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PubMed1994

Cytochrome P450 during ontogenic development: occurrence in the ductus arteriosus and other tissues.

Our previous investigations have implicated a cytochrome P450 mechanism in the oxygen contraction of the ductus arteriosus and, by extension, in the closure of the vessel at birth. This study was undertaken in fetal and newborn sheep to characterize the ductal cytochrome and gather insight into its operation. Other tissues, vascular and extravascular, were used as a reference. Benzo[a]pyrene hydroxylation (a marker for the 3-methylcholanthrene-inducible isozyme) and aminopyrine N-demethylation (a marker for the glucocorticoid-inducible isozyme) had insignificant activity in the ductus and aorta from fetal sheep, and no increase was noted after exposing the animal in utero to beta-naphthoflavone or dexamethasone, both alone and in combination with phenobarbital. However, dexamethasone and, particularly, dexamethasone plus phenobarbital produced a variable constriction of the fetal ductus. No monooxygenase activity was found in the naturally closing ductus of the newborn. Conversely, both enzyme reactions were measurable in the fetal liver, and they became more active after treatment with the inducers or at birth. Scanning immunoelectron microscopy of cultured endothelial and muscle cells from both ductus and aorta showed specific gold labelling for the glucocorticoid-inducible cytochrome P450 only in ductal muscle. By transmission electron microscopy, this immunoreactivity was located along the sarcolemma and in the sarcoplasmic reticulum. These findings indicate the presence in the ductus arteriosus of a cytochrome P450 belonging to the 3A subfamily. However, considering the uneven action of the inducers on enzyme activity in ductal tissue and muscle tone, the role of this cytochrome in closure of the vessel at birth remains to be ascertained.

Aging↗
PubMed2001

In utero remodeling of the fetal lamb ductus arteriosus: the role of antenatal indomethacin and avascular zone thickness on vasa vasorum proliferation, neointima formation, and cell death.

BACKGROUND: The ductus arteriosus (DA) of newborn infants exposed in utero to indomethacin is resistant to postnatal indomethacin; we hypothesized that this is due to ductus constriction in utero, with subsequent remodeling of the vessel. METHODS AND RESULTS: Infusion of fetal lambs with indomethacin for 48 hours constricted the DA and increased the thickness of the avascular zone of the DA, which in turn induced the expression of vascular endothelial growth factor, endothelial nitric oxide synthase (due to ingrowth of vasa vasorum), neointima formation, and loss of smooth muscle cells; moderate degrees of DA constriction in utero increased NO production, which inhibited DA contractility. Marked degrees of DA constriction decreased tissue distensibility and contractile capacity. CONCLUSIONS: DA patency is no longer controlled primarily by prostaglandins once it has been exposed to indomethacin in utero.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Left ventricular contractile state of early human neonates with patent ductus arteriosus.

Using echocardiographic technique, we studied the left ventricular (LV) contractile state in 32 full-term infants within 24 hr after birth. They were divided into 2 groups based on the timing of the examinations; the group 1 (n = 17), < 3 hr after birth; the group 2 (n = 15), > 3 and < 24 hr after birth, and the additional examinations were performed on day 5. The patency of the ductus arteriosus and its internal diameter were determined by pulsed Doppler and two-dimensional echocardiography. The left atrial to aortic root ratio was obtained from M-mode echocardiography, and the LV contractile state was estimated by the relationship between heart rate-corrected velocity of circumferential fiber shortening (mVcfc) and end-systolic meridional wall stress (ESS). The ductus arteriosus was open in all cases of group 1 and in 83% of the cases of group 2, but the ductal diameter and the left atrial to aortic root ratio significantly decreased in group 2. The relationship between mVcfc and ESS showed no significant differences between 2 groups and the control. Afterload, represented as ESS, was significantly lower in group 1 than the control. We suggest that the low afterload condition helps the adequate LV contraction even under the increased preload through the left-to-right ductus arteriosus shunting after birth.

Blood Flow Velocity↗
PubMed1998

Patent ductus arteriosus and neonatal death in prostaglandin receptor EP4-deficient mice.

