Effects of Post-Resuscitation Treatment with N-acetylcysteine on Cardiac Recovery in Hypoxic Newborn Piglets

AIMS: Although N-acetylcysteine (NAC) can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia. METHODS AND RESULTS: Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H-R, n = 6]) and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group). All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion) via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls). The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05). CONCLUSIONS: Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults

Respuesta inflamatoria en el sistema nervioso central secundaria a asfixia perinatal

Objectives: To examine the relation of IL-6 levels in the CSF to the severity of hypoxic-ischemic encephalopathy (HIE) and to the outcome. Methods: Asphyxiated term neonates were included. Cerebrospinal fluid (CSF) IL-6 was measured by a sensitive ELISA. Results: 20 neonates were studied: 3 had no HIE, 5 had stage 1, 6 had stage 2, and 6 had stage 3. CSF IL-6 levels (8 to 90 hours of life) were higher in neonates with mE stage 3 (range 65 to 2250 pg/ml) when compared to neonates with HIE stage o to 2 «2 pg/ml in 12 neonates, lO pg/ml in 1)(P&lt;0.01). 5 neonates had adverse outcome: 4 died, and 1 had cerebral palsy. 13 had normal outcome. CSF IL- 6 levels (10.8±6.1 months) were higher in neonates with adverse outcome (range 65 to 2250 pg/rnl) compared to neonates with favorable outcome (P&lt;0.05). Conclusion: IL-6 levels in the CSF are related to neonatal neurological manifestations and to the outcome. Our results suggest that IL-6 is implicated in the pathogenesis of neonatal hypoxic-ischemic brain damage.Objetivos: Examinar la relación entre los niveles de IL-6 en líquido cefalorraquídeo (LCR) con el grado de encefalopatía hipóxico-isquémica (Em) y la evolución. Métodos: Se estudiaron recién nacidos a término asfixiados. Se determinaron los niveles de IL-6 en LCR mediante ELISA. Resulados: Se incluyeron 20 neonatos: 3 sin EHI, 5 con grado 1, 6 con grado 2, y 6 con grado 3. La concentración de IL-6 en LCR (8 a 90 horas de vida) fue mayor en neo natos con EHI grado 3 (rango 65 a 2250 pg/ml) que en neonatos con EHI grados O a 2 «2 pg/ml en 12 neonatos, 10 pg/rnl en 1) (p&lt;O.OI). 5 neonatos tuvieron una evolución adversa: 4 murieron, y 1 tuvo parálisis cerebral. 13 presentaron una evolución favorable. Los niveles de IL-6 en LCR (l0.8±6.1 meses) fueron mayores en neonatos con evolución adversa (rango 65 a 2250 pg/ml) comparados con neonatos con evolución favorable (p&lt;0.05). Conclusión: Los niveles de IL-6 en LCR se relacionan con el grado de EHI y con la evolución. Nuestros resultados sugieren que la IL-6 está implicada en la patogenia del daño cerebral hipóxico-isquémico neonatal