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.

Keywords:
Middle cerebral arteries, Cerebral autoregulation, Phosphodiesterase 5 expression, Zaprinast
This content is only available via PDF.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.