El tratamiento postnatal con melatonina modula la expresión de agentes prostanoides en pulmón de neonatos de oveja con hipertensión pulmonar / Melatonin modulates the expression of pulmonary prostanoids

Background: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. Aim: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. Material and Methods: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. Results: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. Conclusions: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.

Efecto de la administración prenatal de melatonina en pulmones de neonatos de oveja crónicamente hipóxicos / Effect of prenatal administration of melatonin on lungs of chronic hypoxic sheep neonates

Introducción: Las patologías que podrían motivar el ingreso a una Sala de Reanimación (SR) son múltiples, y asimismo, presentarse en cualquier momento, independientemente del sexo y la edad. A pesar de esta versatilidad, no existen investigaciones que describan la realidad chilena y la literatura extranjera es escasa. En consecuencia, nuestro estudio buscó caracterizar clínico-demográficamente a los pacientes ingresados a SR del Hospital San Juan de Dios de Los Andes, Chile. Materiales y métodos: Estudio de corte transversal. Se trabajó con base de datos anonimizada. El tamaño muestral calculado fue de al menos 1014 sujetos (intervalo de confianza de 95%, precisión de 3%). Se incluyeron los ingresos entre enero de 2013 y junio de 2016, obteniendo una muestra de 1018 pacientes. Variables estudiadas: sexo, edad, diagnóstico general, diagnóstico específico, mes y horario. Se trabajó con Microsoft Excel® utilizando estadística descriptiva. Aprobado por comité éticocientífico. Resultados: 58,1% (n=593) hombres; 42,5% (n=434) mayores de 64 años. Diagnósticos generales más frecuentes: cardiovascular (50,3%) (n=512), neurológico (16,3%) (n=166) y traumático (11,7%) (n=119). Diagnósticos específicos más frecuentes: taquiarritmia (15,9%) (n=162) e infarto miocárdico (12,6%) (n=128). La mayor cantidad de ingresos se registró en enero, febrero y junio (promedio 28 ingresos), y entre las 20 y 00 hrs (22,8%) (n=232). Discusión: Existe un amplio predominio de las enfermedades cardiovasculares.La distribución por mes, sexo y edad parece estar supeditada al comportamiento de dicho grupo; no así la distribución por horarios, ya que las enfermedades cardiovasculares suelen presentarse matinalmente. En general, nuestros resultados coinciden con la literatura extranjera disponible

Introduction: Neonatal pulmonary hypertension (NPHT) caused by chronic hypobaric hypoxia during gestation is associated with oxidative stress and currently lacks of an effective treatment. The aim of this study was to evaluate the effects of melatonin administrated on pregnant sheep on endothelium-dependent vascular reactivity and expression of eNOS, COX-1 and COX-2 on the lungs of lambs gestated and born under chronic hypobaric hypoxia. Material and method: Ten pregnant ewes under chronic hypoxia of highlands (3600 masl) were divided in two groups: 1. Control group (CN), treated with vehicle (5 ml/d ethanol 1, 4%), and 2. Melatonin group (MM), treated with melatonin during gestation (10 mg/d in 5 ml ethanol 1, 4%), during the last third of gestation. Results: Ewes gave birth spontaneously and without assistance, and we obtained lung tissue from 12 days old lambs to determine endothelial vascular reactivity by wire myography. In addition, eNOS, COX-1 and COX-2 RNA and protein expression were measured through RT-PCR and Western Blot, respectively. Discussion: The endothelium dependent vasodilation response was significantly enhanced in MM. Further, MM showed a significant increase in eNOS, COX-1 and COX-2 protein levels, relative to CN group. In conclusion, prenatal melatonin induces endothelium dependent vasodilation mechanisms and positively modulates eNOS-NO and prostanoids pathways, which may favour a treatment for NPHT caused by chronic hypoxia at high-altitude