Experimental Study Of Perfluorocarbon Partial Liquid Ventilation In Rabbits With Acute Lung Injury

Background: Acute lung injury (ALI) can result from either a primary pulmonary process or a systemic insult. ALI is characterized by increased capillary permeability, interstitial and alveolar edema, influx of circulating inflammatory cells, formation of hyaline membranes and severity disproportion of ventilate/blood flow. Studies of animal models of ALI have confirmed that the marked increase in the number of activated neutrophils migrating into the lung plays a key role in the lung injury that develops after the initiating lung insult. Notably, interlukin-1β(IL-1β) and vascular endothelial growth factor (VEGF) are the proinflammatory factor during ALI, and they can be used as the early monitor markers in the development of ALI. Partial liquid ventilation with perfluorocarbon (PFC) has been advocated as a new therapy for ALI in both clinical and animal studies. PFC with High frequency oscillatory ventilation reportedly improves pulmonary mechanics and gas exchange, vascular leakage, and attenuates lung injury. To investigate the efficacy of high frequency oscillation with PFC in rabbits with ALI and the possible roles of interlukin-1β(IL-1β), vascular endothelial growth factor (VEGF) in the lung injury induced by mechanical ventilation, we utilized a previously validated rabbits model that closely replicates many of the physiological and biological aspects of human ALI.Objective: To examine the efficiency of high frequency oscillation with PFC in rabbits with acute lung injury (ALI).And the possible roles of interlukin-1β(IL-1β), vascular endothelial growth factor(VEGF) in the lung injury induced .Methods: Heating the water by the pressure cooker and using the steam as a generate source. Preheating the pipe repeatedly and connecting the pipe with the endotracheal catheter when the steam pressure reached 0.125kgf/cm2 and the temperature was 107℃in the pressure cooker, then releasing the steam to the lung in 2 second. The animal model with ALI was considered to be establishment when the arterial oxygen tension (PaO2) was decreased below 60 mmHg.After steam inhalation lung injury, thirty adult New Zealand white rabbits(male and female, weighing2100~2750g) were randomized into three groups and were rescued with mechanical ventilation :high frequency oscillatory ventilation (HFOV, n=10), conventional mechanical ventilation group (CMV, n=10) and PFC with High frequency oscillatory ventilation (PFC + HFOV, n=10).Conventional mechanical ventilation (CMV) group: In this group, the ventilate strategy was controlled respiration. Ten rabbits were mechanically ventilated with a SLE5000 ventilator in a volume-cycled mode with the following settings: tidal volume 12 ml/kg, respiratory frequency 30 times/min, inspiratory-to-expiratory (I:E) ratio 1:1, inspired oxygen fraction (FiO2) 60%.High frequency oscillatory ventilation (HFOV) group: In this group, the ventilate strategy was changed to HFOV mode with the following settings: frequency 10 HZ, mean airway pressure(MAP) was increased 4cm H2O than CMV group(1 cmH2O = 0.098 kPa), amplitude of vibration(ΔP) 30cm H2O, inspiratory-to- expiratory (I:E) ratio 1:1, inspired oxygen fraction (FiO2) 60%.High frequency oscillatory ventilation with PFC (HFOV +PFC) group: In this group, the ventilate mode was just like HFOV group. The PFC was treated with 6ml/Kg through the endotracheal catheter, and changes the animal's position to make the PFC distributed uniformity at any time.All rabbits were ventilated for two hours. Blood gases were measured and calculated at before treatment, after ALI, ventilating 30, 60, and 120minutes during the experiment. The contents of IL-1β, VEGF were measured at the end of the study. Results: After ALI established, PaO2 in the three groups decreased below 60 mmHg ( P <0.01) , and inter-group differences were not found.PaO2 in the three treatment groups had increased since half an hour after treatment and sustained at favorite levels during treatment period. PaO2 in the HFOV + PFC groups were higher than those in CMV groups (P <0.05) . HFOV + PFC improved oxygenation and ventilation more rapidly than HFOV did. The contents of IL-1β,VEGF in BALF and blood of HOFV + PFC group were significantly lower than CMV and HFOV group (P <0.05).Conclusion: Partial liquid ventilation with perfluorocarbon was effective in achieving adequate oxygenation, decreasing lung edema, reducing the infiltration of inflammatory cells significantly, decreasing the levels of IL-1β, VEGF both in BALF and serum, with a reduction in further lung injury in ALI therapy. Additionally, in this study, we used low does PFC, it will be evaporated along with the lasting of time, so monitoring PFC evaporative loss appears necessary to stabilized intrapulmonary PFC volume.