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PubMed2005

Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus.

After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1alpha/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (>15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1alpha/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.

Adenosine Triphosphate↗
PubMed1992

Aneurysm of the ductus arteriosus in the neonate: three case reports with a review of the literature.

Ductus arteriosus aneurysm was demonstrated in three neonates by echocardiography. One case was already diagnosed in utero. One patient needed surgical resection, whereas in one case the aneurysm of the ductus arteriosus regressed spontaneously. In the third case the patient died of associated lesions. In a review of the literature, 61 previous cases of ductus aneurysm in infants less than 2 months were found. Ductus arteriosus aneurysm may be diagnosed by echocardiography both pre- and postnatally. A ductus aneurysm should be monitored closely by echocardiography. Since a high incidence of complications is reported, surgical resection is indicated if the aneurysm does not regress within a few days.

Adult↗
PubMed2002

Minimal effective dose of indomethacin for the treatment of patent ductus arteriosus in preterm infants.

The aim of this study was to determine if it was possible to decrease the number of boluses of indomethacin for the treatment of patent ductus arteriosus. This retrospective study included 46 preterm neonates (<34 weeks' GA) who had had an ultrasound diagnosis predictive of subsequent symptomatic patent ductus arteriosus. All patients had received a daily intravenous doses of indomethacin, 0.1 mg/kg. Mean age at initiation of treatment was 4.5 +/- 3.1 days. Patency of the ductus arteriosus was controlled echocardiographically each day and treatment was discontinued as soon as the ductus arteriosus was closed. The initial success rate was 84.7%, of which 6.5% reopened. The mean cumulative dose of indomethacin was 0.35 mg/kg. There was no correlation between gestational age or birth weight and total cumulative dose. Overall tolerance was satisfactory with only one case of transient acute renal failure. A weak correlation between the cumulative dose of indomethacin and natremia (r = -0.43) or weight gain (r = 0.35) was noted, and none with serum creatinine or blood urea nitrogen levels. We confirm that lower indomethacin treatment of patent ductus arteriosus in premature neonates are as effective as standard protocols.

Cardiovascular Agents↗
PubMed1994

Transcatheter patent ductus arteriosus occlusion: application in the small child.

OBJECTIVES: This study intended to evaluate application of transcatheter occlusion of the patent ductus arteriosus in children < 10 kg body weight. BACKGROUND: Transcatheter occlusion of the patent ductus arteriosus in the child weighing > 10 kg has been proved safe and effective. METHODS: We reviewed 74 consecutive patients weighing < 10 kg (median 8.1 kg, range 3.98 to 10) and aged 4 to 30 months (median 13 months) who underwent patent ductus arteriosus occlusion between June 1986 and November 1992. A modification of the delivery system to facilitate application in small children is described. RESULTS: A 12-mm device was implanted in 50 patients and a 17-mm device in 24. Three device embolizations occurred early in the experience, and one required removal because of hemolysis associated with a moderate residual shunt. One 17-mm device was removed at catheterization because of acute compromise to left pulmonary artery flow after implantation. Prevalence of residual shunting was 33% at 6 months, 20% at 12 to 18 months and 17% at 2-year follow-up and was not related to device, age, weight or size of the patent ductus. Altered flow to the left pulmonary artery was noted in seven patients (9.9%), with more significant compromise associated with the 17-mm device. CONCLUSIONS: Transcatheter patent ductus arteriosus occlusion is feasible in the small child < 10 kg, particularly with the use of a modified delivery system. However, implantation of a 17-mm device in this patient population may impair flow to the left lung and should be reserved for the symptomatic child.

Cardiac Catheterization↗
PubMed1989

Surgical closure of the patent ductus arteriosus in the neonatal intensive care unit.

