Background: The use of phosphodiesterase 5 (PDE5) inhibitors to treat newborns with pulmonary hypertension is increasing. The effect of PDE5 inhibitors on the neonatal cerebral circulation remains unknown. The neonatal piglet model of chronic hypoxia-induced pulmonary hypertension allows the study of the effects of PDE5 inhibitors on both the pulmonary and cerebral circulations. Objectives: To determine whether the PDE5 inhibitor, zaprinast, causes dilation in pulmonary and middle cerebral arteries (MCA) of normoxic newborn piglets and those with chronic hypoxia-induced pulmonary hypertension, and to evaluate whether zaprinast alters responses to increased pressure (autoregulatory ability) of the MCA. Methods: Two-day-old piglets were raised in normoxia or hypoxia for 3 or 10 days. Pulmonary arteries and MCA were isolated and pressurized, after which changes in diameter to zaprinast were measured. MCA pressure-diameter relationships were determined. Results: Dilation to zaprinast was similar in pulmonary arteries from normoxic and hypoxic piglets. Zaprinast dilated MCA from all groups but the response was diminished in MCA from piglets raised in hypoxia for 10 days. MCA pressure-diameter relationships (autoregulation) did not differ between the groups. Conclusions: Pulmonary artery dilation to zaprinast supports the use of PDE5 inhibitors to treat pulmonary hypertension in neonates. PDE5 inhibitors function as MCA dilators but do not impair the pressure-diameter behavior of the cerebral circulation of either normoxic newborn piglets or those with chronic hypoxia-induced pulmonary hypertension. These findings suggest that cerebral autoregulation is likely to be intact with acute PDE5 inhibitor treatment in infants with pulmonary hypertension in conditions associated with chronic hypoxia.
© 2011 S. Karger AG, Basel
- Cerebral autoregulation
- Phosphodiesterase 5 expression
- Middle cerebral arteries
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Candice D. Fike, MD
Department of Pediatrics, Vanderbilt University School of Medicine and
the Monroe Carell Jr. Children’s Hospital at Vanderbilt
2215 B Garland Ave., 1125 MRB IV/Light Hall, Nashville, TN 37232-0656 (USA)
Tel. +1 615 936 8403, E-Mail Candice.firstname.lastname@example.org
Received: August 11, 2010
Accepted after revision: February 14, 2011
Published online: July 26, 2011
Number of Print Pages : 12
Number of Figures : 9, Number of Tables : 0, Number of References : 49
Neonatology (Fetal and Neonatal Research)
Vol. 101, No. 1, Year 2012 (Cover Date: December 2011)
Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)
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