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PubMed2003

Effects of hypoxia, hypoglycemia, and muscle shortening on cell death in the sheep ductus arteriosus.

After birth, constriction of the full-term ductus arteriosus produces ischemic hypoxia, caspase activation, DNA fragmentation (>70% of cell nuclei are positive by the terminal deoxynucleotidyl transferase nick-end labeling [TUNEL] technique), and permanent ductus closure. In contrast, the preterm ductus frequently fails to develop these changes. We used the TUNEL technique to examine rings of fetal ductus arteriosus (incubated for 24 h at different oxygen and glucose concentrations) to determine the roles of 1) constriction and shortening, 2) hypoxia, and 3) hypoglycemia in producing cell death. Under controlled conditions, late-gestation ductus rings had a low rate of TUNEL-positive staining (0.6 +/- 0.9%) that did not change during muscle shortening. Although hypoxia (6.9 +/- 3.5%) and hypoglycemia (2.4 +/- 1.9%) increased the incidence of TUNEL-positive staining, only the combination of hypoxia-plus-hypoglycemia increased the incidence to the range found in vivo (83 +/- 9.5%). The combination of hypoxia-plus-hypoglycemia was associated with an oligonucleosomal pattern of DNA fragmentation. Under the same experimental conditions, the preterm ductus was capable of developing a similar degree of TUNEL-positive staining as found at term. Although caspase-3 and caspase-7 were activated in rings exposed to hypoxia-plus-hypoglycemia, a nonselective caspase inhibitor, Z-VAD.FMK (which inhibited caspase-3 and caspase-7 cleavage in the rings), did not diminish the degree of TUNEL-positive staining. We hypothesize that the preterm ductus is capable of developing an extensive degree of cell death, if it can develop the same degree of hypoxia and hypoglycemia found in the full-term newborn ductus. We also hypothesize that cell death in the ductus wall may involve pathways that are not dependent on caspase-3 or -7 activation.

Animals↗
PubMed1991

Transcatheter closure of a large patent ductus arteriosus with the clamshell septal umbrella.

In 14 patients undergoing transcatheter closure of a large (greater than 4 mm diameter) patent ductus arteriosus, occlusion was attempted with use of the Bard Clamshell septal umbrella. Patient age ranged from 0.7 to 30.4 years. Isolated patent ductus arteriosus was present in 11 patients; 3 had additional congenital heart lesions. Moderate or severe pulmonary hypertension was present in four patients. The diameter of the patent ductus arteriosus ranged from 4.5 to 14 mm, as determined by contrast injection through an 11F sheath or by balloon sizing; it appeared larger by this method than by the standard angiographic method. All 14 patent ductus arteriosi were successfully closed. Prior embolization of a Rashkind umbrella was the reason for using a Clamshell device in three patients; one additional embolization of a Clamshell device occurred. All errant devices were retrieved at cardiac catheterization, without associated hemodynamic instability. No other complications occurred. Among the 14 patients, 11 had complete ductal closure by Doppler color flow mapping at last follow-up and 3 had trivial residual flow. All four patients having associated complex lesions or pulmonary hypertension, or both, had symptomatic improvement after the procedure, although one child (with Shone's anomaly) died 3 months later. The Clamshell device provides stable and effective closure of a large patent ductus arteriosus, and allows transcatheter closure to be offered to some patients who were previously considered unsuitable for this procedure.

Adolescent↗
PubMed1990

[A methodologic variant in transarterial closure of a persistent ductus arteriosus].

The most severe complications in transarterial closure of the ductus arteriosus persistens are problems with placing the plug into the ductus (misfit plug size/ductus size) and the flow of closure materials into the aorta after instable fixation of the plug. In such cases surgical intervention by arteriotomy or aortotomy for the removal of the plug becomes necessary. Transvenous dilatation of the ductus arteriosus persistens after recognizing unstable plus positions or difficulties in fixing the plug prevents the mentioned complications.

Cardiac Surgical Procedures↗
PubMed1995

Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin.

OBJECTIVE: To examine the role of ductus arteriosus (DA) constriction and loss of luminal blood flow in producing permanent closure of the DA in human infants. METHODS: We studied 77 newborn infants (gestational age, 23 to 33 weeks) with asymptomatic patent ductus arteriosus (PDA), who had "complete clinical closure" (defined as the disappearance of all PDA signs) after treatment with indomethacin (three doses within 36 hours). All infants had an echocardiogram 24 to 36 hours after the last dose of indomethacin. They were then followed for the development of ductus reopening. RESULTS: Despite the absence of clinical signs, 18 (23%) of 77 infants still had some residual luminal blood flow according to their echocardiograms. The failure to obliterate luminal blood flow completely was directly related to the infant's postnatal age when treatment was begun and to the amount of fluid administered before treatment. Subsequently the DA reopened in 16 (21%) of 77 infants. As predicted, infants with residual luminal blood flow after indomethacin treatment had a higher rate of subsequent clinical reopening than did those with no luminal flow. In addition, immature infants had a significantly higher reopening rate than did more mature infants. The increased risk of reopening in immature infants was seen even when indomethacin caused complete obliteration of ductus luminal blood flow. CONCLUSION: The DA of immature infants is resistant to the constriction-induced ischemic damage that is necessary for subsequent permanent closure of the vessel.

