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PubMed1988

Determination of the time of closure of the ductus arteriosus in severely ill premature infants.

In order to investigate the time of ductal closure in the premature infant, we performed multiple echocardiographic examination in each of 42 premature infants. Twenty eight of these infants had spontaneous closure of the ductus arteriosus (median date of closure--3 days). Twelve required medical or surgical closure of the ductus arteriosus and two died of severe lung disease. There was a significant relationship of decreasing birth weight to prolonged patency of the ductus arteriosus.

Ductus Arteriosus↗
PubMed1996

Transforming growth factor-beta protein and messenger RNA expression is increased in the closing ductus arteriosus.

In full-term newborns, permanent closure of the ductus arteriosus is associated with the formation of a neointima that is characterized by extracellular matrix deposition and smooth muscle cell migration. Transforming growth factor-beta (TGF-beta), a potent modulator of extracellular matrix deposition and smooth muscle cell migration, has been found to play a role in the remodeling associated with several forms of vascular disease. We examined the protein and mRNA expression of the three mammalian isoforms of TGF-beta (TGF-beta1, TGF-beta2, and TGF-beta3) during ductus arteriosus closure in full-term lambs. We found that the temporal changes and cellular localization of the proteins and mRNAs of all three TGF-beta isoforms were similar. TGF-beta proteins and mRNAs were present in very low levels in the late-gestation fetal ductus. Within 24 h of delivery, there was enhanced expression of TGF-beta in the newly forming neointima and outer muscle media; this continued to increase over the next 10 d. Increased expression of TGF-beta in the inner muscle media and adventitia lagged behind that of the neointima and outer muscle media. TGF-beta was not found in the luminal endothelial cells at any time. In contrast to the pattern described above, the appearance of TGF-beta protein differed from that of mRNA in the vasa vasorum of the ductus wall. After delivery, there was an increase in TGF-beta immunoreactivity in the smooth muscle cell layers of the vasa vasorum without any concurrent mRNA expression. The appearance of TGF-beta at the time of ductus closure suggests an important role for this growth factor in the reorganization of the ductus wall after birth.

Animals↗
PubMed1981

Prolonged prostaglandin E1 infusion: histologic effects on the patent ductus arteriosus.

An infant with Ebstein's malformation of the tricuspid valve and severe pulmonic stenosis underwent a 39-day course of prostaglandin E1 infusion, and a histologic study of the ductus arteriosus was undertaken after autopsy. There were marked alterations in the ductal and juxtaductal structures following this prolonged infusion of prostaglandin E1. The internal elastic lamella of the ductus was disrupted in many areas. The media showed widespread areas of disruption with cavity formation. The adventitia adjacent to the junction of the ductus with the pulmonary artery was thickened and infiltrated with mononuclear cells. The nerve trunks in the adventitia were markedly infiltrated with mononuclear cells and showed cavitation as well as considerable surrounding edema. Mucopolysaccharides were increased throughout the ductus. These changes produced increased fragility of the ductal and juxtaductal structures, thus increasing the likelihood of spontaneous aneurysms and rupture, or of tearing or rupture at the aortic and pulmonary junctions at the time of surgical closure of the ductus. Unusual fragility of the ductus, pulmonary artery, and aorta has been observed during ligation of the ductus following prostaglandin E infusions lasting seven and ten days. Additionally, another patient who had received prostaglandin E infusion for six days demonstrated aneurysmal fullness to the ductus arteriosus at autopsy. The histologic findings and intraoperative experience in this study suggest that there may be a real danger of spontaneous or surgically related rupture of the ductus arteriosus after prolonged infusion of prostaglandins.

Cardiac Catheterization↗
PubMed1986

Involvement of intramural prostaglandin E2 in prenatal patency of the lamb ductus arteriosus.

