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PubMed1978

Effect of prostaglandins and some methyl derivatives on the ductus arteriosus.

In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients.

Animals↗
PubMed2006

Inhibition of cyclooxygenase isoforms in late- but not midgestation decreases contractility of the ductus arteriosus and prevents postnatal closure in mice.

Use of cyclooxygenase (COX) inhibitors to delay preterm birth is complicated by in utero constriction of the ductus arteriosus and delayed postnatal closure. Delayed postnatal closure has been attributed to loss of vasa vasorum flow and ductus wall ischemia resulting from constriction in utero. We used the murine ductus (which does not depend on vasa vasorum flow) to determine whether delayed postnatal closure may be because of mechanisms independent of in utero constriction. Acute inhibition of both COX isoforms constricted the fetal ductus on days 18 and 19 (term) but not earlier in gestation; COX-2 inhibition constricted the fetal ductus more than COX-1 inhibition. In contrast, mice exposed to prolonged inhibition of COX-1, COX-2, or both COX isoforms (starting on day 15, when the ductus does not respond to the inhibitors) had no contractile response to the inhibitors on days 18 or 19. Newborn mice closed their ductus within 4 h of birth. Prolonged COX inhibition on days 11-14 of gestation had no effect on newborn ductal closure; however, prolonged COX inhibition on days 15-19 resulted in delayed ductus closure despite exposure to 80% oxygen after birth. Similarly, targeted deletion of COX-2 alone, or COX-1/COX-2 together, impaired postnatal ductus closure. Nitric oxide inhibition did not prevent the delay in ductus closure. These data show that impaired postnatal ductus closure is not the result of in utero ductus constriction or upregulation of nitric oxide synthesis. They are consistent with a novel role for prostaglandins in ductus arteriosus contractile development.

Animals↗
PubMed1989

Patent ductus arteriosus with Eisenmenger's syndrome detected by first-pass study.

The case of a 20-year-old man with patent ductus arteriosus complicated with Eisenmenger's syndrome is described. Radionuclide angiocardiography characterized the abnormal pattern of blood flow through the central circulation to establish a diagnosis of patent ductus arteriosus with a significant right-to-left shunt, which had not been indicated by other clinical findings.

Adult↗
PubMed1990

Abnormal renal and splanchnic arterial Doppler pattern in premature babies with symptomatic patent ductus arteriosus.

The flow velocity pattern in the descending aorta, renal arteries, and celiac and superior mesenteric arteries was studied with pulsed Doppler in eight premature babies with symptomatic ductus arteriosus before and after ductal closure, as compared to nine premature babies without ductus arteriosus. There was a decrease or reversal of flow in diastole in the above arteries in babies with ductus and diastolic flow reappeared after ductal closure. This diastolic steal phenomenon has not been previously demonstrated in the abdominal arteries. It may contribute to proneness to ischemic damage of abdominal organs in premature babies.

Aorta, Thoracic↗
PubMed1990

[Non-surgical closure of patent ductus arteriosus in children with the Rashkind double disk occluder].

Since the first clinical application of transcatheter closure technique for patent ductus arteriosus in children and infants in 1977 by Rashkind and Coll., this technique is routinely performed only in a few major Pediatric Cardiology Centers. We report our successful series which is the first of its kind both in Italy and in Southern Europe. The series included 11 children aged 1.6 to 10 years (mean age 4.5 years) all affected with patent ductus arteriosus (PDA). Subaortic stenosis (1) and ventricular septal defect with pulmonary stenosis (1) were associated anomalies. In all of the cases, after the standard percutaneous cardiac catheterization, the Mullins method was attempted to advance and deliver the Rashkind PDA double-disk occluder. Successful closure was accomplished in 10 while almost complete closure was achieved in the 11th. Normal Doppler flow pattern after the procedure confirmed the successful results. No complications occurred. Although our experience is limited, non-surgical PDA closure provided an excellent alternative to surgical procedure.

Cardiac Catheterization↗
PubMed2001

[Percutaneous closure of patent ductus arteriosus with the Amplatzer duct occluder. Results of 29 patients].