Ductus Arteriosus↗
PubMed2001

[Advances in interventional occlusion of persistent ductus arteriosus: comparison of results using different occlusion devices].

This report describes our results with transcatheter closure of patent ductus arteriosus between March 1993 and May 2000 including our early experience with the Amplatzer duct occluder. One hundred and sixty-six consecutive procedures were performed in 160 patients. The mean age was 6.8 years (range 0.8 to 26.2), mean weight 24.3 kg (range 7.7 to 84.0). Single or multiple coils were implanted successfully in 114 cases, a Rashind double umbrella in 35 patients, and an Amplatzer duct occluder in 16 patients. After failure to implant coils in one patient, a second attempt with a Rashkind double umbrella was successful. Complete closure of the patent ductus arteriosus was achieved in a total of 148 patients (92.5%), mean fluoroscopy time was 13.7 min (range 3.1 to 126 min). In 144 patients (90.0%), occlusion without residual shunting was achieved by the first interventional approach. Angiography showed immediate closure in 44%, echocardiography within 48 h revealed complete closure in additional 28%. In a further 18%, a residual shunt disappeared spontaneously in the following months. In five patients a second procedure was performed to terminate residual shunting after placement of a Rashkind occluder system by coils. In three patients, the residual shunt resolved. In 12 patients (7.5%) echocardiography showed a residual shunt 2-1259 days after interventional approach. Occlusion rates of the different devices were 83% for the Rashkind occluder, 92% for detachable coils, and 100% for the Amplatzer duct occluder. Coil embolisation into the pulmonary artery occurred in two patients, interventional removal was successful in one of them. There were no further complications. According to our experience interventional occlusion of patent ductus arteriosus is highly effective and associated with a low complication rate. Transcatheter closure using the Amplatzer duct occluder seems to be safe and effective also in small children with a body weight of 8 kg and a large ductus diameter. Compared to the total group of patients, the occlusion rate of the Amplatzer duct occluder was significantly higher (p = 0.005), and of the Rashkind occluder system significantly lower (p = 0.026). Therefore, we recommend the use of detachable coils in patients with small ductus (diameter < or = 2 mm) and the Amplatzer duct occluder in those with a larger ductus. Transcatheter closure of the patent ductus arteriosus according to this regimen should achieve occlusion rates above 95%.

Adolescent↗
PubMed1985

Cardiovascular changes due to premature closure of the ductus arteriosus: a mathematical model.

Changes in the fetal cardiovascular system due to premature closure of the ductus arteriosus are described using a previously validated mathematical model. Results of the simulated closure of the ductus arteriosus are compared with reported results from animal experiments in which the ductus arteriosus was closed pharmacologically with prostaglandin synthetase inhibitors. The computed cardiovascular changes after ductus closure in the model resemble the changes obtained by administration of indomethacin. This suggests that the central cardiovascular effects of indomethacin (insofar as described here) can be completely attributed to closure of the ductus.

Animals↗
PubMed1995

Effects of ductus arteriosus occlusion on pulmonary artery pressure during in utero ventilation in fetal sheep.

Seven fetal sheep were prepared to study the short-term effects of in utero ventilation and ductus arteriosus occlusion on pulmonary artery pressure and on fetal right ventricular function assessed using the right atrial pressure-right ventricular stroke volume relationship. Nine days post-surgery (140 days gestation), blood gas and haemodynamic values were obtained before and during in utero ventilation with 100% O2, and during ventilation with the ductus arteriosus occluded. Oxygen content increased significantly from 7.2 to 14.5 ml dl-1 with ventilation and remained elevated at 14.4 ml dl-1 with ventilation with the ductus arteriosus occluded. In utero ventilation produced a left to right atrial pressure gradient and depression of the right atrial pressure-right ventricular stroke volume relationship. Ductus arteriosus occlusion during in utero ventilation reduced the left to right atrial pressure gradient, and along with a decrease in pulmonary artery pressure, resulted in an upward shift of the right atrial pressure-right ventricular stroke volume relationship, but only to the preventilation level. This study indicates that the fetal right atrial pressure-right ventricular stroke volume relationship is significantly altered, both by changes in the left to right atrial pressure gradient and by changes in pulmonary artery pressure seen with in utero ventilation and subsequent ductus arteriosus occlusion.

Animals↗
PubMed2006

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants.

