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Effect of indomethacin on cerebral blood flow velocities in very low birth weight neonates with a patent ductus arteriosus.

The effect of repeated doses of indomethacin on mean peak velocity (MPV) and time-averaged mean velocity in the middle cerebral artery was assessed in 10 ventilated neonates with a patent ductus arteriosus using colour/duplex Doppler technique prior to, and 10, 30, and 120 min after the first and the third dose. Velocities were significantly reduced up to 120 min after the first dose. The third dose resulted in a significant reduction in MPV at 10 and 30 min following treatment. This reduction was half of that observed after the first dose. Systemic blood pressure (BP) and heart rate did not change significantly after each separate dose. However, by the third dose, mean and diastolic BP were significantly increased from pretreatment levels. The attenuated response of cerebral blood flow (CBF) velocities to the third dose of indomethacin compared with the first dose is probably related to altered haemodynamics. Indomethacin should be used cautiously in infants with other conditions which are known to decrease CBF such as hypotension, hypocarbia and polycythaemia.

Blood Flow Velocity↗

Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (less than 1,500 g) babies.

The effect of patent ductus arteriosus (PDA) and its therapy on the pharmacokinetic disposition of gentamicin in very low birth weight neonates was studied. Twenty-four neonates weighing less than 1,500 g with PDA were compared to 16 patients without PDA. Patients with PDA had significantly greater apparent volumes of distribution (0.64 +/- 0.20 vs. 0.41 +/- 0.08 l/kg; p less than 0.001) and serum half-life (8.49 +/- 2.69 vs. 6.23 +/- 1.92 h; p less than 0.01). The total body clearance was not significantly different between the two groups (56 +/- 20 ml/kg/h with PDA vs. 50 +/- 24 ml/kg/h without PDA). In addition, 7 patients were studied before and after PDA closure. The apparent volume of distribution fell in every case (p = 0.02). A statistically significant effect on clearance and half-life was not found. These findings suggest that PDA increases extracellular fluid volume, but does not affect glomerular filtration rate adversely. Additionally, serum gentamicin concentrations must be reevaluated after PDA closure in premature neonates.

Ductus Arteriosus, Patent↗

Transfemoral plug closure of patent ductus arteriosus. Experiences in 61 consecutive cases treated without thoracotomy.

We successfully closed the isolated patent ductus arteriosus in 58 of 61 consecutive patients using the transfemoral-catheter method originally introduced by Porstmann in 1968. To perform this technique more safely and reliably, some instrumental and technical improvements were made. The indications for this method have been expanded to include the cylindrical or window-type ductus as well as the conical-shaped ductus. Classification into three groups of the configuration of the ductus by angiography has been useful in selecting the shape of the closing plug. Whenever feasible, we consider the catheter technique to be the method of choice to close the ductus.

Adolescent↗

Left ventricular performance in the critically ill premature infant with patent ductus arteriosus and pulmonary disease.

Left cardiac dimensions and an index of left ventricular performance, the percent shortening of the internal diameter (%SID) of the left ventricle, were evaluated in premature infants who were asymptomatic, others with pulmonary disease and others with patent ductus arteriosus (PDA). In contrast to controls, left atrial and/or left ventricular end-diastolic dimensions were increased in all infants with clinical criteria of significant PDA. Postoperative dimensions decreased significantly. Percent SID values for normal premature infants (m=33.5%; SD=3.5%) and those with pulmonary disease alone did not differ significantly. In those with clinical criteria of PDA, who were subsequently found to have echocardiographic evidence of left cardiac enlargement, values for %SID were increased. As expected %SID values for individual patients represented a wider range of left ventricular function and/or afterload than for controls. Upon spontaneous or surgical closure of the PDA, %SID returned to normal. A PDA which is associated with left cardiac enlargement exhibits increased %SID, whereas decreasing %SID in the presence of increased dimensions suggests deteriorating myocardial performance. Echocardiography provides valuable insight into the cardiac status of these infants and may contribute to their medical and/or surgical management.

Ductus Arteriosus, Patent↗

Flow in the aorta and patent ductus arteriosus in infants with aortic atresia or aortic stenosis: a pulsed Doppler ultrasound study.

