Effect Of Inhaled Low-dose Nitrice Oxide On Antioxidant Capacity Of Meconium Aspiration Syndrome Newborns

Objective: Meconium aspiration syndrome (MAS) remaines a relevant cause of neonatal respiratory failure and was characterized by severe impairment of pulmonary gas exchange, and pronounced inflammatory changes. The aspirated meconium cause severe inflammatory reaction in lung, and inflammatory cell infiltration play an important role in the MAS process. Recently research indicated that meconium can rapidly activate neutrophil with the resulting oxidative burst, produced considerable oxygen radical. Oxygen radical and lipid peroxidation damage taked part in the mechanism of meconium-induced lung injury. There were many researches about the therapy of inhaled nitric oxide for MAS-induced PPHN (persistent pulmonary hypertension of the newborn) at present. But the exact pathophysiology mechanism of MAS was not fully understood. Our experiment was aimed to observe the change of superoxide dismutase (SOD) activity, concentration of malondialdehyde-MDA (one of the lipid peroxidation products) and total antioxidant capacity(T-AOC) in serum to learn that whether there was an imbalance of oxidant /antioxidant in the MAS newborn, and inhaled nitric oxide (iNO) whether benefit for the modulation of oxidant/antioxidant balance. Expected our study may provided theoretical knowledge and laboratory evidence to give MAS newborns iNO early.Methods: This prospective study included 55 MAS newborns (include two groups, group A was the mechanical ventilation newborns, group B was the mechanical ventilation +iNO newborns ) as cases and a group of 30 matched healthy newborns formed the control, and the newborns of group A and B were diagnosed in department of neonate of Hebei Province Children Hospital and treated from 2005.2 to 2006.12, group C was the newborn who were born at the same time in department of gynaecology and obstetrics of Hebei Province Children Hospital. All the study objects'age when enrolled in the experiment was≤24 hours, gestational age among 37-43weeks(group C among 37-42weeks), birth weight 2500-4000g. Group A (n=30) was the MAS newborns who were given mechanical ventilation but not iNO. Group B (n=25) was the MAS newborns who were given both mechanical ventilation and iNO. Both group A and group B were consistent with the MAS diagnostic criteria , and except hyperbilirubinemia, mother-baby blood type incompatibility (ABO and/or RH blood group system), congenital broncho- pulmonary dysplasia, congenital diaphragmatic hernia and congenital heart disease, all of them were given tracheal intubation, irrigation of trachea, mechanical ventilation by STEPHAN baby ventilator with SIMV mode, and intravenous drip antibiotics and keep water-electrolyte balance, et al. None of them were given benzazoline or magnesium sulfate and other medicine that could induce relaxing of pneumoangiogram. In addition, the newborns of group B were given a low-dose nitric oxide when their legal guardian given consent,NO and nitrogen dioxide(NO2) were continuously monitored at the Y-pipe with electrochemical cells (NOxBOX Plus, Bedfont Scientific, England). Group C (n=30) was the normal control group, no evidence of disease, negation of amniotic fluid break early, the mother have a fever or other infectious disease duration of pregnancy or antepartum, hyperbilirubinemia, mother-baby blood type incompatibility (ABO and/or RH blood group system), amniotic fluid stain, amniotic fluid inhaled, asphyxia, inborn dysplasia. For group A, one blood sample (1.5ml) was withdrawn before mechanical ventilation or primarily after mechanical ventilation (0 hour), the second and third sample (1.5ml) was drawn twenty-four and seventy-two hours later, after mechanical ventilation (24 ,72 hour). For group B, one blood sample (1.5ml) was withdrawn before iNO (0 hour), the second and third sample was drawn twenty-four and seventy-two hours later, after iNO (24 ,72 hour). For group C, blood sample (1.5ml) was withdrawn three times, corresponding to group A and group B. Given the blood 3000r for ten minutes and separate 0.4ml serum stored at -30℃refrigerator for subsequent analysis after hemopexis. In this clinical study, we determine the superoxide dismutase activity, malonaldehyde concentration and total antioxidant capacity. All of the tests were measured according to the manufacture's instructions. The statistical analysis was done by SPSS 11.5 software.Result1 There was no statistical difference among the three groups for gestational age, birth weight, postnatal age, delivery mode and sex distribution (P>0.05).2 The time of mechanical ventilation of group A, B was 104.27±10.53h, 77.38±13.97h, group B was more lower than group A, there was significantly statistical difference between them(P<0.05).3 There was no statistical difference between group A and group B of OI and PAP at 0 hour, with the NO inhaled and time went on , the OI and PAP reduced, the change of group B was much more than group A, and there was significant difference(P< 0.05). Simultaneously, the right-to-left shunt decreased obviously, substituted with bidirectional shunt or left-to-right shunt. Among two groups, the shunt was disappeared of six newborns. The average time of iNO was (31.42±13.51) h.4 Comparison of prognosis and turnover indicated that there were no statistical difference of mortality, and incidence rate of frequent hemorrhoid, pneumonorrhagia, ICH(Ⅱ-Ⅳ)between groupA and groupB.5 The SOD activity of group A at 24 hour was lower than the 0 hour, but the change of MDA concentration and T-AOC was opposite to SOD, and there was significant statistical difference (P<0.05). At 72 hour, the SOD and T-AOC showed the tendency of increasing, but the MDA was cut down, and there was significant statistical difference (P<0.05).6 The SOD activity and T-AOC of group B at 24 hour were increased compared with the 0 hour, after statistical analysis, there was significant difference (P<0.05); the change of MDA concentration showed a degrade tendency, but there was no significant difference(P>0.05). At 72 hour, the SOD and T-AOC were increased, but the MDA was decreased, and there was significant statistical difference (P<0.05).7 The SOD and T-AOC of group C at 24 hour were increased significantly compared with the 0 hour, but the change of MDA concentration was opposite to them, and there was significant difference (P<0.05). At 72 hour, the change of SOD,MDA and T-AOC were in coincidence with the 24 hour, and there was significant difference.8 There was no significant difference of SOD activity, MDA concentration and T-AOC between group A and group B at the 0 hour, but there was significantly difference with group C. With the time changed, the SOD,T-AOC of the three groups showed an increased tendency, the MDA was opposite to them, but at the same time , the SOD, T-AOC of group A and B was lower than group C, the MDA of them was higher than group C, and there was significant statistical difference (P<0.05).Conclusion 1 Low-dose iNO could selectively expanding pneumoangio -gram, improving ventilation/perfusion ratio, reducing shunt of lung, decrease pulmonary arterial pressur, thus to shorten time of mechanical ventilationand improve oxygenation condition. 2 Inhaled NO would not increase incidence rate of major concurrent disease such as frequent hemorrhoid, pneumonorrhagia, ICH, and there was no significant decrease of the mortality rate. 3 The pathogenesy of MAS was complicated, the metabolism abnormality of oxygen radical may be a major factor of MAS mechanism, and it takes part in the patho- physiological process of MAS. 4 The newborns of MAS have an imbalance between oxidant and antioxidant to some extent. 5 Inhaled low-dose of nitric oxide shows antioxidant property, was benefit for the modulation of imbalance of oxidant/ antioxidant, and have an antioxidant defenses to the body. 6 The newborns of MAS were given to inhaled low-dose of nitric oxide early to intervention the development of MAS may be lessen injury of lungs.