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Articles by Penny, D. J.
Am. J. Respir. Crit. Care Med., Volume 165, Number 8, April 2002,
1098-1102

Intravenous Sildenafil Lowers Pulmonary Vascular Resistance in a Model
of Neonatal Pulmonary Hypertension
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Lara S. Shekerdemian, Hanne B. Ravn, and Daniel J. Penny

Department of Cardiac Intensive Care, Great Ormond Street Hospital,
London, United Kingdom; and Department of Anaesthesia and Intensive
Care and Institute of Experimental Clinical Research, Aarhus
University Hospital, Aarhus, Denmark
Persistent pulmonary hypertension secondary to meconium aspiration
syndrome is an important cause of morbidity and mortality in the
neonatal population. We investigated the use of the
phosphodiesterase-5 inhibitor sildenafil, in its intravenous form, as
a pulmonary vasodilator in a model of meconium aspiration syndrome.
Pulmonary hypertension was induced in 18 piglets, by endotracheal
instillation of human meconium, 6 piglets subsequently received an
infusion of intravenous sildenafil for 2 hours, 6 received inhaled
nitric oxide for 2 hours, and 6 control animals received no additional
intervention. Meconium aspiration increased pulmonary vascular
resistance by 70%, and increased oxygenation index by over 100%.
Pulmonary vascular resistance remained elevated for the remainder of
the study period in control animals. Inhaled nitric oxide reduced the
pulmonary vascular resistance by 40% after 2 hours of treatment;
intravenous sildenafil completely reversed the increase in pulmonary
vascular resistance within 1 hour of commencing the infusion. Neither
agent had an effect on systemic hemodynamics. Sildenafil also
increased cardiac output by 30%, but while doing so did not adversely
influence oxygenation. Intravenous sildenafil is a selective and
highly effective pulmonary vasodilator, which is at least as effective
as inhaled nitric oxide, in this model of neonatal persistent
pulmonary hypertension.

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Proc. Am. Thorac. Soc.

Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society

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