Plasma Arginine Levels and the Response to Inhaled Nitric Oxide in Neonates

Abstract

Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0.05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2–53) μmol/l, but not significantly lower than that of the controls (median 24, range 3–82 μmol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.

Endothelin-1 andL-Arginine in Preterm Infants with Respiratory Distress

“…Previous studies showed that differences in plasma L-arginine concentrations did not explain the variation in response to inhaled NO therapy. 35 In this study, we obtained arterial blood samples immediately after birth so that the concentrations of the measured markers were not modified by ongoing management. Previously, when blood samples were obtained 18 to 40 hours after birth, ET-1 concentrations correlated with duration of mechanical ventilation.…”

New therapies for pulmonary hypertension in neonates and children

“…Small case reports suggest that sildenafil increases cGMP and facilitates weaning of infants with PPHN from iNO (23) and that use of inhaled PGI 2 can induce rapid improvement in oxygenation in neonates with PPHN refractory to iNO (20). Arginine levels are lower in term and preterm neonates with PH compared with controls (24). Uncontrolled trials suggest improved oxygenation with L-arginine infusion in infants with PPHN (25).…”