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PubMed1982

Increased shunt through the patent ductus arteriosus after surfactant replacement therapy.

Instillation of surfactant into the trachea of preterm infants with respiratory distress syndrome is associated with a 90% incidence of patent ductus arteriosus. We studied the effects of surfactant therapy on the ductus arteriosus in 12 preterm lambs. Flow across the ductus arteriosus and systemic blood flow were calculated from radioactive microsphere injections. All developed respiratory failure (pH less than 7.1, Paco2 greater than 60) by 30 minutes after birth. Between 30 and 60 minutes after birth, six lambs were treated with tracheal instillation of 50 mg/kg surfactant lipid. By two hours after birth, treated lambs differed significantly from controls in pH (7.27 +0.02 vs 6.97 +0.08) and Paco2 (43.3 +4.1 vs 85 + 15). There were no differences in Pao2 or PGE2 concentrations or ductus arteriosus resistance, but there was a significantly larger shunt through the ductus arteriosus in treated lambs. This increased shunt resulted from the significant drop in pulmonary vascular resistance and not from a change in patency of the ductus arteriosus. Surfactant replacement may require interventions directed specifically at the patent ductus arteriosus in sick preterm infants.

Animals↗
PubMed1996

Flow velocity waveforms of the ductus arteriosus in appropriate and small-for-gestational-age fetuses.

OBJECTIVES: To assess ductus arteriosus velocity waveforms in the appropriate and small-for-gestational-age (SGA) fetuses. STUDY DESIGN: Ductus arteriosus flow velocity waveforms were obtained in 14 normal fetuses in a longitudinal study and in 139 normal fetuses in a cross-sectional study with pulsed and continuous Doppler ultrasonography. Ductus velocity waveforms were also determined in 25 SGA fetuses whose gestational age ranged between 20 and 34 weeks (mean +/- SD: 30 +/- 4.1 weeks). RESULTS: Mathematical modeling demonstrated that the peak systolic velocity, lowest diastolic velocity, and mean velocity of the ductus arteriosus increased with advancing gestation in both the longitudinal and cross-sectional study, but considerable individual variability was seen in the longitudinal study. The pulsatility index did not change significantly. The ductal parameters were in the normal range in all the SGA fetuses. CONCLUSIONS: The blood velocity of the ductus arteriosus increase with advancing gestation. Our results suggest that Doppler ultrasonographic study of the fetal ductus arteriosus, unlike Doppler study of the umbilical artery or middle cerebral artery, is not useful as an indicator of adverse fetal outcome.

Blood Flow Velocity↗
PubMed1995

Aneurysm following ligation of patent ductus arteriosus.

Complications following ligation of patent ductus arteriosus are rare. Aneurysm following ligation requires careful evaluation and individualized repair. We report 2 cases that highlight the clinical course and operative management of this unusual but significant postoperative complication.

Adolescent↗
PubMed1992

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus.

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.

Atrial Natriuretic Factor↗
PubMed1987

Role of cyclic nucleotides in relaxation of fetal lamb ductus arteriosus.

Although prostaglandin E1 is used to dilate the constricted ductus arteriosus in infants with cyanotic heart disease, the mechanism is unknown. To test the hypothesis that the cyclic nucleotides adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) play a role in relaxation, isolated rings of the ductus arteriosus of fetal lambs were studied. Tension of isometric contraction was measured by force displacement transducers. After contraction with oxygen, a control group was compared with rings in which the stimulus for relaxation was either nitrogen gas, prostaglandin E1 (PGE1), nitroglycerin (NTG), or nitroprusside (NPS). During relaxation, tissue was frozen at 30 seconds and at 1, 2, and 5 minutes and analyzed for cAMP and cGMP. PGE1 (10(-6) mol/L) decreased tension by 33% compared with 70% for nitrogen gas, 81% for NTG (10(-5) mol/L), and 92% for NPS (10(-5) mol/L). The maximal relaxation induced by PGE1 was associated with an 11-fold increase in cAMP; PGE1 had no significant effect on cGMP tissue levels. Nitrogen gas, NTG, and NPS produced similar increases in cAMP, and eight-, 25-, and nine-fold increases in cGMP, respectively. These results suggest that the patency of the ductus arteriosus is dependent on activation of both guanylate cyclase and adenylate cyclase and that the nitrovasodilators may be clinically useful in maintaining patency of the ductus arteriosus.

Alprostadil↗
PubMed2003

Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants.