We used pulsed Doppler ultrasound to determine the flow dynamics of the aorta and patent ductus arteriosus (PDA) in 21 infants (ages 1 to 16 days) with PDA and aortic atresia (n = 15) or aortic stenosis (n = 6). The flow within the PDA was recorded in 19, and was right-to-left during systole in all. There was a diastolic left-to-right PDA shunt in 11 patients with aortic atresia and in three with aortic stenosis, and the shunt was associated with large (3 to 11 mm in diameter) interatrial communications. In two patients with aortic atresia and three with aortic stenosis, however, the diastolic PDA shunt was from right to left, and the interatrial communications were small (0 to 2 mm in diameter). The right-to-left diastolic PDA shunting may be best explained by the relative pulmonary (high with left-sided inflow obstruction and a small interatrial communication) and systemic resistances. All patients with aortic atresia and three with aortic stenosis had retrograde systolic flow in the transverse aortic arch, probably resulting from inadequate left ventricular output. Antegrade diastolic flow in the transverse aortic arch toward the PDA was observed in all infants with aortic atresia and a left-to-right PDA shunt. Ascending aortic flow was recorded in 11 patients with aortic atresia, and was retrograde during diastole in each, the result of coronary perfusion. Application of pulsed Doppler ultrasound can lead to a better understanding of the hemodynamics and physiology of patients with congenital cardiovascular disease.

Aorta↗

Nonsurgical closure of patent ductus arteriosus: clinical application of the Rashkind PDA Occluder System.

The first successful application of a transcatheter closure technique for patent ductus arteriosus (PDA) suitable for use in infants and children was performed by us in 1977. Since that time, there has been continued improvement and simplification of the equipment as well as in the implantation technique. Following a Food and Drug Administration protocol, a multicenter study was conducted to test the safety and effectiveness of this interventional method. The clinical results from three major regional test centers (Philadelphia, Houston, and New Haven) are presented. One hundred forty-six patients from a test population of 156 were treated for PDA with use of the Rashkind PDA Occluder Systems. Successful closure was accomplished in 94 (66%) of the total cases. Ten patients (7%) retained residual ductal murmurs despite correct placement of the occlusion devices; five additional patients (3%) were considered failures due to the presence of abnormal Doppler flow patterns after the procedure. Postrelease embolizations occurred in 19 (15%) instances. One patient required emergency surgical intervention after attempted retrieval of an embolized occluder. With the improvements in the manufacturing of the double-disk occluder systems as well as the perfection of the transvenous delivery technique, the incidences of closure failure and postrelease complications have decreased. Since January 1984, 78% of all transcatheter closure attempts were successful, with 10% embolization.

Animals↗

Outpatient closure of the patent ductus arteriosus.

We have modified and applied to selected outpatients the transvenous approach to correction of patent ductus arteriosus (PDA) with the Rashkind PDA Occluder. Modifications included establishing the diagnosis and PDA anatomy before catheterization with echocardiography. The sedation/anesthetic regimen was altered to meet the needs with respect to transcatheter PDA closure rather than diagnostic cardiac catheterization. Anticoagulation was avoided. A strategy for management of pin entrapment in the foam was devised. Residual trans-PDA flow after umbrella placement was temporarily occluded with balloon-tipped catheters. These modifications were used in 23 consecutive patients with uncomplicated PDA. Closure was successful in each child. Nineteen of 23 patients were discharged on the day of the procedure. No serious complications were encountered.

Adolescent↗

Endocarditis risk of the USCI PDA umbrella for transcatheter closure of patent ductus arteriosus.

BACKGROUND: The USCI PDA Umbrella is a device to close patent ductus arteriosus (PDA) by a transcatheter technique. Human clinical trials have shown excellent efficacy in reducing or eliminating the PDA shunt, but concerns remain about the risk of infection with this device. The purpose of this study was to evaluate the risk of infection using an animal model. METHODS AND RESULTS: Susceptibility to developing endocarditis was tested by injecting a single intravenous dose of group L streptococcus. Ten piglets with a closed ductus served as controls. Two of these developed valvular vegetations. PDA was produced in 19 animals by balloon dilation of the ductus. Seven of 7 animals with PDA at the time of bacterial injection developed endarteritis of the ductus and valvular vegetations. A PDA Umbrella was placed in the remaining 12 animals, and bacteria were injected 2 weeks after device implantation. Infection was evident in the PDA Umbrella only in the single animal in which the Umbrella had embolized and been left in the left pulmonary artery. Three of the remaining 11 piglets had a significant residual leak, and all developed infection in the ductus and an additional valve. Similar to the control group, none of the animals with complete (n = 8) or nearly complete (n = 2) closure of the ductus by the PDA Umbrella had infection in or around the ductus, and only 1 had a valvular vegetation. CONCLUSIONS: In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis. The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls.

Animals↗

Echocardiographic and radionuclide pulmonary blood flow patterns after transcatheter closure of patent ductus arteriosus.

