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PubMed1981

Constriction of the fetal ductus arteriosus by glucocorticoid hormones.

Hydrocortisone, prednisolone, and betamethasone were injected into a rat that was 21 days pregnant, and the fetal ductus arteriosus was studied using the rapid whole-body freezing technique. All these glucocorticoids constricted the fetal ductus arteriosus in a dose-dependent relationship. Fetal ductal constriction was maximum 1 to 4 hr after injection and was significantly more prominent in premature fetuses than in mature ones.

Animals↗
PubMed1995

Aortic arch dissection from patent ductus arteriosus.

An unusual case of aortic arch dissection from a patent ductus arteriosus (PDA) is described. An adult man had been diagnosed as suffering from pectus excavatum and PDA 10 years before. At that time the pectus was repaired, but he failed to return for surgery on the PDA and the sub-sternal strut for pectus repair was also never removed. Recently he was admitted in a peripheral hospital with chest infection. Patent ductus arteriosus murmur was audible on clinical examination. The chest X-ray showed a widened mediastinum and the pectus strut. On further investigations dissection of the aortic arch was discovered and arch replacement performed.

Adult↗
PubMed1999

Indomethacin and corticosteroids: an additive constrictive effect on the fetal ductus arteriosus.

The objective of this paper is to study the possible additive effect of corticosteroids to the known effect of indomethacin on potency of the human ductus arteriosus. Systolic and diastolic blood flow of the fetal ductus arteriosus was measured by echo Doppler at 26-32 weeks of gestation. Four groups of patients were studied according to the treatment they have received: group A (exposure to indomethacin and betamethasone); group B (indomethacin alone); group C (betamethasone); and group D (controls). Children in whom ductal constriction was noted in utero were followed by repeat cardiac echo Doppler examinations at the age of 1 to 2 years. In group A (indomethacin and betamethasone) fetal ductal constriction was significantly higher (p = 0.02) and occurred in 11 out of 15 fetuses (73.3%), compared with 5 out of 14 (37.2%) of the fetuses in group B (indomethacin alone). In group C (betamethasone) and D fetuses (no treatment), no significant ductal constriction was observed. Pathological tricuspid regurgitation and right ventricular dilation were found more frequently in fetuses from group A. No long-term sequella was noted in the infants in whom ductal constriction had been noted in utero. Corticosteroids and indomethacin have a synergistic effect on the frequency and severity of fetal ductus arteriosus constriction. In short-term treatment this effect is transient, and has no deleterious effects on fetal and neonatal cardiac function.

Adrenal Cortex Hormones↗
PubMed1998

Comparison of muscle-sparing thoracotomy and thoracoscopic ligation for the treatment of patent ductus arteriosus.

PURPOSE: We reviewed our experience with the treatment of patent ductus arteriosus (PDA), and compared two therapeutic techniques; muscle-sparing thoracotomy (MST) and thoracoscopic PDA ligation (TPDAL). METHODS: We reviewed the clinical records and operative reports of 19 nonnewborn patients who were treated at our institution for PDA. Eleven patients underwent TPDAL and eight patients MST. The TPDAL patients underwent thoracoscopic clipping (ligation) of the PDA, whereas the MST group had a complete division of the ductus. A two-tailed Student's t test was used to calculate the 95% confidence intervals for length of operation, number of doses of intravenous narcotics and hospital stay. Costs were also compared. RESULTS: All patients underwent diagnostic echocardiography in the evaluation of an asymptomatic murmur. Both groups were similar in age (average, 4 years) and gender. All procedures were performed electively. Two thoracoscopic attempts were aborted, one for bleeding and the other for inadequate clip size. The length of the procedure averaged 1.3 hours +/- 0.330 SD for TPDAL versus 1.4 hours +/- 0.335 SD for MST. Five of the nine successful TPDAL patients were admitted to the Pediatric Intensive Care Unit (PICU) with an average length of stay of 20 hours, and two of eight MST patients stayed in the PICU for average of 18 hours. All patients were extubated after the procedure. Chest tubes were placed in two TPDAL patients and three MST patients. However, two patients who underwent TPDAL required tube thoracostomy for persistent postoperative pneumothorax. Average number of intravenous narcotics administered for the TPDAL was 1.2 doses per patient and for MST, 1.75 doses per patient. Mean hospital stay for TPDAL was 1.33 +/- 0.71 SD days and for MST 1.8 +/- 0.83 SD days. Ninety-five percent (95%) confidence intervals for the difference in means demonstrated no difference between the two groups for length of operation, hospital stay, or number of doses of intravenous narcotics administered. CONCLUSIONS: The authors were unable to identify any benefit to thoracoscopic patent ductus arteriosus ligation versus muscle-sparing thoracotomy in terms of hospital stay, length of operation, or morbidity. Additionally, with MST there is a complete division of the PDA theoretically decreasing the risk of recurrence in comparison with clip ligation.

