Ductus Arteriosus Blood Flow Research Articles

Open or closed: Changes in ductus arteriosus flow patterns at birth using 4D flow MRI in newborn piglets.

The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA. This was performed in Large White‐Landrace‐Duroc piglets (n = 34) spanning four age groups: term‐9 days, term‐3, term+1, and term+5. Subject's DA status was classified using 4D flow: closed DA, forward DA flow, reversed DA flow, and bidirectional DA flow. Over all states, vessel diameters and flows normalized to body weight increased with age (for example in the ascending aorta flow—term‐9: 126.6 ± 45.4; term+5: 260.2 ± 80.0 ml/min per kg; p = 0.0005; ascending aorta diameter—term‐9: 5.2 ± 0.8; term+5: 7.7 ± 0.4 mm; p = 0.0004). In subjects with reversed DA blood flow there was lower common carotid artery blood flow (forward: 37.5 ± 9.0; reversed: 20.0 ± 7.4 ml/min per kg; p = 0.032). Linear regression revealed that as net DA flow decreases, common carotid artery flow decreases (R2 = 0.32, p = 0.004), and left (R2 = 0.33, p = 0.003) and right (R2 = 0.34, p = 0.003) pulmonary artery flow increases. Bidirectional DA blood flow changed oxygen saturation as determined by MRI between the ascending and descending aorta (ascending aorta: 90.1% ± 8.4%; descending aorta: 75.6% ± 14.2%; p < 0.05). Expanded use of these techniques in preterm animal models will aid in providing new understandings of normal versus abnormal DA transition, as well as to test the effectiveness of related clinical interventions.

Prenatal and postnatal ultrasound assessment and clinical prognostic analysis for Ebstein anomaly

Objective: To investigate the echocardiographic features of fetal Ebstein's anomaly (EA) and to analyze its clinical outcome and prognosis. Methods: A retrospective case-control study was conducted to analyze the echocardiographic features in fetus with EA. Thirty-five EA fetuses (EA group) and 35 normal fetuses matched for gestational age (control group) were enrolled. The main echocardiographic parameters of the two groups were collected and compared. According to the direction of blood flow in the ductus arteriosus (DA),fetuses in EA group were divided into DA reverse perfusion subgroup (n=11) and normal DA blood flow subgroup (n=24). The echocardiographic parameters and GOSE scores were compared between the two subgroups. The echocardiographic features of EA and the difference of fetal hemodynamics were summarized,and the clinical outcome of EA fetus was evaluated by GOSE score. Chi-square test Rank sum test or t test were used for comparison between groups. Results: Nineteen (54%) of the 35 patients terminated the pregnancy and 16 (46%) continued pregnancy until delivery during follow-up. Compared with the normal fetus group,the cardiothoracic ratio was significantly higher (0.47±0.11 vs. 0.34±0.01, t=6.640, P<0.01) and the transverse diameter ratio of right atrium to left atrium was significantly greater (1.42±0.38 vs. 1.08±0.11, t=5.030, P<0.01) in the EA group, and the ratio of pulmonary artery diameter to aortic diameter was significantly lower in the EA group (1.04±0.21 vs. 1.20±0.15, t=-3.770, P<0.01). Compared with the normal DA blood flow subgroup,the GOSE scores ≥ 1.5 was more frequently seen (7/11 vs. 3/24, P=0.004) and the ratio of pulmonary artery diameter to aortic diameter was significantly lower (0.91±0.18 vs. 1.24±0.20, t=-4.696, P=0.002) in the DA reverse perfusion subgroup. Six of the 16 delivery cases underwent EA corrective surgery after birth with 100% successful rate of operation. Among the 6 cases,two had preoperative GOSE score of ≥1.5 who were considered as severe cases,and four had low GOSE score of<1.5. The remaining ten cases who had not undergone the corrective surgery were followed up routinely. Conclusion: Prenatal hemodynamics of EA combined with GOSE score can more accurately evaluate the severity and prognosis of fetal EA, reduce unnecessary labor induction, and improve postpartum cure rate and clinical outcomes.

