Protective Effect Of Milrinone Inhalation On Lung Injury Induced By Smoke Inhalation Injury On Rats

Inhalation injury is respiratory and lung damage which caused by the heat and smoke. Because of its rapid progression, the damage of both heat and chemicals, and its property of hidden and severity, Inhalation injury still is the leading cause of death in burn patients, and the clinical treatment is still a difficult issue. The milrinone is a selective phosphodiesterase III inhibitor. It’s not a dual-pyridine derivative of the digitalis class. In a previous study, inhaled aerosol milrinone can be applied to patients with cardiopulmonary bypass, ischemia-reperfusion model, and play a role in lung protection. It also play a protection role in lung in oleic acid induced experimental acute lung injury. This experiment is studying the lung protective effects in smoke inhalation injury of the inhaled aerosol milrinone, by detecting the inflammatory/antiinflammatory mediators and oxidative/antioxidant mediators.Objectives:1. Detect concentration levels of interleukin-6(IL-6), interleukin-10(IL-10),tumor necrosis factor-α (TNF-α) in serum, to research the effects of the inhaled aerosol milrinone on inflammatory mediators in early smoke inhalation injury;2. Detection activity of malondialdehyde(MDA), myeloperoxidase(MPO) and superoxide dismutase(SOD) in lung homogenates, to research the effects of the inhaled aerosol milrinone on oxidation/anti-oxidation factor in early smoke inhalation injury;3. Investigate whether inhaled aerosol milrinone has a protective effect on early smoke inhalation injury, and its mechanism of protective effect.Methods:Forty male Sprague-Dawley rats were randomized to five experimental groups with8rats each group:normal group, control group receiving normal saline inhalation, low-dose milrinone group receiving0.4mg/ml milrinone inhalation, high-dose milrinone group receiving lmg/ml milrinone inhalation, injured control group.30min later after smoke inhaled, aerosolized solution of0.9%NaCl containing different dose of milrinone was respectively administered for10min in50min interval over4h. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)and interleukin-10(IL-10) in serum and malondialdehyde(MDA), myeloperoxidase (MPO) and Superoxide dismutase(SOD) in lung tissue were detected. The lung tissues were examined under microscope.Results:1. General observation:Shortness of breath, chest auscultation and wheezing, rales, tachycardia appears after injury. Remove the injured rats to outdoor areas to rest for5minutes, the above the performance gradually disappeared.2. Macroscopic observation:light microscope m force agricultural group (group III, IV group) compared with the control lung tissue inflammatory cell infiltration to reduce pulmonary edema.3. The results of TNF-α、IL-6and IL-10:Compared with control group, IL-6、 TNF-a were decreased in milrinone inhalation group, while IL-10was increased especially in high-dose milrinone group (P<0.05)4. The results of MDA、MPO and SOD:Compared with control group, MDA、 MPO were decreased in milrinone inhalation group, while SOD was increased especially in high-dose milrinone group (P<0.05)Conclusions:Inhalation of aerosolized milrinone could protect the lung function against smoke inhalation injury, which may be related to resisting inflammation and oxidation.