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PubMed1983

Factors determining the loss of ductus arteriosus responsiveness to prostaglandin E.

The ductus arteriosus of the newborn infant varies in its ability to dilate when doses of prostaglandin E (PGE) are administered. We infused PGE2 into 15 late-gestation newborn lambs to determine which factors regulate the ability of the ductus arteriosus to respond to PGE. PGE2 dilated the ductus in 10 lambs (responders); in five other lambs, despite similar PGE2 concentrations, there was no effect (nonresponders). The measured ductus resistance after the PGE2 infusion was directly related to the ductus resistance before the infusion. Responders had a larger left-to-right shunt through the ductus before the PGE infusion than nonresponders. Ductus that were isolated and studied in vitro from lambs that were nonresponsive to PGE2 (in vivo) were limited in their ability to relax with PGE2 as well as to actively contract with oxygen and indomethacin. This generalized loss of ductus responsiveness was directly related to the amount of the left-to-right shunt through the lumen of the ductus. These observations are consistent with the hypothesis that the constriction of the ductus arteriosus after birth limits the ability of the ductus to respond to PGE therapy.

Animals↗
PubMed2003

Persistent Doppler flow predicts lack of response to multiple courses of indomethacin in premature infants with recurrent patent ductus arteriosus.

OBJECTIVE: Although indomethacin produces ductus arteriosus constriction in extremely premature newborns, a recurrent symptomatic patent ductus arteriosus (PDA) frequently develops after the initial course of indomethacin. Currently, there is little information available to determine the effectiveness of a second course of indomethacin in producing permanent ductus closure. The objective of this study was to determine the rate of permanent ductus closure after a second course of indomethacin for a recurrent, symptomatic PDA and to identify the factors associated with permanent ductus closure. METHODS: We identified 32 infants (<28 weeks' gestational age) 1) whose ductus was considered to be clinically closed after an initial course of indomethacin and 2) who subsequently developed a symptomatic PDA and received a second course of indomethacin. Clinical variables were evaluated for their association with failure of the second course (defined as surgical ligation after the second course for recurrence of a hemodynamically significant PDA). Data were analyzed by chi(2) analysis, Fisher's exact test, and the Mann-Whitney rank sum test. RESULTS: After the second course of indomethacin, 56% (18 of 32) of the infants had persistent or recurrent PDA-related symptoms that were considered to be hemodynamically significant. The only significant predictor of failure of the second indomethacin course was the demonstration (by Doppler echocardiogram) of persistent ductus flow within 24 hours of completing the initial indomethacin course. All of the 9 newborns with persistent Doppler ductus flow after the initial indomethacin course failed the second course of indomethacin. In contrast, only 39% (9 of 23) of newborns with absent Doppler flow after the initial indomethacin course failed the second course of indomethacin. CONCLUSIONS: Newborns who are <28 weeks' gestational age and develop a recurrent, symptomatic PDA after completion of an initial indomethacin course rarely respond to multiple courses of indomethacin if there was persistent Doppler evidence of ductus flow after completion of the initial course. Additional indomethacin treatment is unlikely to produce permanent ductus closure.

Ductus Arteriosus, Patent↗
PubMed2000

[Ibuprofen--a new application for pharmacological closure of patent ductus arteriosus in preterm infants. Preliminary report].

Patent ductus arteriosus (PDA) remains a frequent problem in premature infants, particularly with very low birth weight. Left-to-right shunting through the ductus may increase the risk of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and death. Indomethacin is the conventional pharmacologic treatment of patent ductus arteriosus (PDA). Although indomethacin is effective in closing PDA, its use may be associated with negative influences on renal, gastrointestinal and cerebral blood flow. More recently Ibuprofen has been tested; it can close the ductus arteriosus, but compared it with indomethacin, it has no negative influence on intestinal haemodynamics. On the basis of relevant literature, ibuprofen and indomethacin have been compared with regard to efficacy for closure of patent ductus arteriosus and side effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Use of an intravascular endoprosthesis (stent) to establish and maintain short-term patency of the ductus arteriosus in newborn lambs.

The feasibility of stenting the ductus arteriosus with a balloon-expandable vascular endoprosthesis was tested in 8 newborn lambs. Tantalum wire and stainless steel mesh coronary stents were implanted antegrade or retrograde by percutaneous transfemoral catheterization. One lamb died during the procedure from perforation of the aorta. In 7 lambs, the ductus arteriosus was crossed using endhole catheters and wires, and stents mounted on angioplasty catheters were expanded in the ductus arteriosus. Six lambs had successful implantation and had maintained a sizeable patent ductus arteriosus at 2 h. We conclude that the feasibility of percutaneous stenting of the newborn ductus was demonstrated. By providing patency of the ductus arteriosus, stents may offer nonsurgical alternatives for palliation of cyanotic congenital heart disease and hypoplastic left heart syndrome.

