Persistent Pulmonary hypertension of the Newborn: Role of Platelet Activating Factor. A Mini Review
Main Article Content
Abstract
The fetus is exposed to chronic low oxygen environment, which is a desirable physiological condition for fetal pulmonary development and hemodynamics. On the other hand, if the newborn is exposed to low oxygen levels, the blood vessels of the lung thicken and narrow due to overgrowth of the smooth muscle cells in the vessel walls, the baby remains blue, resulting in the condition known as persistent pulmonary hypertension of the newborn (PPHN). In the United States, PPHN occurs in 0.43-6.8 newborns per 1000 live births and is most common in term and near-term newborns. Despite the significant advances in management of newborn respiratory diseases, PPHN is still associated with a high morbidity and mortality, accounting for about 10-20% of neonatal mortality. The current mainstay of therapy for PPHN is mechanical ventilation, fluid therapy and use of anti-inflammatory agents for cardiovascular support. Correction of hemodynamic acid/base balance and oxygen supplementation are also commendable therapeutic interventions. New ideas in PPHN therapy should include incorporation of in vivo, ex vivo and in vitro studies on intracellular signaling pathways of pulmonary vascular development in the state of PPHN. These new ideas will entail studies of the cross talk between vasodilators and vasoconstrictors in perinatal pulmonary hemodynamics.
Keywords:
Hypoxia, Hyperoxia, PAF-acetyl hydrolase, PAF receptor, PAF receptor binding, pulmonary smooth muscle
Article Details
How to Cite
IBE, Basil O. et al.
Persistent Pulmonary hypertension of the Newborn: Role of Platelet Activating Factor. A Mini Review.
Medical Research Archives, [S.l.], v. 10, n. 5, june 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2802>. Date accessed: 20 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i5.2802.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Abman SH. Recent advances in the pathogenesis and treatment of persistent pulmonary hypertension of the newborn. Neonatology; 2007;94(4): 283-290. Doi: 10.1159/000101343. PMID: 17575471.
2. Kumar VH, Hutchinson AA, Lakshminrusimha S, Morin FC 3rd, Wynn RJ, Ryan RM. Characteristics of pulmonary hypertension in preterm neonates. J Perinatol 2007;27(4): 214-219. Doi: 10.1038/sj.jp.7211673. PMID: 17330053
3. Teitel DF, Iwamoto HS, Rudolph AM. Changes in the pulmonary circulation during birth-related events. Pediatr Res. 1990;27(4 Pt 1): 372-8. Doi: 10.1203/00006450-199004000-00010.27:372-378. PMID: 2342829
4. Haworth SH, Hislop AA. Adaptation of the pulmonary circulation to extra-uterine life in the pig and its relevance to human infant. Cardiovascular Research. 1981;15: 108-119 DOI: 10.1093/cvr/15.2.108 PMID: 7260976
5. Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO: focus on PPHN Semin Perinatol. 2005;29(1): 8-14. Doi: 10.1053/j.semperi.2005.02.003. PMID: 15921147.
6. Nakwan N, Jain S, Kumar K, Hosono S, Hammoud M, Elsayed YY, et al. An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment, and outcome. The Journal of maternal-fetal and neonatal medicine. 2020;13: 2032-2037. doi.org/10.1080/14767058.2018.1536740. PMID: 30318951
7. Muraskas JK, Juretschke LJ, Weiss MG, Bhola M, Besinger RE. Neonatal-Perinatal Risk Factors for the Development of Persistent Pulmonary Hypertension of the Newborn in Preterm Newborns. Am J Perinatol 2001;18(2): 087-092. Doi: 10.1055/s-2001-13638. PMID: 11383705.
8. Siefkes HM and Lakshminrusimha S. Management of Systemic Hypotension in Term Infants with Persistent Pulmonary Hypertension of the Newborn (PPHN) – An Illustrated Review. Arch Dis Child Fetal Neonatal Ed. 2021;106(4): 446–455. Doi: 10.1136/archdischild-2020-31970. PMID: 33478959.
9. Katz VL, Bowes, Jr. WA. Meconium aspiration syndrome: reflections on a murky subject. Am J Obstet Gynecol. 1992;166(1 Pt 1): 171-83. doi: 10.1016/0002-9378(92)91856-6. PMID: 1733193.
10. Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Semin Perinatol. 2016;40(3): 160-73. Doi: 10.1053/j.semperi.2015.12.004. PMID: 26778236.
11. Conrad C and Newberry D. Understanding the Pathophysiology, Implications, and Treatment Options of Patent Ductus Arteriosus in the Neonatal Population. Adv Neonatal Care. 2019;19(3): 179-187. Doi: 10.1097/ANC.0000000000000590. PMID: 30720481.
12. Abman SH. Pulmonary Hypertension: The Hidden Danger for Newborns. Neonatology. 2021;118(2): 211-217. Doi: 10.1159/000516107. PMID: 33951650.
13. Yum SK, Seo YM, Moon C-J, Youn Y-A, Sung IK. Therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy and reversible persistent pulmonary hypertension: short-term hospital outcomes. J Matern Fetal Neonatal Med. 2018;31(23): 3108-3114. Doi: 10.1080/14767058.2017.1365123. PMID: 28783995.
14. Steurer MA, Baer RJ, Oltman S, Ryckman KK, Feuer SK, Rogers E, Keller RL, Jelliffe-Pawlowski LJ. Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life. J Pediatr. 2019;213: 58-65.e4. Doi: 10.1016/j.jpeds.2019.06.053. PMID: 31399244.
15. Konduri CG, U Olivia Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am. 2009;56(3): 579-600. Doi: 10.1016/j.pcl.2009.04.004. PMID: 19501693.
16. Xu Liu X, Mei M, Chen X, Lu Y, Dong X, Hu L, Hu X, Cheng G, Cao Y, Yang L, Zhou W. Identification of genetic factors underlying persistent pulmonary hypertension of newborns in a cohort of Chinese neonates. Respir Res. 2019;20(1): 174-184. Doi: 10.1186/s12931-019-1148-1. PMID: 31382961.
17. Bin-Nun A, and Schreiber M D. Role of iNO in the modulation of pulmonary vascular resistance. J Perinatol. 2008;28 Suppl 3: S84-92. Doi: 10.1038/jp.2008.161. PMID: 19057617.
18. Farrow KN, Lakshminrusimha S, Czech L, Groh BS, Gugino SF, Davis JM, Russell A, Steinhorn RH. SOD and inhaled nitric oxide normalize phosphodiesterase 5 expression and activity in neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2010;299(1): L109-16. Doi: 10.1152/ajplung.00309.2009. PMID: 20400523.
19. Chester M, Seedorf G, Tourneux P, Gien J, Tseng N, Grover T, Wright J, Stasch J-P, Abman SH. Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2011;301(5): L755-64. Doi: 10.1152/ajplung.00138.2010. PMID: 21856817
20. Chen JY, Su PH, Chen FL, Lee HS. Inhaled nitric oxide in the management of persistent pulmonary hypertension of term infants. J Formos Med Assoc. 2001;100(10): 703-6. PMID: 11760378
21. Deruelle P, Grover TR, Abman SH. Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. Am J Physiol Lung Cell Mol Physiol. 2005;289(5): L798-806. Doi: 10.1152/ajplung.00119.2005. PMID 15964898.
22. Nagy S, Harris MB, Ju H, Bhatia J, Venema RC. pH and nitric oxide synthase activity and expression in bovine aortic endothelial cells Acta Paediatr. 2006;95(7): 814-817. Doi: 10.1080/08035250500462083. PMID: 16801177.
23. Hanouni M, Bernal G, McBride S, Narvaez VRF, Basil O Ibe BO. Hypoxia and hyperoxia potentiate PAF receptor-mediated effects in newborn ovine pulmonary arterial smooth muscle cells: significance in oxygen therapy of PPHN. Physiol Rep. 2016;4(12):e12840. Doi: 10.14814/phy2.12840. PMID: 27354543.
