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Aminophylline Treatment in Young Rabbits with Severe Meconium Aspiration Syndrome

Author: ZhanFeng
Tutor: HuBo
School: Anhui Medical University,
Course: Pediatrics
Keywords: aminophylline synchronized intermittent mandatory ventilation meconium aspiration syndrome ventilator associated lung injury tumor necrosis factor-α interleukin -8
CLC: S858.291
Type: Master's thesis
Year: 2011
Downloads: 6
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Abstract


ObjectiveMeconium aspiration syndrome (MAS) is the symptom of respiratory distress caused by severe fetal distress, fetal inhaled meconium-stained amniotic fluid when being in the womb or during delivery. 5% -15% of newborns may have meconium-stained amniotic fluid when born, and 5% of neonates have meconium aspiration pneumonia, it is common in term infant and post-term infant. The incidence rate in domestic reports is 1.2% -2.2% of live births. In recent years, although perinatal medicine has made significant progress, morbidity and mortality of MAS remains high, and there is no simple, effective and reliable preventive measures and specific treatment at present. The treatments of Meconium aspiration syndrome include meconium suction, oxygen therapy, mechanical ventilation, drug treatment and membrane lung. Recent studies indicated that systemic or intratracheal methylxanthines can improve lung function in meconium aspiration pneumonia. Aminophylline is a methylxanthine derivative. The experiment selected the newborn rabbits which the degree of lung development close to neonatal lung, established the model of severe meconium aspiration syndrome, and applied aminophylline in young rabbits with severe meconium aspiration, then recorded physiological parameters and clinical indicators, tested lung pathology and levels of TNF-αand IL-8 which is the indexs of pulmonary inflammatory after 5 hours of ventilation. We observed the effects of aminophylline on the indicators and treatments of MAS, to provide new treatment strategies and basis for the clinical therapy in MAS.Methods Thirty young Japanese big ear rabbits(20-30 days old, 300-500g) were randomly divided into 4 groups:(1) Amin group (MAS + SIMV + Aminophylline, n = 6): treated by synchronized intermittent mandatory ventilation and aminophylline after meconium instillation;(2) SIMV group (MAS + SIMV, n = 6): treated by synchronized intermittent mandatory ventilation but no aminophylline after meconium instillation;(3) MAS group (MAS, n = 6): not ventilation but give continuous 65% oxygen inhalation after meconium instillation;(4) Saline (Saline, n = 6): give continuous 65% oxygen inhalation after saline instillation.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. All rabbits were given mechanical ventilation or continuous oxygen inhalation after 0.5h. The animals in Amin group received intravenously two doses of aminophylline (2.0mg/kg each) 0.5 h and 2.5 h after meconium instillation. Aminophylline was diluted to 1:10 with saline, and slowly injected in 5 minutes. Related parameters recorded were at before(0 point) and 0.5h after instillation(0′point), and 1, 2, 3, 4, 5h 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, 1h, 3h and 5h in ventilation, calculated oxygenation index (OI) and arterial/alveolar oxygen ratio (a/APO2). The animals were sacrificed after 6 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. Arterial blood gas:(1) PH: PH values of Amin, SIMV and Saline group were with 7.35-7.45 at each time point, PH values of MAS group at 1h, 3h, 5h time point were below 7.35.(2) PaCO2: PaCO2 at 0 time point in each group were between 40.00±3.79 mmHg to 41.00±2.76mmHg. PaCO2 in Amin and SIMV group after meconium instillation. PaCO2 in MAS group at 1h, 3h, 5h time point were 62.17±8.01, 67.50±7.29 and 62.33±5.89 mmHg respectively. PaCO2 in Saline group after meconium instillation were in the normal range.(3) FiO2: FiO2 in Amin group and SIMV group were ranged from 50% to 70%, the difference was no significant (P> 0.05). FiO2 in MAS group and Saline group were set to 65%. There were no statistically significant with the ventilation groups(P> 0.05).(4) OI: before mechanical ventilation:OI1=PaO2/FiO2(normal values 400-500mmHg)After mechanical ventilation:OI2= MAP*FiO2*100/PaO2(normal values<5) The differences between OI2 values in Amin and SIMV group at 1h, 3h, 5h time points were all statistically significant (P<0.05) after mechanical ventilation. Values of OI1 in the four groups is between 384.13±33.22 mmHg to 399.21±36.81 mmHg. OI1 in Amin, SIMV and MAS group dropped to below 200 mmHg after meconium instillation.OI1 values in MAS group were 384.13±33.22 mmHg,384.13±33.22 mmHg,75.38±7.28 mmHg,78.21±7.5 mmHg 0,71.54±7.46 mmHg at 0h,0′h,1h, 3h and 5h time points. OI1 in Saline group were between 289.49±5.71 to 335.90±6.13 mmHg and increased gradually after oxygen inhaled, there were statistically significant differences among the three time points (P <0.05).