The physiological role of the prostaglandin E2 receptor EP4 subtype was investigated by generation of EP4-deficient-mice by gene targeting. Loss of the EP4 receptor was not lethal in utero, but most EP4 (-/-) neonates became pale and lethargic approximately 24 h after birth and died within 72 h. Less than 5% of the EP4 (-/-) mice survived and grew normally more than a year. Histological examination revealed that the ductus arteriosus in dead neonates remained open, while it was partially closed in the survivors. In situ hybridization study showed that EP4 mRNA was strongly expressed in the ductus. These results suggest that neonatal death is at least partly due to patent ductus arteriosus and that the EP4 receptor plays a role in regulation of the patency of this vessel. They also indicate that normal function of the EP4 receptor is essential in neonatal adaptation of the circulatory system.

Animals↗
PubMed1992

Congenital aortic stenosis and patent ductus arteriosus in the adult.

Concurrent aortic stenosis and patent ductus arteriosus are not infrequent in children but are rare in adults. An adult case is described with diagnosis by cardiac catheterization and magnetic resonance imaging and with management by combined aortic valve replacement and patent ductus ligation. Review of the English-language literature produced only 8 such cases in adults, 2 of which were managed by a single-stage operation. Successful diagnosis in the adult requires careful observation at cardiac catheterization, and simultaneous valve replacement and ductus ligation may be a useful option in patient management.

Aged↗
PubMed1986

Operative management of the calcified patent ductus arteriosus.

A technique in which the calcified adult patent ductus arteriosus can be safely divided using a left-sided thoracotomy approach without the need for transient aortic cross-clamping or cardiopulmonary bypass is described. Concentric, nested vascular clamps are placed on the noncalcified pulmonary artery side of the ductus, so that dissection and clamping of the heavily calcified ductus-aortic junction are unnecessary. The pulmonary artery rim surrounding the insertion of the ductus can be divided between the two clamps and oversewn.

Adult↗
PubMed2004

A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus.

UNLABELLED: Ibuprofen (IBU) has previously been shown to be as effective as indomethacin (INDO) in closing the patent ductus arteriosus (PDA) of preterm infants, without severely affecting renal hemodynamics or basal cerebral blood flow. We conducted a meta-analysis of randomized trials to compare the efficacy and safety of IBU and INDO for treatment of PDA. Data from the nine relevant trials ( n =566), showed no significant difference in the efficacy of IBU and INDO in PDA closure ( P =0.70). However, five trials ( n =443) provided serum creatinine concentration data that revealed a significantly lower increase favoring IBU ( P < 0.001), and urine output data that showed a significantly lower decrease favoring IBU ( P < 0.001). In two trials ( n =188) the proportion of infants who required postnatal oxygen therapy at 28 days (defined as chronic lung disease) was significantly higher with IBU (52/94; 55.3%) than with INDO (38/94; 40.4%, P < 0.05). No statistically significant differences were found in mortality, intraventricular hemorrhage, necrotizing enterocolitis, surgical ligation, sepsis, retinopathy of prematurity, periventricular leukomalacia, length of hospital stay, gastrointestinal bleeding, re-opening of PDA, back-up treatment, surfactant therapy, or days on a ventilator. CONCLUSION: ibuprofen and indomethacin have similar efficacy in patent ductus arteriosus closure, but preterm infants treated with ibuprofen experience lower serum creatinine values, higher urine output, and less undesirable decreased organ blood flow and vasoconstrictive adverse effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Comparison of effects of cyclooxygenase inhibitors on myometrial contraction and constriction of ductus arteriosus in rats.