24. Daniela Mokra D, Juraj Mokry J, Katarina Matasova K. Phosphodiesterase inhibitors: Potential role in the respiratory distress of neonates. Pediatr Pulmonol. 2018;53(9): 1318-1325. Doi: 10.1002/ppul.24082. PMID: 29905405.
25. Sikarwar AS, Hinton M, Santhosh KT, Dhanaraj P, Talabis M, Chelikani P, Dakshinamurti S. Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2018;315(6): L933-L944. Doi: 10.1152/ajplung.00130.2018. PMID: 30234376.
26. Majed BH, Khalil RA. Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn Pharmacol Rev. 2012 Jul;64(3):540-82. Doi: 10.1124/pr.111.004770. PMID: 22679221
27. Lakshminrusimha S, Porta NFM, Farrow KN, Chen B, Gugino SF, Kumar VH, Russell JA, Steinhorn RH. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med. 2009 Jan;10(1):106-12. Doi: 10.1097/PCC.0b013e3181936aee. PMID: 19057444.
28. Santhosh KT, Elkhateeb O, Nolette N, Outbih O, Halayko AJ, Dakshinamurti S. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes. Br J Pharmacol. 2011;163(6): 1223-36. Doi: 10.1111/j.1476-5381.2011.01306.x. PMID: 21385177
29. Liu G, Wu H-W, Li Z-G. Study on sildenafil combined with inhalational nitric oxide therapy on the curative effects and serum levels of HIF-1α, ET-1, and calcium in neonatal pulmonary hypertension. Eur Rev Med Pharmacol Sci. 2018;22(14): 4683-4690. Doi: 10.26355/eurrev_201807_15529. PMID: 30058708.
30. B Weinberger B, K Weiss K, D E Heck DE, D L Laskin DL, J D Laskin JD. Pharmacologic therapy of persistent pulmonary hypertension of the newborn Pharmacol Ther. 2001 Jan;89(1):67-79. Doi: 10.1016/s0163-7258(00)00104-2. PMID: 11316514.
31. Haas KM, Suzuki S, Yamaguchi N, Kato I, Ban K, Tanaka T, Fukuda S, Togari H. Nitric oxide further attenuates pulmonary hypertension in magnesium-treated piglets. Pediatr Int. 2002 Dec;44(6):670-674. Doi: 10.1046/j.1442-200x.2002.01632.x. PMID: 12421268.
32. Thébaud B, Petit T, De Lagausie P, Dall'Ava-Santucci J, Mercier J-C, Dinh-Xuan AT. Altered guanylyl-cyclase activity in vitro of pulmonary arteries from fetal lambs with congenital diaphragmatic hernia. Am J Respir Cell Mol Biol. 2002;27(1): 42-47. Doi: 10.1165/ajrcmb.27.1.4712. PMID: 12091244.
33. Shaul PW, Wells LB. Oxygen modulates nitric oxide production selectively in fetal pulmonary endothelial cells. Am J Respir Cell Mol Biol. 1994;11(4): 432-438. Doi: 10.1165/ajrcmb.11.4.7522486. PMID: 7522486.
34. Mandell E, Kinsella JP, Abman SH. Persistent pulmonary hypertension of the newborn. Pediatr Pulmonol. 2021;56(3): 661-669. Doi: 10.1002/ppul.25073. PMID: 32930508.
35. Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol. 2014;38(2):78-91. Doi: 10.1053/j.semperi.2013.11.004. PMID: 24580763.
36. Pedersen J, Hedegaard ER, Simonsen U, Krüger M, Infanger M, Grimm D. Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn. Basic Clin Pharmacol Toxicol. 2018;123(4): 392-406. Doi: 10.1111/bcpt.13051. PMID: 29855164.
37. Mamdouh El-Ghandour M, Bahaa Hammad B, Mohamed Ghanem M, Manal A M Antonios MAM. Efficacy of Milrinone Plus Sildenafil in the Treatment of Neonates with Persistent Pulmonary Hypertension in Resource-Limited Settings: Results of a Randomized, Double-Blind Trial. Paediatr Drugs. 2020;22(6): 685-693. Doi: 10.1007/s40272-020-00412-4. PMID: 32856285
38. Spillers J. PPHN: is sildenafil the new nitric? A review of the literature
Adv Neonatal Care. 2010;10(2):69-74. Doi: 10.1097/ANC.0b013e3181d5c501. PMID: 20386371.
39. Fuloria M, Aschner JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med. 2017;22(4):220-226. Doi: 10.1016/j.siny.2017.03.004. PMID: 28342684.
40. McHoney M, Hammond P. Role of ECMO in congenital diaphragmatic hernia.
Arch Dis Child Fetal Neonatal Ed. 2018;103(2): F178-F181. Doi: 10.1136/archdischild-2016-311707. PMID: 29138242.
41. Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO: focus on PPHN. Semin Perinatol. 2005 Feb;29(1):8-14.
Doi: 10.1053/j.semperi.2005.02.003. PMID: 15921147
42. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl): D34-41. Doi: 10.1016/j.jacc.2013.10.029. PMID: 24355639
43. Lai MY, Chu SM, Lakshminrusimha S, Lin HC. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol. 2018 Feb;59(1):15-23. Doi: 10.1016/j.pedneo.2016.09.011. PMID: 28923474.
44. Wedgwood S, Steinhorn RH, Lakshminrusimha S. Optimal oxygenation and role of free radicals in PPHN. Free Radic Biol Med. 2019;142: 97-106. Doi: 10.1016/j.freeradbiomed.2019.04.001. PMID: 30995536
45. Miller LE, Stoller JZ, Fraga MV. Point-of-care ultrasound in the neonatal ICU. Curr Opin Pediatr. 2020 Apr;32(2):216-227. Doi: 10.1097/MOP.0000000000000863. PMID: 31851056.
46. Geggel RL, Reid LM. The structural basis of PPHN.
Clin Perinatol. 1984;11(3): 525-49. PMID: 6386268.
47. Conrad C, Newberry D. Understanding the Pathophysiology, Implications, and Treatment Options of Patent Ductus Arteriosus in the Neonatal Population. Adv Neonatal Care. 2019 Jun;19(3):179-187. Doi: 10.1097/ANC.0000000000000590. PMID: 30720481.
48. Conlon TW, Nishisaki A, Singh Y, Bhombal S, De Luca D, Kessler DO, Su ER, Chen AE, Fraga MV. Moving Beyond the Stethoscope: Diagnostic Point-of-Care Ultrasound in Pediatric Practice. Pediatrics. 2019;144(4): e20191402. Doi: 10.1542/peds.2019-1402. PMID: 31481415.
49. Bush A, Griese M, Seidl E, Kerem E, Reu S, Nicholson AG. Early onset children's interstitial lung diseases: Discrete entities or manifestations of pulmonary dysmaturity? Paediatr Respir Rev. 2019;30: 65-71. Doi: 10.1016/j.prrv.2018.09.004. PMID: 30552058.
50. Szafranski P, Gambin T, Karolak JA, Popek E, Stankiewicz P. Lung-specific distant enhancer cis regulates expression of FOXF1 and lncRNA FENDRR.
Hum Mutat. 2021;42(6): 694-698. Doi: 10.1002/humu.24198. PMID: 33739555.
51. Dawes GS. Pulmonary circulation in the foetus and newborn. Br Med Bull. 1966;22: 61-65. PMID: 5321818
52. Turner JM, Mitchell MD, Kumar SS. The physiology of intrapartum fetal compromise at term. Am J Obstet Gynecol. 2020 Jan;222(1):17-26. Doi: 10.1016/j.ajog.2019.07.032. PMID: 31351061.
53. Salva AM, Ibe BO, Cliborn E, Reyes G, Raj JU.
Hypoxia attenuates metabolism of platelet activating factor by fetal and newborn lamb lungs. J Lipid Res. 1996;37(4):783-789. PMID: 8732778
54. Ibe BO, Abdallah MF, Portugal AM Raj JU. Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinases. Cell Prolif. 2008;41(2): 208-29. Doi: 10.1111/j.1365-2184.2008.00517.x. PMID: 18336468.