Animals↗
PubMed1998

Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: the role of gestation, oxygen tension, and vasa vasorum.

We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal PO2, but that at neonatal PO2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated PO2. L-NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low PO2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low PO2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.

Aminoquinolines↗
PubMedDate not supplied

Transcatheter management of patent ductus arteriosus in sick ventilated small infants.

BACKGROUND: Large patent ductus arteriosus can present in infancy with congestive cardiac failure and superadded pulmonary infection can necessitate mechanical ventilation. Surgical intervention is traditionally indicated for this subset of patients. We present our experience of transcatheter coil closure of the patent ductus arteriosus in such infants. METHODS AND RESULTS: Five infants weighing between 960 gm and 4.1 kg, aged between 17 days and 3 1/2 months were mechanically ventilated because of congestive cardiac failure with pneumonia. Echocardiography showed patient ductus arteriosus with a size of 1.8 to 4.2 mm and adequate ampulla. Bioptome-assisted coil delivery was done and successful patient ductus arteriosus closure was achieved in all. There were two instances of embolization of coils with successful retrieval and redeployment. All infants could be weaned off mechanical ventilation over the next 24-72 hours. A pre-term infant developed a Doppler gradient of 25 mmHg in the descending aorta that decreased to 12 mmHg five months later. There was no significant obstruction to pulmonary artery flow in any child. At three months follow-up, all the five infants were asymptomatic with no residual flow across the patient ductus arteriosus. CONCLUSIONS: Transcatheter coil closure of moderate to large patent ductus arteriosus is possible in sick ventilated infants weighing below 5 kg. It may be a better alternative to surgery in selected cases in view of minimal morbidity.

Catheter Ablation↗
PubMed2001

Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus.

BACKGROUND AND AIM: A patent ductus arteriosus (PDA) may influence renal and hepatic blood flow and hence pharmacokinetics of drugs in neonates compared to neonates with a closed ductus arteriosus (CDA). A 10-percent difference of gentamicin pharmacokinetic parameters between PDA and CDA has been reported; but its implications are unclear. The relevance of this difference relative to the variability within the neonatal population was investigated. METHODS: Twenty-four neonates (12 with a PDA and 12 with a CDA) treated with gentamicin were retrospectively included. Before closing treatment of the PDA, serum levels were drawn and analysed for regular therapeutic drug monitoring of gentamicin. Data were analysed using the standard two-stage approach (STS) and an iterative 2-stage Bayesian population analysis approach (It2B). RESULTS: Both types of analysis showed no significant differences between both populations for gentamicin total body clearance per kg bodyweight (CL/kg). Volume of distribution per kg bodyweight (Vd/kg) tended to be larger and elimination rate (Kel) tended to be smaller in neonates with PDA. Multiple regression analysis showed for both populations highly significant correlations between total body clearance and body weight (p < 0.0001) or gestational age (p < 0.0001), and between volume of distribution and body weight (p < 0.0001) or gestational age (p < 0.0001). CONCLUSION: Although neonates with a PDA may have small differences in gentamicin pharmacokinetics compared to neonates with a CDA, this is not relevant for clinical practice taking the variability within that population into account.

Anti-Bacterial Agents↗
PubMed1998

Accelerated maturation of fetal ductus arteriosus by maternally administered vitamin A in rats.

Maturation of fetal ductus arteriosus is associated with increased constriction in response to maternally administered indomethacin. Recently retinoic acid has been shown to be important in development of the fetal ductus arteriosus. To determine whether retinoid might be of value in the treatment of patent ductus arteriosus in premature infants, we studied the response of fetal ductus arteriosus to indomethacin with and without pretreatment with vitamin A (1 mg (3000 IU)/kg, intramuscular injection) in near-term and preterm rats. Maturation of the ductus arteriosus was studied by measuring the inner diameters of the ductus arteriosus (D) and main pulmonary artery (P) to get D/P ratio 4 h after orogastric administration of 1 mg/kg indomethacin. D/P was 1.0 in the fetus before administration of indomethacin. In near-term fetuses on the 21st d without vitamin A, D/P decreased to 0.54 with indomethacin, whereas it decreased to 0.27 (p < 0.05) in those with pretreatment with vitamin A on the 19th and 20th d. In preterm fetuses on the 20th d without pretreatment with vitamin A, D/P decreased to 0.82 with indomethacin, whereas it decreased to 0.66 (p < 0.05) in those with pretreatment with vitamin A on the 19th d. It is concluded that maternally administered vitamin A accelerates maturation of the ductus arteriosus in fetal rats.

