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PubMed1987

How a patent ductus arteriosus effects the premature lamb's ability to handle additional volume loads.

A model of patent ductus arteriosus in premature lambs was created to examine the lamb's ability to handle the volume load imposed by a patent ductus arteriosus and to determine the lamb's ability to handle any additional volume load. Fifteen preterm lambs [133 +/- 2 (+/- SD) days gestation, term 145 days], whose ductal diameter could be regulated with a mechanical occluder, were studied to determine the independent effects of ductus patency and a saline volume load (50 ml/kg over 3 min) on left ventricular output and its distribution. During a saline infusion, preterm lambs with a closed ductus could only increase their stroke volume by 40% above baseline stroke volume. When challenged with a saline infusion, lambs with an open ductus still were able to increase their stroke volume significantly; the maximal increase in stroke volume during the saline load with the ductus open was 70% above baseline stroke volume. We hypothesize that the associated reduced left ventricular afterload plays a significant role in the preterm lamb's ability to increase its stroke volume when challenged with a patent ductus arteriosus. Even with a patent ductus arteriosus, the lamb still has the ability to handle additional volume loads.

Animals↗
PubMed2005

Cyclooxygenase isoenzymes and patency of ductus arteriosus.

Prenatal patency of the ductus arteriosus is maintained mainly by prostaglandin (PG) E(2). Accordingly, the vessel is endowed in its muscular component with a complete, cyclooxygenase (COX) and PGE synthase (PGES), system for the synthesis of the compound. COX1 is better expressed than COX2, particularly in the premature, but COX2 is more extensively coupled with microsomal PGES (mPGES). No evidence was obtained of either COX being coupled with cytosolic PGES (cPGES). Functionally, these data translate into a differential constrictor response of the ductus to dual, COX1/COX2, vs. COX2-specific inhibitors (indomethacin vs. L-745,337), with the latter being less effective specifically prior to term. This difference, however, subsides upon treatment with endotoxin and the attendant upregulation of COX2 and mPGES. Furthermore, when studied separately, COX1 and COX2 prove to be unevenly responsive to indomethacin, and an immediate and fast developing contraction of the vessel occurs only when COX2 is inhibited. Deletion of either COX gene results into upregulation of NO synthase, and a similar compensatory reaction is expected when enzymes are suppressed pharmacologically. We conclude that PGE(2) and NO can function synergistically in keeping the ductus patent. This arrangement provides a possible explanation for failures of indomethacin or ibuprofen treatment in the management of the prematurely born infant with persistent ductus. Coincidentally, it opens the way to new therapeutic possibilities being based on interference with the NO effector or a more selective disruption, possibly having mPGES as a target, of the PGE(2) synthetic cascade.

Animals↗
PubMed2005

Transpulmonary surgical closure of patent ductus arteriosus with hypothermic circulatory arrest in an adult patient.

Untreated patent ductus arteriosus carries a higher risk in adults than in children, especially when the defect is large (>4.0 mm in diameter), short, or friable. Therefore, various technical precautions have been suggested for application during surgical closure of a patent ductus arteriosus in an adult. We report the case of a 47-year-old woman with a patent ductus arteriosus who underwent transpulmonary surgical closure of the ductus under hypothermic total circulatory arrest. We discuss the technique in light of the current English-language medical literature.

Cardiac Surgical Procedures↗
PubMed1980

Ultrastructure of developing human ductus arteriosus.