BACKGROUND: Patent ductus arteriosus (PDA) is commonly found in very low-birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS) is also associated with increased frequency of significant PDA. Intravenous indomethacin has been used to treat and to prevent PDA in premature infants since 1976. However, concern remains regarding the safety of indomethacin, which affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has recently been used to treat and to prevent PDA premature infants with PDA without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The aim of the present study is to compare intravenous ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of PDA in preterm infants. METHODS: A total of 63 preterm infants with RDS who had a birthweight of < or =1500 g and gestational age of < or =32 weeks, were enrolled in the present study. All patients were treated with nasal continuous positive airway pressure with additional oxygen supply in inspired air>30%, or with mechanical ventilation. The patients' serum platelet counts were>100,000/uL, and serum creatinine values were <1.5 mg/dL. There were no 3-4 grade intraventricular hemorrhages before randomization, and all patients were aged 2-7 days and had echo-cardio-graphic evidence of significant PDA. Patients were randomized into two groups: the first group of neonates (group A, n = 32) received intravenous ibuprofen lysine 10 mg/kg, followed by 5 mg/kg after 24 and 48 h; the second group (group B, n = 31) received intravenous indomethacin 0.2 mg/kg every 12 h for three doses. RESULTS: Patent ductus arteriosus closed in 27 patients from the ibuprofen group (84.4%) and in 25 patients from the indomethacin group (80.6%). PDA reopened in three patients from the ibuprofen group (9.4%) and in three patients from the indomethacin group (9.7%). One patient in the ibuprofen group and two patients in the indomethacin group required ductal ligation. Serum creatinine and blood urea nitrogen (BUN) concentrations were lower in the ibuprofen group than in the indomethacin group. Urine output and creatinine clearance values were higher in the ibuprofen group than in the indomethacin group. CONCLUSIONS: Ibuprofen therapy is as efficacious as indomethacin for the treatment of PDA in preterm infants. Infants treated with ibuprofen have higher creatinine clearance and urine output and lower serum creatinine and BUN values than infants treated with indomethacin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Expression of cyclooxygenases in ductus arteriosus of fetal and newborn pigs.

OBJECTIVE: We studied the ontogeny of the expression of cyclooxygenase-1 and cyclooxygenase-2 in the ductus arteriosus and evaluated their functional significance. STUDY DESIGN: The expression of cyclooxygenase-1 and cyclooxygenase-2 was studied in ductus arteriosus of fetal (at approximately 75% gestation) and term newborn pig. Effects of selective inhibitors of cyclooxygenase-1 and cyclooxygenase-2 on ductal patency were evaluated by Doppler ultrasonography. RESULTS: Ductus arteriosus of the fetus expressed virtually only cyclooxygenase-1 immunoreactive protein and activity. In contrast, the ductus of the term newborn pig (<45 minutes old) contained proteins of both cyclooxygenase-1 and cyclooxygenase-2, but the latter contributed to >90% of prostaglandin E2 formation. The selective cyclooxygenase-2 inhibitor DuP697 reduced prostaglandin E2 levels in the ductus arteriosus, albeit not in plasma, but did not affect ductal patency in the newborn pig (<1(1/2) hours old); in contrast, the cyclooxygenase-1 inhibitor valeryl salicylate, like indomethacin, markedly reduced levels of prostaglandin E2 in the plasma and ductus arteriosus and caused significant constriction of the ductus arteriosus. CONCLUSION: The ductus arteriosus of the term newborn pig, in contrast to that of the fetus, expresses cyclooxygenase-2, but circulating prostaglandins, arising mostly from cyclooxygenase-1, seem to exert the major control on ductal patency in vivo. Our data suggest that cyclooxygenase-2 inhibitors might be better alternatives for the fetus than nonselective cyclooxygenase blockers if indicated for maternal conditions such as inflammation or for tocolysis.

Animals↗
PubMed1986

Real-time Doppler color flow mapping for detection of patent ductus arteriosus.

In this study, ultrasound Doppler color flow mapping systems were utilized to examine flow in the pulmonary artery in 31 premature and term infants (aged 4 hours to 9 months) with patent ductus arteriosus accompanying respiratory distress syndrome, as an isolated lesion, or with patent ductus in association with other cyanotic or acyanotic congenital heart disorders. The flow mapping patterns were compared with those of a control population of 15 infants who did not have patent ductus arteriosus. In unconstricted ductus arteriosus, the flow from the aorta into the pulmonary artery was detected in late systole and early diastole and was distributed along the superior leftward lateral wall of the main pulmonary artery from the origin of the left pulmonary artery back in a proximal direction toward the pulmonary valve. In constricted patent ductus arteriosus, or especially in a ductus in association with cyanotic heart disease, the position of the ductal shunt in the pulmonary artery was more variable, often directed centrally or medially. Waveform spectral Doppler sampling could be performed in specific positions guided by the Doppler flow map to verify the phasic characteristics of the ductal shunt on spectral and audio outputs. Shunts through a very small patent ductus arteriosus were routinely detected in this group of infants, and right to left ductal shunts could also be verified by the Doppler flow mapping technique. This study suggests substantial promise for real-time two-dimensional Doppler echocardiographic flow mapping for evaluation of patent ductus arteriosus in infants.

Blood Flow Velocity↗