Abstract:Persistent pulmonary hypertension of the newborn (PPHN) secondary to congenital diaphragmatic hernia (CDH) is one of the main reasons for high mortality of the newborn and a factor that leads to respiratory and circulatory failure in newborns with CDH. PPHN secondary to CDH is severe and difficult to treat, with poor prognosis. Therefore, prenatal intervention aims for preventing the pathological process of CDH, especially the etiological treatment for impeding the development of PPHN, has become a research focus. Given unknown causes and poor outcomes of PPHN, this article summarizes the research advances in pathogenesis and treatment of PPHN secondary to CDH based on related studies so as to provide a reference for relevant studies and clinical treatment.
XIAO Bin,LIU Min,XU Chang. Research advances in persistent pulmonary hypertension of the newborn secondary to congenital diaphragmatic hernia[J]. CJCP, 2015, 17(9): 1013-1019.
Mychaliska G, Bryner B, Dechert R, et al. Safety and efficacy of perflubron-induced lung growth in neonates with congenital diaphragmatic hernia:results of a prospective randomized trial[J]. J Pediatr Surg, 2015, 50(7):1083-1087.
[3]
Rollins MD. Recent advances in the management of congenital diaphragmatic hernia[J]. Curr Opin Pediatr, 2012, 24(3):379-385.
[4]
Cabral JE, Belik J. Persistent pulmonary hypertension of the newborn:recent advances in pathophysiology and treatment[J]. J Pediatr (Rio J), 2013, 89(3):226-242.
[5]
Healy F, Lin W, Feng R, et al. An association between pulmonary hypertension and impaired lung function in infants with congenital diaphragmatic hernia[J]. Pediatr Pulmonol, 2014. [Epub ahead of print].
[6]
Acker SN, Mandell EW, Sims-Lucas S, et al. Histologic identification of prominent intrapulmonary anastomotic vessels in severe congenital diaphragmatic hernia[J]. J Pediatr, 2015, 166(1):178-183.
[7]
Storme L, Aubry E, Rakza T, et al. Pathophysiology of persistent pulmonary hypertension of the newborn:impact of the perinatal environment[J]. Arch Cardiovasc Dis, 2013, 106(3):169-177.
Keijzer R, Liu J, Deimling J, et al. Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia[J]. Am J Pathol, 2000, 156(4):1299-1306.
[10]
Hofmann AD, Takahashi T, Duess JW, et al. Increased pulmonary vascular expression of Krüppel-like factor 5 and activated survivin in experimental congenital diaphragmatic hernia[J]. Pediatr Surg Int, 2014, 30(12):1191-1197.
[11]
Schmidt AF, Rojas-Moscoso JA, Gonçalves FL, et al. Increased contractility and impaired relaxation of the left pulmonary artery in a rabbit model of congenital diaphragmatic hernia[J]. Pediatr Surg Int, 2013, 29(5):489-494.
[12]
Acker SN, Seedorf GJ, Abman SH, et al. Pulmonary artery endothelial cell dysfunction and decreased populations of highly proliferative endothelial cells in experimental congenital diaphragmatic hernia[J]. Am J Physiol Lung Cell Mol Physiol, 2013, 305(12):L943-L952.
[13]
Jin Y, Kaluza D, Jakobsson L. VEGF, Notch and TGFβ/BMPs in regulation of sprouting angiogenesis and vascular patterning[J]. Biochem Soc Trans, 2014, 42(6):1576-1583.
[14]
Sbragia L, Nassr AC, Gonçalves FL, et al. VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen[J]. Braz J Med Biol Res, 2014, 47(2):171-178.
[15]
Chang R, Andreoli S, Ng YS, et al. VEGF expression is downregulated in nitrofen-induced congenital diaphragmatic hernia[J]. J Pediatr Surg, 2004, 39(6):825-828.
[16]
Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis[J]. Nat Rev Mol Cell Biol, 2007, 8(6):464-478.
[17]
Okazaki T, Sharma HS, McCune SK, et al. Pulmonary vascular balance in congenital diaphragmatic hernia:enhanced endothelin-1 gene expression as a possible cause of pulmonary vasoconstriction[J]. J Pediatr Surg, 1998, 33(1):81-84.
[18]
Mesdag V, Andrieux J, Coulon C, et al. Pathogenesis of congenital diaphragmatic hernia:additional clues regarding the involvement of the endothelin system[J]. Am J Med Genet A, 2014, 164A(1):208-212.