The effect of breathing on ductus arteriosus blood flow directly after birth

Spontaneous breathing at birth influences ductus arteriosus (DA) flow. This study quantifies the effect of breathing on DA shunting directly after birth. In healthy term infants born by elective cesarean section, simultaneous measurements of DA shunting and tidal volumes during spontaneous breathing were performed at 2–5, 5–8, and 10–13 min after birth. Eight infants with a mean (SD) gestational age of 40 (1) weeks and 3216 (616) grams were studied. Inspiratory tidal volume was 5.8 (3.3–7.7), 5.7 (4.0–7.1), and 5.2 (4.3–6.1) mL/kg at 2–5, 5–8, and 10–13 min. The velocity time integral of left-to-right shunting significantly increased during inspiration when compared to expiration (8.4 (5.2) vs. 3.7 (2.3) cm, 8.9 (4.4) vs. 5.6 (3.4) cm, and 14.0 (6.7) vs. 8.4 (6.9) cm; all p < 0.0001) at 2–5, 5–8, and 10–13 min, respectively. In contrast, right-to-left shunting was not different between inspiration and expiration at 2–5 and 10–13 min (11.1 (2.4) vs. 11.1 (2.6) cm and 10.7 (2.3) vs. 10.6 (3.0) cm; p > 0.05), but there was a small increase at 5–8 min (12.1 (2.4) vs. 10.8 (2.9) cm; p = 0.001) during expiration.Conclusion: Directly after birth, ductal shunting is influenced by breathing effort, predominantly with an increase in left-to-right shunt due to inspiration.What is Known:• Spontaneous breathing at birth influences ductus arteriosus flow and pulmonary blood flow.• Crying causes a significant increase in left-to-right ductus arteriosus shunting.What is New:• Left-to-right ductus arteriosus shunting increases during inspiration compared to expiration.• Breathing is important for ductal shunting and contributes to pulmonary blood flow.

P20.12: Contribution of myocardial performance index and ductus arteriosus blood flow for fetal surveillance during open fetal surgery

<scp>P</scp>20.12: Contribution of myocardial performance index and ductus arteriosus blood flow for fetal surveillance during open fetal surgery

Non-invasive measurements of ductus arteriosus flow directly after birth

ObjectiveTo assess ductus arteriosus (DA) blood flow directly after birth in healthy term infants after elective caesarean section.DesignIn healthy term newborns, echocardiography was performed at 2, 5 and 10 min...

Fetal Echocardiographic Measurements and the Need for Neonatal Surgical Intervention in Tetralogy of Fallot

This study aimed to evaluate fetal echocardiographic measurements at the time of the first fetal echocardiogram as predictors of neonatal outcome for tetralogy of Fallot (TOF). The study reviewed all infants with a prenatal diagnosis of TOF from January 2004 to June 2011. Aortic valve (AoV), pulmonary valve (PV), main pulmonary artery (MPA), left and right pulmonary artery diameters, and ductus arteriosus flow were evaluated on fetal echocardiograms, and associations between the fetal echocardiogram and the neonatal echocardiogram measurements and outcomes were assessed. The study identified 67 TOF patients who had an initial fetal echocardiogram at a mean gestational age of 25.0 ± 5.2 weeks. Patients with absent PV syndrome or major aortopulmonary collaterals were excluded from the study, as were those without anterograde pulmonary blood flow at the first fetal echocardiogram. Of the remaining 44 patients, 10 were ductal dependent and required neonatal surgery. Infants who were ductal dependent had lower fetal PV (-5.38 ± 2.95 vs. -3.51 ± 1.66; p < 0.05) and MPA (-3.94 ± 1.66 vs. -2.87 ± 1.04; p < 0.05) z-scores. A fetal PV z-score of -5 predicted ductal dependence with 78 % sensitivity and 87 % specificity, and a PV z-score of -3 showed 100 % sensitivity and 34 % specificity (p < 0.001). Fetuses with a reversed left-to-right flow across the ductus arteriosus (DA) were more likely to be ductal dependent (odds ratio, 25; p < 0.001) than those who had normal ductal flow. In TOF, fetal PV and MPA z-scores and direction of the DA blood flow predict neonatal ductal dependence. Patients with fetal PV z-scores lower than -3 or any left-to-right flow at the level of the DA should be admitted to a center where prostaglandin is available.