Histological and ultrastructural studies were made of 25 specimens of human ductus arteriosus obtained from abortion of autopsy, and ranging in age from 15 weeks of gestation to 7 years. Samples of ductus with normal muscular type structure exhibited active intimal thickening as early as 15 weeks' gestational age when the internal elastic lamina was found to be focally discontinuous. At the same time, intimal smooth muscle cells were closely arranged, and often intimately connected to cells of the tunica media. Ultrastructurally, both smooth muscle cells and endothelial cells at 15 weeks' gestational age contained abundant glycogen deposits. From 18-32 weeks' gestational age, glycogen deposits gradually disappeared, collagen fibres began to appear in the extracellular space and the first signs of smooth collagen fibres began to appear in the extracellular space and the first signs of smooth muscle cell degeneration became apparent. After birth, intimal thickening and degeneration of smooth muscle cells was much more pronounced. The ultrastructure of intimal smooth muscle cells indicated that intimal thickening was caused by smooth muscle cell migration as opposed to rapid proliferation; and both intracellular and extracellular membrane-bound lipid-filled vacuoles were commonly seen in the more advanced stages of degeneration. Of the ductus specimens examined, three were rich in elastic fibres. Two of these three specimens were from a group of 10 abortion cases, and the third was from a 2 weeks old full term infant who had been exposed to maternal rubella. The 2 weeks old infant had a widely patent ductus arteriosus; whether the two fetal specimens with ductus elastosis would have eventually developed into clinical patent ductus arteriosus was not clear.

Ductus Arteriosus↗
PubMed1976

Pre- and postoperative growth in persistent ductus arteriosus.

Children with a persistent ductus arteriosus requiring ligation under 6 months of age show evidence of intrauterine growth retardation. By the time of operation the weight centile of 17 (71%) of 24 such infants had fallen, but 20(84%) of the 24 gained weight postoperatively. Those who did not so were either large-for-dates infants growing towards the normal or small-for-dates infants who remained small postoperatively.

Birth Weight↗
PubMed1994

Effect of maternal paraquat administration on the fetal ductus arteriosus in the rat.

The ductus arteriosus (DA) in the fetal rat was calibrated using a whole-body freezing method, 3 hr after maternal treatment with paraquat at a dose of 25 mg/kg of body weight on days 19-21 of gestation. On days 20 and 21, the DA was significantly constricted. The DA was also significantly constricted on day 19 2/3 but not on day 19 1/2. It is concluded that paraquat has a constrictive effect on the DA and that the onset of this effect occurs in the first half of day 19 of gestation.

Animals↗
PubMed2006

Patent ductus arteriosus: pathophysiology and management.

Patent ductus arteriosus (PDA) in preterm newborns prior to 28 weeks of gestation has led to many challenges regarding the type and timing of treatment regimens. A PDA results in increased pulmonary blood flow and redistribution of flow to other organs. Several co-morbidities (i.e., necrotizing enterocolitis, intracranial hemorrhage, pulmonary edema/hemorrhage, bronchopulmonary dysplasia, and retinopathy) are associated with the presence of a PDA, but whether or not a PDA is responsible for their development is still unclear. The prostaglandin inhibitor, indomethacin, is effective in the treatment of PDA. Questions regarding the optimal timing of the intervention--early prophylaxis or treatment, once signs and symptoms become evident--have challenged physicians for decades. Both evidence and experience are explored in this article. Comparative physiology between the full-term and preterm newborn and the barriers preventing the necessary cascade of events leading to permanent constriction of the PDA are reviewed.

Cardiac Surgical Procedures↗
PubMed2004

Acquired aortic regurgitation after coil occlusion of patent ductus arteriosus.

Some patients with patent ductus arteriosus (PDA) may develop new aortic regurgitation (AR) after coil occlusion. This study evaluated the risk factors for the development of AR after coil occlusion of PDA. A total of 23 patients with PDA were managed with coil embolization over a three-and-a-half-year period. Three patients with pre-embolization AR were excluded. A post-occlusion transthoracic echocardiogram was performed within 24 hours after the procedure. Ten patients developed AR and 10 did not. Gender, age, weight, body surface area (BSA), pulmonary artery pressure, and pulmonary vascular resistance did not differ significantly between the 2 groups. Both larger PDA size (either corrected for weight or BSA, p = 0.008 and 0.002, respectively) and a higher ratio of pulmonary to systemic flow (Qp/Qs) [p = 0.013] were significant risk factors for the development of AR after coil occlusion. Re-evaluation of the patients at 3 and 6 months after the procedure revealed 7 patients still had a regurgitant jet. The results of this study suggest that the larger the PDA and larger the shunt, the greater the likelihood of developing AR after coil occlusion.