Case-Control Studies↗
PubMed2003

Inhibition of in vivo constriction of fetal ductus arteriosus by endothelin receptor blockade in rats.

The fetal ductus can be constricted by drugs, including cyclooxygenase inhibitors (indomethacin), nitric oxide synthesis antagonists [N-nitro-L-arginine monomethyl ester (L-NAME)], and glucocorticoid hormones (dexamethasone). Constriction of the fetal ductus by endothelin (ET) 1 was reported in an in vitro study. We studied the preventive effect of a dual ET receptor antagonist (bosentan) and a selective ET-A blocker (CI-1020) on pharmacologic fetal ductal constriction in rats. Near-term pregnant Wistar rats at d 21 and preterm rats at d 19 were used. The fetal ductus was constricted by four medications: orogastric administration of indomethacin (10 mg/kg) on fetal d 21, orogastric indomethacin 1 mg/kg combined with muscular injection of L-NAME (10 mg/kg) on fetal d 21, and muscular injection of L-NAME or dexamethasone (1 mg/kg) on fetal d 19. Bosentan (0.1, 1, 10, or 100 mg/kg) was injected intraperitoneally either simultaneously with indomethacin, L-NAME, or dexamethasone, or 4 h after administration of 10 mg/kg indomethacin. CI-1020 (0.01, 0.1, 1, or 10 mg/kg) was injected intraperitoneally simultaneously with indomethacin. After maternal atlas dislocation, cesarean section, fetal whole-body freezing, and cutting on the freezing microtome, measurements were made of the inner diameters of the ductus, main pulmonary artery, and ascending aorta. Bosentan blocked fetal ductal constriction by indomethacin, indomethacin plus L-NAME in the near-term rats, and constriction by L-NAME and dexamethasone in the preterm rats dose dependently. Fetal ductal constriction was nearly completely blocked by simultaneously administered 100 mg/kg of bosentan or 10 mg/kg of CI-1020. Dual ET receptor antagonist (bosentan) and selective ET-A blocker (CI-1020) prevent constriction of the fetal ductus arteriosus induced by ductus-constricting agents in rats, indicating that ET and ET-A receptors are essential in fetal ductal constriction.

Animals↗
PubMed1993

Transcatheter occlusion of patent ductus arteriosus with Gianturco coils.

BACKGROUND: Transcatheter occlusion with Gianturco coils has been attempted in a small number of patients with tiny (< or = 1.5-mm diameter) patent ductus arteriosus, and preliminary results have been encouraging. The present study extends this method to larger ductus sizes and makes recommendations for proper coil size selection. METHODS AND RESULTS: Coil occlusion was attempted in 24 consecutive patients with patent ductus arteriosus who did not require other cardiac surgery. Median patient age was 4.2 years (8 months to 30 years), and mean ductus diameter was 1.7 +/- 0.8 mm. Two instances of coil embolization occurred in the first 4 patients, with successful coil retrieval. Based on this experience, we proposed that the coil helical diameter should be twice or more the minimum ductus diameter, with coil length sufficient for three or more loops. With these recommendations, coils were successfully implanted in the subsequent 20 consecutive patients. Of the 22 patients with successful coil implantation, 15 (68%) had no residual shunting, and 7 had trace residual shunting by angiography. The continuous murmur was abolished in all 22 patients. No significant complications occurred, and all patients were discharged within 24 hours of successful coil implantation. No change in the systolic pressure gradient between main and left pulmonary artery or ascending and descending aorta was observed. CONCLUSIONS: Transcatheter occlusion of patent ductus arteriosus can be safely and effectively achieved in patients with ductus diameters up to 3.3 mm. Coil occlusion does not cause obstruction to flow in the left pulmonary artery or descending aorta. Coils should be selected to provide a helical diameter twice or more the minimum ductus diameter and a length sufficient for three or more loops.

