Seminars in Perinatology
Volume 34, Issue 3 , Pages 222-230 , June 2010

Inadvertent Relaxation of the Ductus Arteriosus by Pharmacologic Agents that are Commonly Used in the Neonatal Period

  • Jeff Reese, MD

      Affiliations

    • Department of Pediatrics, Monroe Carrell Jr. Children's Hospital at Vanderbilt, Vanderbilt University School of Medicine, Nashville, TN
    • Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN
    • Corresponding Author InformationAddress reprint requests to Jeff Reese, MD, Department of Pediatrics, Vanderbilt University Medical Center, 1125 MRB IV Bldg., 2215 B Garland Ave, Nashville, TN 37232-0656
    • ,
  • Alex Veldman, MD

      Affiliations

    • Monash Newborn and Ritchie Centre for Baby Health Research, Monash Medical Centre, Monash Institute of Medical Research, Melbourne, Vic., Australia
    • ,
  • Lisa Shah

      Affiliations

    • Southern Illinois University School of Medicine, Springfield, IL
    • ,
  • Megan Vucovich

      Affiliations

    • Department of Pediatrics, Monroe Carrell Jr. Children's Hospital at Vanderbilt, Vanderbilt University School of Medicine, Nashville, TN
    • ,
  • Robert B. Cotton, MD

      Affiliations

    • Department of Pediatrics, Monroe Carrell Jr. Children's Hospital at Vanderbilt, Vanderbilt University School of Medicine, Nashville, TN