The aim of this study was to compare the tocolytic effect of a selective cyclooxygenase-2 inhibitor, DFU (5,5-dimethyl-3(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), indomethacin and nimesulide on myometrial strips isolated from rats in both lipopolysaccharide-induced preterm labour and term labour. We also compared the constrictor effects of DFU and indomethacin on the fetal ductus arteriosus. Myometrial strips were obtained from preterm and term labour Wistar albino rats and were mounted in organ baths for the recording of isometric tension. DFU, nimesulide and indomethacin significantly inhibited KCl-, oxytocin-, prostaglandin E(2)- and prostaglandin F(2 alpha)-stimulated contractions of myometrial strips isolated from rats in preterm and term labour. The E(max) value of indomethacin was significantly lower than those for DFU and nimesulide (P<0.05), with no change-log (10) EC(50) values. There was no significant difference between in -log (10) EC(50) and E(max) values of DFU and nimesulide for any of the tissues (P>0.05). In addition, there was no significant difference between -log (10) EC(50) and E(max) values for each of these three agents in myometrial tissues isolated from rats in preterm and term labour (P>0.05). Fetal ductus arteriosus was significantly constricted by DFU (10 or 100 mg/kg) in preterm and term rats, although DFU (10 or 100 mg/kg)-induced constriction ratios were significantly lower than those for indomethacin (P<0.05). These data demonstrate that DFU, a specific cyclooxygenase-2 inhibitor, could be considered as a new therapeutic agent for preterm labour. However, careful attention should be given to constriction of the fetal ductus arteriosus.

Animals↗
PubMed1991

Transcatheter occlusion of the persistently patent ductus arteriosus. Forty-month follow-up and prevalence of residual shunting.

BACKGROUND: Percutaneous closure of the persistently patent ductus arteriosus with the Rashkind prosthesis is an established effective therapeutic modality, although some patients are left with residual shunting. To evaluate this, a retrospective study of the prevalence of persistent shunting over a 40-month period in the first 190 patients was undertaken. METHODS AND RESULTS: All patients (male 45, female 145; mean age, 3.9 +/- 3.6 years; range, 5 months to 20 years) had serial clinical and color-flow echocardiographic follow-up at 6-12-month intervals (range, 6-40 months). Four patients required surgical removal of an embolized device, leaving a cohort of 186 patients in whom 196 procedures were performed, resulting in successful placement of 195 devices (43 17-mm [22%] and 152 12-mm [78%]). Complications occurred in seven of 195 procedures (3.6%). Nine of 10 attempted reocclusions (all with 12-mm devices) were successful. The prevalence of residual shunting was 38% at 1 year, 18% at 2 years, and 8% at 40 months. Patients with ductus measuring less than 4 mm had a higher success of initial occlusion. Thirty-four patients were left with residual shunting determined by color-flow Doppler study, but no anatomic or echocardiographic features were found predictive for residual shunting. All remain asymptomatic with 26 (76%) having no detectable murmur, two (6%) a continuous murmur, and six (18%) a systolic murmur. CONCLUSIONS: Catheter occlusion will obviate the need for surgery in the majority of patients presenting with persistently patent ductus arteriosus. Reocclusion has been found feasible in those with continuous murmurs (nine of nine) and should be offered early because it is unlikely for spontaneous closure to occur in this group. It appears prudent to follow those with small residual shunting because further spontaneous closure can occur.

Adolescent↗
PubMed2003

Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome.

BACKGROUND: Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low-birth-weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS. METHODS: Extremely low-birth-weight infants (birth-weight <1000 g) treated with surfactant for RDS were studied by serial Doppler flow examinations. Doppler flow variables in 19 infants in whom hsPDA developed (hsPDA group) were compared with those in 19 infants without hsPDA matched for gestational age, birth-weight, and postnatal age (non-hsPDA group). All infants in the hsPDA group had pharmacologic closure of ductus arteriosus when hsPDA developed. RESULTS: Before pharmacological closure of PDA, the hsPDA group had significantly higher LVO, lower blood flow volume of the abdominal aorta, and lower mean blood flow velocities in the celiac artery, superior mesenteric artery, and renal artery than the non-hsPDA group. These alterations in the hsPDA group reverted to the levels in the non-hsPDA group after the closure of PDA and had no deleterious effects on the cardiorespiratory status. No significant differences between the groups were found in mean blood flow velocities of the anterior cerebral artery throughout the study period. CONCLUSION: These results indicate that although LVO is increased, the splanchnic and renal blood flows are decreased when hsPDA develops in ELBW infants with RDS. The effects of these alterations of LVO and organ blood flows on the cardiorespiratory course seem to be minor when early pharmacologic closure of PDA is done.

