224 Early Increase of Nitric Oxide in A Model of Perinatal Asphyxia in Fetal Lambs

Abstract

Background: The function of exogenous pulmonary surfactant depends of an adequate stability of its components, a highly complex mixture of lipids (mainly phospholipids) and two hydrophobic polypeptides, SP-B and SP-C. This composition could become instable with long time surfactant storage. The Butantan Institute (Brazil) produced a new porcine pulmonary surfactant preparation composed mainly of 76% of phosphatidylcholine (30 -35% of the phosphatidylcholine is saturated dipalmitoyl phosphatidylcholine), 6 -8% of phosphatidyllethanolamine, 6% of phosphatidylinositolϩphosphatidylserine, and 4 -6% of sphingomyelin, with 5.6% of two hydrophobic polypeptides, SP-B and SP-C. The objective of this study was to evaluate the Butantan exogenous surfactant function one year after its production, using the premature rabbit model.Methods: 16 New Zealand White premature rabbits were delivered by c-section at 27 days gestation and randomized into two study groups according to the type of surfactant treatment: Butantan surfactant (nϭ8, animals treated with Butantan surfactant kept in refrigerator at 4o C for one year), and Curosurf (Farmalab-Chiesi) group (nϭ8; surfactant used 4 months after its production). Animals were ventilated with a preset tidal-volume of 8 ml/kg for 15 minutes, using a ventilator-pletismograph system with the following ventilator settings: respiratory rate (RR), 60 cycles/min; FiO2, 0.21; peak inspiratory pressure (PIP) needed to acquire the target tidal-volume ( 8 ml/kg); PEEP, 0 cmH2O; inspiratory and expiratory time, 0.5 seconds. Ventilatory pressure (VPϭPIP-PEEP), tidal-volume (TV), and dynamic compliance (DCϭTV/VP) were recorded each five minutes until sacrifice. Statistical analysis was performed by t-test. Significance level was set at 0.05.Results: Conclusion:The Butantan surfactant showed to be as effective as a newly synthesized Curosurf to treat respiratory distress syndrome in the premature rabbit model, one year after storage at 4°C in refrigerator. Background:Endogenous nitric oxide (NO) production increases in perinatal asphyxia and inflammatory processes. Histological lesion (necrosis and/or apoptosis) secondary to hypoxic-ischemic (H-I) injury appears in several hours after the insult but biological markers appear earlier. In our previous studies (1,2) we have observed early changes in cerebral blood flow and in O2-uptake. Aim: To study the early changes of serum NO concentration in a model of perinatal asphyxia induced by prolonged umbilical cord clamping in premature lambs. EARLY INCREASE OF NITRIC OXIDE IN A MODEL OF PERINATAL ASPHYXIA IN FETAL LAMBSMethods:10 preterm lambs (80 -90% GE) were randomly assigned to: Control group, after Cesarean section, lambs were managed on conventional mechanical ventilation for 3 hours (nϭ5); Asphyctic group, H-I injury was performed by partial cord clamping during 60 min and later, lambs were managed similar to the control group (nϭ5). NO was measured in serum samples by fluorometric assay at baseline (B), immediately after H-I injury and at the en...