55. Bixby CE, Ibe BO, Abdallah MF, Zhou W, Hislop AA, Longo LD, Raj JU. Role of platelet-activating factor in pulmonary vascular remodeling associated with chronic high altitude hypoxia in ovine fetal lambs. Am J Physiol Lung Cell Mol Physiol. 2007;293(6): L1475-L1482. Doi: 10.1152/ajplung.00089.2007. PMID: 17951313.
56. Hinton M, Mellow L, Halayko AJ, Gutsol A, Dakshinamurti S. Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L375-84. Doi: 10.1152/ajplung.00307.2005. PMID: 16214814.
57. Haworth SG. Eur Pulmonary hypertension in childhood.
Respir J. 1993;6(7):1037-43. PMID: 8370430.
58. Perreault T, Coceani F. Endothelin in the perinatal circulation.
Can J Physiol Pharmacol. 2003;81(6): 644-53. Doi: 10.1139/y03-013. PMID: 12839275
59. Ibe BO, Ameer A, Portugal AM, Renteria L, Raj JU. Platelet-activating factor modulates activity of cyclic nucleotides in fetal ovine pulmonary vascular smooth muscle. J Pharmacol Exp Ther. 2007;320(2): 728-37. Doi: 10.1124/jpet.106.111914. PMID: 17085546
60. Argiolas L, Fabi F, del Basso P. Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in guineapig: role of platelets and cyclo-oxygenase metabolites. Br. J. Pharmacol. 1995;114: 203-209.
61. Beqaj S, Jakkaraju S, Mattingly RR, Pan Desi, Schuger L. High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. J. Cell. Biol. 2002;156: 893-903. Doi: 10.1111/cpe.12052. PMID: 24033386.
62 Berk BC (2001) Vascular smooth muscle cell growth: autocrine growth mechanisms. Physiol. Rev. 81: 999-1032.
63. Dewachter L, Adnot S, Gulgnabert C, Tu L, Marcos E, Fadel E, Humbert M, Dartevelle P, Simonneau G, Naeije R, Eddahibi S. Bone morphogenetic protein signaling in heritable versus idiopathic pulmonary hypertension. Eur. Respir. J. 2009;34: 1100-1110.
64. Dupre DJ, Rola-Pleszcynski M, Stankova J. (2012) Rescue of internalization-defective platelet-activating factor receptor function by EB50/NHERF1. J. Cell Commun. Signal. 2012;6: 205-216. Doi: 10.1007/s12079-012-0175-1 PMID: 22878922.
65. Etienne-Manneville S, Hall A. (2002) Rho GTPases in cell biology. Nature 2002:420: 629-635. DOI: 10.1038/nature01148. PMID: 12478284.
66. Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, McMurtry IF. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am. J. Physiol. Lung Cell Mol. Physiol. 2004;287: L656-664. DOI: 10.1152/ajplung.00090.2003. PMID: 14977625
67. Ibe BO, Douglass AM, Douglass SM, Renteria LS. Platelet activating factor receptor binding and contractile protein expression by ovine fetal pulmonary vascular smooth muscle cells: Role in rho kinase mediation of PAF receptor-linked physiological responses. Medical Research Archives. 2021 July;9: 1-29.
68. Renteria LS, Austin M, Lazaro M, Andrews MA, Lustina J, Raj JU, Ibe BO. RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation. Cell Prolif. 2013 Oct;46(5):563-75. Doi: 10.1111/cpr.12052. Epub 2013 Aug 22. PMID: 24033386
69. Gao Y, Raj JU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev 2010;90: 1291-1335. Doi: 10.1152/physrev.00032.2009. PMID:20959617.
70. Ward JPT, McMurtry IF. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem. Curr. Opin. Pharmacol. 2009;9: 287-296.Doi: 10.1016/j.coph.2009.02.006. PMID: 19297247.
71. Given J. Tseng N, Seedorf G, Roe G, Abman SH. Peroxisome proliferator activated receptor-ү-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014;306: L299-L308. Doi: 10. 1152/ ajplung.00271.2013. PMID: 24375792.
72. Ibe BO, Abdallah MF, Portugal AM, Raj JU. Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation. Role of nuclear factor-kappa B and cyclin-dependent kinases. Cell. Prolif. 2008;41: 208-229. Doi: 10. 1111/.1365.2184.2008.00517.x. PMID18336468.
73. Ibe BO, Hibler S, Raj JU. Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb. J. Appl. Physiol. 1998;85: 1079-1085. Doi:10.1152/jappl.1998.85.3.1079. PMID: 9729586.
74. Ibe BO, Portugal AM, Chaturvedi S, Raj JU. Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fatal pulmonary vascular smooth muscle. Am. J. Physiol. Lung Cell Mol. Physiol. 2005;288: L879-L886. Doi: 10. 1152/ajplung.00341.2004. PMID: 15618453.
75. Alvira CM, Sukovich DJ, Lyu S-C, Cornfield DN (2010) Rho kinase modulates postnatal adaptation of the pulmonary circulation through separate effects on pulmonary artery and smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 2010;299: L872-L878. Doi: 10. 1152/ajplung.00199.2010. PMID:20709731.
76. Parikh VN, Jin RC, Rabello S, Gulbahce N, White K, Hale A, Cottrill KA, Shaik RS, Waxman AB, Zhang YY, Maron BA, Hartner JC, Fujiwara Y, Orkin SH, Haley KJ, Barabási AL, Loscalzo J, Chan SY. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation. 2012;125(12): 1520-1532. Doi: 10.1161/CIRCULATIONAHA.111.060269. PMID: 22371328.
77. Renteria LS, Austin M, Lazaro M, Andrews MA, Lustina J, Raj JU, Ibe BO. RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation. Cell Prolif. 2013;46(5): 563-575. Doi: 10.1111/cpr.12052. PMID: 24033386
78. Martin C, Göggel R, Ressmeyer AR, Uhlig S. Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase. Am J Physiol Lung Cell Mol Physiol. 2004;287(1): L250-257. Doi: 10.1152/ajplung.00420.2003. PMID: 15064228.
79. Badejo AM Jr, Dhaliwal JS, Casey DB, Gallen TB, Greco AJ, Kadowitz PJ. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol. 2008;295(5): L828-836. Doi: 10.1152/ajplung.00042.2008. PMID: 18689606
80. Caplan MS, Hsueh W, Sun XM, Gidding SS, Hageman JR. Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1): 1258-1262. Doi: 10.1164/ajrccm/142.6_Pt_1.1258. PMID: 2252241.
81. Caplan MS, Adler L, Kelly A, Hsueh W. Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. Biochim Biophys Acta 1992 Oct 30;1128(2-3): 205-510. Doi: 10.1016/005-2760(92)90309-j. PMID: 1420292
82. Renteria LS, Cruz E, Ibe BO. Platelet activating factor synthesis and receptor-mediated signalling are down-regulated in ovine newborn lungs: Relevance in postnatal pulmonary adaptation and persistent pulmonary hypertension of the newborn. J Dev Orig Health Dis. 2013 Dec;4(6): 458-569. Doi: 10.1017/S2040174413000366. PMID: 24924225.
83. Ibe BO, Sander FC, Raj JU. Ibe BO, Platelet activating factor acetylhydrolase activity in lamb lungs is up-regulated in the immediate newborn period. Mol Genet Metab. 2000 Jan;69(1): 46-55. Doi: 10.1006/mgme.1999.2940. 2000. PMID: 10655157.
84. Ogbozor UD, Opene M, Renteria LS, McBride S, Ibe BO. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation. Mol Genet Metab Rep. 2015 Jun 3;4: 11-18. Doi: 10.1016/j.ymgmr.2015.05.003. PMID: 26966681
85. Renteria LS, Raj JU, Ibe BO. Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells. Mol Genet Metab. 2010 Dec;101(4): 400-408. Doi: 10.1016/j.ymgme.2010.08.005. PMID: 20813571.
