Effect of early adjunctive use of oral sildenafil and inhaled nitric oxide on the outcome of pulmonary hypertension in newborn infants. A feasibility study

Objective: We aimed to compare the effect of the combined therapy, sildenafil and inhaled nitric oxide with inhaled nitric oxide monotherapy for the treatment of Pulmonary Hypertension of the Newborn.Study Design: Newborn infants (gestational age greater than 34 weeks) who were diagnosed with pulmonary hypertension between December 2008 and 2010 were retrospectively evaluated. Group I (n=14) received monotherapy with inhaled nitric oxide and Group II (n=9) received combined therapy with inhaled nitric oxide and oral sildenafil. Primary outcome was to compare the duration of inhaled nitric oxide therapy between groups.Results: Demographic characteristics were similar between the groups. Combination therapy was associated with early weaning of inhaled nitric oxide (4.8±1.5 vs. 13.5±7.6 hours). The duration of inhaled nitric oxide therapy was slightly shorter in combined therapy group (75[24-125] vs. 109[24-210] hours), however, the difference was insignificant (p=0.2). The incidence of mortality and neonatal outcomes were similar between the groups (p>0.05).Conclusion: Combined therapy did not result in shorter duration of inhaled nitric oxide therapy. Further well designed and larger studies that will elucidate the benefits of combination therapies and optimal therapy whereinhaled nitric oxide is not available are warranted.

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Time limits for a failed response to inhaled nitric oxide in newborn infants with persistent pulmonary hypertension: A retrospective observational study

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-2010-0106 ◽

2010 ◽

Vol 3 (2) ◽

pp. 141-146

Author(s):

Husam Salama ◽

Wissam Adlburaki ◽

Amani Saeed Ibrahim ◽

Samawal Lutfi ◽

Nawal Magzoob

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Observational Study ◽

Newborn Infants ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension ◽

Retrospective Observational Study ◽

Time Limits

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SOD and inhaled nitric oxide normalize phosphodiesterase 5 expression and activity in neonatal lambs with persistent pulmonary hypertension

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00309.2009 ◽

2010 ◽

Vol 299 (1) ◽

pp. L109-L116 ◽

Cited By ~ 46

Author(s):

Kathryn N. Farrow ◽

Satyan Lakshminrusimha ◽

Lyubov Czech ◽

Beezly S. Groh ◽

Sylvia F. Gugino ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Soluble Guanylate Cyclase ◽

Pulmonary Arteries ◽

Newborn Infants ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension ◽

The Impact ◽

Phosphodiesterase 5 ◽

Expression And Activity

Phosphodiesterase 5 (PDE5) and soluble guanylate cyclase (sGC) are key regulators of cGMP and pulmonary vascular tone. We sought to determine the impact of mechanical ventilation with O2 with or without inhaled nitric oxide (iNO) or recombinant human Cu/Zn SOD (rhSOD) on sGC, PDE5, and cGMP in the ovine ductal ligation model of persistent pulmonary hypertension of the newborn (PPHN). PPHN lambs were ventilated with 100% O2 for 24 h alone or combined with either inhalation of 20 parts per million (ppm) iNO continuously or a single intratracheal dose of rhSOD (5 mg/kg). Ventilated PPHN lambs were compared with PPHN fetuses, control fetuses, and 1-day-old spontaneously breathing lambs (1DSB). In the small pulmonary arteries of 1DSB lambs, sGC expression increased, PDE5 expression decreased, and cGMP concentrations increased relative to fetal levels. In PPHN lambs ventilated with 100% O2, sGC activity increased to levels comparable with 1DSB levels. However, PDE5 expression and activity increased, and cGMP levels remained at fetal levels. Addition of either iNO or rhSOD decreased PDE5 expression and activity in PPHN lambs and increased cGMP levels to levels comparable with 1DSB lambs. These data suggest that ventilation of PPHN lambs with 100% O2 impairs cGMP-mediated vasodilation in part due to increased PDE5 expression and activity. The addition of either iNO or rhSOD normalized PDE5 and cGMP levels. Thus therapies designed to decrease PDE5 and increase cGMP, such as iNO and rhSOD, may prove useful in the treatment of PPHN in newborn infants.

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Acute Hemodynamic Responses to Inhaled Nitric Oxide in Patients With Limited Scleroderma and Isolated Pulmonary Hypertension

Circulation ◽

10.1161/01.cir.94.3.477 ◽

1996 ◽

Vol 94 (3) ◽

pp. 477-482 ◽

Cited By ~ 23

Author(s):

D.J. Williamson ◽

C. Hayward ◽

P. Rogers ◽

L.L. Wallman ◽

A.D. Sturgess ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Inhaled Nitric Oxide ◽

Hemodynamic Responses ◽

Limited Scleroderma

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Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs

Children ◽

10.3390/children8050378 ◽

2021 ◽

Vol 8 (5) ◽

pp. 378

Author(s):

Satyan Lakshminrusimha ◽

Sylvia F. Gugino ◽

Krishnamurthy Sekar ◽

Stephen Wedgwood ◽

Carmon Koenigsknecht ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Vascular Resistance ◽

Preterm Infants ◽

Vascular Resistance ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension ◽

Inhaled No ◽

Birth Preterm

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

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