Cardiac Catheterization↗
PubMed1987

Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.

We created a model for studying the cardiovascular and pulmonary effects of patent ductus arteriosus (PDA) in premature lambs with respiratory distress. In 47 fetal lambs at 129 to 133 days gestation (term, 145 days), we infiltrated the ductus arteriosus with formalin and placed a mechanical occluder about it so that its patency could be regulated. Two days later the lambs were delivered, given sheep surfactant, paralyzed, and their lungs mechanically ventilated. These premature lambs could more than double their left ventricular output when challenged with increasing degrees of left-to-right shunts through the PDA. This was accomplished by an increase in stroke volume, not by an increase in heart rate. During the 40-minute observation period, there was no change in dynamic compliance or functional residual capacity while the ductus was patent. When the ductus was patent, there was a significant increase in arterial PaO2 (even with small left-to-right shunts) and a decrease in PaCO2 (with large shunts). Despite the heart's ability to handle the increased volume load of a PDA, there were significant alterations in individual organ blood flows, resulting from a combination of decreased perfusion pressure and localized vasoconstriction. The abdominal organs had significant reductions in blood flow even with small PDA shunts. This decrease in organ blood flow may explain some of the pathophysiologic manifestations of PDA in preterm infants.

Animals↗
PubMed1989

Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.

To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2 production with only twofold increase in 6-keto-PGF1 alpha (the stable metabolite of PGI2). PGE2 is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2.

Animals↗
PubMed1978

Radiographic and echocardiographic evaluation of newborns treated with indomethacin for patent ductus arteriosus.

A series of 33 consecutive preterm newborns who were treated with indomethacin, a drug which acts to close the patent ductus arteriosus, were studied retrospectively to examine the efficacy of chest radiography and echocardiography in diagnosing the presence of a significant patent ductus arteriosus. Radiographic changes in pulmonary vascular engorgement, pulmonary edema, and cardiac size on the anteroposterior film tended to precede the clinical changes of shunt appearance and resolution. The echocardiographic left atrial to aortic ratio (LA/Ao) supplemented the radiographic findings. The time of disappearance of the ductus arteriosus shunt, as judged by clinical findings, was identified accurately by radiographic and echocardiographic findings in the majority of cases; errors of under- and overestimation occurred in a minority of patients. In assessing both the presence and the resolution of the shunt, greater reliability was possible by using both radiographic and echocardiographic findings than by using either method alone.

Diagnostic Errors↗
PubMed2000

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

BACKGROUND AND METHODS: Percutaneous closure of a moderate-to-large sized patent ductus arteriosus using multiple coils or a Rashkind double-umbrella may be technically demanding and raises a significant rate of embolization and residual shunting. This is why we tried a new self-expandable device called Amplatzer Duct Occluder to close transvenously large ductuses in eighteen patients at a median age of 2.8 years (range: 0.7 to 34). They had a patent ductus arteriosus with a minimal diameter > 3 mm (mean: 5 +/- 2 mm). The device had a mean diameter of 9 +/- 2 mm and was delivered through a 6F venous sheath. Aortography was done 5 to 10 minutes after the release and follow-up evaluation was performed with color Doppler echocardiography within 24 h, 1 and 3 to 6 months after the procedure. RESULTS: Placement was successful in all but the first patient (95%). Complete closure was achieved immediately in 4/17 patients (24%) and in 13/17 (76%) 24 h later. Two patients were lost for follow-up. Complete closure was confirmed in 14 of the 15 (93%) reviewed patients at 1 and 3 months. In all patients with a ductal diameter < or = 7.5 mm the closure was complete at 1 month. Embolization occurred in one patient with a 9.7 mm duct and surgery was undertaken. A mild and transient hematuria was observed in one patient. No pulmonary artery stenosis nor aortic obstruction were observed on follow-up. CONCLUSION: The Amplatzer Duct Occluder device offers a safe and effective option to treat patients with a ductus arteriosus which minimal diameter is up to 7.5 mm.