86. Surmeli Onay O, Korkmaz A, Yigit S, Yurdakok M. Hypoxic-ischemic enterocolitis: a proposal of a new terminology for early NEC or NEC-like disease in preterm infants, a single-center prospective observational study. Eur J Pediatr. 2020 Apr;179(4): 561-570. Doi: 10.1007/s00431-019-03539-w. PMID: 31853687.
87. Turner-Gomes SO, Boudreau N, Rabinovitch M. Effect of ambient oxygen changes on platelet activating factor production by fetal ovine endothelial cells. Prostaglandins. 1991 May;41(5):463-72. Doi: 10.1016/0090-6980(91)90052-h. PMID: 1862226.
88. Ibe BO, Pham HH, Kääpä P, Raj JU. Maturational changes in ovine pulmonary metabolism of platelet-activating factor: implications for postnatal adaptation. Mol Genet Metab. 2001 Nov;74(3): 385-395. Doi: 10.1006/mgme.2001.3253. PMID: 11708870
89. Muguruma K, Gray PW, Tjoelker LW, Johnston JM. The central role of PAF in necrotizing enterocolitis development. Adv Exp Med Biol. 1997;407: 379-382. Doi: 10.1007/978-1-4899-1813-0_56. PMID: 9321979.
90. Ibe BO, Sander FC, Raj JU. Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4): H1168-1176. Doi: 10.1152/ajpheart.2000.278.4.H1168. PMID: 10749711.
91. Ishii S, Nagase T, Shindou H, Takizawa H, Ouchi Y, ShimizuT. Platelet-activating factor receptor develops airway hyperresponsiveness independently of airway inflammation in a murine asthma model J Immunol. 2004 Jun 1;172(11): 7095-7102. doi: 10.4049/jimmunol.172.11.7095. Doi: 10.4049/jimmunol.172.11.7095. PMID: 15153532.
92. Shukla SD. Platelet-activating factor receptor and signal transduction mechanisms. FASEB J. 1992 Mar;6(6):2296-2301. Doi: 10.1096/fasebj.6.6.1312046. PMID: 1312046
93. Snyder F. Platelet-activating factor and its analogs: Metabolic pathways and related intracellular processes. Biochim Biophys Acta. 1995 Feb 9;1254(3): 231-249. Doi: 10.1016/0005-2760(94)00192-2. PMID: 7857964.
94. Argiolas L, Fabi F, and del Basso P. Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in guinea-pig: role of platelets and cyclo-oxygenase metabolites. Br J Pharmacol. 1995 Jan;114(1): 203-209. Doi: 10.1111/j.1476-5381. 1995.tb14926.x. PMID: 7712019
95. Gao Y, Zhou H, and Raj JU. PAF induces relaxation of pulmonary arteries but contraction of pulmonary veins in the ferret. Am J Physiol Heart Circ Physio. 1995 Aug;269(2 Pt 2): H704-709. Doi: 10.1152/ajpheart.1995.269.2.H704. PMID: 7653635.
96. Kono N, Arai H. Platelet-activating factor acetylhydrolases: An overview and update. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6): 922-931.
Doi: 10.1016/j.bbalip.2018.07.006. PMID: 30055287.
97. Deng M, Guo H, Tam J, Johnson BM, Brickey WJ, New JS, Lenox A, et al. Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR J Exp Med. 2019 Dec 2;216(12):2838-2853. Doi: 10.1084/jem.20190111. PMID: 31558613.
98. Maclennan KM, Smith PF, Darlington CL. Platelet-activating factor in the CNS. Prog Neurobiol. 1996 Dec;50(5-6): 585-596. Doi: 10.1016/s0301-0082(96)00047-0.Prog Neurobiol. 1996. PMID: 9015828.
99. Ishii S, Nagase T, Tashiro F, Ikuta S, Sato S, Waga I, Kume K, Miyazaki J, Shimizu T. Shimizu. Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor. EMBO J. 1997 Jan 2; 16(1): 133–142. Doi: 10.1093/emboj/16.1.133. PMID: 9009274
100. Ishii S, Shimizu T. Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog Lipid Res. 2000 Jan;39(1):41-82.
Doi: 10.1016/s0163-7827(99)00016-8. PMID: 10729607.
101. Ishii S, Nagase T, Shimizu T. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69: 599-609. Doi: 10.1016/s0090-6980(02)00058-8. PMID: 12432946.
102. Reznichenko A and Korstanje R. The Role of Platelet-Activating Factor in Mesangial Pathophysiology. Am J Pathol. 2015 Apr;185(4): 888-96. Doi: 10.1016/j.ajpath.2014.11.025. PMID: 25655028
103. Derek Strassheim D, Karoor V, Stenmark K, Verin A, Gerasimovskaya E. A current view of G protein-coupled receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention. Vessel Plus. Vessel Plus. 2018;2: 1-32. Doi: 10.20517/2574-1209.2018.44. PMID: 31380505.
104. Heuer HO, Casals-Stenzel J, Muacevic G, Weber KG. Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. J Pharmacol Exp Ther. 1990;255: 962-968. PMID: 2262914.
105. Ono S, Westcott JY, Voelkel NF. PAF antagonist inhibit pulmonary vascular remodeling induced by hypobaric hypoxia in rat. J Appl Physiol. 1992 73(3);1084-1092.
Doi: 10.1152/jappl.1992.73.3.1084. PMID: 1400021.
106. Dent G, Ukena D, Chanez P, Sybrecht G, Barnes P. Characterization of PAF receptors on human neutrophils using the specific antagonist, WEB 2086. Correlation between receptor binding and function. FEBS Lett. 1989;244(2): 365-368. Doi: 10.1016/0014.5793(89)80564-2. PMID: 2537761.
107. Adamus WS, Heuer HO, Meade CJ, Schilling JC. Inhibitory effects of the new PAF acether antagonist WEB-2086 on pharmacologic changes induced by PAF inhalation in human beings. Clin Pharmacol Ther. 1990;47(4): 456-62. Doi: 10.1038/clpt.1990.57. PMID: 2328553.
108. Carlson SA, Chattergee TK Fisher RA. The third intracellular domain of platelet-activating factor receptor is a critical determinant in receptor coupling to phosphoinositide phospholipase C-activating G proteins. Studies using intracellular domain minigenes and receptor chimeras. J Biol Chem. 1996;271(38): 23146-23153. Doi: 10.1074/jbc.271.38.23146. PMID: 8798508.
109. Shukla SD, Fairbairn RL, Gell DA, Latham RD, Sohal SS Waalters EH, O’Toole RF. An antagonist of platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptcoccus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 2016;11: 1647-1655. Doi: 10.2147/COPD.S108698. PMID: 27524890.
110. Ibe BO, Abdallah MF, Raj JU. Physiological and biochemical consequences of Exposure of neonatal rats to chronic hypoxia. Medical Research Archives. 2020 Oct;8: 1-16.
111. Terashita Z, Imura Y, Nishikawa K. Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet. Biochem Pharmacol. 1985;34(9): 1491-1495. Doi: 10.1016/0006-2952(85)90689-6. PMID: 2986648.
112. Platelet-activating factor antagonists.
Negro Alvarez JM, Miralles López JC, Ortiz Martínez JL, Abellán Alemán A, Rubio del Barrio R. Allergol Immunopathol (Madr). 1997 Sep-Oct;25(5): 249-258. Allergol Immunopathol (Madr). 1997. PMID: 9395010.
113. Hayashi M, Kimura J, Oh-Ishi S, Tsushima S, Nomura H. Characterization of the activity of a platelet activating factor antagonist, CV-3988. Jpn J Pharmacol. 1987 Jun;44(2): 127-134. Doi: 10.1254/jjp.44.127. PMID: 2888915.
114. Shimada T, Hirose T, Matsumoto I, Aikawa T Platelet-activating factor acts on cortisol secretion by perfused guinea-pig adrenals via calcium-/phospholipid-dependent mechanisms. J Endocrinol. 2005;184(2): 381-91. Doi: 10.1677/joe.1.05937. PMID: 15684346.