The authors report their experience of percutaneous closure of large patent ductus arteriosus with the Amplatzer duct occluder. The age of the patients ranged from 3 months to 72 years (average 24 months) with body weights of 3.9 to 74 Kg (average 16 Kg). The smallest angiographic diameter of the ductus was 4.0 +/- 1.3 mm at angiography (range 1.8 to 6 mm). The occluder was inserted under local anaesthetic with control aortography in all but one case who required general anaesthesia. In two small babies, the implantation was performed after venous puncture alone with transthoracic echocardiographic monitoring. The implantation was successful in all but one case in which there was a distensible duct. Early angiographic control showed suppression of the shunt in 61% of patients. Secondary haemolysis was observed in one case and was corrected by a second catheterisation 4 days later, with occlusion of the duct with a balloon catheter. The patients were followed up clinically, radiologically and echocardiographically. Doppler echocardiography showed absence of a residual shunt in 24 patients (86%) one month after the procedure, in 25 patients (89%) 3 months after the procedure and in 26 patients (93%) one year after the procedure. Two patients were left with mild or moderate shunts 12 and 16 months after the attempted occlusion. No cases of aortic or pulmonary obstruction were observed. The authors conclude that the Amplatzer duct occluder is a reliable device for closing large patent ductus arteriosus. It may be proposed in young symptomatic children over 4 Kg in body weight. A high rate of occlusion is obtained with a minimal risk of complications.

Adolescent↗
PubMed1995

Early echocardiographic prediction of symptomatic patent ductus arteriosus in preterm infants undergoing mechanical ventilation.

OBJECTIVE: To identify early echocardiographic markers allowing prediction of subsequent symptomatic patent ductus arteriosus (PDA). METHODS: One hundred sixteen preterm infants ( < 1500 gm) requiring mechanical ventilation underwent echocardiography at a mean postnatal age of 19 hours (range, 7 to 31 hours). Four potential markers were studied: the left atrial to aortic root ratio, pulsed Doppler signal within the course of the duct (ductal diameter), and the direction of postductal aortic diastolic flow. Subsequent ductal closure or significant patency (if suspected clinically) was confirmed echocardiographically. RESULTS: A significant PDA developed in 42 infants (36%). Ductal diameter was the most accurate echocardiographic marker in predicting subsequent significant most accurate echocardiographic marker in predicting subsequent significant PDA. With a ductal diameter of 1.5 mm or greater there were 34 true-positive, 11 false-positive, 63 true-negative, and 8 false-negative results, giving a positive likelihood ratio of 5.5 and a negative likelihood ratio of 0.22 for prediction of development of a PDA requiring treatment. The sensitivity was 81% and the specificity was 85%. Only one infant older than 28 weeks of gestational age had a significant PDA, and limiting the analysis to infants younger than 29 weeks of gestation further improved the predictive accuracy of ductal diameter. The positive likelihood ratio was 8.1 and the negative likelihood ratio was 0.19, with a sensitivity of 83% and a specificity of 90%. CONCLUSION: Color Doppler measurement of the internal ductal diameter allows early prediction of significant PDA in preterm infants.

Ductus Arteriosus↗
PubMed1986

Single Doppler detection of left to right shunt through the ductus arteriosus.

Forty-two infants and children were examined with unguided continuous and pulsed Doppler echocardiography before and/or after surgical closure of ductus arteriosus or in connection with cardiac catheterization. Presence or absence of diastolic reverse flow in the main pulmonary artery was evaluated for sensitivity and specificity to detect left to right ductus shunt. Diastolic reverse flow was detected in 15 of 16 patients with such a shunt and in 3 of 38 patients without a left to right ductus shunt. This corresponds to 94% sensitivity and 92% specificity. It is concluded that the accuracy of a single Doppler system in diagnosing patent ductus arteriosus is comparable to the results obtained with a Doppler interfaced to M-mode or cross-sectional echocardiography.

Blood Flow Velocity↗
PubMed1988

Further evidence implicating a cytochrome P-450-mediated reaction in the contractile tension of the lamb ductus arteriosus.

The authors have recently provided evidence implicating the cytochrome P-450 system in the generation of contractile tension of the ductus arteriosus. To confirm this possibility, carbon monoxide (CO/O2 ratio, 0.27) and cytochrome P-450 inhibitors [4-phenylimidazole; 14-isocyano,15-(methoxymethyleneoxy)-5Z,8Z,11 Z-eicosatrienoic acid; 9-hydroxyellipticine; alpha-naphthoflavone] were tested on the isolated ductus arteriosus from mature fetal lambs equilibrated at low (4-26 mm Hg) or high (229-694 mm Hg) O2 partial pressure (PO2). Carbon monoxide completely relaxed intact vessel wall preparations and preparations consisting of only the muscle. Carbon monoxide relaxation was reversed by illumination with monochromatic light and the peak for the photoactivated contraction occurred at 450 nm. 4-Phenylimidazole (100 and 1,000 microM) was also a relaxant agent, and its action was manifest at both low and high PO2. Unlike 4-phenylimidazole, the isonitrile compound (5 microM) and 9-hydroxyellipticine (10 and 100 microM) were relaxant only at low PO2 and were also less potent. At the same PO2, alpha-naphthoflavone (10 microM) barely reduced ductal tension. Treatment of the ductus with either a combination of superoxide dismutase (60 or 150 U/ml) and catalase (40 or 1,000 U/ml) or mannitol alone (80 mM) failed to alter the steady-state tone at low PO2 and the contractile response to O2. Arachidonic acid was tested on tissues pretreated with the dual cyclooxygenase and lipoxygenase inhibitor, BW755C (10 microM), and produced a weak relaxation at a concentration of 1 microM or higher. 5,6-Epoxytrienoic acid relaxed the untreated tissue, and its action was abolished by indomethacin (2.8 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Amplatzer Duct Occluder device: a new technology for the closure of the moderate-to-large-sized patent ductus arteriosus.