Adolescent↗
PubMed1985

Hormonal role of adenosine in maintaining patency of the ductus arteriosus in fetal lambs.

The hypothesis that endogenously released adenosine plays an important role in maintaining patency of the fetal lamb ductus arteriosus was tested. The design of the study was (1) to determine the effect, if any, of exogenous adenosine on blood flow through the ductus arteriosus and (2) to evaluate the relationship among the partial pressure of oxygen in arterial blood, circulating endogenous plasma adenosine concentration, and the rate of blood flow through the ductus. When exogenous adenosine (5 mumoles) was administered during oxygen-induced ductal constriction, ductal blood flow increased from 101 +/- 6 ml/min to 153 +/- 4 ml/min (p less than 0.01). When fetal blood adenosine concentrations were measured during nonventilation and ventilation with 100% oxygen, endogenous adenosine concentrations fell to less than one-half of the preventilation levels, i.e., from 1.12 +/- 0.17 to 0.49 +/- 0.03 microM (p less than 0.01). Finally, when fetal lambs were ventilated with increasing concentrations of oxygen (0%, 10%, 20%, 60%, and 100%) and measurements obtained simultaneously at each level, there was a significant monoexponential relationship among the rise in PO2, the fall in plasma adenosine concentration, and the decrease in ductal blood flow. These data suggest that: (1) adenosine is a potent vasodilator of the lamb ductus arteriosus during oxygen-induced vasoconstriction; (2) fetal endogenous plasma adenosine levels fall significantly when PO2 is increased; and (3) the fall in adenosine concentrations parallels a decrease in ductal blood flow. The findings suggest that the endogenous vasodilator adenosine plays an important role in maintaining ductal patency in utero.

Adenosine↗
PubMed1978

Bilateral ductus arteriosus in d-transposition of the great arteries with right aortic arch.

The rare anomaly of a right aortic arch, distal origin of the left subclavian artery, and posterior left ductus arteriosus (forming a vascular ring) plus a right ductus arteriosus is described in an infant with d-transposition of the great arteries with an intact septum. The presence of a right aortic arch and distal left subclavian artery with bilateral ductus arteriosus has not been described previously.

Aorta, Thoracic↗
PubMedDate not supplied

Division or occlusion of patent ductus arteriosus?

The traditional and most effective form of treatment of persistent ductus arteriosus is surgical ductal division. New therapeutic techniques such as intraluminal ductal occlusion are currently recommended to replace the traditional treatment procedure. The purpose of this paper is to analyze the state of the art of these new therapeutic modalities. From reports in the medical literature, the authors analyzed the indications, results, and complications of the intraluminal ductal occlusion procedures. They applied the Student's t test for independent samples to evaluate the results of intraluminal patent ductus arteriosus occlusion by means of umbrellas, buttons, coils, and Gianturco-Grifka and Amplatzer occluders, respectively, in 2,691 patients collected from the medical literature. According to their analysis the results of intraluminal ductal occlusion with coils were as follows: success 83.7 +/- 12.2%, failure 3.9 +/- 2.8%, incomplete ductal occlusion 17.5 +/- 15.3%, need for surgery 2.8 +/- 3.8%, need for a second intraluminal procedure 5.8 +/- 9.9%, and device embolization 6.2 +/- 7.2%. The use of the Gianturco-Grifka device showed the following results: success 96.0 +/- 5.6%, failure 4.0 +/- 5.6%, incomplete ductal occlusion 4.0 +/- 5.6%, need for surgery 0%, need for a second intraluminal procedure 4.0 +/- 5.6%, and device embolization 4.0 +/- 5.6%. The Amplatzer occluder showed the following results: success 92.8 +/- 6.1%, failure 7.2 +/- 6.1%, incomplete ductal occlusion 2.0 +/- 4.3%, need for surgery 0%, need for a second intraluminal procedure 0.8 +/- 1.7%, and device embolization 0.5 +/- 1.3%. According to the state of the art, intraluminal ductal occlusion with Gianturco-Grifka device and Amplatzer occluder reduces the proportion of incomplete obstructions and need for surgery. Additionally, the use of the Amplatzer occluder reduces need for a second procedure and the embolization rate. Although the results obtained with the new procedures are better than those obtained previously, they are still not totally satisfactory.