115. Lee CM, Jung WK, Na G, Lee DS, Park SG, Seo SK, Yang JW, Yea SS, Lee YM, Park WS, Choi IW. Inhibitory effects of the platelet-activating factor receptor antagonists, CV-3988 and Ginkgolide B, on alkali burn-induced corneal neovascularization. Cutan Ocul Toxicol. 2015;34(1): 53-60.
Doi: 10.3109/15569527.2014.903573. PMID: 24754407.
2. Kumar VH, Hutchinson AA, Lakshminrusimha S, Morin FC 3rd, Wynn RJ, Ryan RM. Characteristics of pulmonary hypertension in preterm neonates. J Perinatol 2007;27(4): 214-219. Doi: 10.1038/sj.jp.7211673. PMID: 17330053
3. Teitel DF, Iwamoto HS, Rudolph AM. Changes in the pulmonary circulation during birth-related events. Pediatr Res. 1990;27(4 Pt 1): 372-8. Doi: 10.1203/00006450-199004000-00010.27:372-378. PMID: 2342829
4. Haworth SH, Hislop AA. Adaptation of the pulmonary circulation to extra-uterine life in the pig and its relevance to human infant. Cardiovascular Research. 1981;15: 108-119 DOI: 10.1093/cvr/15.2.108 PMID: 7260976
5. Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO: focus on PPHN Semin Perinatol. 2005;29(1): 8-14. Doi: 10.1053/j.semperi.2005.02.003. PMID: 15921147.
6. Nakwan N, Jain S, Kumar K, Hosono S, Hammoud M, Elsayed YY, et al. An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment, and outcome. The Journal of maternal-fetal and neonatal medicine. 2020;13: 2032-2037. doi.org/10.1080/14767058.2018.1536740. PMID: 30318951
7. Muraskas JK, Juretschke LJ, Weiss MG, Bhola M, Besinger RE. Neonatal-Perinatal Risk Factors for the Development of Persistent Pulmonary Hypertension of the Newborn in Preterm Newborns. Am J Perinatol 2001;18(2): 087-092. Doi: 10.1055/s-2001-13638. PMID: 11383705.
8. Siefkes HM and Lakshminrusimha S. Management of Systemic Hypotension in Term Infants with Persistent Pulmonary Hypertension of the Newborn (PPHN) – An Illustrated Review. Arch Dis Child Fetal Neonatal Ed. 2021;106(4): 446–455. Doi: 10.1136/archdischild-2020-31970. PMID: 33478959.
9. Katz VL, Bowes, Jr. WA. Meconium aspiration syndrome: reflections on a murky subject. Am J Obstet Gynecol. 1992;166(1 Pt 1): 171-83. doi: 10.1016/0002-9378(92)91856-6. PMID: 1733193.
10. Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Semin Perinatol. 2016;40(3): 160-73. Doi: 10.1053/j.semperi.2015.12.004. PMID: 26778236.
11. Conrad C and Newberry D. Understanding the Pathophysiology, Implications, and Treatment Options of Patent Ductus Arteriosus in the Neonatal Population. Adv Neonatal Care. 2019;19(3): 179-187. Doi: 10.1097/ANC.0000000000000590. PMID: 30720481.
12. Abman SH. Pulmonary Hypertension: The Hidden Danger for Newborns. Neonatology. 2021;118(2): 211-217. Doi: 10.1159/000516107. PMID: 33951650.
13. Yum SK, Seo YM, Moon C-J, Youn Y-A, Sung IK. Therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy and reversible persistent pulmonary hypertension: short-term hospital outcomes. J Matern Fetal Neonatal Med. 2018;31(23): 3108-3114. Doi: 10.1080/14767058.2017.1365123. PMID: 28783995.
14. Steurer MA, Baer RJ, Oltman S, Ryckman KK, Feuer SK, Rogers E, Keller RL, Jelliffe-Pawlowski LJ. Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life. J Pediatr. 2019;213: 58-65.e4. Doi: 10.1016/j.jpeds.2019.06.053. PMID: 31399244.
15. Konduri CG, U Olivia Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatr Clin North Am. 2009;56(3): 579-600. Doi: 10.1016/j.pcl.2009.04.004. PMID: 19501693.
16. Xu Liu X, Mei M, Chen X, Lu Y, Dong X, Hu L, Hu X, Cheng G, Cao Y, Yang L, Zhou W. Identification of genetic factors underlying persistent pulmonary hypertension of newborns in a cohort of Chinese neonates. Respir Res. 2019;20(1): 174-184. Doi: 10.1186/s12931-019-1148-1. PMID: 31382961.
17. Bin-Nun A, and Schreiber M D. Role of iNO in the modulation of pulmonary vascular resistance. J Perinatol. 2008;28 Suppl 3: S84-92. Doi: 10.1038/jp.2008.161. PMID: 19057617.
18. Farrow KN, Lakshminrusimha S, Czech L, Groh BS, Gugino SF, Davis JM, Russell A, Steinhorn RH. SOD and inhaled nitric oxide normalize phosphodiesterase 5 expression and activity in neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2010;299(1): L109-16. Doi: 10.1152/ajplung.00309.2009. PMID: 20400523.
19. Chester M, Seedorf G, Tourneux P, Gien J, Tseng N, Grover T, Wright J, Stasch J-P, Abman SH. Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2011;301(5): L755-64. Doi: 10.1152/ajplung.00138.2010. PMID: 21856817
20. Chen JY, Su PH, Chen FL, Lee HS. Inhaled nitric oxide in the management of persistent pulmonary hypertension of term infants. J Formos Med Assoc. 2001;100(10): 703-6. PMID: 11760378
21. Deruelle P, Grover TR, Abman SH. Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. Am J Physiol Lung Cell Mol Physiol. 2005;289(5): L798-806. Doi: 10.1152/ajplung.00119.2005. PMID 15964898.
22. Nagy S, Harris MB, Ju H, Bhatia J, Venema RC. pH and nitric oxide synthase activity and expression in bovine aortic endothelial cells Acta Paediatr. 2006;95(7): 814-817. Doi: 10.1080/08035250500462083. PMID: 16801177.
23. Hanouni M, Bernal G, McBride S, Narvaez VRF, Basil O Ibe BO. Hypoxia and hyperoxia potentiate PAF receptor-mediated effects in newborn ovine pulmonary arterial smooth muscle cells: significance in oxygen therapy of PPHN. Physiol Rep. 2016;4(12):e12840. Doi: 10.14814/phy2.12840. PMID: 27354543.
24. Daniela Mokra D, Juraj Mokry J, Katarina Matasova K. Phosphodiesterase inhibitors: Potential role in the respiratory distress of neonates. Pediatr Pulmonol. 2018;53(9): 1318-1325. Doi: 10.1002/ppul.24082. PMID: 29905405.
25. Sikarwar AS, Hinton M, Santhosh KT, Dhanaraj P, Talabis M, Chelikani P, Dakshinamurti S. Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2018;315(6): L933-L944. Doi: 10.1152/ajplung.00130.2018. PMID: 30234376.
26. Majed BH, Khalil RA. Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn Pharmacol Rev. 2012 Jul;64(3):540-82. Doi: 10.1124/pr.111.004770. PMID: 22679221
27. Lakshminrusimha S, Porta NFM, Farrow KN, Chen B, Gugino SF, Kumar VH, Russell JA, Steinhorn RH. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med. 2009 Jan;10(1):106-12. Doi: 10.1097/PCC.0b013e3181936aee. PMID: 19057444.
28. Santhosh KT, Elkhateeb O, Nolette N, Outbih O, Halayko AJ, Dakshinamurti S. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes. Br J Pharmacol. 2011;163(6): 1223-36. Doi: 10.1111/j.1476-5381.2011.01306.x. PMID: 21385177
29. Liu G, Wu H-W, Li Z-G. Study on sildenafil combined with inhalational nitric oxide therapy on the curative effects and serum levels of HIF-1α, ET-1, and calcium in neonatal pulmonary hypertension. Eur Rev Med Pharmacol Sci. 2018;22(14): 4683-4690. Doi: 10.26355/eurrev_201807_15529. PMID: 30058708.