[19]
Dingemann J, Doi T, Ruttenstock E, et al. Upregulation of endothelin receptors A and B in the nitrofen induced hypoplastic lung occurs early in gestation[J]. Pediatr Surg Int, 2010 Jan, 26(1):65-69.
[20]
Hofmann AD, Friedmacher F, Hunziker M, et al. Upregulation of serotonin-receptor-2a and serotonin transporter expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia[J]. J Pediatr Surg, 2014, 49(6):871-874.
[21]
de Buys Roessingh A, Fouquet V, Aigrain Y, et al. Nitric oxide activity through guanylate cyclase and phosphodiesterase modulation is impaired in fetal lambs with congenital diaphragmatic hernia[J]. J Pediatr Surg, 2011, 46(8):1516-1522.
[22]
Hofmann A, Gosemann JH, Takahashi T, et al. Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia[J]. Birth Defects Res B Dev Reprod Toxicol, 2014, 101(4):341-346.
[23]
Hofmann AD, Takahashi T, Duess J, et al. Increased expression of activated pSTAT3 and PIM-1 in the pulmonary vasculature of experimental congenital diaphragmatic hernia[J]. J Pediatr Surg, 2015, 50(6):908-911.
[24]
Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease[J]. Physiol Rev, 2004, 84(3):767-801.
[25]
Li X, Zhang X, Leathers R, et al. Notch3 signaling promotes the development of pulmonary arterial hypertension[J]. Nat Med, 2009, 15(11):1289-1297.
[26]
Sluiter I, van der Horst I, van der Voorn P, et al. Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia[J]. Exp Mol Pathol, 2013, 94(1):195-202.
[27]
Hansmann G, de Jesus Perez VA, Alastalo TP, et al. An antiproliferative BMP-2/PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension[J]. J Clin Invest, 2008, 118(5):1846-1857.
[28]
Makanga M, Dewachter C, Maruyama H, et al. Downregulated bone morphogenetic protein signaling in nitrofen-induced congenital diaphragmatic hernia[J]. Pediatr Surg Int, 2013, 29(8):823-834.
[29]
Gosemann JH, Friedmacher F, Fujiwara N, et al. Disruption of the bone morphogenetic protein receptor 2 pathway in nitrofeninduced congenital diaphragmatic hernia[J]. Birth Defects Res B Dev Reprod Toxicol, 2013, 98(4):304-309.
[30]
Gosemann JH, Friedmacher F, Hunziker M, et al. Increased activation of NADPH oxidase 4 in the pulmonary vasculature in experimental diaphragmatic hernia[J]. Pediatr Surg Int, 2013, 29(1):3-8.
[31]
Hofmann AD, Friedmacher F, Takahashi T, et al. Increased pulmonary vascular expression of receptor for advanced glycation end products (RAGE) in experimental congenital diaphragmatic hernia[J]. J Pediatr Surg, 2015, 50(5):746-749.
[32]
Hofmann AD, Friedmacher F, Takahashi H, et al. Decreased apelin and apelin-receptor expression in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia[J]. Pediatr Surg Int, 2014, 30(2):197-203.
Takayasu H, Masumoto K, Hagiwara K, et al. Increased pulmonary RhoA expression in the nitrofen-induced congenital diaphragmatic hernia rat model[J]. J Pediatr Surg, 2015. [Epub ahead of print].
[35]
Sakai M, Unemoto K, Solari V, et al. Decreased expression of voltage-gated K+ channels in pulmonary artery smooth muscles cells in nitrofen-induced congenital diaphragmatic hernia in rats[J]. Pediatr Surg Int, 2004, 20(3):192-196.
[36]
de Buys Roessingh AS, de Lagausie P, Barbet JP, et al. Role of ATP-dependent potassium channels in pulmonary vascular tone of fetal lambs with congenital diaphragmatic hernia[J]. Pediatr Res, 2006, 60(5):537-542.
[37]
Yamamura A. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension[J]. J Smooth Muscle Res, 2014, 50:8-17.
[38]
Lusk LA, Wai KC, Mood-Grady AJ, et al. Fetal ultrasound markers of severity predict resolution of pulmonary hypertension in congenital diaphragmatic hernia[J]. Am J Obstet Gynecol, 2015. [Epub ahead of print].
[39]
Fleck S, Bautista G, Keating SM, et al. Fetal production of growth factors and inflammatory mediators predicts pulmonary hypertension in congenital diaphragmatic hernia[J]. Pediatr Res, 2013, 74(3):290-298.