Adolescent↗
PubMed2001

Endothelin-1-endothelin receptor type A mediates closure of rat ductus arteriosus at birth.

1. The ductus arteriosus (DA) undergoes rapid closure after birth as pulmonary circulation is established. The involvement of endothelin-1 (ET1) in this closure mechanism is controversial. 2. The effect of ATZ1993 (ATZ), a non-peptide antagonist for the ET(A) and ET(B) receptors, on postnatal closure and O2-induced contraction of the rat DA was investigated both in vivo and in vitro. Rat pups were delivered by Caesarean section and were given ATZ intraperitoneally. The minimum external DA diameter and the extent of DA constriction in vivo were evaluated at 2.5 h after birth. ATZ caused a dose-dependent inhibition of DA closure in vivo. When rat pups were given ATZ at 2.5 h after birth, re-opening of the DA was observed. 3. In vitro, ATZ also caused a marked inhibition of O2-induced and ET1-induced DA contractions as did BQ123, an ET(A)-specific antagonist. In contrast, sarafotoxin S6c, an ET(B)-specific agonist, did not cause DA contraction and BQ788, an ET(B)-specific antagonist, did not affect O2-induced DA contraction. 4. In conclusion, ET1 and its cognate receptor ET(A) may play a physiological role in the postnatal closure of the rat DA in vivo.

Animals↗
PubMed2006

Attenuated cyclooxygenase-2 expression contributes to patent ductus arteriosus in preterm mice.

Patent ductus arteriosus (DA) is the second most common congenital heart defect, the incidence of which is increased in premature infants, although mechanisms responsible are not clear. Our previous studies with genetic or pharmacological inactivation of cyclooxygenase-2 (COX-2) in mice, emphasized the importance of this enzyme in normal DA closure. The current study was designed to determine whether reduced COX-2 expression contributes to patent DA in preterm mice. Real-time PCR analysis indicated that COX-2 expression in the fetal mouse DA significantly increased with advancing gestational age. Furthermore, we observed a significant induction in COX-2 expression in the DA at 3 h after birth at full-term gestation. In contrast, COX-2 expression was significantly attenuated in the DA of preterm neonatal mice. DA closure was incomplete in preterm mice at 3 h postpartum, a time-point when the DA of full-term neonates was completely remodeled. Additionally, COX-2 expression was significantly attenuated in the DA of mice deficient in the prostanoid receptor EP4, which also show a patent DA phenotype, suggesting the importance of this receptor for the induction of COX-2 required for DA closure. Overall, these studies suggest that attenuated expression of COX-2 may contribute to increased patent DA at preterm gestation.

Animals↗
PubMed2002

Plasma brain natriuretic peptide as a predictor of haemodynamically significant patent ductus arteriosus in preterm infants.

Patent ductus arteriosus (PDA) is an important cause of morbidity in extremely preterm infants. As increased plasma brain natriuretic peptide (BNP) is a common feature of adult cardiac disease, we investigated the value of plasma BNP concentration as a predictor of haemodynamically significant PDA in very preterm infants. We studied 18 preterm infants (12 male) of median gestational age 30 weeks (range 24-34), median birth weight 1.46 kg (0.54-2.13) and 11 healthy term controls. Plasma BNP levels were measured by double-antibody radioimmunoassay on days 3, 5 and 7 of life, and an echocardiogram was performed on day 7. Six infants of median gestation 26 weeks (26-30), median birth weight 0.92 kg (0.54-1.04) had PDA proven by echocardiography on day 7. BNP concentrations (pg/ml) on day 3 were significantly higher in these infants than in the remaining twelve [median 2012 (786-2759) versus 42 (7-704), P<0.001]. In four infants PDA was treated successfully (one surgically, three with non-steroidal anti-inflammatory drugs). Two had haemodynamically insignificant closing ducts. In these infants with therapeutic or spontaneous resolution of a PDA, plasma BNP fell to normal values [median after treatment 9 pg/ml (8-27)]. Early measurement of plasma BNP in the first few days of life is a useful method for predicting those preterm infants who may require intervention for PDA.