30. B Weinberger B, K Weiss K, D E Heck DE, D L Laskin DL, J D Laskin JD. Pharmacologic therapy of persistent pulmonary hypertension of the newborn Pharmacol Ther. 2001 Jan;89(1):67-79. Doi: 10.1016/s0163-7258(00)00104-2. PMID: 11316514.
31. Haas KM, Suzuki S, Yamaguchi N, Kato I, Ban K, Tanaka T, Fukuda S, Togari H. Nitric oxide further attenuates pulmonary hypertension in magnesium-treated piglets. Pediatr Int. 2002 Dec;44(6):670-674. Doi: 10.1046/j.1442-200x.2002.01632.x. PMID: 12421268.
32. Thébaud B, Petit T, De Lagausie P, Dall'Ava-Santucci J, Mercier J-C, Dinh-Xuan AT. Altered guanylyl-cyclase activity in vitro of pulmonary arteries from fetal lambs with congenital diaphragmatic hernia. Am J Respir Cell Mol Biol. 2002;27(1): 42-47. Doi: 10.1165/ajrcmb.27.1.4712. PMID: 12091244.
33. Shaul PW, Wells LB. Oxygen modulates nitric oxide production selectively in fetal pulmonary endothelial cells. Am J Respir Cell Mol Biol. 1994;11(4): 432-438. Doi: 10.1165/ajrcmb.11.4.7522486. PMID: 7522486.
34. Mandell E, Kinsella JP, Abman SH. Persistent pulmonary hypertension of the newborn. Pediatr Pulmonol. 2021;56(3): 661-669. Doi: 10.1002/ppul.25073. PMID: 32930508.
35. Nair J, Lakshminrusimha S. Update on PPHN: mechanisms and treatment. Semin Perinatol. 2014;38(2):78-91. Doi: 10.1053/j.semperi.2013.11.004. PMID: 24580763.
36. Pedersen J, Hedegaard ER, Simonsen U, Krüger M, Infanger M, Grimm D. Current and Future Treatments for Persistent Pulmonary Hypertension in the Newborn. Basic Clin Pharmacol Toxicol. 2018;123(4): 392-406. Doi: 10.1111/bcpt.13051. PMID: 29855164.
37. Mamdouh El-Ghandour M, Bahaa Hammad B, Mohamed Ghanem M, Manal A M Antonios MAM. Efficacy of Milrinone Plus Sildenafil in the Treatment of Neonates with Persistent Pulmonary Hypertension in Resource-Limited Settings: Results of a Randomized, Double-Blind Trial. Paediatr Drugs. 2020;22(6): 685-693. Doi: 10.1007/s40272-020-00412-4. PMID: 32856285
38. Spillers J. PPHN: is sildenafil the new nitric? A review of the literature
Adv Neonatal Care. 2010;10(2):69-74. Doi: 10.1097/ANC.0b013e3181d5c501. PMID: 20386371.
39. Fuloria M, Aschner JL. Persistent pulmonary hypertension of the newborn. Semin Fetal Neonatal Med. 2017;22(4):220-226. Doi: 10.1016/j.siny.2017.03.004. PMID: 28342684.
40. McHoney M, Hammond P. Role of ECMO in congenital diaphragmatic hernia.
Arch Dis Child Fetal Neonatal Ed. 2018;103(2): F178-F181. Doi: 10.1136/archdischild-2016-311707. PMID: 29138242.
41. Farrow KN, Fliman P, Steinhorn RH. The diseases treated with ECMO: focus on PPHN. Semin Perinatol. 2005 Feb;29(1):8-14.
Doi: 10.1053/j.semperi.2005.02.003. PMID: 15921147
42. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl): D34-41. Doi: 10.1016/j.jacc.2013.10.029. PMID: 24355639
43. Lai MY, Chu SM, Lakshminrusimha S, Lin HC. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol. 2018 Feb;59(1):15-23. Doi: 10.1016/j.pedneo.2016.09.011. PMID: 28923474.
44. Wedgwood S, Steinhorn RH, Lakshminrusimha S. Optimal oxygenation and role of free radicals in PPHN. Free Radic Biol Med. 2019;142: 97-106. Doi: 10.1016/j.freeradbiomed.2019.04.001. PMID: 30995536
45. Miller LE, Stoller JZ, Fraga MV. Point-of-care ultrasound in the neonatal ICU. Curr Opin Pediatr. 2020 Apr;32(2):216-227. Doi: 10.1097/MOP.0000000000000863. PMID: 31851056.
46. Geggel RL, Reid LM. The structural basis of PPHN.
Clin Perinatol. 1984;11(3): 525-49. PMID: 6386268.
47. Conrad C, Newberry D. Understanding the Pathophysiology, Implications, and Treatment Options of Patent Ductus Arteriosus in the Neonatal Population. Adv Neonatal Care. 2019 Jun;19(3):179-187. Doi: 10.1097/ANC.0000000000000590. PMID: 30720481.
48. Conlon TW, Nishisaki A, Singh Y, Bhombal S, De Luca D, Kessler DO, Su ER, Chen AE, Fraga MV. Moving Beyond the Stethoscope: Diagnostic Point-of-Care Ultrasound in Pediatric Practice. Pediatrics. 2019;144(4): e20191402. Doi: 10.1542/peds.2019-1402. PMID: 31481415.
49. Bush A, Griese M, Seidl E, Kerem E, Reu S, Nicholson AG. Early onset children's interstitial lung diseases: Discrete entities or manifestations of pulmonary dysmaturity? Paediatr Respir Rev. 2019;30: 65-71. Doi: 10.1016/j.prrv.2018.09.004. PMID: 30552058.
50. Szafranski P, Gambin T, Karolak JA, Popek E, Stankiewicz P. Lung-specific distant enhancer cis regulates expression of FOXF1 and lncRNA FENDRR.
Hum Mutat. 2021;42(6): 694-698. Doi: 10.1002/humu.24198. PMID: 33739555.
51. Dawes GS. Pulmonary circulation in the foetus and newborn. Br Med Bull. 1966;22: 61-65. PMID: 5321818
52. Turner JM, Mitchell MD, Kumar SS. The physiology of intrapartum fetal compromise at term. Am J Obstet Gynecol. 2020 Jan;222(1):17-26. Doi: 10.1016/j.ajog.2019.07.032. PMID: 31351061.
53. Salva AM, Ibe BO, Cliborn E, Reyes G, Raj JU.
Hypoxia attenuates metabolism of platelet activating factor by fetal and newborn lamb lungs. J Lipid Res. 1996;37(4):783-789. PMID: 8732778
54. Ibe BO, Abdallah MF, Portugal AM Raj JU. Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinases. Cell Prolif. 2008;41(2): 208-29. Doi: 10.1111/j.1365-2184.2008.00517.x. PMID: 18336468.
55. Bixby CE, Ibe BO, Abdallah MF, Zhou W, Hislop AA, Longo LD, Raj JU. Role of platelet-activating factor in pulmonary vascular remodeling associated with chronic high altitude hypoxia in ovine fetal lambs. Am J Physiol Lung Cell Mol Physiol. 2007;293(6): L1475-L1482. Doi: 10.1152/ajplung.00089.2007. PMID: 17951313.
56. Hinton M, Mellow L, Halayko AJ, Gutsol A, Dakshinamurti S. Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L375-84. Doi: 10.1152/ajplung.00307.2005. PMID: 16214814.
57. Haworth SG. Eur Pulmonary hypertension in childhood.
Respir J. 1993;6(7):1037-43. PMID: 8370430.
