Proportion Assisted Ventilation In Newborn Rabbits With Severe Meconium Aaspiration Syndrome

Meconium aspiration syndrome (MAS) is a serious respiratory disease in newborn. About 30% infants with MAS require mechanical ventilation for survival. The common modes of MV in clinical application of MAS are conventional ventilation (SIMV, A/C), CPAP, high-frequency oscillatory ventilation (HFOV) and so on. SIMV was testified as a preferred mode of treating with severe MAS. Although they have the corresponding advantages, those modes of ventilation often result in different degrees of lung injury (ventilator associated lung injury, VALI) treating with MAS in clinical, and VALI aggratated the lung inflammation of infants with MAS.Proportional assist ventilation (PAV) developed as a new mode of mechanical ventilation in recent years. Related studys proved its good effect on treatment of neonatal acute respiratory distress syndrome and indicated its good prospects. Pulmonary compliance reduced and airway resistance increased when MAS occurred which exactly meet the conditions of appling PAV (elastic unloading and resistance unloading). However, its efficacy in MAS and change of physiological parameters have not been reported. Also, studies have not shown that PAV generated VALI when treated with MAS.Most studies of zoopery used pigs, rats and adult rabbits to prepare model of meconium aspiration. There is a certain difference in the simulation of neonatal meconium aspiration syndrome, and the unified standard has not yet been instituted that severe meconium aspirated model required mechanical ventilation .Therefore, we chose neonatal rabbits which closed to newborn in the development of lung, observed the impact of several concentrations of meconium suspension on rabbits, and to establish the appropriate rabbit model of severe meconium aspirated. The rabbits were enforced PAV and SIMV mode respectively. The physiological parameters and clinical indexes were recorded, and the therapeutic effects of PAV on MAS were observed. Detected lung pathology and pulmonary inflammatory indexes after 8 hours of ventilation, to determine the level of VALI caused by PAV, aimed to provide a new clinical treatment strategy and basis in MAS.Part 1 Model of Severe Meconium Aspiration Syndrome in Newborn RabbitsObjective: Investigate the effects of meconium suspensions on newborn rabbits, to establish a suitable model of meconium aspiration syndrome which needs to apply mechanical ventilation.Methods: Twentyfour newborn rabbits were randomly divided into four groups(six in each group): 25mg/ml group, 45mg/ml group, 65mg/ml group and the control group. Meconium suspensions were injected into the endotracheal tube by 4ml/kg while the control group injected equivalent saline. Mechanical ventilation when achieved the ventilation indications. Observed the mortality within 8 hours, blood gases, oxygenation index, lung tissue in general pathology and accounted lung injury score.Results: 25mg/ml group and the control group failed to meet within the indications for mechanical ventilation among the eight hours. 45mg/ml group were able to achieve the indications in the frist 0.5 hours, and less lung injury; 65mg/ml concentration group all reached the indications in the frist 0.5 hours, its lung pathology revealed severe lung injury, pulmonary consolidation and hemorrhage focus were larger, and the mortality rate were higher.Conclusion: 45mg/ml concentration group achieved the indications of mechanical ventilation in ideal time , the degree of the lung injury is appropriate.This group is suitable as a severe meconium aspiration syndrome model which can be applied in the research related to mechanical ventilation.Part 2 Parameters's Comparison of PAV and SIMV in Newborn Rabbits with Severe Meconium Aspiration SyndromeObjective:To observe the effects of PAV on the parameters compared SIMV when treated in newborn rabbits with severe meconium aspiration syndrome, and investigate the therapeutic effects of PAV in MAS.Methods:Thirty newborn Japanese big ear rabbits(20-30 days old, 300-500g) were randomly divided into 4 groups: (1) PAV group (PAV, n=8): treated by PAV after meconium inhaled; (2 ) SIMV group (SIMV, n=8): treated by SIMV after meconium inhaled; (3) MAS group (MAS, n=8): not ventilation but give continuous 65% oxygen inhalation after meconium inhaled; saline group (saline, n=6): give continuous 65% oxygen inhalation after saline inhaled. To induce lung injury, two doses of 2 mL/kg of saline or 45mg/ml meconium suspension were introduced deep into the trachea. After injection, each group were given 50% oxygen inhalation. A half hour later all rabbits were given the homologus mode of mechanical ventilation or continuous oxygen inhalation. Related parameters recorded were at before(0 point) and 0.5h after inhaled(0 ' point), and 1, 2, 3, 4, 5, 6, 7, 8h in ventilation, including heart rate, breathing rate, tidal volume, peak airway pressure and mean airway pressure. Detected arterial blood gas before and 0.5h after irrigation, 4h and 8h in ventilation, calculated oxygenation index (OI) and arterial/alveolar oxygen ratio (a/APO₂).Results:1. Arterial blood gas: PH values of PAV, SIMV and saline group were with 7.381±0.031-7.429±0.073 at each time point, there was no significant difference(p>0.05). PH values of MAS group at 4h, 8h time point were below 7.35. There was no significant difference in PaCO₂ at 0 time point(P>0.05). PaCO₂ of PAV, SIMV and saline group in 4h, 8h time points were in the normal range, compared