Compartilhar
Publique nesta revista
Informação da revista
Vol. 89. Núm. 3.Maio - Junho 2013
Páginas 211-326
Compartilhar
Compartilhar
Baixar PDF
Mais opções do artigo
Vol. 89. Núm. 3.Maio - Junho 2013
Páginas 211-326
ARTIGO DE REVISÃO
DOI: 10.1016/j.jpedp.2012.11.002
Persistent pulmonary hypertension of the newborn: Recent advances in pathophysiology and treatment
Hipertensão pulmonar persistente neonatal: recentes avanços na fisiopatologia e tratamento
Visitas
5692
Joaquim E.B. Cabrala,
Autor para correspondência
dr.jcabral@terra.com.br

Corresponding author.
, Jaques Belikb
a Neonatologista. Hospital São Luiz, São Paulo, SP, Brasil
b Neonatologista. Professor of Pediatrics and Physiology, University of Toronto, The Hospital for Sick Children, Toronto, Canadá
Este item recebeu
5692
Visitas
Informação do artigo
Abstract
Objectives

Although recognized for decades, little is known about the etiology, physiopathology, and prevention of persistent pulmonary hypertension of the newborn (PPHN). and its treatment remains a major challenge for neonatologists. In this review, the clinical features and physiopathology of the syndrome will be addressed, as well as its general and specific treatments.

Data source

A review was carried out in PubMed, Cochrane Library, and MRei consult databases, searching for articles related to the syndrome and published between 1995 and 2011.

Data synthesis

Risk factors and the physiopathological mechanisms of the syndrome are discussed. The clinical picture depends on the different factors involved, which are probably related to the etiology and physiopathological mechanisms. In addition to the measures used to allow the decrease in pulmonary vascular resistance after birth, some cases will require pulmonary vasodilators. Although nitric oxide has proved effective, other vasodilators have been recently used, but clinical evidence is still lacking to demonstrate their benefits in the treatment of PPHN.

Conclusions

Despite recent technological advances and new physiopathological knowledge, mortality associated with PPHN remains at 10%. More clinical research and evidence-based experimental results are needed to prevent, treat, and reduce the morbidity/mortality associated with this neonatal syndrome.

Keywords:
Pulmonary hypertension
Pulmonary vasodilators
Nitric oxide
Resumo
Objetivos

: Embora reconhecida há décadas, ainda pouco se sabe a respeito da etiologia, fisiopatologia e prevenção da hipertensão pulmonar persistente neonatal (HPPN), e seu tratamento continua a ser um grande desafio para os neonatologistas. Nesta revisão, vamos abordar as características clínicas e os mecanismos fisiopatológicos da síndrome, assim como seu tratamento geral e específico.

Fontes de dados

Fizemos uma revisão nas bases de dados PubMed, Cochrane Library e MRei Consult, procurando por artigos relacionados à síndrome e publicados entre 1995 e 2011.

Síntese de dados

São discutidos os fatores de risco e os mecanismos fisiopatológicos da síndrome. O quadro clínico depende dos diferentes fatores envolvidos, que provavelmen- te estão relacionados com a etiologia e o mecanismo fisiopatológico. Além das medidas utilizadas para permitir a queda da resistência vascular pulmonar após o nascimento, alguns casos necessitam de vasodilatadores pulmonares. Embora o óxido nítrico tenha se provado efetivo, recentemente, outros vasodilatadores têm sido usados, mas ainda faltam evidências clínicas para comprovar seus benefícios no tratamento da HPPN.

Conclusões

Apesar dos recentes avanços tecnológicos e dos novos conhecimentos fisio- patológicos, a mortalidade associada à HPPN ainda é de 10%. São necessárias mais pes- quisas clínicas e resultados experimentais baseados em evidências para prevenir, tratar e reduzir a morbimortalidade associada a esta síndrome neonatal.