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

Prediction of pulmonary hypoplasia in mid‐trimester preterm prelabor rupture of membranes: research or clinical practice?

Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus

Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction (P < 0.05) in conjunction with a reduction (P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction (P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA (P < 0.025), and increased retrograde diastolic flow from compliant major branch PA (P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.

Dynamic changes in the direction of blood flow through the ductus arteriosus at birth

Major cardiovascular changes occur at birth, including increased pulmonary blood flow (PBF) and closure of the ductus arteriosus (DA), which acts as a low resistance shunt between the fetal pulmonary and systemic circulations. Although the pressure gradient between these circulations reverses after birth, little is known about DA blood flow changes and whether reverse DA flow contributes to PBF after birth. Our aim was to describe the changes in PBF and DA flow before, during and after the onset of pulmonary ventilation at birth. Flow probes were implanted on the left pulmonary artery (LPA) and DA in preterm fetal sheep (n = 8) approximately 3 days before they were delivered and ventilated. Blood flow was measured in the LPA and DA, before and after umbilical cord occlusion (UCO) and for 2 h after ventilation onset. Following UCO, DA flow decreased from 534 +/- 57 ml min(1) to 237 +/- 29 ml min(1) which reflected a similar reduction in right ventricular output. Within 5 min of ventilation onset, PBF increased from 11 +/- 6 ml min(1) to 230 +/- 13 ml min(1) whereas DA flow decreased to 172 +/- 54 ml min(1); negative values indicate reverse DA flow (left-to-right shunting). Reverse flow through the DA contributed up to 50% of total PBF at 30 min and a decrease in this contribution accounted for 71 +/- 13% of the time-related decrease in PBF after birth. DA blood flow is very dynamic after birth and depends upon the pressure gradient between the pulmonary and systemic circulations. Following ventilation, reverse DA flow provided a significant contribution to total PBF after birth.

Ductus arteriosus wave intensity analysis in fetal lambs: midsystolic ductal flow augmentation is due to antegrade pulmonary arterial wave transmission

In midsystole, fetal pulmonary trunk (PT) and arterial (PA) blood flows characteristically fall, despite pulmonary blood pressure increasing, while ductus arteriosus (DA) flow continues to rise to a delayed peak. Wave intensity (WI) analysis indicates that midsystolic fetal PT and PA flow reductions are related to a very large midsystolic PA backward-running compression wave (BCW(ms)), which originates in the pulmonary microvasculature and is partially transmitted into the PT. This study tested the hypothesis that midsystolic augmentation of DA blood flow was related to transmission of the PA BCW(ms) into the DA. DA, PT, and PA WI analysis was performed in eight anesthetized late-gestation fetal sheep instrumented with DA, PT, and left PA micromanometer catheters to measure pressure (P) and transit-time flow probes to obtain blood velocity (U). In a subgroup (n = 5), the main PA was briefly occluded to abolish wave transmission from the lungs. WI was calculated as the product of P and U rates of change. PA and PT WI profiles both contained a prominent BCW(ms), approximately 5-fold larger in the PA (P < 0.005), which increased P but decreased U. By contrast, the DA WI profile demonstrated a large midsystolic forward-running compression wave (FCW(ms)), which increased DA P and U, and occurred 5 ms after PA BCW(ms). Furthermore, both DA FCW(ms) and PT BCW(ms) were abolished by main PA occlusion. These results suggest that the fetal PA BCW(ms) undergoes retrograde transmission into the PT as a BCW(ms), but antegrade transmission into the DA as a FCW(ms) that augments midsystolic DA flow.