BACKGROUND: Antenal indomethacin reportedly decreases the responses of a symptomatic patent ductus arteriosus (sPDA) to postnatal indomethacin treatment. Whether a similar exposure affects the responses to indomethacin prophylaxis is unknown. OBJECTIVE: To evaluate the clinical responsiveness of ductus arteriosus to indomethacin prophylaxis and to the treatment of sPDA in extremely low birth weight (ELBW) infants following indomethacin tocolysis. METHODS: Retrospective cohort study of 58 ELBW infants whose mothers received indomethacin tocolysis (study) and 58 ELBW infants whose mothers did not (controls), matched by gender, gestational age (GA), birth weight and postnatal sPDA management (prophylaxis or early treatment). RESULTS: Indomethacin was used as a tocolytic at a median dose of 250 mg, for a duration of 2 days, and ending 1 day before delivery. Study and control mothers were comparable in demographics, antenatal steroid use, cesarean delivery, but were different in the incidence of preeclampsia and preterm labor. Study and control infants were similar in birth weight, GA, indomethacin prophylaxis, early sPDA treatment, mortality, necrotizing enterocolitis, severe intraventricular hemorrhage and stage 3-5 retinopathy of prematurity. Seventeen of 43 study and 16 of 43 control infants who received indomethacin prophylaxis developed sPDA and were combined with early treatment sPDA infants (15 to each group). Two of 32 study and two of 31 control infants underwent surgical ligation whereas the remaining were treated with indomethacin. Sixteen of 30 (53%) and 13 of 29 (45%) were successfully treated and did not require ligation. Study infants were divided according to their mothers' indomethacin total dose (28 infants received 225 mg). Both subgroups were demographically and clinically comparable and their response to indomethacin prophylaxis and treatment were similar. CONCLUSION: In ELBW infants, exposure to indomethacin tocolysis does not affect the clinical responsiveness of the ductus arteriosus to prophylaxis or that of the sPDA to indomethacin treatment.

Ductus Arteriosus↗
PubMed1996

Changes in endothelial cell and smooth muscle cell integrin expression during closure of the ductus arteriosus: an immunohistochemical comparison of the fetal, preterm newborn, and full-term newborn rhesus monkey ductus.

Anatomical closure of the ductus arteriosus requires normally quiescent luminal endothelial cells and medial smooth muscle cells to migrate into the subendothelial space forming intimal mounds that eventually coalesce and occlude the vessel's lumen. The migration of endothelial cells and smooth muscle cells requires the presence of integrin receptors that interact with the surrounding matrix. We used immunohistochemical staining to examine the repertoires of integrins expressed by endothelial cells and smooth muscle cells during postnatal closure of the ductus arteriosus in full-term and preterm rhesus monkeys. In the fetal ductus, luminal endothelial cells have a limited repertoire of integrins. During postnatal ductus closure, luminal endothelial cells, of both term and preterm monkeys, change their phenotype and express the full repertoire of integrins found on growing capillary endothelial cells (alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha v beta 1, alpha 6 beta 4, and alpha v beta 5). Similarly, during ductus closure, smooth muscle cells of both term and preterm monkeys expand their integrin repertoire to include the alpha 5 beta 1 and alpha v beta 3 integrins; these two integrins have been shown to be essential for smooth muscle cell migration in vitro. These changes in integrin profile occur at the same time the endothelial and smooth muscle cells invade their neighboring compartments. In contrast, preterm monkeys with a persistently patent ductus lumen fail to develop these changes in integrin expression and fail to develop neointimal mounds. No evidence of intimal thickening occurs in the absence of changes in integrin expression. Therefore, endothelial cells and smooth muscle cells change phenotypes to produce the intimal thickening required for ductus closure.

Aging↗
PubMed2005

Asymptomatic patent ductus arteriosus in a 41-year-old woman.

Patent ductus arteriosus is a rare adult congenital heart disease, especially asymptomatic cases are uncommon in older ages. We report here the case of a 41-year-old woman, who was incidentally found to have a patent ductus arteriosus. The patient also was asymptomatic. For anatomical demonstration, computerized tomography angiography was performed and then surgical intervention was applied.

Adult↗
PubMedDate not supplied

Prevention of symptomatic patent ductus arteriosus with ethamsylate in babies treated with exogenous surfactant.

Some trials in premature infants with respiratory distress syndrome have shown an increased incidence of patent ductus arteriosus after exogenous surfactant therapy. The effect of prophylactic ethamsylate on patent ductus arteriosus after intratracheal administration of a single dose of porcine surfactant preparation (Curosurf, 2.5 ml/kg) was studied in a group of 20 preterm infants with severe respiratory distress syndrome. Gestational age of the patients was 29.2 +/- 2.5 weeks (mean +/- SD), and birth weight was 1158 +/- 319 gm. Ethamsylate (12.5 mg/kg) was given prophylactically within the first 4 hours of life followed by 6-hourly doses for 4 days. Hemodynamically significant patent ductus arteriosus occurred more frequently in the untreated group (8 of 10) than in the ethamsylate group (2 of 10) (p < 0.02). No acute adverse effects were attributed to the therapy. This preliminary experience suggests that ethamsylate, an inhibitor of prostaglandin biosynthesis, could be useful in reducing the incidence of patent ductus arteriosus in very low birth weight infants treated with exogenous surfactant.

Biological Products↗