Release of prostaglandin E2 (PGE2) was studied in isolated ductus arteriosus preparations from immature (103 or 104 days gestation; term, 147 days) and near-term fetal lambs. Mature preparations produced measurable amounts of the compound in most cases and the release rate was 19 +/- 2 pg/(100 mg wet weight X min) at a PO2 of 3-8 Torr (1 Torr = 133.3 Pa). PGE2 release increased with the PO2 of the medium, peak values (about 125 pg/(100 mg X min)) being attained at 106-276 Torr when the oxygen-induced contraction was still submaximal. Experiments in which tissues were either contracted with excess potassium or relaxed with CO proved that PGE2 formation is independent from the contractile state. PGE2 was also released from ductus preparations lacking the adventitia, the intima, or both; however, release values were maximal when the adventitia was preserved. The magnitude of the intrinsic tone in these stripped preparations was inversely related to the rate of PGE2 formation. Reduced glutathione increased PGE2 release from the mature ductus, whole or stripped, and also relaxed hypoxic preparations; both effects were reversed by concomitant treatment with indomethacin. PGE2 synthesis tended to be greater in the immature than the mature ductus, maximal values (115 +/- 27 pg/(100 mg X min)) being observed at 6-8 Torr. We conclude that the ductus arteriosus is endowed with an enzyme system for the synthesis of PGE2 whose function accords with an effector role of the compound in the regulation of tone. These findings, together with the potent relaxation exerted by PGE2 at low PO2, indicate that the locally generated prostaglandin is well suited for keeping the ductus patent in the fetus.

Animals↗
PubMed1977

[The wall in persistent ductus arteriosus (author's transl)].

A light microscopy study of the wall in ductus arteriosus was performed in 13 cases of isolated persistent ductus. The specimens were obtained surgically in 11 cases and by necropsy in 2. Four patients were male, 9 female. The eldest was a 9-year-old girl and the youngest, a 4-month-old girl. Morphologically, a progressive transformation of the duct wall to the elastic-type artery was observed. In this transformation three stages were determined; stage I: laminar elastosis of the intima; stage II: same as stage I plus incomplete elastic transformation of the media; and stage III: fully developed elastic-type artery. A neat correlation between morphologic stages and clinical data was not found. The course of events in this transformation is apparently determined in great measure by individual factors.

Child↗
PubMed2005

Endovascular surgery using an original occluder for patent ductus arteriosus in an adult patient.

The patient was a 67-year-old woman in whom patent ductus arteriosus was diagnosed in childhood but not treated. In April 2000, she was hospitalized for exacerbation of heart failure. Marked restrictive impairment was seen: %VC was 36.1%, and FEV1% was 77.0% (respiratory function tests). As calcification was present, and since the aortic opening measured 20 mm, coil occlusion or thoracoscopic surgical interruption were considered difficult to perform. Because of concerns about postoperative respiratory complications associated with thoracotomy, the ductus was occluded under local anesthesia using an original occluder consisting of a vascular graft and modified Z-stent. Postoperatively, during more than three years of follow-up, the patient has remained well with no residual shunt or occluder migration. Consequently, patent ductus arteriosus occlusion using an original occluder appears to be a superior, minimally invasive technique that can successfully treat large ductus arteriosus complicated by calcification.

Aged↗
PubMed2003

Morphologic assessment of patent ductus arteriosus in adults using retrospectively ECG-gated multidetector CT.

OBJECTIVE: Noninvasive imaging of a persistently patent ductus arteriosus in adults remains a challenge. Bearing in mind the excellent spatial resolution provided by multidetector CT (MDCT), we postulated that MDCT might be used to evaluate this anatomic defect. We sought to show that MDCT can depict in detail patent ductus arteriosus in adults and allow determination of the size of the duct, degree of calcification, and morphologic classification. CONCLUSION: MDCT represents a novel method of noninvasively assessing patent ductus arteriosus in adults that provides detailed anatomic information. Comparison with invasive angiographic findings is needed to validate the technique of sizing of ducts using MDCT.