Palavras chave:
Hipertensão pulmonar
Vasodilatadores pulmonares
Óxido nítrico
O texto completo está disponível em PDF
Referências
[[1]]
J.R. Klinger
The nitric oxide/cGMP signaling pathway in pulmonary hypertension
Clin Chest Med., 28 (2007), pp. 143-167 http://dx.doi.org/10.1016/j.ccm.2006.12.002
[[2]]
M.J. Nowicki,D. Shi,Z. Cai,P.R. Bishop,W.L. May
Developmental expression of endothelial nitric oxide synthase (eNOS) in the rat liver
[[3]]
T.A. Parker,T.D. le Cras,J.P. Kinsella,S.H. Abman
Developmental changes in endothelial nitric oxide synthase expression and activity in ovine fetal lung
Am J Physiol Lung Cell Mol Physiol., 278 (2000), pp. L202-L208
[[4]]
T. Lucke,N. Kanzelmeyer,M.J. Kemper,D. Tsikas,A.M. Das
Developmental changes in the L-arginine/nitric oxide pathway frominfancytoadulthood:plasmaasymmetricdimethylarginine levels decrease with age
Clin Chem Lab Med., 45 (2007), pp. 1525-1530 http://dx.doi.org/10.1515/CCLM.2007.300
[[5]]
J. Belik,D. Shehnaz,J. Pan,H. Grasemann
Developmental changes in arginase expression and activity in the lung
Am J Physiol Lung Cell Mol Physiol., 294 (2008), pp. L498-L504 http://dx.doi.org/10.1152/ajplung.00242.2007
[[6]]
H.H. Schmidt,P.M. Schmidt,J.P. Stasch
NO- and haem-independent soluble guanylate cyclase activators
Handb Exp Pharmacol., (2009), pp. 309-339
[[7]]
J.P. Stasch,A.J. Hobbs,NO-independent
haem-dependent soluble guanylate cyclase stimulators
Handb Exp Pharmacol., (2009), pp. 277-308
[[8]]
S. Behrends,J. Kempfert,A. Mietens,M. Koglin,H. Scholz,R. Middendorff
Developmental changes of nitric oxide- sensitive guanylyl cyclase expression in pulmonary arteries
Biochem Biophys Res Commun., 283 (2001), pp. 883-887 http://dx.doi.org/10.1006/bbrc.2001.4869
[[9]]
S. Behrends,A. Mietens,J. Kempfert,M. Koglin,H. Scholz,R. Middendorff
The expression pattern of nitric oxide-sensitive guanylyl cyclase in the rat heart changes during postnatal development
J Histochem Cytochem., 50 (2002), pp. 1325-1332
[[10]]
J. Belik,N. Hehne,J. Pan,S. Behrends
Soluble guanylate cyclase-dependent relaxation is reduced in the adult rat bronchial smooth muscle
Am J Physiol Lung Cell Mol Physiol., 292 (2007), pp. L699-L703 http://dx.doi.org/10.1152/ajplung.00108.2006
[[11]]
K.D. Bloch,G. Filippov,L.S. Sanchez,M. Nakane,S.M. de la Monte
Pulmonary soluble guanylate cyclase, a nitric oxide recep- tor, is increased during the perinatal period
Am J Physiol, 272 (1997), pp. L400-L406
[[12]]
B. Zhu,S.J. Strada
The novel functions of cGMP-specific phosphodiesterase 5 and its inhibitors in carcinoma cells and pulmonary/cardiovascular vessels
Curr Top Med Chem., 7 (2007), pp. 437-454
[[13]]
M.D. Patel,S.D. Katz
Phosphodiesterase 5 inhibition in chro- nic heart failure and pulmonary hypertension
Am J Cardiol., 96 (2005), pp. 47M-51M http://dx.doi.org/10.1016/j.amjcard.2005.10.005
[[14]]
K.A. Hanson,J.W. Ziegler,S.D. Rybalkin,J.W. Miller,S.H. Abman,W.R. Clarke
Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity
Am J Physiol., 275 (1998), pp. L931-L941
[[15]]
T. Reffelmann,R.A. Kloner
Cardiovascular effects of phospho- diesterase 5 inhibitors
Curr Pharm Des., 12 (2006), pp. 3485-3494
[[16]]
A.E. Juliana,F.C. Abbad
Severe persistent pulmonary hyper- tension of the newborn in a setting where limited resources exclude the use of inhaled nitric oxide: successful treatment with sildenafil