TOCOX—A randomised, double‐blind, placebo‐controlled trial of rofecoxib (a COX‐2‐specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk

To assess the safety and efficacy of the long term prophylactic use of rofecoxib (a COX-2-specific inhibitor) in women at high risk of preterm delivery. A randomised, double-blind, placebo-controlled trial. Queen Charlotte's and Chelsea Hospital, London and Guys and St Thomas' Hospitals, London. Ninety-eight singleton pregnancies at high risk of preterm labour. Treatment from 16 to 32 weeks. Weekly ultrasound surveillance. Fetal renal function and ductus arteriosus blood flow changes. Preterm delivery rates and neonatal outcome. Rofecoxib caused a reduction in hourly fetal urine production rates (-34%, 95% CI -13 to -50%, P = 0.004) and amniotic fluid index (-2.2, 95% CI -3.2 to -1.2, P < 0.001). This effect did not increase with time on treatment and reversed in all cases on discontinuation of treatment. Rofecoxib had an effect on the ductus arteriosus, increasing maximum systolic velocity (0.1 m/s, 95% CI 0.03-0.16, P = 0.02) and minimum diastolic velocity (0.007 m/s, 95% CI 0.0007-0.013, P= 0.03). This effect increased with time on treatment but was reversed with discontinuation of treatment and had no long term clinical sequelae. There was no difference in preterm delivery rates <30 weeks (28% on placebo vs 33% on rofecoxib, Mantel-Haensel [M-H]-adjusted risk 1.11, 95% CI 0.67-1.87). There were more deliveries <37 weeks in those on rofecoxib (40%vs 67%, M-H-adjusted risk 1.59, 95% CI 1.09-2.32). Rates of preterm prelabour rupture of membranes (PPROM) were higher in those on rofecoxib (RR 2.5, 95% CI 1.3-4.7). Rofecoxib has a significant but reversible effect on fetal renal function and the ductus arteriosus. It does not reduce the incidence of early preterm delivery <30 weeks and is associated with an increased risk of delivery before 37 weeks in women at high risk.

Endothelin-receptor blockade does not alter closure of the ductus arteriosus.

Endothelin-1 (ET-1) is synthesized within the wall of the ductus arteriosus (DA) and is a potent constrictor of the DA in vitro. However, the role of endogenous ET-1 in closure of the DA at birth remains unclear. Therefore, we studied the effects of a selective ETA-receptor antagonist (PD-156707), or its vehicle, on DA closure in 13 late-gestation fetal lambs during the first 5 h after birth. We also studied the effects of ETA-receptor blockade on DA constriction induced by oxygen, indomethacin (a cyclooxygenase inhibitor), and LY-83583 (a soluble guanylate cyclase inhibitor) in vitro (n = 9 ductus arteriosus rings). In vehicle-treated lambs in vivo, the DA constricted during the 5-h study period after birth: DA resistance increased (from 0.007 +/- 0.01 to 3.406 +/- 4.15 mmHg. ml-1. min. kg-1; P < 0.05); the pressure gradient across the DA increased (from 1.4 +/- 2.1 to 25.2 +/- 9.4 mmHg; P < 0.05); and DA blood flow decreased (from 193.5 +/- 48.0 to 19.3 +/- 14.3 ml. kg-1. min-1; P < 0.05). In vitro, the DA was constricted by exposure to 30% oxygen (23 +/- 14% net active tension; P < 0.05), indomethacin (5 x 10(-6) M, 22 +/- 5% net active tension; P < 0.05), LY-83583 (10(-5) M, 24 +/- 10% net active tension; P < 0.05), and ET-1 (10(-7) M, 19 +/- 4% net active tension; P < 0.05). Although PD-156707 blocked both the in vivo and in vitro effects of exogenous ET-1, it had no effect on postnatal ductus constriction nor on in vitro ductus contractile responses to oxygen, indomethacin, or LY-83583. This study suggests that endogenous ET-1 does not play an important role in closure of the DA at birth.