Adult↗
PubMed2006

Persistent ductus arteriosus in the Brown-Norway inbred rat strain.

Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.

Animals↗
PubMed1984

Long-term patency of the ductus arteriosus after balloon dilatation: an experimental study.

Balloon dilatation of the ductus arteriosus was carried out in vivo in eight piglets that were 12 to 16 days old. The ductus was functionally closed in all animals before dilatation. Long-term patency for periods of up to 6 months after the procedure was demonstrated in six animals by angiography, Doppler ultrasound examination, and at autopsy. The presence of hemodynamically significant shunts was indicated by clinical development of heart failure, pulmonary infections, and left ventricular hypertrophy. These results confirm the value of this laboratory preparation to create left-to-right shunts at the ductus level.

Angioplasty, Balloon↗
PubMed1981

Furosemide use in premature infants and appearance of patent ductus arteriosus.

Furosemide is a known stimulant of the renal release of prostaglandin E2, a potent dilator of the ductus arteriosus. A possible relationship between furosemide use in infants with respiratory distress syndrome (RDS) and the incidence of patent ductus arteriosus (PDA) was investigated using two different retrospective analyses. The amount of furosemide administered prior to the day a murmur was heard in the infants with PDA was higher than the amount given to patients without PDA during the same period. In a historical analysis of patients treated for RDS in the years 1970 through 1979, furosemide use and fluid intake appeared to be independent factors contributing to the incidence of PDA. The proposed relationship between furosemide use and the occurrence of PDA in patients with RDS warrants further study.

Ductus Arteriosus↗
PubMed2005

Increased constriction of the ductus arteriosus by dexamethasone, indomethacin, and rofecoxib in fetal rats.

BACKGROUND: To find a better treatment for patent ductus arteriosus (PDA) in premature infants, the present study investigated the synergism of clinical doses of dexamethasone, indomethacin, and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the fetal ductus arteriosus (DA) in rats. METHODS AND RESULTS: Dexamethasone (0.3 mg/kg), indomethacin (0.3 mg/kg), and rofecoxib (0.3 mg/kg), alone or in combination, were administered to preterm (d19) and near-term (d21) fetal rats. The ratio of the inner diameter of the DA to that of the main pulmonary artery (PA) (DA/PA) was studied at 2, 4 and 8 h after drug administration, using a rapid whole-body freezing method. In near-term rats, the combined administration of dexamethasone and indomethacin caused severe constriction, with a DA/PA ratio of 0.52+/-0.08 at 8 h, whereas the DA/PA ratios were 0.83+/-0.03 and 0.90+/-0.02 with dexamethasone and indomethacin, respectively. Combined administration of dexamethasone and rofecoxib also caused severe constriction, with a DA/PA ratio of 0.64+/-0.07 at 8 h, compared with the DA/PA ratio of 0.92+/-0.03 with rofecoxib alone. CONCLUSIONS: Combined therapy may be an option in the medical management of PDA in premature infants before considering surgical treatment.

Animals↗
PubMed1998

Closure of short, wide patent ductus arteriosus with cardiopulmonary bypass and balloon occlusion.

The wide, short patent ductus arteriosus in adults and older adolescents poses an extreme hazard with standard closed ligation techniques. The method of transpulmonary balloon catheter occlusion and repair of pediatric ductus arteriosus is herein reported in older patients using a Foley catheter and normothermic bypass. Transesophageal echocardiography is crucial in assessing the size of the ductus and confirming adequacy of repair. The technique is simple and safe even in the presence of a wide, short ductus.

Adolescent↗
PubMed1996

Transcatheter occlusion of the patent ductus arteriosus with Cook detachable coils.