Analysis of Variance↗
PubMed1986

Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding.

Patent ductus arteriosus is common among premature neonates, especially those with birth weights less than 1,500 g. In vitro, room light inhibits the contraction of immature piglet's ductal rings. Because phototherapy is used frequently from the first days of life to treat jaundice in preterm neonates, we compared the occurrence of patent ductus arteriosus among premature infants exposed to this intense light source with those whose chests were shielded. Seventy-four babies with respiratory distress syndrome were randomly assigned to either a treatment group (chest shielded with aluminum foil while on phototherapy, 36 babies) or control group (no shield, 38 babies). All were on radiant warmers, received mechanical ventilation for respiratory distress syndrome, and phototherapy (Air Shields model PTU 78-1) from day 1 of life. Irradiance was maintained at greater than 4.0 microW/cm2/nm in all cases. Although both groups had similar birth weights, gestational ages, severity of respiratory distress syndrome, intravenous fluid intake, and duration of phototherapy, the incidence of patent ductus arteriosus was significantly less in the shield group (shield 11/36 v No shield 23/38; P = .009). Patent ductus arteriosus murmurs developed in shielded patients at a later date, they required less vigorous treatment (ie, indomethacin), and they had shorter hospitalizations (74 v 85 days; P less than .05). The significant reduction of patent ductus arteriosus with shielding suggests that phototherapy may play a role in the occurrence of patent ductus arteriosus in premature infants. Shielding may be a practical method to decrease this common complication should this initial observation be confirmed.

Ductus Arteriosus, Patent↗
PubMedDate not supplied

[Early closure of ductus arteriosus with indomethacin].

The open ductus arteriosus was closed with indomethacin on the first days of life in 13 out of 27 preterm infants with respiratory distress syndrome. The early medical closure of the ductus arteriosus shortened the duration of the ventilatory assistance and need of additional oxygen in these infants.

Ductus Arteriosus, Patent↗
PubMed2003

[Transcatheter closure of persistent ductus arteriosus].

BACKGROUND: Transcatheter occlusion of persistent ductus arteriosus has replaced surgery as the treatment of choice. We wanted to evaluate the results of this treatment in our hospital. MATERIAL AND METHODS: From September 1989 through 2001, a total of 217 patients with persistent ductus arteriosus were scheduled for transcatheter occlusion at Rikshospitalet. Six ducts were too small for treatment. In the remaining 211 patients, 224 procedures were performed. Patients' median age was 3.4 years (range 4 months-82 years), their median weight 14 kilograms (range 4-90 kilograms). RESULTS: The Rashkind double umbrella was implanted successfully in 61/63 cases, coils in 99/102 cases, and an Amplatzer duct occluder in 57/59 cases. Complete closure of the duct was achieved in 197/211 patients (93%) after reintervention in 11. The complete occlusion rate for first procedures were 77% for the Rashkind device, 93% for coils and 100% for the Amplatzer plug. Only coils embolised, in 2 out of 102 procedures. Removed interventionally, they were replaced by an Amplatzer occluder. One patient developed haemolytic anaemia from residual shunting through a coil; the shunt and the anaemia both disappeared after implantation of a second coil. INTERPRETATION: Transcatheter occlusion of persistent ductus arteriosus is safe and efficient. The Amplatzer duct occluder seems superior to the Rashkind double umbrella and probably also to coils.

Adolescent↗
PubMed1997

Effectiveness of five-loop coils to occlude patent ductus arteriosus.

Coil occlusion of patent ductus arteriosus with 5-loop coils was undertaken in 10 patients without coil embolizations, and with 90% immediate occlusion and 100% occlusion at follow-up. We conclude that 5-loop coil occlusion of patent ductus arteriosus is safe and effective.

Adult↗
PubMed1980

Interruption of persistent ductus arteriosus with metal clips.

Persistent ductus arteriosus was interrupted with Hemoclips (Weck) in two children, 4 and 6 years of age, and four premature infants. After follow-up of 14 to 19 months, there were no recurrences. The use of Hemoclips to interrupt the persistent ductus arteriosus appears to be a safe procedure.

