Effects Of High Frequency Oscillatory Ventilation Combined With Incremental Positive End-expiratory Pressure On Myocardial Ischemia And Cardiomyocyte Apoptosis Of Dogs With Smoke Inhalation Injury

Objective:To study the effects of high frequency oscillatory ventilation combined with incremental positive end-expiratory pressure on cardiomyocyte apoptosis and myocardial ischemia of dogs with smoke inhaltion injury and to research the possible mechanism.Method:1.Building the model of inhalation injury:12local and healthy male dogs were randomly divided into HFOV group and HFOV+IP group according to the random number table,with6dogs in each group.Anesthetized dogs were inserted endotracheal tube.Then they received conventional mechanical ventilation (FIO20.21,Vt15ml/kg,I:E1:2,R=18/min) and inhaled smoke accroding to the method designed by The Third Military Medical University.2.Ventilating mode:After modeling, dogs in HFOV group received high frequency oscillatory ventilation.Ventilator settings:FiO21.0,VT15ml/kg,I:E1:2,RR20Hz,MAP10cmH2O,△P4Mpa,PEEP0cmH2O.Dogs in HFOV+IP group were applied to HFOV for30minutes.Then increased the PEEP gradually by5cmH2O each time from0cmH2O until it reached25cmH2O.After that,reduced the PEEP gradually by5cmH2O every5minutes,and then dogs went on with HFOV instead for0.5hour followed by repeated experiment cycle. Ventilating time lasting8hours.3.The hemodynamic parameters and blood gas analysis results of the injured dogs were recorded. TNF-a and IL-10in myocardium and cardiomyocyte apoptosis rate were observed.Myocardical tissue of all dogs were obtained for histopathological observation and immunohistochemistry of HHF35.Results:(1)Blood gas analysis:pH,PaO2and PaCO2had no differences before injury between the two groups.The PaO2levels in these two groups significantly decreased immediately after injury(P<0.05),while no obvious changes in the pH value and PaCO2levels were observed immediately after injury.The PaCO2level in both groups significantly increased after treatment.At PVH2,4and8, PaCO2level in HFOV+IP group were significantly higher when compared with HFOV group(P<0.05).No statistically significant differences were observed in pH value and PaCO2level at each time point between the two groups(P>0.05).(2) Hemodynamic parameters:HR,MAP and CO had no differences before injury between the two groups.At PVH4,6and8,CO value in HFOV+IP group were significantly decreased,compared with those observed immediately after injury (P<0.05). At PVH4,6and8,CO value in HFOV+IP group were significantly lower than HFOV group(P<0.05),while HR levels in HFOV+IP group were considerably higher than HFOV group(P<0.05).(3)Tumor necrosis factor-α and interleukin-10in myocardium:The concentration of TNF-α in myocardium decreased significantly in HFOV+IP group when compared with HFOV group(P<0.05),while the concentration of IL-10in HFOV+IP group were dramaticlly higher than HFOV group(P<0.05).(4) Cardiomyocyte apoptosis:Cardiomyocyte apoptosis rate in HFOV+IP group were significantly decreased after treatment compared with those observed in HFOV group(P<0.05),and there was a positive correlation between the changes of TNF-α and cardiomyocyte apoptosis rate (r=0.677, P<0.05).(5) Immunohistochemistry of HHF35:The staining intensity of actin in HFOV+IP group was significantly deeper than that in HFOV group,and the IOD value of Immunohistochemistry in HFOV+IP group were considerably higher than those observed in HFOV group(P<0.05).(6)Pathological examination:Myocardium anoxia were found in HFOV group.The change occurred less in HFOV+IP group.Conclusion:HFOV combined with IP can not only improve pulmonary gas exchange,but also alleviate the inflammatory reaction in myocardium and reduce cardiomyocyte apoptosis rate.Additionally,the myocardial ischemia was also alleviated.We guessed the mechanism was based on the improvement of pulmonary oxygenation.