Experimental Study Of High Frequency Oscillatory Ventilation Combined With Pulmonary Surfactant For The Treatment Of Inhalation Injury

Inhalation injury is a so complicated disease with high morality and mortality and need to be supported with ventilator once accompanied by acute respiratory failure or acute respiratory distress syndrome. Conventional mandatory ventilation could cause ventilator-induced lung injury while used for respiratory support and could accentuate original pulmonary pathyological injury. So reducing the ventilator- induced lung injury and finding a better respiratory support method for inhalation injury have a very important significance.Thirty-seven New Zealand rabbits were randomly divided into five groups and severe inhalation injury model accompanied by acute respiratory failure was established through intratracheal steam inhalation. Then they were ventilated by CMV,HFOV,CMV+PS or HFOV+PS,respectively. The control group did not receive mechanical ventilation after recovery from anaesthesia and muscle relax. Femoral arterial blood samples were obtained respectively at 0.5,1.5,2.5,3.5h treatment timepoints for blood gas examination. At 0.5,1.5,2.5,3.5h treatment timepoints, respiratory mechanics and hemodynamic parameters were tested and recorded. After the animals were euthanized at 3.5h treatment timepoint, for assessment of inflammation of lung tissue, the right middle lobe of rabbit lung was excised for the examination of mRNA expression of TNF-α, IL-18, IL-10, IL-13 and their values by the method of enzyme linked immunosorbent assay (ELISA) and Real-Time PCR respectively. Partial excised lung tissue was used for pathological assessment and myeloperoxidease (MPO),cysteinyl aspartate-specific protease(caspase-1)activity analysis. For assessment of apoptosis of pulmonary cells, the right middle lobe of rabbit lung was excised for the examination of the contents and mRNA expression of caspase-3 and p73 by the method of Real-Time PCR and colorimetric assay and western blot respectively respectively. For assessment of the effect of HFOV and CMV on heart, MLC-ATPase and MLCK were tested by the method of biochemistry andγ-32P incorporate. Results 1. blood gas analysis (A) PaO2 in the five groups all decreased below 60mmHg and PaO2 of postinjury had statistical significance comparing with pre-injury at the same group(P<0.01), Between-group comparison of PaO2 at postinjury and pre-injury showd no statistical significance(P>0.05). (B) OI in the HFOV and HFOV+PS groups were lower than the corresponding data in CMV and CMV+PS groups respectively (P<0.01). OI in the CMV+PS group at 1.5h treatment timepoint and OI in HFOV+PS group at 1.5h and 2.5h treatment timepoints showed significant decreases over the data in the corresponding non-PS groups at the same timepoints (P<0.05).At the 1.5h of HFOV groups and at the 1.5h,2.5h of HFOV+PS groups, OI were lower than the corresponding values of postinjury (P<0.05). (C) P(A-a)O2 in the HFOV and HFOV+PS groups were lower than the corresponding data in the CMV and CMV+PS groups (P<0.05), P(A-a)O2 in the two groups with PS at 1.5h,2.5h and 3.5h treatment timepoints were statistically lower than those in the two corresponding groups without PS (P<0.05). 2. Respiratory mechanics and hemodynamic parameters: (A) The dynamic compliance of respiratory system were higher and airway resistence of respiratory system were lower at the time points of 1.5h and 2.5 in the HFOV groups than the values of corresponding timepoints in the CMV groups(P<0.01). (B) there were no obvious differences in circulatory function (P>0.05). 3. Inflammation of lung tissue: (A) The contents of TNF-α, IL-18 and their mRNA expression in lung tissue homogenates in HFOV group and HFOV +PS group were lower than them in CMV group and CMV +PS group respectively, and the contents of IL-10, IL-13 and their mRNA expression in lung tissue homogenates in HFOV group and HFOV +PS group were higher than them in CMV group and CMV+PS group respectively(p<0.01); the contents of TNF-α, IL-18 and their mRNA expression in lung tissue homogenates were lower , the contents of IL-10, IL-13 and their mRNA expression in lung tissue homogenates were higher in the two group with exogenous PS than them in the two corresponding groups without exogenous PS(p<0.05). (B) The MPO,caspase-1 activity and lung tissue injury scores in HFOV group and HFOV +PS group were lower than them in CMV group and CMV +PS group respectively(p<0.01), and the MPO,caspase-1 activity and lung tissue injury scores were lower in the two group with exogenous PS than them in the two corresponding groups without exogenous PS in the HFOV +PS group(p<0.05). 4. Apoptosis of pulmonary cell: Caspase-3, p73 mRNA expression in lung tissue in HFOV group and HFOV +PS group were lower than them in CMV group and CMV +PS group respectively(P<0.01), and caspase-3 , p73 mRNA expression in lung tissue in groups with exogenous PS group were lower than corresponding one without exogenous PS (P<0.05). Contents of caspase-3 and p73 in lung tissue homogenates and lung tissue apoptosis index in HFOV group and HFOV +PS group were lower than them in CMV group and CMV +PS group(P<0.01), and also contents of caspase-3 and p73 in lung tissue homogenates and lung tissue apoptosis index in groups with exogenous PS were lower than them in groups without exogenous PS(P<0.05). 5. MLC phosphorylation system in myocardium: the effects of HFOV on Activities of MLC-ATPase and MLCK in myocardium were lesser than CMV. Conclusion: HFOV combined with exogenous PS can improve arterial oxygenation,alleviate inflammatory injury and pulmonary apoptosis,and also showed lesser effects on MLC phosphorylation system than CMV , which may be a optimal method for the treatment of acute respiratory failure caused by inhalation injury.