at each time point showed no significant difference (P>0.05). PaCO₂ of MAS group at 4h, 8h time point were over 50mmHg. FiO₂ of PAV group and SIMV group range from 50% to 70%, the difference was no significant (P> 0.05). MAS group and the saline group FiO₂ were set to 65%. OI(PaO₂/FiO₂) values of PAV, SIMV and MAS group were lower after meconium inhalation, and reached the indication of ventilation, the differences among the three groups were no statistically significant(P>0.05). OI values of PAV group was similar to SIMV group at each time point, the difference was no statistically significant (P>0.05). MAS group's OI values were below 120mmHg after meconium inhalation. a/APO₂ values of PAV, SIMV and MAS group were lower after meconium inhalation, the differences among the three groups were no statistically significant(P>0.05). PAV group was similar to SIMV group at each time point, the difference was no statistically significant (P>0.05). MAS group's a/APO₂ values were fall-off after meconium inhalation, there were statistically significant between each time point (P<0.05).2. Parameter of respiratory mechanics: Tidal volume in PAV group and SIMV group was obviously decreased after meconium inhalation compared with perfusion, the difference was statistically significant(P<0.05). During the ventilation, SIMV group's tidal volume is higher than PAV group, but the two groups was no significant difference besides of 3h time point (P>0.05). During the ventilation, peak airway pressure and mean airway pressure in SIMV group were higher than PAV group, the differences at each time point were statistically significant (P<0.05). Each group showed an increase in respiratory rate(RR) after meconium inhalation, the differences in each group between 0 and 0'time point were statistically significant (P<0.05). SIMV's RR decreased slightly in ventilation. PAV group's RR reached peak at 3h time point, then gradually decreased, and similar to SIMV group at the end of the experiment, the difference was no statistically significant (P>0.05). MAS group's RR were higher than other groups throughout the 8 hours(P<0.05).3. Heart rate(HR): Each group showed an increase in HR after meconium inhalation, the differences in each group between 0 and 0' time point were statistically significant (P<0.05). HR of each group at 0 and 0' time point were no statistically significant (P>0.05). HR in PAV group, SIMV group and MAS group were similar, the differences were not statistically significant at each time point (P<0.05). The three groups changed a little at each time point, the difference were not statistically significant (P>0.05), but until the end of the experiment, the HR in three groups were still exceeded 170/min. HR of saline group decreased, but was still higher than baseline at the end of the experiment, the difference was statistically significant (P<0.05).Conclusion:1. PAV improved oxygenation state of lung in rabbits with severe meconium aspiration syndrome effectively in a short term, maintained ventilated function of lungs.2. Comparing with SIMV, PAV had lower peak airway pressure and mean airway pressure when treated in rabbits with severe meconium aspiration syndrome.3. PAV had little influence on heart rate of the rabbits with severe meconium aspiration syndrome. 4. PAV can reduce the compensatory rapid shallow breathing caused by ventilation dysfunction.Part 3 Ventilator Associated Lung Injury's Comparison of PAV and SIMV in Newborn Rabbits with Severe Meconium Aspiration SyndromeObjective: To investigate the differences of Ventilator associated lung injury between PAV and SIMV treated in newborn rabbits with severe meconium aspiration syndrome.Methods: The animals were sacrificed after 8 hours continuous ventilation or oxygen inhalation, accounted wet/dry weight ratio, enzyme-linked immunosorbent assay (ELISA) to detect TNF-α, IL-8 in the lung tissue and bronchoalveolar lavage fluid(BALF). Histological lung injury was observed and scored.Results:1. Pathology of lung tissue: In addition to the saline group, each group has the phenomenon of uneven alveolar ventilation, alveolar septum edema and widened, with inflammatory cell infiltration in diffuse pulmonary interstitial and visible meconium particles in small bronchial. PAV group and SIMV group's lung injury score was statistically significant(P<0.05), PAV group's scores was lower than MAS group and SIMV group(P<0.05), and no significant difference between MAS group and SIMV group(P= 0.093), the three groups compared with the saline group was statistically significant (P= 0.00).2. Lung wet/dry weight ratio: PAV group was lower than other meconium inhalation groups(P<0.05), the difference between SIMV group and MAS group was not statistically significant (P>0.05). 3. TNF-α,IL-8 in lung tissue and BALF: TNF-α,IL-8 in meconium application groups's lung tissue and BALF were higher than saline group(P<0.05). Compared with SIMV and MAS group, TNF-α, IL-8 content in PAV group's lung tissue and BALF was lower, the difference was statistically significant (P<0.05).The difference between SIMV group and MAS group was no statistically significant (P>0.05).Conclusion:1. Meconium led to over release of inflammatory cytokines, resulted in accute lung injury.2. Compared with SIMV, PAV maintained the normal structure of lungs in the treatment of rabbits with severe meconium aspiration syndrome, and less likely to formate lung bullae.3. Compared with SIMV, PAV reduced the release of inflammatory cytokines, caused to lower ventilator associated lung injury.