HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits / [HMGB1 e citocinas inflamatórias em lesão pulmonar aguda experimental induzida em coelhos]

The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.(AU)

O objetivo deste trabalho é determinar os níveis de HMGB1, TNF-alfa e IL-8 no lavado broncoalveolar (BAL), bem como quantificar a expressão sérica de TLR2 e TLR4 mRNA em tecido pulmonar de coelhos com dois graus de lesão pulmonar aguda (LPA). Os animais foram distribuídos aleatoriamente em grupos com LPA grave (S) e leve / moderada (MM), induzidas com solução salina morna, e um grupo controle. HMGB1, TNF-alfa, IL-8, TLR2mRNA e TLR4mRNA foram medidos após a indução de LPA e quatro horas de ventilação mecânica. Os resultados mostraram níveis aumentados de IL-8, TNF-alfa, HMGB1 e TLR4mRNA nos grupos com LPA. As concentrações de HMGB1, IL-8 e TNF-alfa no LBA foram maiores no S comparado ao MM. Aumento de TLR4mRNA foi observado em S e MM versus controle. Os resultados sugerem uma participação precoce da HMGB1 na LPA em conjunto com IL-8 e TNF-alfa e associação com a gravidade da LPA. O TLR4 foi expresso na ALI e possivelmente possui papel precoce na fisiopatologia da LPA, mas sem associação com a gravidade.(AU)

Early administration of inhaled nitric oxide to children with acute respiratory distress syndrome and its effects on oxygenation and ventilator settings: prospective preliminary report of ten patients.

AIM: To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to assess its acute and sustained effects on oxygenation and ventilator settings. PATIENTS AND METHODS: Ten children with ARDS, aged 1 to 132 months (median, 11 months), with arterial saturation of oxygen <88% while receiving a fraction of inspired oxygen (FiO2) >or=0.6 and a positive end-expiratory pressure of >or=10 cm H2O were included in the study. The acute response to iNO was assessed in a 4-hour dose-response test, and positive response was defined as an increase in the PaO2/FiO2 ratio of 10 mm Hg above baseline values. Conventional therapy was not changed during the test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO2, oxygenation index, gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules. RESULTS: At the end of the 4-hour test, all the children showed significant improvement in the PaO2/FiO2 ratio (63.6%) and the oxygenation index (44.9%) compared with the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FiO2 and peak inspiratory pressure could be quickly and significantly reduced. No toxicity from methemoglobin or nitrogen dioxide was observed. CONCLUSION: Administration of iNO to children is safe. iNO causes rapid and sustained improvement in oxygenation without adverse effects. Ventilator settings can safely be reduced during iNO treatment.