References 

  1. Coceani F, Olley PM. The response of the ductus arteriosus to prostaglandins. Can J Physiol Pharmacol. 1973;51:220–225
  2. Kajino H, Taniguchi T, Fujieda K, et al. An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo. Pediatr Rev. 2004;56:586–590
  3. Momma K, Toyoshima K, Takeuchi D, et al. In vivo reopening of the neonatal ductus arteriosus by a prostanoid EP4-receptor agonist in the rat. Prostaglandins Other Lipid Mediat. 2005;78:117–128
  4. Leonhardt A, Glaser A, Wegmann M, et al. Expression of prostanoid receptors in human ductus arteriosus. Br J Pharmacol. 2003;138:655–659
  5. Gonzalez A, Sosenko IR, Chandar J, et al. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr. 1996;128:470–478
  6. Rojas MA, Gonzalez A, Bancalari E, et al. Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr. 1995;126:605–610
  7. Friedman Z, Demers LM, Marks KH, et al. Urinary excretion of prostaglandin E following the administration of furosemide and indomethacin to sick low-birth-weight infants. J Pediatr. 1978;93:512–515
  8. Green TP, Thompson TR, Johnson DE, et al. Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome. N Engl J Med. 1983;308:743–748
  9. Arcilla RA, Thilenius OG, Ranniger K. Congestive heart failure from suspected ductal closure in utero. J Pediatr. 1969;75:74–78
  10. Friedman WF, Hirschklau MJ, Printz MP, et al. Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976;295:526–529
  11. Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976;295:530–533
  12. Moise KJ. Effect of advancing gestational age on the frequency of fetal ductal constriction in association with maternal indomethacin use. Am J Obstet Gynecol. 1993;168:1350–1353
  13. Norton ME, Merrill J, Cooper BA, et al. Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med. 1993;329:1602–1607
  14. Hammerman C, Glaser J, Kaplan M, et al. Indomethacin tocolysis increases postnatal patent ductus arteriosus severity. Pediatrics. 1998;102:E56
  15. Clyman RI, Chen YQ, Chemtob S, et al. In utero remodeling of the fetal lamb ductus arteriosus: The role of antenatal indomethacin and avascular zone thickness on vasa vasorum proliferation, neointima formation, and cell death. Circulation. 2001;103:1806–1812
  16. Reese J, Waleh N, Poole SD, et al. Chronic in utero cyclooxygenase inhibition alters PGE2-regulated ductus arteriosus contractile pathways and prevents postnatal closure. Pediatr Review. 2009;66:155–161
  17. Sodini D, Baragatti B, Barogi S, et al. Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse. Br J Pharmacol. 2008;153:1631–1640
  18. Momma K, Toyono M. The role of nitric oxide in dilating the fetal ductus arteriosus in rats. Pediatr Review. 1999;46:311–315
  19. Richard C, Gao J, LaFleur B, et al. Patency of the preterm fetal ductus arteriosus is regulated by endothelial nitric oxide synthase and is independent of Vasa vasorum in the mouse. Am J Physiol Regul Integr Comp Physiol. 2004;287:R652–R660
  20. Keller RL, Tacy TA, Fields S, et al. Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and indomethacin increases ductus constriction in extremely premature newborns. Pediatr Rev. 2005;58:1216–1221
  21. Reese J, O'Mara PW, Poole SD, et al. Regulation of the fetal mouse ductus arteriosus is dependent on interaction of nitric oxide and COX enzymes in the ductal wall. Prostaglandins Other Lipid Mediat. 2009;88:89–96
  22. Kinsella JP, Walsh WF, Bose CL, et al. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: A randomised controlled trial. Lancet. 1999;354:1061–1065
  23. Schreiber MD, Gin-Mestan K, Marks JD, et al. Inhaled nitric oxide in premature infants with the respiratory distress syndrome. N Engl J Med. 2003;349:2099–2107
  24. Mentzer RM, Ely SW, Lasley RD, et al. Hormonal role of adenosine in maintaining patency of the ductus arteriosus in fetal lambs. Ann Surg. 1985;202:223–230
  25. Smith GC, McGrath JC. Characterisation of the effect of oxygen tension on response of fetal rabbit ductus arteriosus to vasodilators. Cardiovasc Res. 1993;27:2205–2211
  26. Toyoshima K, Momma K, Imamura S, et al. In vivo dilatation of the postnatal ductus arteriosus by atrial natriuretic peptide in the rat. J Neonatol. 2007;92:139–144
  27. Liu H, Manganiello V, Waleh N, et al. Expression, activity, and function of phosphodiesterases in the mature and immature ductus arteriosus. Pediatr Rev. 2008;64:477–481
  28. Thebaud B, Michelakis E, Wu XC, et al. Sildenafil reverses O2 constriction of the rabbit ductus arteriosus by inhibiting type 5 phosphodiesterase and activating BK(Ca) channels. Pediatr Rev. 2002;52:19–24
  29. Arishima K, Takizawa T, Oda T, et al. Propranolol inhibits the spontaneous closure of the ductus arteriosus in newborn rats. J Vet Med Sci. 1995;57:943–944
  30. Friedman WF, Printz MP, Kirkpatrick SE, et al. The vasoactivity of the fetal lamb ductus arteriosus studied in utero. Pediatr Rev. 1983;17:331–337
  31. Clyman RI, Roman C. The effects of caffeine on the preterm sheep ductus arteriosus. Pediatr Rev. 2007;62:167–169
  32. del Moral T, Gonzalez-Quintero VH, Claure N, et al. Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birthweight infants. J Perinatol. 2007;27:154–157