Ductus Arteriosus, Patent↗
PubMed2004

Angiographic and hemodynamic predictors for successful outcome of transcatheter occlusion of patent ductus arteriosus in infants less than 8 kilograms.

Transcatheter occlusion of patent ductus arteriosus (PDA) using Gianturco coils (GCs) has been performed for the past decade. However, little has been written regarding anatomical and hemodynamic predictors for successful occlusion of the PDA in infants. This report is to evaluate the outcome of transcatheter occlusion of PDA in symptomatic infants less than 8 kg and to assess predictors of successful occlusion. Retrospective review of catheterization charts and cineangiograms of 42 symptomatic infants who underwent cardiac catheterization for attempted transcatheter occlusion of their PDA was conducted. The hemodynamic and angiographic data evaluated included the length/diameter (L/D) ratio, defined as the length divided by the narrowest diameter of the ductus arteriosus, and preocclusion pulmonary artery pressures. Thirty-one out of 42 patients (74%) had successful occlusion. Twenty-nine out of 42 infants had an L/D ratio > 3. Of these, 26 (90%) had successful occlusion of their PDA. Thirteen out of 42 patients had an L/D ratio < or = 3. Of these, 8 (62%) had unsuccessful occlusion. Complications encountered were transient loss of femoral arterial pulse (n = 6), coil embolization (n = 5), hemolysis (n = 2), and mild left pulmonary artery obstruction (n = 2). No permanent loss of femoral arterial pulse was noted. These complications resulted in no mortality and minimal morbidity. The L/D ratio was the strongest predictor of successful outcome, with an L/D ratio greater than 3.0 being more amenable to transcatheter occlusion (odds ratio of 4.6). Other predictors for success included lower preocclusion systolic, diastolic, and mean pulmonary artery pressure and smaller ductal diameter. Our conclusion was that infants less than 8 kg with an L/D ratio > 3.0 can safely and successfully undergo transcatheter occlusion of their PDA using transcatheter coils.

Body Weight↗
PubMed1993

Aneurysmal dilatation of ductus arteriosus during lipo-prostaglandin E1 therapy for diaphragmatic hernia.

We report a case of congenital diaphragmatic hernia in which aneurysmal dilatation of ductus arteriosus developed after lipo-prostaglandin E1 (PGE1) therapy for persistent fetal circulation. After surgery Lipo-PGE1 was used at a dosage of 5 ng/kg per minute from days 2-9 during which aneurysmal dilatation (7 mm in diameter) developed and remained thereafter. Ductus arteriosus ligation was then performed. Lipo-PGE1 may promote ductus arteriosus dilatation in cases of persistent fetal circulation.

Alprostadil↗
PubMed1990

Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.

The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde--diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.

Blood Flow Velocity↗
PubMed1991

Aneurysm of the ductus arteriosus. A review of the literature and the surgical implications.

One hundred and forty-four cases of aneurysms of the ductus arteriosus (DAA) have been reported in the literature of which 106 appeared spontaneously and 38 followed surgical treatment of a patent ductus arteriosus (PDA). Within the last few years there has been an increasing number of reported spontaneous DAA. However, the real incidence is presumably still underestimated. Aortography is a well established diagnostic method. In neonates, transthoracic echocardiography has shown convincing potential, whereas in older children and adults, transoesophageal echocardiography has yielded very promising results. Serious complications following spontaneous DAA are rupture, erosion, infection and thromboembolism. In infants younger than 2 months of age, the complication rate is 31%, in children between 2 months and 15 years, 66%, in adults, 47%. The rate of complications following postoperative DAA is even higher: 91% of the unoperated cases died due to rupture or infection. The operative mortality in children older than 2 months and adults is low. In the neonate group, 2 of 8 died during operation. The operative mortality in patients with postoperative DAA was 26%. Based on information from the literature, we suggest prompt surgical treatment of all spontaneous DAA in patients older than 2 months of age, and in all patients with postoperative DAA. In infants, a DAA should be closely followed with echocardiography, as spontaneous regression has been reported in this age group. If no regression is seen within a few days, it should be surgically corrected.

Adult↗