Efficacy of surgical closure versus indomethacin for treatment of patent ductus arteriosus in symptomatic neonates is an ongoing controversy. In recent years, surgical closure has been performed in the neonatal intensive care unit rather than the operating room in some centers, creating further controversy. In a retrospective study of the charts of 115 sequential patent ductus arteriosus surgical closures performed in the neonatal intensive care unit in premature infants, we found no surgical morbidity or mortality. Ninety-nine of these infants of less than 33 weeks gestational age were evaluated for various factors that might influence outcome. All were operated on within 72 hours of diagnosis, with an extra-pleural approach and metal clips used for closure of the ductus. All infants were extubated at an average of 33 weeks in each age group studied unless they had underlying severe bronchopulmonary dysplasia. We conclude that surgical closure of the symptomatic patent ductus arteriosus in neonates is safe and 100% effective, with none of the reported complications of indomethacin therapy, and should be the treatment of choice in neonates aged less than 33 weeks (gestational age) at birth with symptomatic patent ductus arteriosus. Closure performed in the neonatal intensive care unit eliminates transport risks and is ultimately safer and easier than transport to an operating room.

Ductus Arteriosus, Patent↗
PubMed1996

Spontaneous closure of the human fetal ductus arteriosus--A cause of fetal congestive heart failure.

OBJECTIVE: Closure of the fetal ductus arteriosus, which is usually due to nonsteroidal antiinflammatory agents, may be detrimental. Therefore prenatal and postnatal clinical and echocardiographic findings in four human fetuses with spontaneous ductus arteriosus occlusion are reported. STUDY DESIGN: Echocardiographic and clinical data were retrospectively analyzed. RESULTS: Spontaneous closure of the ductus arterious was discovered in four fetuses (gestational age 34 to 38 weeks). No mother had received nonsteroidal antiinflammatory agents. Enlargement of the right heart and pulmonary arteries and tricuspid and pulmonary regurgitation were present in all cases. Two fetuses had right ventricular hypertension. Postnatally their right ventricular function recovered promptly. The others had severe right heart failure with abnormal umbilical venous pulsations. After immediate delivery none had signs of persistent pulmonary hypertension. However, they have echocardiographic evidence of right ventricular dysfunction 2 to 6 months after delivery. CONCLUSIONS: Occlusion of the fetal ductus arteriosus may also occur in the absence of treatment with nonsteroidal antiinflammatory agents. Immediate delivery resulted in good clinical outcome, although right ventricular dysfunction may persist.

Constriction, Pathologic↗
PubMed2005

Prenatal sonographic diagnosis of congenital ductus arteriosus aneurysm: a case report.

UNLABELLED: The objective of this report was to demonstrate prenatal sonographic features of congenital ductus arteriosus aneurysm (DAA), a rare, but possibly fatal abnormality. It is characterized by a saccular or fusiform dilatation of the ductus arteriosus. The majority of affected neonates are clinically asymptomatic and tend to progressively diminish in size of DAA and spontaneous closure. However, serious complications can occur during waiting periods, including spontaneous rupture or thromboembolism. CASE: A 35 year-old Thai woman, G2P1, underwent ultrasound examination at 34 weeks' gestation. Fetal echocardiography revealed markedly enlarged and tortuous ductus arteriosus with saccular dilation at the distal end, just before joining the descending aorta. The cross-sectional diameter of the saccular portion of the ductus arteriosus was 10 mm. The active female baby was vaginally delivered at 34 weeks' gestation, weighing 1050 grams. Postnatal echocardiography confirmed the prenatal findings. The DAA was gradually decreased in size and finally spontaneously closed without medical or surgical intervention.

Adult↗
PubMed1998

[Videoscopic resection of a thrombosed aneurysm of a patent ductus arteriosus in a neonate].

Aneurysmal dilatation of a patent ductus arteriosus is a rare condition. One hundred and fifty three cases have been reported, of which 59 (39%) were operated, with an operative mortality of 16%. The authors report a case detected in a premature neonate on chest X-ray showing a mass in the mid-mediastinal region. Surgical resection was undertaken by video-thoracoscopy. Peroperative analysis of the resected specimen suggested a vascular structure and this was confirmed by histological study, which showed spontaneous aneurysm of a thrombosed patent ductus arteriosus or cystic residue of a patent ductus arteriousus. The authors underline the importance of peroperative puncture of structures of uncertain origin and the possibility of conversion of such a procedure to that of an extreme emergency.

