Pharmacological Closure of Patent Ductus Arteriosus: Effects on Pulse Pressure and on Endothelin-1 and Vasopressin Excretion

ABSTRACT

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.

KEYWORDS

ET-1 - AVP - ibuprofen - indomethacin - PDA - pulse pressure

REFERENCES

• 1 Endo A, Ayusawa M, Minato M, Takalda M, Takahashi S, Harada K. Physiologic significance of nitric oxide and endothelin-1 in circulatory adaptation.  Pediatr Int. 2000;  42 26-30
• 2 Ramin S M, Porter J C, Gilstrap L C, Rosenfeld C R. Stress hormones and acid-base status of human fetuses at delivery.  J Clin Endocrinol Metab. 1991;  73 182-186
• 3 Bernstein D. Acyanotic congenital heart diseases: the left-to-right shunt lesions. In: Behrman RE, Kliegman RM, Jenson HB Nelson Textbook of Pediatrics. 16th ed. Philadelphia; WB Saunders 2000: 1372-1373
• 4 Lubetzky R, Mendel D, Mimouni F B et al.. Indomethacin-induced early patent ductus arteriosus closure cannot be predicted by a decrease in pulse pressure.  Am J Perinatol. 2004;  21 257-261
• 5 Evans N, Moorcraft J. Effect of patency of ductus arteriosus in blood pressure in very preterm infants.  Arch Dis Child. 1992;  67 1169-1173
• 6 Evans N, Iyer P. Changes in blood pressure after treatment of patent ductus arteriosus with indomethacin.  Arch Dis Child. 1993;  24 584-587
• 7 Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics.  Am J Ther. 2000;  7 63-74
• 8 Tsukahara H, Sekine K, Miura M et al.. Vasoactive and natriuretic mediators in umbilical cord blood: a report of our observation and review of the literature.  Early Hum Dev. 2002;  69 57-64
• 9 Aranda J V, Varvarigou A, Beharry K et al.. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant.  Acta Paediatr. 1997;  86 289-293
• 10 Moore P, Book M M, Heymann M A. Patent ductus arteriosus. In: Allen HD, Gutgessel HP, Clark EB, Driscol DJ Moss and Adam's Hearth Disease in infants, Childhood, and Adolescent. 6th ed. Philadelphia; Lippincott Williams & Wilkins 2001: 652-669
• 11 Ratner I, Perelmuter B, Toews W, Whitfields J. Association of low systolic and diastolic blood pressure with significant patent ductus arteriosus in the very low birth weight infant.  Crit Care Med. 1985;  13 497-500
• 12 Lago P, Bettiol T, Salvadori S et al.. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomized controlled trial.  Eur J Pediatr. 2002;  161 202-207
• 13 Guignard J P. The adverse renal effect of prostaglandin-synthesis inhibitors in the newborn rabbit.  Semin Perinatol. 2002;  26 398-405
• 14 Johnson G L, Breart G L, Gewitz M H et al.. Echocardiographic characteristics of premature infants with patent ductus arteriosus.  Pediatrics. 1983;  72 864-871
• 15 Lee J, Rajadurai V S, Tan K W. Blood pressure standards for low birthweight infants during the first day of life.  Arch Dis Child Fetal Neonatal Ed. 1999;  81 168-170
• 16 Sulyok E, Ertl T, Adamovits K, Hovanyovszky S, Rascher W. Urinary endothelin excretion in the neonate: influence of maturity and perinatal pathology.  Pediatr Nephrol. 1993;  7 881-885
• 17 Bhat R, John E, Chari G et al.. Renal actions of endothelin-1 in newborn piglets: dose-effect relation and the effects of receptor antagonist (BQ-123) and cyclooxygenase inhibitor (indomethacin).  J Lab Clin Med. 1995;  126 458-469
• 18 Munger K A, Takahashi K, Ebert J, Badr K F. Role of cyclooxygenase products in mediating renal responses to endothelin.  Kidney Int. 1990;  37 375
• 19 Haynes W G, Ferro C I, O'Kane K P, Somerville D, Lomax C C, Webb D I. Systemic endothelin blockade decreases peripheral vascular resistance and blood pressure in humans.  Circulation. 1996;  93 1960-1970
• 20 Chou S-Y, Porush I G. Renal action of endothelin-1 and endothelin-3: interaction with the prostaglandin system and nitric oxide.  Am J Kidney Dis. 1995;  26 116-123
• 21 Kojima T, Isozaki F Y, Takedatsu A, Oho Y, Kohayashi Y. Plasma endothelin-1 like immunoreactivity levels in neonates.  Eur J Pediatr. 1992;  151 913-915
• 22 Ivy D D, Parker T A, Kinsella J P, Abman S H. (1998) Endothelin A receptor blockade decreases pulmonary vascular resistance in premature lambs with hyaline membrane disease.  Pediatr Res. 1998;  44 175-180
• 23 Stewart D J, Levy R D, Cernacek P, Langleben D. Increased plasma endothelin 1 in pulmonary hypertension: marker or mediator of disease?.  Ann Intern Med. 1991;  114 464-469
• 24 de Vroomen M, Lopes Cardozo R H, Stendijk P, Frolich M, Boan J, van Bel F. Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome: a study in newborn lambs.  Early Hum Dev. 2001;  63 9-21
• 25 Miller W L, Redfield M M, Burnett J C. Integrated cardiac, renal and endocrine actions of endothelin.  J Clin Invest. 1989;  83 317-320
• 26 Dobyns E L, Eells P, Griebel J L, Abman S H. Elevated plasma endothelin-1 and cytokine levels in children with severe acute respiratory distress syndrome.  J Pediatr. 1999;  135 246-249
• 27 Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor.  Nature. 1990;  348 730-732
• 28 Sakurai T, Yanagisawa M, Takuwa Y et al.. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor.  Nature. 1990;  348 732-735
• 29 Shetty S S, Toshikazu O, Webb R L, DelGrande D, Lapp R W. Functionally distinct endothelin b receptors in vascular endothelium and smooth muscle.  Biochem Biophys Res Commun. 1993;  191 459-464
• 30 Meyer S, Gottschling S, Baghai A, Wurm D, Gortner L. Arginine-vasopressin in catecholamine-refractory septic versus non-septic shock in extremely low birth weight infants with acute renal injury.  Crit Care. 2006;  10 71-74
• 31 Barrett L K, Singer M, Clapp L H. Vasopressin: mechanisms of action on the vasculature in health and in septic shock.  Crit Care Med. 2007;  35 33-40
• 32 Ervin M G, Ross M G, Leake R D, Fisher D A. V1- and V2-receptor contributions to ovine fetal renal and cardiovascular responses to vasopressin.  Am J Physiol. 1992;  262 R636-643
• 33 Shi L, Guerra C, Yao J, Xu Z. Vasopressin mechanism-mediated pressor responses caused by central angiotensin II in the ovine fetus.  Pediatr Res. 2004;  56 756-762