OBJECTIVE: To report initial experience with a new occlusion device for native and residual patent ductus arteriosus. DESIGN: Descriptive study of consecutive non-randomised patients undergoing a new method of patent ductus arteriosus closure with detachable coils. SETTING: Tertiary centres for paediatric cardiology. PATIENTS: 71 consecutive patients, aged 1.2-22 years, with a patent ductus arteriosus (PDA) underwent elective transcatheter closure. 45 had native PDAs (group A) with a minimum diameter of 1.0 mm-5.0 mm (median 2.0 mm). A further 26 had undergone one or more previous occlusion attempts (group B). INTERVENTIONS: A total of 133 detachable (Cook) spring coils were successfully implanted in 70 patients. The procedure was performed transvenously in 51 patients, retrograde arterially in 13, and by both routes in a further 6 patients. One 5 mm coil migrated but was successfully retrieved. MAIN OUTCOME MEASURES: In group A colour flow Doppler echocardiography showed that complete occlusion was achieved in 40/45 (89%) at 24 hours, 41/45 (91%) at 1 month, and 44/45 (98%) by 6 months post procedure. Occlusion rates in residual PDAs were 22/25 (88%) occluded at 24 hours, 23/25 (92%) at 1 month, and 24/25 (96%) at 6 months follow up. CONCLUSIONS: Transcatheter occlusion using detachable (Cook) spring coils is a safe and effective alternative to presently available devices. The delivery system allows full retrieval of the coil until a satisfactory position is obtained.

Adolescent↗
PubMed1993

Postnatal closure of the ductus arteriosus in West African dwarf goats.

Fifteen West African dwarf goats aged between 0 and 42 days were used to study the closure time of the ductus arteriosus using dye injection and histological techniques. The ductus arteriosus appeared haemodynamically patent in kid goats 0 to three days old. There was a progressive contraction of the smooth muscle cells of the wall of the ductus from birth, resulting in the obliteration of the lumen in four and six days at the pulmonary and aortic ends, respectively. This contraction phase was followed by disruption of the luminal endothelium, intimal thickening and necrosis of smooth muscle cells in goats nine to 18 days old. Beyond 21 days there was connective tissue formation resulting in the permanent sealing of the ductal lumen in goats 28 to 33 days old. Although lumina of varying sizes were observed in histological sections of the ductuses of four- to 32-day-old goats, these were haemodynamically insignificant. The results suggest three phases in the closure of the ductus arteriosus of West African dwarf goats which was completed between 28 and 33 days.

Aging↗
PubMed1991

Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.

To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared by in situ cannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1-2, 7, and 18 mm Hg (0.13-0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined: 1) with ductus closed, 2) with ductus open, and 3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 mumol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism.

Animals↗
PubMed2003

Echocardiographic features of adult tetralogy of Fallot with natural palliative correction by patent ductus arteriosus.

A thirty-year-old man with the diagnosis of the tetralogy of Fallot and patent ductus arteriosus was admitted to our hospital because of a syncope. He reported no previous symptoms. We diagnosed adult tetralogy of Fallot, which included all four characteristic anomalies: ventricular septal defect, overriding aorta, pulmonary artery stenosis, and right ventricular hypertrophy. The associated persistent ductus arteriosus and the presence of compensatory arteriovenous communications produced a continuous flow load on the left ventricle, which resulted in moderate left ventricular hypertrophy, but without symptoms of pulmonary congestion or cardiac decompensation. Anatomic diagnosis and hemodynamic assessment were established by transthoracic and transesophageal echocardiography, with incidental finding of a quadricuspid aortic valve. To the best of our knowledge, our case of the adult form of Fallot's tetralogy associated with both patent ductus arteriosus and quadricuspid aortic valve is the first one ever described. It is well known that patients with tetralogy of Fallot who do not undergo operation in childhood have short survival, which depends predominantly on the degree of pulmonary artery stenosis and early development of collateral circulation to the lungs. Long-term persistence of natural aortopulmonary anastomosis with systemic collateral circulation to the lungs and remodeling of the heart, with better hemodynamic balance as well as the presence of mild pulmonary artery stenosis probably enhanced the survival of our patient.

Adult↗