Biomarkers↗
PubMed1997

Video-assisted thoracoscopic operation for interruption of patent ductus arteriosus in adults.

BACKGROUND: Patent ductus arteriosus (PDA) is a frequent congenital heart disease encountered in premature neonates, infants, and children. Video-assisted endoscopic techniques have been used in PDA interruption since 1993. Almost all the experiences are in pediatric patients. Applications in adults with PDA have been limited. METHODS: We report our experience of video-assisted thoracoscopic surgical ligation of PDA in adults. From August 1995 to January 1996, 60 patients with PDA were operated on with a video-assisted thoracoscopic technique. Twelve adults were identified with mean age of 30 years (range, 20 to 57 years). With the patient under general anesthesia and double-lumen endotracheal intubation, two 5-mm holes were made in the left lateral chest wall. Another 4-cm incision was made in the left third intercostal space for manipulation, dissection, and ligation. Conventional surgical instruments were used except an endoscopic grasper and an endoscopic tube that connected to a video camera. The surgical procedure was viewed on a video screen. Transesophageal echocardiography was used for monitoring during PDA ligation. RESULTS: All patients had successful ligation of the PDA. There was no surgical mortality, but there was one morbidity; transient recurrent nerve injury, which recovered 3 months later. Ten patients were extubated in operative room and 2 patients were extubated 2 hours after the operation. Tube thoracostomy was performed in the first 2 cases; it was omitted thereafter. No patients needed narcotic to control chest pain. Postoperative follow-up by echocardiography showed faint ductal flow in 1 patient without any murmur. All patients were discharged within 3 days after the operation. CONCLUSIONS: Our experience suggests that with refinement of instruments and surgical technique, video-assisted thoracoscopic surgical ligation can be safely applied not only in pediatric patients, but also in adults with PDA.

Adult↗
PubMed2002

Effect of age and birth weight on indomethacin pharmacodynamics in neonates treated for patent ductus arteriosus.

OBJECTIVES: To determine patent ductus arteriosus (PDA) closure rates, and indomethacin (INDO) toxicity rates in neonates dosed with INDO using an individualized pharmacokinetic/pharmacodynamic (PK/PD) dosing approach. In addition, develop PD curves evaluating dose-response and concentration-response relationships for closure and renal toxicity, especially in select subgroups historically known as "poor responders" (<1000 g and > or = 10 days postnatal age). DESIGN: Prospective, cohort study. SETTING: Level III neonatal intensive care unit. SUBJECTS: One hundred thirty-nine patients receiving 151 courses of INDO for PDA closure were evaluated. INTERVENTIONS: Patients initially received 0.25 mg/kg of INDO, followed immediately by 1 mg/kg of furosemide. INDO concentrations were obtained 2 hrs and 8 hrs after the dose and were assayed using high-performance liquid chromatography. Individualized PK parameters were calculated with subsequent INDO dosing based on the individualized PK variables to increase trough serum concentrations by 0.3-0.5 mg/L. MEASUREMENTS AND MAIN RESULTS: Ductal closure was successful in 127 patients (91%). Renal toxicity occurred in 21 (15%) patients and was temporary and reversible. No significant differences in response rates based on treatment weight or postnatal age were observed. PD curves were similar for neonates <1000 g vs. > or = 1000 g. PD curves were also similar for neonates with postnatal age <10 days vs. > or = 10 days. Statistically significant differences were noted between neonates categorized for postnatal age <10 days vs. > or = 10 days in total days of therapy (1.8 vs. 2.3 days), total number of doses required to close PDA (3.5 vs. 5.6 doses), critical INDO dose (0.9 vs. 1.4 mg/kg), critical INDO concentration (1.9 vs. 1.4 mg/L), and critical dose/critical concentration ratio (0.52 vs. 2.2). CONCLUSIONS: These findings support the hypothesis that the poor PDA closure rates with INDO for neonates >10 days postnatal age are the result of pharmacokinetic differences only and that weight does not impact response rates. Individualized pharmacokinetic/pharmacodynamic dosing of INDO continues to achieve higher closure rate than current dosing standards. Patients historically known as poor responders significantly benefit from this dosing approach.