  33. Stigson L, Kjellmer I. Serum levels of magnesium at birth related to complications of immaturity. Acta Paediatr. 1997;86:991–994
  34. McGuirl J, Arzuaga B, Lee B: Increased risk for patent ductus arteriosus with antenatal calcium channel blocker exposure in extremely low birthweight infants. Annual Meeting of the Pediatric Academic Societies. EPAS 461, 2009 (abstr)
  35. Watterberg KL, Kelly HW, Johnson JD, et al. Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birthweight (less than 1,500 g) babies. Dev Pharmacol Ther. 1987;10:107–117
  36. Adams HR, Goodman FR, Weiss GB. Alteration of contractile function and calcium ion movements in vascular smooth muscle by gentamicin and other aminoglycoside antibiotics. Antimicrob Agents Chemother. 1974;5:640–646
  37. Belus A, White E. Effects of antibiotics on the contractility and Ca2+ transients of rat cardiac myocytes. Eur J Pharmacol. 2001;412:121–126
  38. Descotes J, Evreux JC. Cardiac depressant effects of some recent aminoglycoside antibiotics. J Antimicrob Chemother. 1981;7:197–200
  39. Gotanda K, Yanagisawa T, Satoh K, et al. Are the cardiovascular effects of gentamicin similar to those of calcium antagonists?. Jpn J Pharmacol. 1988;47:217–227
  40. Coceani F, Liu Y, Seidlitz E, et al. Endothelin A receptor is necessary for O(2) constriction but not closure of ductus arteriosus. Am J Physiol. 1999;277:H1521–H1531
  41. Gergawy M, Vollrath B, Cook D. The mechanism by which aminoglycoside antibiotics cause vasodilation of canine cerebral arteries. Br J Pharmacol. 1998;125:1150–1157
  42. Keith RA, Mangano TJ, Defeo PA, et al. Actions of neomycin on neuronal L-, N-, and non-L/non-N-type voltage-sensitive calcium channel responses. J Mol Neurosci. 1992;3:147–154
  43. Martinez C, Albet C, Agundez JA, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999;65:369–376
  44. Rendic S, Kajfez F, Ruf HH. Characterization of cimetidine, ranitidine, and related structures' interaction with cytochrome P-450. Drug Metab Dispos Biol Fate Chem. 1983;11:137–142
  45. Levine M, Bellward GD. Effect of cimetidine on hepatic cytochrome P450: Evidence for formation of a metabolite-intermediate complex. Drug Metab Dispos Biol Fate Chem. 1995;23:1407–1411
  46. Hazinski TA, France M, Kennedy KA, et al. Cimetidine reduces hyperoxic lung injury in lambs. J Appl Physiol. 1989;67:2586–2592
  47. Cotton RB, Hazinski TA, Morrow JD, et al. Cimetidine does not prevent lung injury in newborn premature infants. Pediatr Review. 2006;59:795–800
  48. Cotton RB, Reese J. Symptomatic patent ductus arteriosus is significantly associated with cimetidine treatment in premature newborn infants at risk for chronic lung disease Pediatr Review, 1999. EPAS. 2009;5511:178;(abstr.)
  49. Coceani F. Cytochrome P450 in the contractile tone of the ductus arteriosus: Regulatory and effector mechanisms. In:  Weir EK,  Archer SL,  Reeves JT editor. The Fetal and Neonatal Pulmonary Circulations. Armonk, NY: Futura Publishing; 1999;p. 331–341
  50. Barrington KJ. Umbilical artery catheters in the newborn: Effects of heparin. Cochrane Database System Rev. 2002;(2):CD000507
  51. Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database of System Rev. 2008;(2):CD002772
  52. Gilbert NC, Nalefski LA. The effect of heparin and dicumarol in increasing the coronary flow volume. J Lab Clin Med. 1949;34:797–805
  53. Urban P, Scheidegger D, Buchmann B, et al. The hemodynamic effects of heparin and their relation to ionized calcium levels. J Thorac Cardiovasc Surg. 1986;91:303–306
  54. Tangphao O, Chalon S, Moreno HJ, et al. Heparin-induced vasodilation in human hand veins. Clin Pharmacol Ther. 1999;66:232–238
  55. Susic D, Mandal AK, Jovovic D, et al. Antihypertensive action of heparin: Role of the renin-angiotensin aldosterone system and prostaglandins. J Clin Pharmacol. 1993;33:342–347
  56. Tasatargil A, Golbasi I, Sadan G, et al. Unfractioned heparin produces vasodilatory action on human internal mammary artery by endothelium-dependent mechanisms. J Cardiovasc Pharmacol. 2005;45:114–119
  57. VanTeeffelen JW, Brands J, Jansen C, et al. Heparin impairs glycocalyx barrier properties and attenuates shear dependent vasodilation in mice. Hypertension. 2007;50:261–267
  58. Ojala TH, Lehtonen L. A preliminary report—Heparin counteracts indomethacin effect on ductus arteriosus in very low birthweight infants. Pediatr Crit Care Med. 2007;8:258–260
  59. Cotton RB, Lindstrom DP, Stahlman MT. Early prediction of symptomatic patent ductus arteriosus from perinatal risk factors: A discriminant analysis model. Acta Paediatr Scand. 1981;70:723–727
  60. Furzan JA, Reisch J, Tyson JE, et al. Incidence and risk factors for symptomatic patent ductus arteriosus among inborn very-low-birth-weight infants. Early Hum Dev. 1985;12:39–48
  61. Chorne N, Jegatheesan P, Lin E, et al. Risk factors for persistent ductus arteriosus patency during indomethacin treatment. J Pediatr. 2007;151:629–634
  62. Itabashi K, Ohno T, Nishida H. Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin. J Pediatr. 2003;143:203–207