(5) a/APO2: Values of a/APO2 in the four groups is between 0.82±0.08 to 0.85±0.09. a/APO2 in PAV, SIMV and MAS group decreased obviously after meconium instillation(P <0.05). a/APO2 in Amin group at 1h, 3h and 5h time points ascented gradually, and all higher than 0’time pionts(P <0.05). The differences among the three time points were no statistically significant(P>0.05). a/APO2 in SIMV group at 1h, 3h and 5h time points were similar(P>0.05), but all higher than 0’time pionts(P <0.05). The differences between a/APO2 in Amin and SIMV group at 1h, 3h, 5h time points were all statistically significant (P<0.05). MAS group’s a/APO2 values were declined gradually after meconium instillation, but there were no statistically significant among 1h, 3h and 5h time points (P<0.05). OI in Saline group were increased gradually during oxygen inhalation, there were statistically significant differences among the three time points (P <0.05).2. Parameters of respiratory mechanics:(1)Tidal volume(VT): VT in Amin group and SIMV group were 14.17±0.75ml/kg and 14.08±1.04ml/kg, descented to 6.50±1.05ml/kg and 6.33±0.66ml/kg at 0′time piont respectively. VT in the two groups were obviously decreased after meconium instillation 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).(2) Peak airway pressure(PIP) and mean airway pressure(MAP): During the ventilation, peak airway pressure in Amin group were lower than SIMV group, the differences at each time point were statistically significant (P<0.05). Mean airway pressure in Amin group were lower than SIMV group, the differences at 1h, 4h time point were statistically significant (P<0.05), the differences at 2h, 3h time point had no statistically significant (P>0.05).(3) Respiratory rate(RR): 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). RR in Amin and SIMV group decreased slightly in ventilation, the difference between the two groups was no statistically significant (P>0.05). MAS group’s RR were higher than other groups throughout the 8 hours(P<0.05). RR in Saline group also increased after instillation, and lower than other groups decreased(P<0.05), and still higher than baseline at the end of the experiment, the difference was statistically significant (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). The differences among the four groups 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). HR in Saline group decreased, but was still higher than baseline at the end of the experiment, the difference was statistically significant (P<0.05).4. Pathology of lung tissueIn 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. The difference between Amin group and SIMV group’s lung injury score was statistically significant(P<0.05), there was no significant difference between MAS group and Amin group(P>0.05).5. Lung wet/dry weight ratio(W/D)W/D in Amin group was lower than other meconium inhalation groups(P<0.05), W/D in meconium application groups were higher than saline group(P<0.05).The difference between Amin group and MAS group was not statistically significant (P>0.05).6. TNF-α,IL-8 in lung tissue and BALF TNF-α,IL-8 in Amin group’s lung tissue and BALF is lower than those in SIMV group, The difference was statistically significant (P<0.05). 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 Amin group’s lung tissue and BALF was lower, the difference was statistically significant (P<0.05).Conclusions:1. Meconium led to over release of inflammatory cytokines, resulted in accute lung injury.2. Aminophylline treatment helped mechanical ventilation improving the state of lung oxygenation effectively in rabbits with severe meconium aspiration syndrome.3. Aminophylline treatment reduced the peak airway pressure and mean airway pressure as treatment of rabbit when treated in rabbits with severe meconium aspiration syndrome.4. Aminophylline treatment had little influence on heart rate of the rabbits with severe meconium aspiration syndrome.5.Compared with not applied aminophylline, aminophylline treatment maintained the normal structure of lungs in the treatment of rabbits with severe meconium aspiration syndrome, and less likely to formate lung leak and lung bullae.6. Aminophylline reduced the release of inflammatory cytokines which caused to lower ventilator associated lung injury.7. Mechanical ventilation increased the release of inflammatory cytokines which causing ventilator associated lung injury.

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CLC: > Agricultural Sciences > Livestock, animal medicine,hunting,silkworm,bee > Animal Medicine ( Veterinary Medicine) > Livestock, poultry, wildlife diseases > Livestock > Rabbit
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