Age Factors↗
PubMed1990

[MR imaging of aortic arch anomalies--an analysis of MR visualization of ductus arteriosus].

MR imaging of 10 patients with aortic arch anomaly was performed on a 1.0 T system. Coronal and sagittal images with a 5 to 6-mm-thick slice were taken in each patient and the visibility of the ductus arteriosus (ductus ligament) was detected on the sagittal images including its anatomical connection between the pulmonary trunk and arch vessel. The result indicates that MR imaging is of great help for detection of the ductus in case of aortic arch anomaly.

Adult↗
PubMed2002

Isolated neonatal ductus arteriosus aneurysm.

OBJECTIVE: A prospective study was performed to evaluate the incidence, clinical manifestations and outcome of ductus arteriosus aneurysm (DAA) in full-term neonates. BACKGROUND: Ductus arteriosus aneurysm has been considered to be a rare congenital lesion and a potentially fatal abnormality. METHODS: A total of 548 full-term neonates received echocardiographic screening. RESULTS: There were 48 (8.8%) patients (28 boys and 20 girls) with DAA detected by echocardiography. The maximal diameter of the DAA ranged from 6.5 to 11.2 mm (8.2 +/- 1.2 mm). All cases were asymptomatic. There were no significant differences in gender, gestational age, maternal age or Apgar score between the newborns with or without DAA. Newborns with DAA had a higher birth body weight, higher incidence of maternal gestational diabetes mellitus and more mothers with blood group A, compared with newborns without DAA (p < 0.05). Follow-up echocardiograms showed spontaneous closure of the ductus arteriosus in all patients except those without DAA. The DAA became progressively smaller after ductal closure in 33 patients (70.2%) and completely disappeared by 7 to 35 days of life. The other 14 patients (29.8%) with DAA had echocardiographic evidence of progressive formation of thrombi between the third and tenth day of life. The DAA and thrombi spontaneously disappeared in all patients by one month after birth. CONCLUSIONS: There is a higher incidence of DAA with a good outcome in our series compared with previous reports. We speculate that the presence of DAA may be a normal variant of the ductal bump and part of a normal process of spontaneous ductal closure in full-term neonates.

Aneurysm↗
PubMed2003

Percutaneous closure of window-type patent ductus arteriosus: using the CardioSEAL and STARFlex devices.

Transcatheter closure of patent ductus arteriosus is routinely performed using various devices. After the withdrawal of the Rashkind umbrella device from the market, the wide window-type patent ductus arteriosus has been difficult to close percutaneously. Two patients with this condition are presented: a 17-year-old man and a 62-year-old woman with short (4.5- and 5.2-mm-diameter, respectively) ductus. We successfully implanted a 17-mm CardioSEAL device in the 1st patient and a 23-mm STARFlex in the 2nd, with no residual shunt at follow-up (22 and 8 months, respectively). Although these devices (which follow the general design of the Rashkind umbrella) are usually applied to atrial septal defect closure, we believe that CardioSEAL and STARFlex implants could be the treatment of choice in percutaneous treatment.of window-type patent ductus arteriosus.

Adolescent↗
PubMed2001

Aneurysm of the ductus arteriosus in a neonate with 13q-deletion.

Aneurysm of the ductus arteriosus is a rare abnormality for which different ways of pathogenesis are described. We report the case of a fatal thrombosis of an aneurysm of the ductus arteriosus in an infant presenting feeding difficulties and a mild dysmorphic facies. Karyotype analysis revealed a de novo chromosomal deletion 46,XY, del (13)(q12.3,q22.3). To the best of our knowledge, this is the first case of an aneurysm of the ductus arteriosus associated with a chromosomal aberration.

Aneurysm↗