Aorta, Abdominal↗
PubMed1994

[A new video-assisted thoracoscopic surgical interruption of patent ductus arteriosus].

A new video-assisted thoracoscopic surgery was applied to patients with patent ductus arteriosus (PDA). After the ductus was carefully dissected and exposed, two or one titanium clips which were 11 mm in length were used to interrupt the ductus completely. Eight patients with PDA were successfully treated by the new technique between July 1992 and September 1993, which was the first successful series in Japan. Mean age was 4.3 years (range 1.7 approximately 6.7 years) and mean weight was 15.6 kg (range 10.0 approximately 24.0 kg). All patients had immediate complete PDA closure after the procedure which was proved to be successful by an esophageal stethoscope and color doppler echocardiogram. One patient had mild left recurrent laryngeal nerve dysfunction which was completely cured on 7th postoperative day. There were no other complications and the usual hospital stay was 4 or 5 days. No residual PDA shunt in all cases was revealed by color doppler echocardiogram during follow-up periods (range 3 approximately 12 months). The advantages of thoracoscopic surgery for PDA are: less postoperative pain and discomfort, early recovery and short hospital stay, and cosmetic preservation. Availability of smaller sized surgical instruments should allow this technique indicated for smaller children and premature infants.

Child↗
PubMedDate not supplied

Single therapeutic catheterization for treatment of native coarctation of aorta and large patent ductus arteriosus using a covered stent.

A 20-year-old girl was diagnosed to have severe coarctation of the aorta, large patent ductus arteriosus and severe pulmonary artery hypertension. She underwent single therapeutic catheterization for the treatment of native coarctation of aorta and closure of ductus arteriosus using 39 mm long Cheatham-Platinum covered stent. The procedure was done successfully under local anesthesia without any complication. This appears to be a safe strategy while dealing with an adolescent or an adult with this combination of lesions.

Abnormalities, Multiple↗
PubMed1985

Vasoactivity of trimetazidine on guinea-pig isolated ductus arteriosus.

The effect of trimetazidine (TMZ), an anti-anginal drug, on the mechanical response of the guinea-pig ductus arteriosus placed under conditions of mild hypoxia (PO2 approximately equal to 75 mmHg) was investigated. When the PO2 of the bathing solution was 75 mmHg, TMZ caused a dose-dependent increase in tension. The median effective dose (ED50) for the drug was 8 X 10(-5)M. TMZ-induced increase in tension was not significantly affected by pretreatment of the preparation with adrenoceptor blocking agents, or indomethacin. The amplitude of the PO2-dependent tension was significantly augmented by exposure of the strip to TMZ 10(-4)M, whereas neither the resting tone (low PO2), nor the oxygen-induced contraction (high PO2) were altered. This ability of TMZ to increase the tension response during hypoxia was dependent on the external calcium concentration. Under low PO2 conditions, a contractile activity of 10(-4)M TMZ was unmasked in preparations perfused with 18 mM K+-PSS medium. This response to TMZ disappeared after the removal of calcium from the bath. At the maximally effective dose of 10(-3)M, and during low PO2, the TMZ-induced contractile response changed to a relaxation response when the external K+ concentration was raised more than five fold. The possibility that TMZ stimulates the mechanism by which oxygen normally controls the concentration of free intracellular calcium in the ductus arteriosus is proposed.

Animals↗
PubMed1995

Patent ductus arteriosus. Clinical relevance of prostaglandins and prostaglandin inhibitors in PDA pathophysiology and treatment.

This article presents a comprehensive review of the patent ductus arteriosus which so often affects the premature neonate. Included are a discussion of the unique anatomy and physiology of the ductus, a review of the mechanisms involved in normal closure, and factors leading to persistent patency. Various therapeutic options also are discussed, including some new and innovative approaches.

Ductus Arteriosus↗