58. Perreault T, Coceani F. Endothelin in the perinatal circulation.
Can J Physiol Pharmacol. 2003;81(6): 644-53. Doi: 10.1139/y03-013. PMID: 12839275
59. Ibe BO, Ameer A, Portugal AM, Renteria L, Raj JU. Platelet-activating factor modulates activity of cyclic nucleotides in fetal ovine pulmonary vascular smooth muscle. J Pharmacol Exp Ther. 2007;320(2): 728-37. Doi: 10.1124/jpet.106.111914. PMID: 17085546
60. Argiolas L, Fabi F, del Basso P. Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in guineapig: role of platelets and cyclo-oxygenase metabolites. Br. J. Pharmacol. 1995;114: 203-209.
61. Beqaj S, Jakkaraju S, Mattingly RR, Pan Desi, Schuger L. High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. J. Cell. Biol. 2002;156: 893-903. Doi: 10.1111/cpe.12052. PMID: 24033386.
62 Berk BC (2001) Vascular smooth muscle cell growth: autocrine growth mechanisms. Physiol. Rev. 81: 999-1032.
63. Dewachter L, Adnot S, Gulgnabert C, Tu L, Marcos E, Fadel E, Humbert M, Dartevelle P, Simonneau G, Naeije R, Eddahibi S. Bone morphogenetic protein signaling in heritable versus idiopathic pulmonary hypertension. Eur. Respir. J. 2009;34: 1100-1110.
64. Dupre DJ, Rola-Pleszcynski M, Stankova J. (2012) Rescue of internalization-defective platelet-activating factor receptor function by EB50/NHERF1. J. Cell Commun. Signal. 2012;6: 205-216. Doi: 10.1007/s12079-012-0175-1 PMID: 22878922.
65. Etienne-Manneville S, Hall A. (2002) Rho GTPases in cell biology. Nature 2002:420: 629-635. DOI: 10.1038/nature01148. PMID: 12478284.
66. Fagan KA, Oka M, Bauer NR, Gebb SA, Ivy DD, Morris KG, McMurtry IF. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am. J. Physiol. Lung Cell Mol. Physiol. 2004;287: L656-664. DOI: 10.1152/ajplung.00090.2003. PMID: 14977625
67. Ibe BO, Douglass AM, Douglass SM, Renteria LS. Platelet activating factor receptor binding and contractile protein expression by ovine fetal pulmonary vascular smooth muscle cells: Role in rho kinase mediation of PAF receptor-linked physiological responses. Medical Research Archives. 2021 July;9: 1-29.
68. Renteria LS, Austin M, Lazaro M, Andrews MA, Lustina J, Raj JU, Ibe BO. RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation. Cell Prolif. 2013 Oct;46(5):563-75. Doi: 10.1111/cpr.12052. Epub 2013 Aug 22. PMID: 24033386
69. Gao Y, Raj JU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev 2010;90: 1291-1335. Doi: 10.1152/physrev.00032.2009. PMID:20959617.
70. Ward JPT, McMurtry IF. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem. Curr. Opin. Pharmacol. 2009;9: 287-296.Doi: 10.1016/j.coph.2009.02.006. PMID: 19297247.
71. Given J. Tseng N, Seedorf G, Roe G, Abman SH. Peroxisome proliferator activated receptor-ү-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014;306: L299-L308. Doi: 10. 1152/ ajplung.00271.2013. PMID: 24375792.
72. Ibe BO, Abdallah MF, Portugal AM, Raj JU. Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation. Role of nuclear factor-kappa B and cyclin-dependent kinases. Cell. Prolif. 2008;41: 208-229. Doi: 10. 1111/.1365.2184.2008.00517.x. PMID18336468.
73. Ibe BO, Hibler S, Raj JU. Platelet-activating factor modulates pulmonary vasomotor tone in the perinatal lamb. J. Appl. Physiol. 1998;85: 1079-1085. Doi:10.1152/jappl.1998.85.3.1079. PMID: 9729586.
74. Ibe BO, Portugal AM, Chaturvedi S, Raj JU. Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fatal pulmonary vascular smooth muscle. Am. J. Physiol. Lung Cell Mol. Physiol. 2005;288: L879-L886. Doi: 10. 1152/ajplung.00341.2004. PMID: 15618453.
75. Alvira CM, Sukovich DJ, Lyu S-C, Cornfield DN (2010) Rho kinase modulates postnatal adaptation of the pulmonary circulation through separate effects on pulmonary artery and smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 2010;299: L872-L878. Doi: 10. 1152/ajplung.00199.2010. PMID:20709731.
76. Parikh VN, Jin RC, Rabello S, Gulbahce N, White K, Hale A, Cottrill KA, Shaik RS, Waxman AB, Zhang YY, Maron BA, Hartner JC, Fujiwara Y, Orkin SH, Haley KJ, Barabási AL, Loscalzo J, Chan SY. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation. 2012;125(12): 1520-1532. Doi: 10.1161/CIRCULATIONAHA.111.060269. PMID: 22371328.
77. Renteria LS, Austin M, Lazaro M, Andrews MA, Lustina J, Raj JU, Ibe BO. RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation. Cell Prolif. 2013;46(5): 563-575. Doi: 10.1111/cpr.12052. PMID: 24033386
78. Martin C, Göggel R, Ressmeyer AR, Uhlig S. Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase. Am J Physiol Lung Cell Mol Physiol. 2004;287(1): L250-257. Doi: 10.1152/ajplung.00420.2003. PMID: 15064228.
79. Badejo AM Jr, Dhaliwal JS, Casey DB, Gallen TB, Greco AJ, Kadowitz PJ. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol. 2008;295(5): L828-836. Doi: 10.1152/ajplung.00042.2008. PMID: 18689606
80. Caplan MS, Hsueh W, Sun XM, Gidding SS, Hageman JR. Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1): 1258-1262. Doi: 10.1164/ajrccm/142.6_Pt_1.1258. PMID: 2252241.
81. Caplan MS, Adler L, Kelly A, Hsueh W. Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. Biochim Biophys Acta 1992 Oct 30;1128(2-3): 205-510. Doi: 10.1016/005-2760(92)90309-j. PMID: 1420292
82. Renteria LS, Cruz E, Ibe BO. Platelet activating factor synthesis and receptor-mediated signalling are down-regulated in ovine newborn lungs: Relevance in postnatal pulmonary adaptation and persistent pulmonary hypertension of the newborn. J Dev Orig Health Dis. 2013 Dec;4(6): 458-569. Doi: 10.1017/S2040174413000366. PMID: 24924225.
83. Ibe BO, Sander FC, Raj JU. Ibe BO, Platelet activating factor acetylhydrolase activity in lamb lungs is up-regulated in the immediate newborn period. Mol Genet Metab. 2000 Jan;69(1): 46-55. Doi: 10.1006/mgme.1999.2940. 2000. PMID: 10655157.
84. Ogbozor UD, Opene M, Renteria LS, McBride S, Ibe BO. Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation. Mol Genet Metab Rep. 2015 Jun 3;4: 11-18. Doi: 10.1016/j.ymgmr.2015.05.003. PMID: 26966681
85. Renteria LS, Raj JU, Ibe BO. Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells. Mol Genet Metab. 2010 Dec;101(4): 400-408. Doi: 10.1016/j.ymgme.2010.08.005. PMID: 20813571.
86. Surmeli Onay O, Korkmaz A, Yigit S, Yurdakok M. Hypoxic-ischemic enterocolitis: a proposal of a new terminology for early NEC or NEC-like disease in preterm infants, a single-center prospective observational study. Eur J Pediatr. 2020 Apr;179(4): 561-570. Doi: 10.1007/s00431-019-03539-w. PMID: 31853687.
87. Turner-Gomes SO, Boudreau N, Rabinovitch M. Effect of ambient oxygen changes on platelet activating factor production by fetal ovine endothelial cells. Prostaglandins. 1991 May;41(5):463-72. Doi: 10.1016/0090-6980(91)90052-h. PMID: 1862226.