BACKGROUND: Transcatheter occlusion of patent ductus arteriosus (PDA) has been associated with protrusion of the occluder device into the left pulmonary artery (LPA). This study was conducted to evaluate the significance of occluder protrusion and its implications for potential obstruction of the LPA and associated decrease of left lung perfusion. METHODS AND RESULTS: Fifty-two patients underwent successful transcatheter PDA occlusion over a period of 5 years. In this study, 49 were reexamined between March and June 1995. In addition to clinical and echocardiographic examination, lung scintigraphy was performed. Protrusion into the LPA was present in 5 of 49 patients (10%). In these patients, maximal flow velocity in the LPA was significantly (P < .01) increased. Decreased left lung perfusion, defined as < 40% of total pulmonary blood flow, was found in 7 of 49 patients (14%). Although mean left pulmonary perfusion was significantly (P = .02) decreased in patients with protrusion, there was considerable overlap with patients without protrusion, and only a weak correlation was found (r = -.35, P = .01) between flow-velocity and left lung perfusion. CONCLUSIONS: Our results demonstrate that protrusion of the device in the LPA is an infrequent finding. If present, it is associated with increased maximal flow velocity in the LPA and diminished left lung perfusion. However, echocardiography and lung scintigraphy are weakly correlated: Increased maximal blood flow velocities in the proximal LPA proved to be a poor indicator or impaired left lung perfusion. Also, decreased perfusion occurs in the absence of echocardiographic evidence of device protrusion.

Blood Flow Velocity↗

Char syndrome, an inherited disorder with patent ductus arteriosus, maps to chromosome 6p12-p21.

BACKGROUND: Patent ductus arteriosus (PDA) is a relatively common form of congenital heart disease. Although polygenic inheritance has been implicated, no specific gene defects causing PDA have been identified to date. Thus, a positional cloning strategy was undertaken to determine the gene responsible for the Char syndrome, an autosomal dominant disorder characterized by PDA, facial dysmorphism, and hand anomalies. METHODS AND RESULTS: A genome scan was performed with 46 members of 2 unrelated families in which the disease was fully penetrant but the phenotype differed. Significant linkage was achieved with several polymorphic DNA markers mapping to chromosome 6p12-p21 (maximal 2-point LOD score of 8.39 with D6S1638 at theta=0.00). Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3. 1-cM region between D6S459/D6S1632/D6S1541 and D6S1024. CONCLUSIONS: A familial syndrome in which PDA is a common feature was mapped to a narrow region of chromosome 6p12-p21. Additional analysis with other families and polymorphic markers as well as evaluation of potential candidate genes should lead to the identification of the Char syndrome gene, which will provide insights into cardiogenesis as well as limb and craniofacial development.

Chromosome Mapping↗

Mapping of familial thoracic aortic aneurysm/dissection with patent ductus arteriosus to 16p12.2-p13.13.

BACKGROUND: Three loci have been shown to be responsible for nonsyndromic familial thoracic aortic aneurysms (TAAs) and aortic dissections (ADs). We recently described a large family in which TAA/AD associates with patent ductus arteriosus (PDA) and provided genetic arguments for a unique pathophysiological entity. METHODS AND RESULTS: Genome-wide scan was performed in 40 subjects belonging to 3 generations in this large pedigree. Using the 7 TAA/AD cases as affected, we observed positive 2-point LOD scores on adjacent markers at chromosome 16p, with a maximum LOD score value of 2.73 at theta=0, a value that increased to 3.56 when 5 PDA cases were included. Multipoint linkage analysis yielded a maximum LOD score of 4.14 in the vicinity of marker D16S3103. Fine mapping allowed the observation of recombinant haplotypes that delimited a critical 20-cM interval at 16p12.2-p13.13. Automatic determination of aortic compliance with cine MRI showed that all subjects bearing the disease haplotype, even asymptomatic, displayed a very low level of aortic compliance and distensibility. Aortic stiffness was strongly associated with disease haplotype with a marked effect of age, indicating subclinical and early manifestation of the disease. CONCLUSIONS: Genetic analysis of this family identified a unique locus responsible for both TAA/AD and PDA at chromosome 16p12.2-p13.13 with aortic stiffness as an early hallmark of the disease. TAA/AD with PDA is a new monogenic entity among the genetically heterogeneous group of TAA/AD disease.

Aorta↗

Comparison of the one-and-a-half-year results of closure of patent ductus arteriosus by transcatheter coils placement with surgical ligation.

Patent ductus arteriosus (PDA) is a common type of congenital cardiovascular lesion. It usually needs surgical ligation in a full-term baby after 1 year of age. Transcatheter implantation of coils was introduced for the closure of small- to moderate-sized PDA in 1992. From November 1995 to November 1998, the authors closed the PDA in 153 patients by transcatheter implantation of coils and by surgical ligation in 10 patients. One hundred fourteen of them were studied for more than 1(1/2) years. The regular follow-up studies, including physical examination; electrocardiography; and pulsed, continuous-wave, and color Doppler flow mapping, were performed on day one and day 2, and 1 week, 1 month, 3 months, 6 months, and 1 year after the procedure. The results of the closure of PDA by surgical ligation or coil placement were compared and analyzed in all the patients.

