Early inhaled nitric oxide improves oxidative balance in very preterm infants.

Inhaled nitric oxide (iNO) improves oxygenation in premature infants, but concern has been raised about its potential oxidative toxicity. We designed this study to assess the oxidative balance in premature infants who were exposed to low dose iNO and the relationship with their clinical outcome on day 28 of life. A total of 274 infants who were <32 wk gestation were randomized at birth to receive 5 ppm of iNO if they presented with hypoxemic respiratory failure. Nonhypoxemic infants were studied as the reference group. Blood samples were withdrawn 24 h apart, within the first 4 d of life, to assess malondialdehyde (MDA) concentration as oxidative stress marker and total plasmatic glutathione (GSH), intraerythrocyte GSH peroxidase, and GSH reductase activities as antioxidant defenses. After 24 h, the rise in MDA was blunted in the iNO group compared with controls and was close to the reference infants. Conversely, GSH was more stable in the iNO group, when there was no difference for the GSH peroxidase and GSH reductase activities. On day 28, Oxygen dependence was linked with a higher increase in MDA as was the risk for death, whereas intraventricular hemorrhage was associated with a higher initial drop in GSH. Early low-dose iNO in hypoxemic preterm infants improves oxidative balance and seems to be clinically beneficial up to day 28 of life.

Comparative effects of dexamethasone and L-canavanine in experimental septic shock.

Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexamethasone, a glucocorticoid and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in a rodent model of sepsis. Mean arterial pressure was restored by dexamethasone and L-canavanine administration at 24 h, no longer at 30 h. Dexamethasone but not L-canavanine improved aortic blood flow at 24 and 30 h. Although both dexamethasone and L-canavanine administration significantly reduced nitrite/nitrate production, and improved survival, steroids did better for survival. In conclusion, dexamethasone and L-canavanine displayed similar vasopressor effects. In addition, steroids improved blood flow suggesting that steroid-induced hemodynamic improvement in sepsis is not solely due to inhibition of inducible nitric oxide synthase.