Eur J Pediatr., 164 (2005), pp. 626-629 http://dx.doi.org/10.1007/s00431-005-1724-x
[[17]]
B.G. Sood,V. Delaney-Black,J.V. Aranda,S. Shankaran
Aerosolized PGE1: a selective pulmonary vasodilator in neonatal hypoxe- mic respiratory failure results of a Phase I/II open label clini- cal trial
[[18]]
F. Murray,M.R. MacLean,N.J. Pyne
Increased expression of the cGMP-inhibited cAMP-specific (PDE3) and cGMP binding cGMP- specific (PDE5) phosphodiesterases in models of pulmonary hypertension
Br J Pharmacol., 137 (2002), pp. 1187-1194 http://dx.doi.org/10.1038/sj.bjp.0704984
[[19]]
R.P. Jankov,X. Luo,J. Cabacungan,R. Belcastro,H. Frndova,S.J. Lye
Endothelin-1 and O2-mediated pulmonary hyperten- sion in neonatal rats: a role for products of lipid peroxidation
[[20]]
T. Munzel,C. Sinning,F. Post,A. Warnholtz,E. Schulz
Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction
[[21]]
J. Belik,R.P. Jankov,J. Pan,A.K. Tanswell
Peroxynitrite inhibits relaxation and induces pulmonary artery muscle contraction in the newborn rat
Free Radic Biol Med., 37 (2004), pp. 1384-1392 http://dx.doi.org/10.1016/j.freeradbiomed.2004.07.029
[[22]]
T.R. Grover,J.P. Zenge,T.A. Parker,S.H. Abman
Vascular endothelial growth factor causes pulmonary vasodilation through activa- tion of the phosphatidylinositol-3-kinase-nitric oxide pathway in the late-gestation ovine fetus
[[23]]
T.D. Le Cras,N.E. Markham,R.M. Tuder,N.F. Voelkel,S.H. Abman
Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure
Am J Physiol Lung Cell Mol Physiol., 283 (2002), pp. L555-L562 http://dx.doi.org/10.1152/ajplung.00408.2001
[[24]]
A.I. Papaioannou,K. Kostikas,P. Kollia,K.I. Gourgoulianis
Clinical implications for vascular endothelial growth factor in the lung: friend or foe?
[[25]]
L. Taraseviciene-Stewart,Y. Kasahara,L. Alger,P. Hirth,M.G. Mc,J. Waltenberger
Inhibition of the VEGF receptor 2 com- bined with chronic hypoxia causes cell death-dependent pul- monary endothelial cell proliferation and severe pulmonary hypertension
FASEB J., 15 (2001), pp. 427-438 http://dx.doi.org/10.1096/fj.00-0343com
[[26]]
R.T. Schermuly,J.P. Stasch,S.S. Pullamsetti,R. Middendorff,D. Muller,K.D. Schluter
Expression and function of soluble guan-ylate cyclase in pulmonary arterial hypertension
Eur Respir J., 32 (2008), pp. 881-891 http://dx.doi.org/10.1183/09031936.00114407
[[27]]
B. Braam,M.C. Verhaar
Understanding eNOS for pharmacologi- cal modulation of endothelial function: a translational view
Curr Pharm Des., 13 (2007), pp. 1727-1740
[[28]]
J. Belik,E. Kerc,M.D. Pato
Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activi- ties decrease with age
Am J Physiol Lung Cell Mol Physiol., 290 (2006), pp. L509-L516 http://dx.doi.org/10.1152/ajplung.00145.2005
[[29]]
K.A. Fagan,M. Oka,N.R. Bauer,S.A. Gebb,D.D. Ivy,K.G. Morris
Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho- kinase
Am J Physiol Lung Cell Mol Physiol., 287 (2004), pp. L656-L664 http://dx.doi.org/10.1152/ajplung.00090.2003
[[30]]
Y. Fukumoto,S. Tawara,H. Shimokawa
Recent progress in the treatment of pulmonary arterial hypertension: expectation for rho-kinase inhibitors
Tohoku J Exp Med., 211 (2007), pp. 309-320
[[31]]
J.M. Hyvelin,K. Howell,A. Nichol,C.M. Costello,R.J. Preston,P. McLoughlin
Inhibition of Rho-kinase attenuates hypoxia- induced angiogenesis in the pulmonary circulation
Cir Res., 97 (2005), pp. 185-191
[[32]]