Aneurysm↗
PubMedDate not supplied

Patent ductus arteriosus: how important to which babies?

An overview is presented of 21 randomised controlled trials of either surgical closure of the ductus arteriosus or indomethacin therapy in preterm infants. All trials included backup treatment if the ductus arteriosus persisted. Overall, there is no significant effect on mortality or chronic lung disease. In trials treating at a presymptomatic stage, there is a trend to reduce the incidence of chronic lung disease. Early treatment with indomethacin reduces the incidence of periventricular haemorrhage. An ultrasound study of 110 very low birth weight infants showed ductus arteriosus size at 3 days to be related to factors reflecting the infants' condition (ventilation indices, blood product administration), but not to birth weight or gestational age. Infants with a moderate to large ductus arteriosus at 3 days had a significantly lower blood pressure from 12 h of age onwards than those with a closed or small ductuses.

Ductus Arteriosus, Patent↗
PubMed1991

Potential diagnosis of hemodynamic abnormalities in patent ductus arteriosus by cine magnetic resonance imaging.

Cine magnetic resonance imaging was performed in 11 patients with communication between systemic and pulmonary circulation. In five patients with uncomplicated patent ductus arteriosus (PDA), ductus arteriosus was delineated by a persistent band of low signal intensity, whereas in two patients who also had severe pulmonary hypertension the signal intensity was varied. Two separate low signal intensities in the main pulmonary artery and the descending aorta were each uniformly recorded in the five patients with uncomplicated PDA, consistent with continuous left-to-right shunt and turbulent flow acceleration, respectively. In one of the patients with severe pulmonary hypertension but not Eisenmenger's syndrome, the areas of low signal intensity from left-to-right shunt and turbulent flow acceleration diminished. In the patient with Eisenmenger's PDA the right-to-left shunt was also characterized by an area of low signal intensity but with a reversal in direction. Cine MR imaging has the potential to be a noninvasive and supplemental method for evaluating PDA.

Adolescent↗
PubMed1989

Influence of increased pulmonary vascular pressures on the closure of the ductus arteriosus in newborn lambs.

Neonatal conditions associated with increased pulmonary artery pressure have an increased incidence of patent ductus arteriosus. We operated on 15 near term fetal lambs and placed mechanical occluders into or around both branch pulmonary arteries so that main pulmonary artery blood pressure could be controlled. The lambs were delivered and ventilated for 4 h. In seven lambs, the branch vessels were obstructed so that pulmonary artery pressure increased to equal aortic pressure; in eight lambs (control), the branch vessels were not obstructed. There were no significant differences between the two groups in circulating prostaglandin E2 or 6 keto F1 alpha concentrations, PaO2, pH, or PaCO2. Despite these similarities, ductus resistance in the lambs with elevated pulmonary pressure was significantly less than that in the control lambs. After the 4 h measurements, we studied the ductus in vitro. We have previously found that ductus arteriosus constriction produces ischemia of its muscle wall that limits its ability to dilate or constrict any further. Ductus from lambs with elevated pulmonary pressure had a significantly increased ability to respond to oxygen, prostaglandin E2, and indomethacin compared with ductus from control lambs; these findings are consistent with less ductus constriction in vivo. Thus, the high incidence of patent ductus arteriosus in neonates with elevated pulmonary vascular resistance may be due in part to the increased pulmonary vascular pressure, which opposes ductus constriction and preserves ductus responsiveness. Conversely, the normal drop in pulmonary pressure that occurs in full term infants may facilitate the closure of the ductus after delivery.

Animals↗
PubMed1999

Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation.

Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.

Animals↗
PubMed1993

Results of transcatheter closure of the patent ductus arteriosus with the Botallooccluder.