Child↗
PubMed1993

Thoracoscopic clipping of patent ductus arteriosus in premature infants.

Patent ductus arteriosus is a frequent indication for surgical intervention in preterm infants. Commonly this operation is performed through a dorsolateral thoracotomy. In an animal trial (piglets smaller than 1,400 g) instruments and technique for thoracoscopic clipping of patent ductus arteriosus were developed. Since January 1993, 3 premature infants have been treated with this new minimally invasive procedure. The instruments and the surgical technique are demonstrated.

Ductus Arteriosus, Patent↗
PubMed1994

Occurrence of endothelium-derived relaxing factor--nitric oxide in the lamb ductus arteriosus.

To determine whether the ductus arteriosus can form endothelium-derived relaxing factor--nitric oxide, we used isolated ductal strips from near-term fetal lamb and examined their response to bradykinin (a nitric oxide stimulator), L-arginine (a nitric oxide precursor), and agents interfering with the synthesis (N omega-nitro-L-arginine) and action (methylene blue) of nitric oxide. Bradykinin relaxed the indomethacin-contracted ductus dose dependently from a threshold of about 10(-10) M, and peak relaxation was greater at high (176-210 mmHg; 1 mmHg = 133.3 Pa) than low (15-25 mmHg) PO2. Bradykinin relaxation was nearly completely or completely abolished in endothelium-denuded preparations and, in its place, there was often a small contraction. Pretreatment with nitric oxide inhibitors also prevented, in part (methylene blue, 1 microM) or in full (N omega-nitro-L-arginine, 100 microM), the relaxant effect of bradykinin. Paradoxically, L-arginine (10 microM) had an inhibiting rather than an enhancing effect on the bradykinin relaxation. N omega-Nitro-L-arginine (100 microM) and methylene blue (1-100 microM) contracted by themselves the untreated ductus, and their action persisted after removal of the endothelium. These findings indicate the presence in the ductus arteriosus of a nitric oxide based relaxing mechanism, which may supplement prostaglandin E2 in keeping the vessel patent in the fetus. This mechanism may, on one hand, afford protection against nonsteroidal anti-inflammatory drugs in utero and may, on the other hand, complicate the management of prematures with persistent ductus and account for failures of the indomethacin therapy.

Animals↗
PubMed2002

Safety and efficacy of using 0.052-inch Gianturco coil for closure of large ( > or = 4mm) patent ductus arteriosus.

Transcatheter closure of patent ductus arteriosus (PDA) is now a well-established treatment alternative to surgery in many cardiology centers. Of all the methods used, transcatheter coil occlusion is the preferred therapy. For small PDA, the method using 0.038" Gianturco coils has proven safe and effective. However, this therapeutic strategy has encountered some difficulties with large PDA. This study provides an alternative strategy, using 0.052" Gianturco coil and complete closure of residual shunt with multiple coils to close large PDA. Fifteen patients underwent transcatheter coil occlusion of large ( > or = 4mm) patent ductus arteriosus. The intermediate success rate was 86.7%. There were four complications and only two patients had to be referred for surgery.

Adolescent↗
PubMed1985

Assessment of the ductus arteriosus in preterm infants utilizing suprasternal two-dimensional/Doppler echocardiography.

Evaluation for patent ductus arteriosus by both Doppler examination and direct two-dimensional echocardiographic visualization has been reported in infants and children. However, visualization of a patent ductus arteriosus in preterm infants with lung disease has been difficult. Using a recently developed 7.5 MHz mechanical scanner with interfaced two-dimensional directed pulsed Doppler ultrasonography, 36 examinations were performed from a suprasternal approach in 27 patients (age range 1 day to 3 months, mean 18 days; weight range 490 to 2,500 g, mean 1,260). Complete imaging for evaluation of patency of the ductus arteriosus was successful in 33 (92%) of 36 examinations, and imaging of the pulmonary end of the ductus arteriosus was successful in all. In 18 examinations, the ductus arteriosus was closed by both two-dimensional echocardiography and Doppler examination. In four cases the ductus arteriosus was widely patent by both two-dimensional echocardiography and Doppler examination. Eleven echocardiographic examinations revealed a narrowed ductus arteriosus, and of these, 10 (91%) showed Doppler findings of patent ductus arteriosus. It is concluded that combined two-dimensional/Doppler echocardiographic assessment allows confident detection of both a large unrestrictive and a small, stenotic patent ductus arteriosus in preterm infants with lung disease.

Aortography↗