[40]
Brindle ME, Cook EF, Tibboel D, et al. A clinical prediction rule for the severity of congenital diaphragmatic hernias in newborns[J]. Pediatrics, 2014, 134(2):e413-e419.
[41]
Partridge EA, Hanna BD, Rintoul NE, et al. Brain-type natriuretic peptide levels correlate with pulmonary hypertension and requirement for extracorporeal membrane oxygenation in congenital diaphragmatic hernia[J]. J Pediatr Surg, 2015, 50(2):263-266.
[42]
Patel N, Moenkemeyer F, Germano S, et al. Plasma vascular endothelial growth factor A and placental growth factor:novel biomarkers of pulmonary hypertension in congenital diaphragmatic hernia[J]. Am J Physiol Lung Cell Mol Physiol, 2015, 308(4):L378-L383.
[43]
Gonçalves FL, Figueira RL, Simoes AL, et al. Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats[J]. Pediatr Surg Int, 2014, 30(12):1207-1215.
[44]
Liu W, Feng J, Jia H, et al. Effect of prenatal tetrandrine therapy on pulmonary vascular structural remodeling in the nitrofeninduced CDH rat model[J]. Chin Med J (Engl), 2000, 113(9):813-816.
[45]
Lin H, Wang Y, Xiong Z, et al. Effect of antenatal tetrandrine administration on endothelin-1 and epidermal growth factor levels in the lungs of rats with experimental diaphragmatic hernia[J]. J Pediatr Surg, 2007, 42(10):1644-1651.
[46]
Ruano R, Peiro JL, da Silva MM, et al. Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia:preliminary results[J]. Ultrasound Obstet Gynecol, 2013, 42(1):70-76.
[47]
Ruano R, da Silva MM, Campos JA, et al. Fetal pulmonary response after fetoscopic tracheal occlusion for severe isolated congenital diaphragmatic hernia[J]. Obstet Gynecol, 2012, 119(1):93-101.
[48]
Lemus-Varela Mde L, Soliz A, Gomez-Meda BC, et al. Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia[J]. World J Pediatr, 2014, 10(4):354-359.
[49]
Shue EH, Schecter SC, Gong W, et al. Antenatal maternallyadministered phosphodiesterase type 5 inhibitors normalize eNOS expression in the fetal lamb model of congenital diaphragmatic hernia[J]. J Pediatr Surg, 2014, 49(1):39-45.
[50]
Schmidt AF, Gonçalves FL, Regis AC, et al. Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat[J]. Am J Obstet Gynecol, 2012, 207(1):76.e25-e32.
[51]
Makanga M, Maruyama H, Dewachter C, et al. Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia[J]. Am J Physiol Lung Cell Mol Physiol, 2015, 308(7):L672-L682.
[52]
Chang YT, Ringman Uggla A, Osterholm C, et al. Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 302(11):L1159-L1166.
[53]
Gallindo RM, Gonçalves FL, Figueira RL, et al. Ventilation causes pulmonary vascular dilation and modulates the NOS and VEGF pathway on newborn rats with CDH[J]. J Pediatr Surg, 2015, 50(5):842-848.
[54]
Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic hernia:survival treated with very delayed surgery, spontaneous respiration, and no chest tube[J]. J Pediatr Surg, 1995, 30(3):406-409.
[55]
Garcia A, Stolar CJ. Congenital diaphragmatic hernia and protective ventilation strategies in pediatric surgery[J]. Surg Clin North Am, 2012, 92(3):659-668.
[56]
Coleman AJ, Brozanski B, Mahmood B, et al. First 24-h SNAPII score and highest PaCO2 predict the need for ECMO in congenital diaphragmatic hernia[J]. J Pediatr Surg, 2013, 48(11):2214-2218.
[57]
Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO:focus on PPHN[J]. Semin Perinatol, 2005, 29(1):8-14.
[58]
Partridge EA, Peranteau WH, Rintoul NE, et al. Timing of repair of congenital diaphragmatic hernia in patients supported by extracorporeal membrane oxygenation (ECMO)[J]. J Pediatr Surg, 2015, 50(2):260-262.
[59]
Campbell BT, Herbst KW, Briden KE, et al. Inhaled nitric oxide use in neonates with congenital diaphragmatic hernia[J]. Pediatrics, 2014, 134(2):e420-e426.
[60]
Rojas-Moscoso JA, Antunes E, Figueira RR, et al. The soluble guanylyl cyclase activator BAY 60-2770 potently relaxes the pulmonary artery on congenital diaphragmatic hernia rabbit model[J]. Pediatr Surg Int, 2014, 30(10):1031-1036.