P.J. McNamara,P. Murthy,C. Kantores,L. Teixeira,D. Engelberts,T. van Vlie
Acute vasodilator effects of Rho-kinase inhi- bitors in neonatal rats with pulmonary hypertension unres- ponsive to nitric oxide
Am J Physiol Lung Cell Mol Physiol., 294 (2008), pp. L205-L213 http://dx.doi.org/10.1152/ajplung.00234.2007
[[33]]
S. Cassin,T. Tyler,R. Wallis
The effects of prostaglandin E on fetal pulmonary vascular resistance (38588)
Proc Soc Exp Biol Med., 148 (1975), pp. 584-587
[[34]]
C.W. Leffler,J.R. Hessler,R.S. Green
The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis
Pediatr Res., 18 (1984), pp. 938-942
[[35]]
O. Danhaive,R. Margossian,T. Geva,S. Kourembanas
Pulmonary hypertension and right ventricular dysfunction in growth-res- tricted, extremely low birth weight neonates
J Perinatol., 25 (2005), pp. 495-499 http://dx.doi.org/10.1038/sj.jp.7211299
[[36]]
M.C. Walsh-Sukys,J.E. Tyson,L.L. Wright,C.R. Bauer,S.B. Korones,D.K. Stevenson
Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes
Pediatrics., 105 (2000), pp. 14-20
[[37]]
G. Boden,C. Bennett
The management of persistent pul- monary hypertension of the newborn
Current Paediatrics., 14 (2004), pp. 290-297
[[38]]
S. Hernández-Diaz,L.J. Van Marter,M.M. Werler,C. Louik,A.A. Mitchell
Risk Factors for Persistent Pulmonary Hypertension of the Newborn
Pediatrics., 120 (2007), pp. e272-e282 http://dx.doi.org/10.1542/peds.2006-3037
[[39]]
G.G. Konduri,A. Solimano,G.M. Sokol,J. Singer,R.A. Ehrenkranz,N. Singhal
A randomized trial of early versus standard inhaled nitric oxide therapy in term and near-term new- born infants with hypoxic respiratory failure
Pediatrics., 113 (2004), pp. 559-564
[[40]]
A. Ramachandrappa,L. Jain
Elective cesarean section: its impact on neonatal respiratory outcome
Clin Perinatol., 35 (2008), pp. 373-393 http://dx.doi.org/10.1016/j.clp.2008.03.006
[[41]]
L. Jain,D.C. Eaton
Physiology of fetal lung fluid clearance and the effect of labor
Semin Perinatol., 30 (2006), pp. 34-43 http://dx.doi.org/10.1053/j.semperi.2006.01.006
[[42]]
J. Belik,A.J. Halayko,K. Rao,N.L. Stephens
Fetal ductus arterio- sus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes
Cir Res., 72 (1993), pp. 588-596
[[43]]
S.H. Abman,F.J. Accurso
Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation
Am J Physiol., 257 (1989), pp. H626-H634
[[44]]
R. Levy,A. Matitiau,A.A. Ben,D. Milman,Y. Or,Z. Hagay
Indomethacin and corticosteroids: an additive constric- tive effect on the fetal ductus arteriosus
Am J Perinatol., 16 (1999), pp. 379-383
[[45]]
H. Weiss,B. Cooper,M. Brook,M. Schlueter,R. Clyman
Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin
J Pediatr., 127 (1995), pp. 466-471
[[46]]
M. Respondek,S.R. Weil,J.C. Huhta
Fetal echocardiography during indomethacin treatment
Ultrasound Obstet Gynecol., 5 (1995), pp. 86-89 http://dx.doi.org/10.1046/j.1469-0705.1995.05020086.x
[[47]]
E. Wooltorton
Persistent pulmonary hypertension of the new-born maternal use of SSRIs
CMAJ, 174 (2006), pp. 1555-1556 http://dx.doi.org/10.1503/cmaj.060509
[[48]]
B. Kallen,P.O. Olausson
Maternal use of selective serotonin re- uptake inhibitors and persistent pulmonary hypertension of the newborn
Pharmacoepidemiol Drug Saf., 17 (2008), pp. 801-806 http://dx.doi.org/10.1002/pds.1570
[[49]]
C.D. Chambers,S. Hernandez-Diaz,L.J. Van Marter,M.M. Werler,C. Louik,K.L. Jones