The Amplatzer Duct Occluder is a novel device designed to allow for the transcatheter closure of virtually all sized patent ductus arteriosuses. Prior technologies have been cumbersome and challenging to deploy with somewhat less than ideal closure rates associated with their use. This article summarizes the present knowledge about the Amplatzer Duct Occluder device and its various indications. With the introduction of this device as well as the use of embolization coils, all but the neonatal patent ductus arteriosuses can now be safely, consistently and successfully closed in the cardiac catheterization laboratory.

Biotechnology↗
PubMed1983

Evaluation of the preterm infant for patent ductus arteriosus.

As a first step in a multicenter, collaborative project to study the role of indomethacin in the management of patent ductus arteriosus in premature infants, a diagnostic scheme was developed, on an a priori basis, by a consensus of the participating neonatologists and pediatric cardiologists. The scheme, which utilizes clinical and noninvasive findings, was designed to detect infants with a "hemodynamically significant" patent ductus arteriosus (PDA). Among 1,689 infants with birth weight less than 1,750 g who were monitored during the first year of the study, 342 (20.2%) met the criteria for PDA. Rates were higher for smaller infants (42% with birth weight less than 1,000 g) than for larger infants (7% with birth weight 1,500 to 1,750 g). Although study protocol did not require a direct procedure to confirm the diagnosis of PDA, a marked decrease in the presence of most criteria was noted following surgical ligation of the ductus. Although the echocardiographic criterion (ratio of left atrium to aorta [LA/Ao] greater than or equal to 1.15) proved to have a low specificity for PDA, the data suggest that the overall scheme led to a very low rate of false-positive diagnosis. Following the application of the scheme for 1 year at 13 clinical centers, it has been shown to be a highly acceptable means of detecting infants with PDA.

Clinical Trials as Topic↗
PubMed2000

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants.

UNLABELLED: This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. CONCLUSION: Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen.

Ductus Arteriosus, Patent↗
PubMed1990

[Endoluminal closure of ductus arteriosus. A cooperative study].

Thirty-two patients from 3 Pediatric Cardiological Centres underwent attempted endoluminal transcatheter closure of a patent ductus arteriosus. The patients' age ranged from 8 months to 67 years, but there were only 2 adults (18 and 67 years) in this series. All patients had a murmur which was continuous in 28 cases and systolic in 4 cases. Nine patients had left ventricular hypertrophy on the electrocardiogram and radiological cardiomegaly. Closure of the patent ductus was attempted by Rashkind's technique using a double umbrella of 12 mm diameter for ductus less than 4 mm diameter (26 cases), and an umbrella of 17 mm diameter when the ductus was wider (6 cases). The immediate results judged by retrograde aortography showed total occlusion in 12 patients and incomplete closure in 17 others with persistence of a minimal left-to-right shunt. In 3 cases, embolisation of the umbrella into the left pulmonary artery (2 cases) or right pulmonary artery (1 case), required thoracotomy to extract the umbrella and at the same time section-suture of the ductus arteriosus. Color Doppler echocardiographic follow-up showed the disappearance of the residual shunt in seven children.

Adolescent↗
PubMed2004

Association of patent ductus arteriosus and severe hypothyroidism in term newborns: coincidence or causal?

We report on 3 term newborns with the association of patent ductus arteriosus (PDA) and severe hypothyroidism attributed to thyroid agenesis (n = 2) or feto-maternal pit-1 deficiency (n = 1). This association suggests that sufficient thyroid hormone availability is among the prerequisites for normal postnatal ductal closure. Unravelling the maturational effects of thyroid hormone on the ductus arteriosus might also be relevant in preterm infants as further studies of the perinatal thyroid axis may clarify the potential role of thyroid hormone in PDA closure in preterm infants. Based on our observation, hypothyroidism should be considered in term infants with PDA.

Ductus Arteriosus, Patent↗