Effects of Maternal Oxygen Administration on the Ductus Arteriosus and Pulmonary Circulation in Fetal Sheep. 129

Maternal oxygen administration combined with fetal ultrasound is used for testing fetal activity. To evaluate the effects of maternal oxygen administration on the ductus arteriosus (DA) and pulmonary circulation, we studied 8 near-term fetal sheep. During fetal surgery, catheters were inserted into the main pulmonary artery and the ascending aorta to measure pressures. An ultrasonic flow transducer was placed around the DA and the left pulmonary artery (LPA) to measure blood flow simultaneously. In 3 fetuses, the DA was formalinized in order to prevent its constriction. We performed 11 studies in 8 fetuses: 6 studies in 5 fetuses without and 5 studies in 3 fetuses with DA formalinization. 100% oxygen was administered for 30 minutes via a face mask to the maternal sheep. Hemodynamic data were measured continuously and the pressure gradient and resistance across the DA were calculated. Arterial blood gas samples were obtained before and after maternal oxygen administration. Hemodynamic changes were analyzed statistically within the group, and compared between the two groups with and without DA formalinization. Maternal oxygen administration increased fetal arterial oxygen tension from 21.0 ± 3.5 to 25.4 ± 3.3 mmHg in total. In the fetuses without DA formalinization, DA blood flow decreased significantly from 907 ± 123 to 647 ± 217 ml/min, while the LPA blood flow increased significantly from 33 ± 21 to 153 ± 61 ml/min. The pressures in the main pulmonary artery and the ascending aorta did not change significantly. The calculated resistance across the DA did not change significantly (from 0.003 ± 0.002 to 0.005± 0.002 [mmHg*min/ml]). In the fetuses with DA formalinization, hemodynamic changes were quite similar to those without formalinization. There were no significant differences in changes between the two groups. These data suggest that maternal oxygen administration decreases the DA blood flow and increases LPA blood flow in fetal sheep and that this redistribution of blood flow is due not to DA constriction, but to diversion of blood flow into pulmonary circulation as a result of pulmonary vasodilatation.

Retinal disease masquerading as spasmus nutans

Two children with congenital stationary night blindness were originally diagnosed as having spasmus nutans. Both children had the typical features of spasmus nutans including asymmetric nystagmus, head shaking, and torticollis. The diagnosis of congenital stationary night blindness was established only after each child underwent electroretinography. The nystagmus associated with retinal disease can mimic many of the features of spasmus nutans. Children suspected of having spasmus nutans should undergo complete ophthalmologic examination and electroretinography if they are myopic.

Ductus arteriosus blood flow during first 48 hours of life.

A volumetric Doppler technique was used to measure net ductus arteriosus shunt during the first 48 hours of life in 30 infants of less than 33 weeks' gestation, and in 10 full term infants. In the full term infants a left to right shunt of 62 ml/kg/minute (95% confidence limits 43-82) shortly after birth decreased rapidly over the first 12 hours and was not measurable by 48 hours. The preterm infants had smaller left to right shunts shortly after birth--49 ml/kg/minute (95% confidence limits 38-59). There was no obvious subsequent change in the mean shunt, although by 48 hours there was greater variation in the size of the shunt. The respiratory distress syndrome did not affect the size of the ductal shunt, but the shorter the gestation period the larger the shunt by 48 hours. A ductal flow of greater than 70 ml/kg/minute at 48 hours of age predicted the subsequent development of a ductal murmur with 75% sensitivity and 100% specificity.

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)