Selective serotonin-reuptake inhi- bitors and risk of persistent pulmonary hypertension of the newborn
N Engl J Med., 354 (2006), pp. 579-587 http://dx.doi.org/10.1056/NEJMoa052744
[[50]]
E. Fornaro,D. Li,J. Pan,J. Belik
Prenatal exposure to fluoxe- tine induces fetal pulmonary hypertension in the rat
Am J Respir Crit Care Med., 176 (2007), pp. 1035-1040 http://dx.doi.org/10.1164/rccm.200701-163OC
[[51]]
J.W. Ziegler,D.D. Ivy,J.P. Kinsella,S.H. Abman
The role of nitric oxide, endothelin, and prostaglandins in the transition of the pulmonary circulation
Clin Perinatol., 22 (1995), pp. 387-403
[[52]]
K.R. Stenmark,E. Gerasimovskaya,R.A. Nemenoff,M. Das
Hypoxic activation of adventitial fibroblasts: role in vascular remodeling
Chest., 122 (2002), pp. 326S-S334
[[53]]
R.L. Keller,P. Moore,D. Teitel,S. Hawgood,J. McQuitty,J.R. Fineman
Abnormal vascular tone in infants and children with lung hypoplasia: Findings from cardiac catheterization and the response to chronic therapy
Pediatr Crit Care Med., 7 (2006), pp. 589-594 http://dx.doi.org/10.1097/01.PCC.0000244401.53189.CB
[[54]]
J. Belik,S.T. Davidge,W. Zhang,J. Pan,J.J. Greer
Airway smooth muscle changes in the nitrofen-induced congenital diaphrag- matic hernia rat model
[[55]]
A.M. Kunig,T.A. Parker,L.M. Nogee,S.H. Abman,J.P. Kinsella
ABCA3 deficiency presenting as persistent pulmonary hypertension of the newborn
J Pediatr., 151 (2007), pp. 322-324 http://dx.doi.org/10.1016/j.jpeds.2007.05.054
[[56]]
S.A. Singh,T. Ibrahim,D.J. Clark,R.S. Taylor,D.H. George
Persistent pulmonary hypertension of newborn due to congenital capi- llary alveolar dysplasia
Pediatr Pulmonol., 40 (2005), pp. 349-353 http://dx.doi.org/10.1002/ppul.20244
[[57]]
G. Plat,I. Rouquette,M.O. Marcoux,M.C. Bloom,P. Acar,Y. Dulac
Alveolar capillary dysplasia and persistent pulmonary hyper- tension of the newborn
Arch Mal Coeur Vaiss., 100 (2007), pp. 458-461
[[58]]
R. Tessler,S. Wu,R. Fiori,C.K. Macgowan,J. Belik
Sildenafil acutely reverses the hypoxic pulmonary vasoconstriction res- ponse of the newborn pig
Pediatr Res., 64 (2008), pp. 251-255 http://dx.doi.org/10.1203/PDR.0b013e31817d9b93
[[59]]
J. Belik,R.B. Light
Effect of increased afterload on right ven- tricular function in newborn pigs
J Appl Physiol., 66 (1989), pp. 863-869
[[60]]
A.L. Peterson,S. Deatsman,M.A. Frommelt,K. Mussatto,P.C. Frommelt
Correlation of echocardiographic markers and therapy in persistent pulmonary hypertension of the newborn
Pediatr Cardiol., 30 (2009), pp. 160-165 http://dx.doi.org/10.1007/s00246-008-9303-3
[[61]]
V.E. Fabris,M.D. Pato,J. Belik
Progressive lung and cardiac changes associated with pulmonary hypertension in the fetal rat
Pediatr Pulmonol., 31 (2001), pp. 344-353
[[62]]
C.P. Ricachinevsky,S.L. Amantea
Treatment of pulmonary arte- rial hypertension
J Pediatr (Rio J)., 82 (2006), pp. S153-S165
[[63]]
J.C. Roze,C. Tohier,C. Maingueneau,M. Lefevre,A. Mouzard
Response to dobutamine and dopamine in the hypotensive very preterm infant
Arch Dis Child., 69 (1993), pp. 59-63
[[64]]
E.M. Dempsey,K.J. Barrington
Evaluation and treatment of hypotension in the preterm infant
Clin Perinatol., 36 (2009), pp. 75-85 http://dx.doi.org/10.1016/j.clp.2008.09.003
[[65]]
Evans N. Which inotrope for which baby? Arch Dis Child Fetal Neonatal Ed. 2006; 91:F213-20.
[[66]]
P. Tourneux,T. Rakza,A. Bouissou,G. Krim,L. Storme
Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension
J Pediatr., 153 (2008), pp. 345-349 http://dx.doi.org/10.1016/j.jpeds.2008.03.007
[[67]]
S. Jaillard,V. Houfflin-Debarge,Y. Riou,T. Rakza,S. Klosowski,P. Lequien
Effects of catecholamines on the pulmonary circulation in the ovine fetus
Am J Physiol Regul Integr Comp Physiol., 281 (2001), pp. R607-R614
[[68]]
E. Magnenant,S. Jaillard,P. Deruelle,V. Houfflin-Debarge,Y. Riou,S. Klosowski
Role of the alpha2-adrenoceptors on the pulmonary circulation in the ovine fetus
[[69]]
W.H. Drummond,G.A. Gregory,M.A. Heymann,R.A. Phibbs
The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension
J Pediatr., 98 (1981), pp. 603-611
[[70]]
M.D. Schreiber,M.A. Heymann,S.J. Soifer
Increased arterial pH, not decreased PaCO2, attenuates hypoxia-induced pulmonary vasoconstriction in newborn lambs
[[71]]
The Neonatal Inhaled Nitric Oxide Study Grou p. Inhaled Nitric Oxide in Full-Term and Nearly Full-Term Infants with Hypoxic Respiratory Failure. N Engl J Med. 1997;336:597-604. in press.
[[72]]
D.L. Wessel,I. Adatia,L.J. Van Marter,J.E. Thompson,J.W. Kane,A.R. Stark
Improved oxygenation in a randomized trial of inhaled nitric oxide for persistent pulmonary hypertension of the newborn
Pediatrics., 100 (1997), pp. E7
[[73]]
Committee on Fetus and Newborn. Use of Inhaled Nitric Oxide. Pediatrics. 2000;106:344-5. in press.
[[74]]
D.N. Cornfield,R.C. Maynard,R.A. deRegnier,S.F. Guiang III,J.E. Barbato,C.E. Milla
Randomized, controlled trial of low- dose inhaled nitric oxide in the treatment of term and near- term infants with respiratory failure and pulmonary hyper- tension
Pediatrics., 104 (1999), pp. 1089-1094
[[75]]
D. Davidson,E.S. Barefield,J. Kattwinkel,G. Dudell,M. Damask,R. Straube
Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose- response, multicenter study
The I-NO/PPHN Study Grou p. Pediatrics., 101 (1998), pp. 325-334
[[76]]
R.H. Clark,T.J. Kueser,M.W. Walker,W.M. Southgate,J.L. Huckaby,J.A. Perez
Low-dose nitric oxide therapy for per- sistent pulmonary hypertension of the newborn Clinical Inhaled Nitric Oxide Research Group
N Engl J Med., 342 (2000), pp. 469-474 http://dx.doi.org/10.1056/NEJM200002173420704
[[77]]
J. Albert,P. Harbut,S. Zielinski,S. Ryniak,C. Gillis-Haegerstrand,R. Lindwall
Prolonged exposure to inhaled nitric oxi- de does not affect haemostasis in piglets
Intensive Care Med., 33 (2007), pp. 1594-1601 http://dx.doi.org/10.1007/s00134-007-0666-3
[[78]]
M. Beghetti,C. Sparling,P.N. Cox,D. Stephens,I. Adatia,Inhaled NO
inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers
Am J Physiol Heart Circ Physiol., 285 (2003), pp. H637-H642 http://dx.doi.org/10.1152/ajpheart.00622.2002
[[79]]
A.P. Bos,D. Tibboel,V.C. Koot,F.W. Hazebroek,J.C. Molenaar
Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy
J Pediatr Surg., 28 (1993), pp. 1463-1465
[[80]]
T. Nakayama,H. Shimada,S. Takatsuki,H. Hoshida,T. Ishikita,H. Matsuura
Efficacy and limitations of continuous intra- venous epoprostenol therapy for idiopathic pulmonary arte- rial hypertension in Japanese children
Circ J., 71 (2007), pp. 1785-1790
[[81]]
R. Ewert,C. Schaper,M. Halank,S. Glaser,C.F. Opitz
Inhalative iloprost – pharmacology and clinical application
Expert Opin Pharmacother., 10 (2009), pp. 2195-2207 http://dx.doi.org/10.1517/14656560903164228
[[82]]
H.H. Leuchte,J. Behr
Iloprost for idiopathic pulmonary arterial hypertension
