OBJECTIVE: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro. DESIGN AND SETTING: Prospective study in a university pediatric intensive care ward and research laboratory. PATIENTS AND MATERIALS: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro. INTERVENTIONS: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro. MEASUREMENTS AND RESULTS: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 +/- 0.24 cmH2O/torr (mean +/- SEM) to 4.90 +/- 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 +/- 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 +/- 0.17 cmH2O/ torr;p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 +/- 4.0 microM/min) than in control cells (37.6 +/- 7.0 microM/ min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 +/- 10.0 microM/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot). CONCLUSION: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.
OBJECTIVE: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro. DESIGN AND SETTING: Prospective study in a university pediatric intensive care ward and research laboratory. PATIENTS AND MATERIALS: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro. INTERVENTIONS: NO inhalation and withdrawal in patients; exposure to NO donorsodium nitroprusside (SNP) and gaseous NO in vitro. MEASUREMENTS AND RESULTS: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 +/- 0.24 cmH2O/torr (mean +/- SEM) to 4.90 +/- 0.26 cmH2O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 +/- 0.23 cmH2O/torr) 30 min after weaning, a significant drop after 4 h (3.72 +/- 0.17 cmH2O/ torr;p < 0.001), values restored after 12 h. In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 +/- 4.0 microM/min) than in control cells (37.6 +/- 7.0 microM/ min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 +/- 10.0 microM/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot). CONCLUSION: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.
Authors: Duncan J Macrae; David Field; Jean-Christophe Mercier; Jens Møller; Tom Stiris; Paolo Biban; Paul Cornick; Allan Goldman; Sylvia Göthberg; Lars E Gustafsson; Jürg Hammer; Per-Arne Lönnqvist; Manuel Sanchez-Luna; Gunnar Sedin; Nim Subhedar Journal: Intensive Care Med Date: 2004-01-13 Impact factor: 17.440