Total Liquid Ventilation Reduced Lung Inflammatory Reaction In Piglets After Oleic Acid-induced Acute Lung Injury

Part I A stable and reproducible piglets model of an acute lung injury induced by small injections of oleic acidObjective:To develope a stable and reproducible piglets model of acute lung injury induced by modified injection of oleic acid.Methods:The conventional method of establishing oleic acid-induced acute lung injury model was modified:Oleic acid(Cat NO 01008; Sigma St Louis, MO,Purity:99.96 %)0.1 ml/kg was firstly mixed with 10ml self-made piglet serum. Then the diluted oleic acid was infused into the pulmonary circulation within 15 minutes slowly and steadily,using a micropump syring connected to the jugular venous cannula.12 piglets were randomized into two groups:Study group (01eic acid was administered with the above method) and Control group (Saline was administered as control). And both groups hemodynamic were stable for at least 4h. Hemodynamic and pulmonary function data were monitored. Histopathology of lung tissue was detected.Results:There was obvious decrease in PaO2, PH and obvious increase in PaCO2 in Study group. Study group showed the moderate decrease in blood pressure, heart rate and cardiac output. There was no significant change in hemodynamics and pulmonary function in Control group. Sever lung injury in histopathology was found in Study group.Conclusion:With the use of modified injection of oleic acid, a stable model of early respiratory distress in piglets can be achieved. Such a stable model allows for further studies on early respiratory distress. Part II Development and application of a home-made liquid ventilatorObjective:Total liquid ventilation with perfluorocarbon was a new technology in the therapy of acute lung injury. A special liquid ventilator is necessary for total liquid ventilation. The aim of this study is to design a simple volume controlled liquid ventilator and investigate its effect on the gas exchange and hemodynamics in piglets.Methods:After general anesthesia and conventional mechanichal ventilation established, the lung were then filled with perfluorocarbon (20 ml/kg) and tidal volume liquid ventilation was instituted, utilizing a volume controlled liquid ventilatior. Liquid ventilatory settings were 4 seconds for inspiration time,8 seconds for expiration time.5 breaths/min for respiratory rate. The counter-sweep flow of O2 was lOL/min. Samples for blood gas analysis and hemodynamics were collected before and at 30-minute interval after Total liquid ventilation.Result:The PaO2 values were at the range of 280-310 mmHg, the PaCO2 values 36.8-43.5 mmHg in the liquid-ventilated animals. No significant changes in PaCO2 and PaO2 were observed during total liquid ventilation. The tidal volume was 24±2.31 ml/kg. The hemodynamics index was stable during total liquid ventilation. This experiment demonstrated 65.5-71.2% elimination of CO2 and 20.1±2.32 ml/kg/hr loss of perfluorocarbon across the oxygenator. No significant changes in heart rate, mean arterial pressure, or right atrial pressure were observed during the 240-minute observation period.Conclusion:The novel liquid ventilator can adequately support gas exchange and maintain stable hemodynamics, allowing safe performance of total liquid ventilation in piglets. Part III Total liquid ventilation reduced lung inflammatory reaction in piglets after oleic acid—induced acute lung injuryObjective:To investigate the effect of total liquid ventilation on pulmonary inflammatory reaction in piglets after oleic acid-induced acute lung injury.Method:Acute lung injury was induced in twelve Chinese immature piglets by oleic acid. The animal were randomly divided into control group (received conventional mechanical ventilation)and study group(received total liquid ventilation with FC-770). Sample for blood gas analysis were collected before and after lung injury every 30 minute. After 240 minute of acute lung injury, the levels of interleukin-6(IL-6), interleukin-8(IL-8), myeloperoxidase(MPO) in plasma and tissue were measured. The right lung tissue was also taken for the pathological examination.Results:There is no significant changes in hemodynamics and pulmonary function in both groups at baseline. After OA administration, obviously hemodynamic changes in both groups were found. The PaO2 level were significantly improved in study group. The concentrations of IL-6, IL-8, MPO in plasma and tissue were significantly lower in study group than that in control group. The pathological examination demonstrated that in control group,there were hyperemia and haemorrhage in the capillary, obvious inflammatory exudate and neutrophils in alveoli. However the lung tissue examination of study group showed well-preserved alveolar structure with milder alveolar exudate and less neutrophil accumulation in alveoli.Conclusion:Total liquid Ventilation improves the pulmonary function obviously and provides protetive effects against inflammatory responses in the lung during oleic acid-induced lung injury period in immature piglets.