OBJECTIVES: Evaluation of the immediate and long-term efficacy of a novel method of transvenous closure of the patent ductus arteriosus was the purpose of this study. BACKGROUND: In 1981 at the First Moscow Hospital, a new method of transvenous patent ductus arteriosus closure with the Botallooccluder was developed. METHODS: Transvenous closure of the patent ductus arteriosus with the Botallooccluder was carried out in 273 patients. All patients were regularly followed up as outpatients at intervals of 3, 6 and 12 months after intervention. A total of 171 patients were examined at a mean of 3.2 +/- 1.1 years (range 1 to 8) after the procedure. Late evaluation with cardiac catheterization was performed in 62 patients (36%); 50 (29%) of these 62 also underwent right heart catheterization. RESULTS: Successful implantation was achieved in 266 patients (97%). The late follow-up findings testify to the favorable clinical course, with disappearance of the continuous murmur and regression of the electrocardiographic signs of ventricular overloading in the vast majority of patients. In no case after complete patent ductus arteriosus closure was a late ductus recanalization observed. No patient had even a minor degree of postprocedural lower extremity venous damage. In 29 patients (24%), the femoral artery was imaged by ultrasonography at late follow-up, without evidence of any vascular abnormality. CONCLUSIONS: The clinical data suggest high long-term efficacy and reliability of this technique. Introducer sheaths (12F to 16F outer diameter) did not cause any long-term entry site sequelae.

Adolescent↗
PubMed1987

Detection and quantitation of constriction of the fetal ductus arteriosus by Doppler echocardiography.

Pulmonary hypertension may occur in the fetus in the presence of constriction of the ductus arteriosus. The feasibility of detection and quantitation of fetal ductal constriction by Doppler echocardiography was assessed in an animal preparation in which ductal constriction was created in the fetal lamb with a variable ligature causing varying degrees of fetal pulmonary hypertension (fetal pulmonary arterial systolic pressure 57 to 97 mm Hg and ductal gradient 9 to 42 mm Hg). Comparison of blinded, continuous-wave peak Doppler velocity (V) measurements of the ductal gradient with the modified Bernoulli assumption (gradient = 4V2) compared well with direct catheter measurements of instantaneous peak systolic gradient (r = .99, catheter = 0.95 X Doppler + 0.6), peak-to-peak gradient (r = .97), and mid-diastolic gradient (r = .85). Ductal constriction was characterized by an increase in the peak systolic and diastolic velocities. The normal human fetal ductus arteriosus blood flow velocity pattern was assessed by pulsed Doppler techniques in 25 normal human fetuses after 20 weeks gestation. The peak systolic flow velocity in the ductus arteriosus measured by image-directed pulsed Doppler echocardiography ranged from 50 to 141 cm/sec (mean 80 cm/sec) and increased with gestational age (r = .50). Diastolic velocity in the ductus arteriosus was consistently directed toward the descending aorta and ranged from 6 to 30 cm/sec. The ductal systolic velocities were the highest blood flow velocities in the fetal cardiovascular system. Application of these techniques to fetuses whose mothers were receiving indomethacin for treatment of premature labor at 30 to 31 weeks gestation confirmed this method to be sensitive for detection of fetal ductal constriction, which developed in three fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

[Surgical treatment of difficult patent ductus arteriosus and related operative complications].

Sixty-nine patients with difficult patent ductus arteriosus (PDA) were retrospectively studied. The PDA included window type (9 patients), aneurysms of the ductus arteriosus(13), large ductus(15), false aneurysms(3), calcified(3), recurrence of ductal patency(5), endarteritis(5) and severe pulmonary hypertension(16). Surgical procedures included ligation of PDA in 51 patients, ligation with Dacron pledget or ribbon in 9, division of PDA under temporary cardiopulmonary bypass in 5. Ruptures of PDA or aorta in 4 patients were repaired respectively with Dacron patch(2) and conduit (2). There were 2 early deaths (2.9%). The mean follow-up was 119 months clinically. All surviors were free from symptoms andcardiac murmur. We conclude that satisfied surgical results rely mainly on proper operative techniques according to different situations of difficult PDA. Surgical correction with Dacron patch or conduit seems to be a simple, safte and reliable method in dealing with the rupture of PDA or aorta.

Adult↗
PubMed1999

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus.

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.

Animals↗