  63. Siassi B, Blanco C, Cabal LA, et al. Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: A prospective analysis of 150 consecutively born infants. Pediatrics. 1976;57:347–351
  64. van de Bor M, Verloove-Vanhorick SP, Brand R, et al. Patent ductus arteriosus in a cohort of 1338 preterm infants: A collaborative study. Paediatr Perinat Epidemiol. 1988;2:328–336
  65. Robel-Tillig E, Knupfer M, Vogtmann C. Cardiac adaptation in small for gestational age neonates after prenatal hemodynamic disturbances. Early Hum Dev. 2003;72:123–129
  66. Cunningham MD, Ellison RC, Zierler S, et al. Perinatal risk assessment for patent ductus arteriosus in premature infants. Obstet Gynecol. 1986;68:41–45
  67. Kreft-Jais C, Plouin PF, Tchobroutsky C, et al. Angiotensin-converting enzyme inhibitors during pregnancy: A survey of 22 patients given captopril and nine given enalapril. Br J Obstet Gynaecol. 1988;95:420–422
  68. Shotan A, Widerhorn J, Hurst A, et al. Risks of angiotensin-converting enzyme inhibition during pregnancy: Experimental and clinical evidence, potential mechanisms, and recommendations for use. Am J Med. 1994;96:451–456
  69. Thomas SV, Ajaykumar B, Sindhu K, et al. Cardiac malformations are increased in infants of mothers with epilepsy. Pediatr Cardiol. 2008;29:604–608
  70. Dusick AM, Covert RF, Schreiber MD, et al. Risk of intracranial hemorrhage and other adverse outcomes after cocaine exposure in a cohort of 323 very low birthweight infants. J Pediatr. 1993;122:438–445
  71. Levy HL, Guldberg P, Guttler F, et al. Congenital heart disease in maternal phenylketonuria: Report from the maternal PKU collaborative study. Pediatr Rev. 2001;49:636–642
  72. Rouse B, Matalon R, Koch R, et al. Maternal phenylketonuria syndrome: Congenital heart defects, microcephaly, and developmental outcomes. J Pediatr. 2000;136:57–61
  73. Treszl A, Szabo M, Dunai G, et al. Angiotensin II type 1 receptor A1166C polymorphism and prophylactic indomethacin treatment induced ductus arteriosus closure in very low birthweight neonates. Pediatr Rev. 2003;54:753–755
  74. Keller RL, Clyman RI. Persistent Doppler flow predicts lack of response to multiple courses of indomethacin in premature infants with recurrent patent ductus arteriosus. Pediatrics. 2003;112:583–587
  75. Cambonie G, Guillaumont S, Luc F, et al. Haemodynamic features during high-frequency oscillatory ventilation in preterms. Acta Paediatr. 2003;92:1068–1073
  76. Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000;343:674–681
  77. Botto LD, Correa A, Erickson JD. Racial and temporal variations in the prevalence of heart defects. Pediatrics. 2001;107:E32
  78. Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database of System Rev. 2008;(1):CD000503
  79. Hammoud MS, Elsori HA, Hanafi EA, et al. Incidence and risk factors associated with the patency of ductus arteriosus in preterm infants with respiratory distress syndrome in Kuwait. Saudi Med J. 2003;24:982–985
  80. Rothman KJ, Fyler DC. Sex, birth order, and maternal age characteristics of infants with congenital heart defects. Am J Epidemiol. 1976;104:527–534
  81. Samanek M, Voriskova M. Congenital heart disease among 815,569 children born between 1980 and 1990 and their 15-year survival: A prospective Bohemia survival study. Pediatr Cardiol. 1999;20:411–417
  82. Forsey JT, Elmasry OA, Martin RP. Patent arterial duct. Orphanet J Rare Dis. 2009;4:17
  83. Bhandari V, Zhou G, Bizzarro MJ, et al. Genetic contribution to patent ductus arteriosus in the premature newborn. Pediatrics. 2009;123:669–673
  84. Dagle JM, Lepp NT, Cooper ME, et al. Determination of genetic predisposition to patent ductus arteriosus in preterm infants. Pediatrics. 2009;123:1116–1123
  85. Seppanen MP, Ojanpera OS, Kaapa PO, et al. Delayed postnatal adaptation of pulmonary hemodynamics in infants of diabetic mothers. J Pediatr. 1997;131:545–548
  86. Alzamora-Castro V, Battilana G, Abugattas R, et al. Patent ductus arteriosus and high altitude. Am J Cardiol. 1960;5:761–763
  87. Miao CY, Zuberbuhler JS, Zuberbuhler JR. Prevalence of congenital cardiac anomalies at high altitude. J Am Coll Cardiol. 1988;12:224–228
  88. Doyle PE, Beral V, Botting B, et al. Congenital malformations in twins in England and Wales. J Epidemiol Community Health. 1991;45:43–48
  89. Layde PM, Erickson JD, Falek A, et al. Congenital malformation in twins. Am J Hum Genet. 1980;32:69–78
  90. Gibson S, Lewis KC. Congenital heart disease following maternal rubella during pregnancy. AMA. 1952;83:317–319
  91. Nakagawa T. Delayed closure of ductus arteriosus in premature infants with transient hypothyroidism. Lancet. 1993;341:839
  92. Williams FL, Ogston SA, van Toor H, et al. Serum thyroid hormones in preterm infants: Associations with postnatal illnesses and drug usage. J Clin Endocrinol Metab. 2005;90:5954–5963
  93. Barefield ES, Dwyer MD, Cassady G. Association of patent ductus arteriosus and phototherapy in infants weighing less than 1000 grams. J Perinatol. 1993;13:376–380

 Supported by NIH HL077395 (J. Reese).

PII: S0146-0005(10)00021-2

doi: 10.1053/j.semperi.2010.02.007

Seminars in Perinatology
Volume 34, Issue 3 , Pages 222-230 , June 2010

Article Tools

* Image Usage & Resolution