone inhalation and group Ⅳ intravenous milrinone.The animals were anesthetized with intraperitoneal 2% pentobarbital 40 mg/kg,tracheostomized and mechanically ventilated (FiO2 30%,VT 10 ml/kg,RR 80 bpm,IE=12).The chest was opened and the heart was exposed.Pulmonary artery was catheterized via fight ventricle.MAP,CVP,airway pressure and pulmonary artery pressure (PAP) were monitored.ALI was induced with 10% oleic acid 2 ml/kg administered through fight external jugular vein in group Ⅱ,Ⅲ and Ⅳ.In control group 0.1% BSA solution 2 ml/kg was administered iv instead of oleic acid.In group Ⅲ at 30 min after oleic acid administration aerosolized milrinone 1 mg/ml was inhaled 4 times at 60 min interval.Each time milrinone was inhaled for 10 min.In group Ⅳ at 30 min after oleic acid administration a bolus of 10 μg/kg milrinone was given iv followed by 10 min milrinone infusion at 1 μ·kg-1·min-1.The same procedure was repeated 4 times at 60 min interval.MAP and PAP were recorded and blood samples were taken from carotid artery and pulmonary artery for blood gas analysis at the 1st,2nd,3rd and 4th treatment.PaO2/FiO2 and Qs/Qt were calculated.The animals were sacrificed by exsanguination after the 4th treatment.The lungs were removed.The left lung was lavaged.Neutrophil count and protein content in broncho-alveolar lavage fluid (BALF) were determined.W/D lung weight ratio and lung myeloperoxidase (MPO) activity were measured.The uhrastructure of the lung was examined with electron microscope.Results The MAP was significantly lower after oleic acid adminstration in group Ⅳ than in other 3 groups.PaO2/FiO2 was significantly decreased and Qs/Qt increased by iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ.PAP was significantly increased after iv oleic acid in group Ⅱ ,Ⅲ and Ⅳ but was significantly lower in group Ⅲ and Ⅳ than in group Ⅱ .The neutrophil count and total protein content in BALF,W/D ratio and lung MPO activity were significantly increased in group Ⅱ ,Ⅲ and Ⅳ as compared with control group(Ⅰ) and were significantly higher in group Ⅳ than in group Ⅲ.The lung damage induced by oleic acid was less serious in group Ⅲ and Ⅳ than in group Ⅱ .Conclusion Inhaled aerosoLized milrinone has better therapeutic effect than intravenous milrinone in rats with oleic acid-induced ALI and is safer.