Expert Rev Cardiovasc Ther., 3 (2005), pp. 215-223 http://dx.doi.org/10.1586/14779072.3.2.215
[[83]]
M. Ehlen,B. Wiebe
Iloprost in persistent pulmonary hyperten- sion of the newborn
Cardiol Young., 13 (2003), pp. 361-363
[[84]]
U. Chotigeat,S. Jaratwashirakul
Inhaled iloprost for severe persistent pulmonary hypertension of the newborn
J Med Assoc Thai., 90 (2007), pp. 167-170
[[85]]
U. Krishnan
Management of pulmonary arterial hypertension in the neonatal unit
[[86]]
A. Vargas-Origel,G. Gomez-Rodriguez,C. Aldana-Valenzuela,M.M. Vela-Huerta,S.B. Alarcon-Santos,N. Amador-Licona
The use of sildenafil in persistent pulmonary hypertension of the newborn
Am J Perinatol., 27 (2010), pp. 225-230 http://dx.doi.org/10.1055/s-0029-1239496
[[87]]
R.H. Steinhorn,J.P. Kinsella,C. Pierce,G. Butrous,M. Dilleen,M. Oakes
Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension
J Pediatr., 155 (2009), pp. 841-847 http://dx.doi.org/10.1016/j.jpeds.2009.06.012
[[88]]
M.R. Bentlin,A. Saito,A.K. De Luca,G. Bossolan,R.C. Bonatto,A.S. Martins
[Sildenafil for pulmonary hypertension treatment after cardiac surgery]
J Pediatr (Rio J)., 81 (2005), pp. 175-178
[[89]]
E.C. Oliveira,C.F. Amaral
Sildenafil in the management of idio- pathic pulmonary arterial hypertension in children and ado- lescents
J Pediatr (Rio J)., 81 (2005), pp. 390-394
[[90]]
L. Leibovitch,I. Matok,G. Paret
Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension
Drugs., 67 (2007), pp. 57-73
[[91]]
C. Stocker,D.J. Penny,C.P. Brizard,A.D. Cochrane,R. Soto,L.S. Shekerdemian
Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery
Intensive Care Med., 29 (2003), pp. 1996-2003 http://dx.doi.org/10.1007/s00134-003-2016-4
[[92]]
P. Shah,A. Ohlsson
Sildenafil for pulmonary hypertension in neonates
Cochrane Database Syst Rev., (2007), pp. CD005494
[[93]]
R.B. Tessler,M. Zadinello,H. Fiori,M. Colvero,J. Belik,R.M. Fiori
Tadalafil improves oxygenation in a model of newborn pulmonary hypertension
Pediatr Crit Care Med., 9 (2008), pp. 330-332 http://dx.doi.org/10.1097/PCC.0b013e31816c7035
[[94]]
S. Lakshminrusimha,N.F. Porta,K.N. Farrow,B. Chen,S.F. Gugino,V.H. Kumar
Milrinone enhances relaxation to prosta- cyclin and iloprost in pulmonary arteries isolated from lam- bs with persistent pulmonary hypertension of the newborn
Pediatr Crit Care Med., 9 (2009), pp. 106-112
[[95]]
P.J. McNamara,F. Laique,S. Muang-In,H.E. Whyte
Milrinone improves oxygenation in neonates with severe persis- tent pulmonary hypertension of the newborn
J Crit Care., 21 (2006), pp. 217-222 http://dx.doi.org/10.1016/j.jcrc.2006.01.001
[[96]]
D. Bassler,K. Choong,P. McNamara,H. Kirpalani
Neonatal per- sistent pulmonary hypertension treated with milrinone: four case reports
Biol Neonate., 1 (2006), pp. 1-5
[[97]]
A.A. Rosenberg,J. Kennaugh,S.L. Koppenhafer,M. Loomis,B.A. Chatfield,S.H. Abman
Elevated immunoreactive endo- thelin-1 levels in newborn infants with persistent pulmonary hypertension
J Pediatr., 123 (1993), pp. 109-114
[[98]]
C. Goissen,L. Ghyselen,P. Tourneux,G. Krim,L. Storme,P. Bou
Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan
Eur J Pediatr., 167 (2008), pp. 437-440 http://dx.doi.org/10.1007/s00431-007-0531-y
[[99]]
N. Nakwan,D. Choksuchat,R. Saksawad,P. Thammachote
Successful treatment of persistent pulmonary hypertension of the newborn with bosentan
Acta Paediatr., 98 (2009), pp. 1683-1685 http://dx.doi.org/10.1111/j.1651-2227.2009.01386.x