88. Ibe BO, Pham HH, Kääpä P, Raj JU. Maturational changes in ovine pulmonary metabolism of platelet-activating factor: implications for postnatal adaptation. Mol Genet Metab. 2001 Nov;74(3): 385-395. Doi: 10.1006/mgme.2001.3253. PMID: 11708870
89. Muguruma K, Gray PW, Tjoelker LW, Johnston JM. The central role of PAF in necrotizing enterocolitis development. Adv Exp Med Biol. 1997;407: 379-382. Doi: 10.1007/978-1-4899-1813-0_56. PMID: 9321979.
90. Ibe BO, Sander FC, Raj JU. Platelet-activating factor receptors in lamb lungs are downregulated immediately after birth. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4): H1168-1176. Doi: 10.1152/ajpheart.2000.278.4.H1168. PMID: 10749711.
91. Ishii S, Nagase T, Shindou H, Takizawa H, Ouchi Y, ShimizuT. Platelet-activating factor receptor develops airway hyperresponsiveness independently of airway inflammation in a murine asthma model J Immunol. 2004 Jun 1;172(11): 7095-7102. doi: 10.4049/jimmunol.172.11.7095. Doi: 10.4049/jimmunol.172.11.7095. PMID: 15153532.
92. Shukla SD. Platelet-activating factor receptor and signal transduction mechanisms. FASEB J. 1992 Mar;6(6):2296-2301. Doi: 10.1096/fasebj.6.6.1312046. PMID: 1312046
93. Snyder F. Platelet-activating factor and its analogs: Metabolic pathways and related intracellular processes. Biochim Biophys Acta. 1995 Feb 9;1254(3): 231-249. Doi: 10.1016/0005-2760(94)00192-2. PMID: 7857964.
94. Argiolas L, Fabi F, and del Basso P. Mechanisms of pulmonary vasoconstriction and bronchoconstriction produced by PAF in guinea-pig: role of platelets and cyclo-oxygenase metabolites. Br J Pharmacol. 1995 Jan;114(1): 203-209. Doi: 10.1111/j.1476-5381. 1995.tb14926.x. PMID: 7712019
95. Gao Y, Zhou H, and Raj JU. PAF induces relaxation of pulmonary arteries but contraction of pulmonary veins in the ferret. Am J Physiol Heart Circ Physio. 1995 Aug;269(2 Pt 2): H704-709. Doi: 10.1152/ajpheart.1995.269.2.H704. PMID: 7653635.
96. Kono N, Arai H. Platelet-activating factor acetylhydrolases: An overview and update. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6): 922-931.
Doi: 10.1016/j.bbalip.2018.07.006. PMID: 30055287.
97. Deng M, Guo H, Tam J, Johnson BM, Brickey WJ, New JS, Lenox A, et al. Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR J Exp Med. 2019 Dec 2;216(12):2838-2853. Doi: 10.1084/jem.20190111. PMID: 31558613.
98. Maclennan KM, Smith PF, Darlington CL. Platelet-activating factor in the CNS. Prog Neurobiol. 1996 Dec;50(5-6): 585-596. Doi: 10.1016/s0301-0082(96)00047-0.Prog Neurobiol. 1996. PMID: 9015828.
99. Ishii S, Nagase T, Tashiro F, Ikuta S, Sato S, Waga I, Kume K, Miyazaki J, Shimizu T. Shimizu. Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor. EMBO J. 1997 Jan 2; 16(1): 133–142. Doi: 10.1093/emboj/16.1.133. PMID: 9009274
100. Ishii S, Shimizu T. Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog Lipid Res. 2000 Jan;39(1):41-82.
Doi: 10.1016/s0163-7827(99)00016-8. PMID: 10729607.
101. Ishii S, Nagase T, Shimizu T. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat. 2002 Aug;68-69: 599-609. Doi: 10.1016/s0090-6980(02)00058-8. PMID: 12432946.
102. Reznichenko A and Korstanje R. The Role of Platelet-Activating Factor in Mesangial Pathophysiology. Am J Pathol. 2015 Apr;185(4): 888-96. Doi: 10.1016/j.ajpath.2014.11.025. PMID: 25655028
103. Derek Strassheim D, Karoor V, Stenmark K, Verin A, Gerasimovskaya E. A current view of G protein-coupled receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention. Vessel Plus. Vessel Plus. 2018;2: 1-32. Doi: 10.20517/2574-1209.2018.44. PMID: 31380505.
104. Heuer HO, Casals-Stenzel J, Muacevic G, Weber KG. Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. J Pharmacol Exp Ther. 1990;255: 962-968. PMID: 2262914.
105. Ono S, Westcott JY, Voelkel NF. PAF antagonist inhibit pulmonary vascular remodeling induced by hypobaric hypoxia in rat. J Appl Physiol. 1992 73(3);1084-1092.
Doi: 10.1152/jappl.1992.73.3.1084. PMID: 1400021.
106. Dent G, Ukena D, Chanez P, Sybrecht G, Barnes P. Characterization of PAF receptors on human neutrophils using the specific antagonist, WEB 2086. Correlation between receptor binding and function. FEBS Lett. 1989;244(2): 365-368. Doi: 10.1016/0014.5793(89)80564-2. PMID: 2537761.
107. Adamus WS, Heuer HO, Meade CJ, Schilling JC. Inhibitory effects of the new PAF acether antagonist WEB-2086 on pharmacologic changes induced by PAF inhalation in human beings. Clin Pharmacol Ther. 1990;47(4): 456-62. Doi: 10.1038/clpt.1990.57. PMID: 2328553.
108. Carlson SA, Chattergee TK Fisher RA. The third intracellular domain of platelet-activating factor receptor is a critical determinant in receptor coupling to phosphoinositide phospholipase C-activating G proteins. Studies using intracellular domain minigenes and receptor chimeras. J Biol Chem. 1996;271(38): 23146-23153. Doi: 10.1074/jbc.271.38.23146. PMID: 8798508.
109. Shukla SD, Fairbairn RL, Gell DA, Latham RD, Sohal SS Waalters EH, O’Toole RF. An antagonist of platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptcoccus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke. Int J Chron Obstruct Pulmon Dis. 2016;11: 1647-1655. Doi: 10.2147/COPD.S108698. PMID: 27524890.
110. Ibe BO, Abdallah MF, Raj JU. Physiological and biochemical consequences of Exposure of neonatal rats to chronic hypoxia. Medical Research Archives. 2020 Oct;8: 1-16.
111. Terashita Z, Imura Y, Nishikawa K. Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet. Biochem Pharmacol. 1985;34(9): 1491-1495. Doi: 10.1016/0006-2952(85)90689-6. PMID: 2986648.
112. Platelet-activating factor antagonists.
Negro Alvarez JM, Miralles López JC, Ortiz Martínez JL, Abellán Alemán A, Rubio del Barrio R. Allergol Immunopathol (Madr). 1997 Sep-Oct;25(5): 249-258. Allergol Immunopathol (Madr). 1997. PMID: 9395010.
113. Hayashi M, Kimura J, Oh-Ishi S, Tsushima S, Nomura H. Characterization of the activity of a platelet activating factor antagonist, CV-3988. Jpn J Pharmacol. 1987 Jun;44(2): 127-134. Doi: 10.1254/jjp.44.127. PMID: 2888915.
114. Shimada T, Hirose T, Matsumoto I, Aikawa T Platelet-activating factor acts on cortisol secretion by perfused guinea-pig adrenals via calcium-/phospholipid-dependent mechanisms. J Endocrinol. 2005;184(2): 381-91. Doi: 10.1677/joe.1.05937. PMID: 15684346.
115. Lee CM, Jung WK, Na G, Lee DS, Park SG, Seo SK, Yang JW, Yea SS, Lee YM, Park WS, Choi IW. Inhibitory effects of the platelet-activating factor receptor antagonists, CV-3988 and Ginkgolide B, on alkali burn-induced corneal neovascularization. Cutan Ocul Toxicol. 2015;34(1): 53-60.
Doi: 10.3109/15569527.2014.903573. PMID: 24754407.