Adolescent↗

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↗

Pulmonary endarteritis and subsequent embolization to the lung as a complication of a patent ductus arteriosus--a case report.

The authors describe a case of pulmonary endarteritis and subsequent embolization to the lungs as a complication of a patent ductus arteriosus (PDA). Although 2-dimensional echocardiography has been shown to be of great value in the diagnosis of patients with infective endocarditis, echocardiographic detection of vegetation within the pulmonary artery and subsequent embolization to the lung is extremely rare and, to our knowledge, has been previously reported only in a few cases. In brief, our case not only shows the importance of echocardiography in making this rare diagnosis but also emphasizes the role of echocardiography as an effective means of following up such a case.

Child↗

Successful transcatheter closure of a patent ductus arteriosus: using two Gianturco coils in a 41-year-old woman. A case report.

Patent ductus arteriosus (PDA) is a form of congenital heart disease uncommonly diagnosed in adult patients. Transcatheter closure of PDA has been widely used in children. However, the experience is limited in adults especially with use of Gianturco coils. The authors describe a case of successful transcatheter closure of a PDA, incidentally diagnosed in a 41-year-old woman, by successively deploying two coils by a transarterial approach. No residual shunting was seen angiographically after the procedure. A literature review of similar procedures in adult patients is discussed.

Adult↗

Red blood cell survival in patients with ventricular septal defect and patent ductus arteriosus.

Hemolysis of red blood cells (RBC) in stenotic or regurgitant cardiac valvular lesions has been felt to be due to mechanical trauma and shearing stress caused by turbulence of blood. RBC are also under a shearing stress from turbulence in high-pressure shunts, such as ventricular septal defect (VSD) and patent ductus arteriosus (PDA). The RBC survival time was measured in five patients with VSD and in 11 patients with PDA to determine if there was hemolysis of RBC. Six children without cardiac disease were also studied to obtain the control values for RBC survival times in th laboratory. Two patients with PDA were restudied one year postoperatively. Additional parameters studied were hemoglobin, packed cell volume, reticulocyte cell count, peripheral smear, and urinary hemosiderin. The hemoglobin values and the packed cell volumes were comparable in the two groups. The reticulocyte cell count was normal in all. Urinary hemosiderin was negative in all and the peripheral smear did not reveal abnormal red cell morphology. Mean red cell survival half-life in the two groups was identical. The red cell survival was abnormally low in two patients of PDA. Since one of these two patients had persistently low RBC survival postoperatively, the authors believe that the low red cell survival in this patient was unrelated to the presence of PDA. Based on findings in the small number of cases, the authors conclude that left to right shunt through a VSD or PDA is probably not associated with significant red blood cell destruction.

Adolescent↗

Indomethacin for closure of patent ductus arteriosus in prematures.

A controlled, double blind trial of indomethacin versus placebo was conducted in prematures of birth weight less than 1750 g, with a murmur of patent ductus arteriosus (PDA). The dose of indomethacin was 0.2 mg/kg for 2 doses, orally, 24 hours apart. Forty-seven patients entered the trial. Twenty-four received indomethacin and 12 of these met the criteria for response; 23 received the placebo and two met the criteria for response (p less than 0.01). Subsequent surgical ligation for symptomatic PDA was required in 13 of 23 in the placebo group and 4 of 24 in the indomethacin group (p less than 0.01). When administered early, indomethacin is moderately effective in closing PDA in premature infants.

Clinical Trials as Topic↗

Left ventricular dysfunction after closure of large patent ductus arteriosus.

Changes in left ventricular dimensions and performance were studied in 43 patients after transcatheter occlusion or surgical ligation of patent ductus arteriosus. The patients were assigned to 2 groups based on their ductal diameter: >/= 3.1 mm to group A (n = 27) and </= 3 mm to group B (n = 16). The mean age and weight of the groups were comparable. Before intervention, group A had a significantly larger mean left ventricular end-diastolic diameter than group B, while all patients had normal shortening fraction and ejection fraction. Within 1 month after intervention, left ventricular end-diastolic diameter showed a trend towards regression while shortening fraction and ejection fraction decreased significantly in group A. There were no significant changes in these parameters in group B. Between 1 and 6 months after intervention, left ventricular performance improved in most of the group A patients who were followed up. We conclude that closure of large ductus arteriosus in children leads to significant immediate deterioration of left ventricular performance, which appears to recover within a few months. Echocardiographic study before hospital discharge is recommended in these patients. Serious deterioration of ventricular performance after closure may warrant the use of angiotensin converting enzyme inhibitors.

Cardiac Catheterization↗