Experimental Study Of High Frequency Oscillatory Ventilation Combined With Partial Liquid Ventilation For The Treatment Of Inhalation Injury

Inhalation injury with respiratory failure or acute lung injury has high morality, need to be supported with ventilator .Conventional mandatory ventilation could cause ventilator-induced lung injury and could deteriorate pulmonary injury. As the protective lung ventilation strategy, high frequency oscillatory ventilation (HFOV) and partial liquid ventilation have important significance. Methods Thirty-two New Zealand rabbits were randomly divided into four groups after acute respiratory failure models caused by severe steam inhalation injury were established. Then they were ventilated by CMV,HFOV,CMV+PLV or HFOV+PLV,respectively. Femoral arterial blood samples were obtained respectively at 0.5,1.5,2.5,3.5h treatment timepoints for blood gas examination. respiratory mechanics and hemodynamic parameters were recorded. After the experimental period,the lowest lobe of the right lung was weighed for calculating weight ratio of lung water and lung tissue [(W-D)/W] , the middle lobe in the right lung were excised for histological sections. The right middle lobe of rabbit was excised for the examination of mRNA expression of E-selectin, P-selectin,ICAM-1 and ET-1 and their contents by the method of RT-PCR ( reverse transcription polymerase chain reaction ) and enzyme linked immunosorbent assay (ELISA) respectively. Partial excised lung tissue was used for pathological assessment and histological sections. The middle lobe in the right lung were excised for examination of mRNA expression of caspase-3 by the method of Real Time PCR (real time polymerase chain reaction ). Caspase-3 contents in lung tissue homogenates was examined by the method of colorimetric assay. Apoptosis indexes in the lung tissue were assessed with TUNEL FragELTM(Fragment End Labeling). Each one underwent whole-lung lavage. Cells were removed from bronchoalveolar lavage fluid (BALF) by low-speed centrifugation, and the resulting pellets were analyzed for total cell﹑differential counts and apoptosis analysis . Total white-cell numbers were determined by manual counting. Cell-free lavage fluid was processed for total protein (TP) and malondialdehyde (MDA) determinations. Results 1.(A) PaO2 in the four groups all decreased below 60mmHg and PaO2 of postinjury had statistical significance compared with pre-injury at the same group(P<0.01). PaO2 of postinjury and pre-injury between-group comparison showed no significance(P>0.05). (B) PaO2 in the four groups had increased since 0.5h treatment timepont,and values of PaO2 sustained continuously within 3.5 h treatment time. PaO2,PaO2/FiO2 in the HFOV and HFOV+PLV groups were higher than the corresponding data in CMV and CMV+PLV groups respectively (P<0.05, P<0.01). PaO2 in the CMV+PLV group at 1.5h and 2.5h treatment timepoint and PaO2 in HFOV+PLV group at 3.5h treatment timepoints showed significant advantages over the data in the corresponding non-PLV groups at the same timepoints (P<0.05, P<0.01). (C) Histological injury score found the HFOV groups were more alleviated than the CMV group,the lowest in the HFOV+PLV group and the highest in the CMV group. 2. (A) The contents of E-selectin,P-selectin, ICAM-1 and their mRNA expression in lung tissue homogenates in HFOV group, HFOV+PLV group were lower than them in CMV group ,CMV+PLV group respectively, and their comparison showed statistical significance(p<0.01). The contents of E-selectin, P-selectin, ICAM-1 and their mRNA expression in lung tissue homogenates in HFOV group, CMV group were higher than them in HFOV+PLV group , CMV+PLV group respectively , and their comparison showed statistical significance (p<0.01). The contents of ET-1 and mRNA expression in lung tissue homogenates in HFOV, HFOV+PLV, CMV, CMV+PLV showed no statistical significance (P>0.05). (B) Histological injury found the HFOV groups were more alleviated than the CMV group,the lowest in the HFOV+PLV group and the highest in the CMV group. 3. (A) Lung tissue apoptosis indexes in HFOV group and HFOV+PLV group were lower than them in CMV group and CMV+PLV group , between-group comparison had significant difference(P<0.01). HFOV+PLV group showed lowest apoptosis indexes.(B) caspase-3 and caspase-3 mRNA expression in the lung tissue in HFOV group and HFOV+PLV group were lower than them in CMV group and CMV+PLV group (P<0.01). caspase-3 and caspase-3 mRNA expression in the lung tissue in CMV+PLV group and HFOV+PLV group were lower than them in CMV group and HFOV group (P<0.05). 4. (A)in the CMV group ,the number of total and polymorphonuclear cell was obviously increased compared with other group( P<0.01) , HFOV+PLV have the lowest total and polymorphonuclear cell number .polymorphonuclear cell number in the CMV+PLV and HFOV+PLV groups comparison showed significance( P>0.05). (B) polymorphonuclear cell apoptosis in HFOV+PLV group were higher than other group, There was significant difference when compared with CMV,HFOV or CMV+PLV group. CMV group have the lowest polymorphonuclear cell apoptosis, There was no significant difference between CMV and CMV+PLV group. Conclusion high frequency oscillatory ventilation ; combined with partial liquid ventilation can improve arterial oxygenation; decreased the concentration and mRNA expression of E-selectin, P-selectin, ICAM-1 ;suppress lung tissue apoptosis induced by inhalation injury ,reduced the caspase-3 concentration and mRNA expression ;HFOV combined with PLV can increase polymorphonuclear cell apoptosis,alleviate polymorphonuclear cell infiltration in inhalation lung injury , reduce lung injury.high frequency oscillatory ventilation combined with partial liquid ventilation may be a optimal method for the treatment of acute respiratory failure caused by inhalation injury .