[[100]]
S. Lakshminrusimha,J.A. Russell,S. Wedgwood,S.F. Gugino,J.A. Kazzaz,J.M. Davis
Superoxide dismutase improves oxygenation and reduces oxidation in neonatal pulmonary hypertension
Am J Respir Crit Care Med., 174 (2006), pp. 1370-1377 http://dx.doi.org/10.1164/rccm.200605-676OC
[[101]]
G.G. Konduri,D.C. Garcia,N.J. Kazzi,S. Shankaran
Adenosine infusion improves oxygenation in term infants with respira- tory failure
Pediatrics., 97 (1996), pp. 295-300
[[102]]
C. Ng,O. Franklin,M. Vaidya,C. Pierce,A. Petros
Adenosine infusion for the management of persistent pulmonary hyper- tension of the newborn
Pediatr Crit Care Med., 5 (2004), pp. 10-13 http://dx.doi.org/10.1097/01.CCM.0000105309.27519.27
[[103]]
A. Motti,C. Tissot,P.C. Rimensberger,A. Prina-Rousso,Y. Aggoun,M. Berner
Intravenous adenosine for refractory pul- monary hypertension in a low-weight premature newborn: a potential new drug for rescue therapy
Pediatr Crit Care Med., 7 (2006), pp. 380-382 http://dx.doi.org/10.1097/01.PCC.0000225000.78627.EB
[[104]]
F. Raimondi,F. Migliaro,L. Capasso,G. Ausanio,M. Bisceglia,P. Giliberti
Intravenous magnesium sulphate vs. inhaled nitric oxide for moderate, persistent pulmonary hypertension of the newborn. A Multicentre, retrospective study
J Trop Pediatr., 54 (2008), pp. 196-199 http://dx.doi.org/10.1093/tropej/fmm101
[[105]]
J.J. Ho,G. Rasa
Magnesium sulfate for persistent pulmonary hypertension of the newborn
Cochrane Database Syst Rev., (2007), pp. CD005588
[[106]]
J.P. Kinsella,S.H. Abman
High-frequency oscillatory ventilation augments the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn: Nitric Oxide Study Group
Chest., 114 (1998), pp. 105
[[107]]
R.D. Findlay,H.W. Taeusch,F.J. Walther
Surfactant replace- ment therapy for meconium aspiration syndrome
Pediatrics., 97 (1996), pp. 48-52
[[108]]
A. Lotze,B.R. Mitchell,D.I. Bulas,E.M. Zola,R.A. Shalwitz,J.H. Gunkel
Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Survanta in Term Infants Study Group
J Pediatr., 132 (1998), pp. 40-47

Como citar este artigo: Cabral JE, Belik J. Persistent pulmonary hypertension of the newborn: recent advances in pathophysiology and treatment. J Pediatr (Rio J). 2013;89:226–42.

Copyright © 2013. Sociedade Brasileira de Pediatria
Idiomas
Jornal de Pediatria

Receba a nossa Newsletter

Opções de artigo
Ferramentas
en pt
Taxa de publicaçao Publication fee
Os artigos submetidos a partir de 1º de setembro de 2018, que forem aceitos para publicação no Jornal de Pediatria, estarão sujeitos a uma taxa para que tenham sua publicação garantida. O artigo aceito somente será publicado após a comprovação do pagamento da taxa de publicação. Ao submeterem o manuscrito a este jornal, os autores concordam com esses termos. A submissão dos manuscritos continua gratuita. Para mais informações, contate assessoria@jped.com.br. Articles submitted as of September 1, 2018, which are accepted for publication in the Jornal de Pediatria, will be subject to a fee to have their publication guaranteed. The accepted article will only be published after proof of the publication fee payment. By submitting the manuscript to this journal, the authors agree to these terms. Manuscript submission remains free of charge. For more information, contact assessoria@jped.com.br.
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.