ABSTRACT
BACKGROUND: Bronchopulmonary dysplasia is one of the main complications associated with extreme prematurity. Oxidative stress is suspected to be a trigger event of this lung disease, which is characterized by impaired alveolar development. Peroxides, mainly ascorbylperoxide and H2O2, are known contaminant of parenteral nutrition. We hypothesize that these oxidant molecules induce bronchopulmonary dysplasia development. The aim was to determine if the infusion of ascorbylperoxide, whether in presence or absence of H2O2, is associated with oxidative stress, apoptosis and loss of alveoli in the lungs of newborn guinea pigs. METHOD: Three-day-old guinea pigs received parenteral solutions containing 0, 20, 60 or 180 µM ascorbylperoxide in the presence or not of 350 µM H2O2 (concentrations similar to those measured in parenteral nutrition). After 4 days, the lungs were collected for determination of glutathione's redox potential, caspase-3 activation (an apoptosis marker), alveolarization index (by histology), activation of Nrf2 and NF?B (biological markers of oxidative stress), and IL-6 and PGJ2 levels (markers of NF?B activation). Groups were compared by ANOVA, p < 0.05. RESULTS: Loss of alveoli was associated with ascorbylperoxide in a dose-dependent manner, without an influence of H2O2. The dose-dependent activation of caspase-3 by ascorbylperoxide was lower in the presence of H2O2. Ascorbylperoxide induced an increase of redox potential in a dose-dependent manner, which reached a plateau in presence of H2O2. Nrf2 and NF?B were activated by H2O2 but not by ascorbylperoxide. CONCLUSION: Results suggest that ascorbylperoxide, generated in parenteral nutrition, is involved in the development of bronchopulmonary dysplasia, independently of the increase of the redox potential. This study underlines the importance of developing a safer formulation of parenteral nutrition.
Subject(s)
Ascorbic Acid/analogs & derivatives , Glutathione/metabolism , Lung/drug effects , Peroxides/toxicity , Pulmonary Alveoli/physiopathology , Animals , Animals, Newborn , Ascorbic Acid/toxicity , Caspase 3/metabolism , Guinea Pigs , Hydrogen Peroxide/toxicity , Interleukin-6/metabolism , Lung/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Parenteral Nutrition , Prostaglandin D2/analogs & derivatives , Prostaglandin D2/analysisABSTRACT
BACKGROUND: The influence of the first immunization on cardiorespiratory (CR) stability in very preterm infants is still a controversial subject. OBJECTIVES: To describe the changes induced by immunization on heart and respiratory rate variability (HRV-RRV) and to test a potential association between preimmunization profiles and postimmunization CR events. METHODS: Continuous 72-hour CR recordings and 2.5-hour polysomnographic recordings were performed on very preterm infants immunized after 7 weeks. The results are expressed as medians (interquartile ranges). RESULTS: Immunization was performed on 31 very preterm infants [28 weeks' gestation (26.9-29), birth weight: 965 g (795-1,105)], and was associated with an increased incidence (p < 0.01) of events lasting more than 10 s: bradycardia <80 bpm [2.2 (1.1-7) vs. 1.8 (1-4)/12 h], desaturation [17.6 (9.4-36.4) vs. 13.9 (7.7-33.8)/12 h] and associated bradycardia-desaturation [IB+D, 4.1 (1.4-7.3) vs. 2.4 (1-4.6)/12 h], with mild changes in HRV and no change in RRV. The changes in IB+D frequency were correlated with preimmunization IB+D frequency (r = 0.44, p < 0.05), HRV spectral parameter low frequency/high frequency ratio (LF/HF, r = 0.55, p < 0.01) and approximate entropy of HRV (r = -0.39, p < 0.05). CONCLUSION: The increase in CR events after the first immunization in very preterm infants was associated with: (1) sympathetic predominance in heart rate control (high LF/HF ratio), (2) abnormal oversimplification of HRV (low entropy) and (3) persistent respiratory rhythm control immaturity (high IB+D before vaccine).
