How a patent ductus arteriosus effects the premature lamb's ability to handle additional volume loads

A model of patent ductus arteriosus in premature lambs was created to examine the lamb's ability to handle the volume load imposed by a patent ductus arteriosus and to determine the lamb's ability to handle any additional volume load. Fifteen preterm lambs [133 +/- 2 (+/- SD) days gestation, term 145 days], whose ductal diameter could be regulated with a mechanical occluder, were studied to determine the independent effects of ductus patency and a saline volume load (50 ml/kg over 3 min) on left ventricular output and its distribution. During a saline infusion, preterm lambs with a closed ductus could only increase their stroke volume by 40% above baseline stroke volume. When challenged with a saline infusion, lambs with an open ductus still were able to increase their stroke volume significantly; the maximal increase in stroke volume during the saline load with the ductus open was 70% above baseline stroke volume. We hypothesize that the associated reduced left ventricular afterload plays a significant role in the preterm lamb's ability to increase its stroke volume when challenged with a patent ductus arteriosus. Even with a patent ductus arteriosus, the lamb still has the ability to handle additional volume loads.     

Effect of patent ductus arteriosus on doppler-derived right ventricular systolic time intervals

Summary Right ventricular systolic time intervals (RVSTI) and noninvasive Dopplerderived pulmonary blood flow were measured before and after surgical ductus ligation in 18 otherwise healthy infants and children who were older than 3 months of age. Right ventricular preejection period (PEP) and the ratio of preejection period and right ventricular ejection time (PEP/REVET), both corrected or uncorrected for heart rate, decreased significantly following surgery (PEP 71±14 vs. 50±13,p<0.001 and PEP/RVET 0.29±0.06 vs. 0.21±0.05,p<0.001). The volume of pulmonary blood flow correlated with PEP/RVET (r=0.48,p=0.003). The magnitude of the change in pulmonary blood flow correlated with the change in PEP/RVET (r÷0.56,p=0.016). The velocity of circumferential fiber shortening (VCFc) increased after surgery, but not significantly. We speculate that patent ductus arteriosus has a similar effect on right ventricular performance when other congenital heart defects are present.     

Indomethacin and cerebral blood flow in premature infants treated for patent ductus arteriosus

Central blood flow (CBF) was estimated by an intravenous 133-xenon technique in six preterm infants before and after administration of indomethacin for closure of patent ductus arteriosus. CBF fell in all infants (range 12%–40%), the mean fall was 24% (P<0.005). Though none of the infants showed signs of impaired cerebral function during or following the injections, the results do not indicate whether or not the use of indomethacin is a potential hazard.Abbreviations PDA patent ductus arteriosus - CBF cerebral blood flow - PaCO₂ arterial carbon dioxide tension - MAP mean arterial blood pressure     

Renal function in sick,very low-birth-weight infants

Renal immaturity is pronounced in very low-birth-weight infants with a gestational age ≤ 30 weeks. We attempted to elucidate if conditions requiring mechanical ventilation, including patent ductus arteriosus, might further compromise renal function due to decreased renal perfusion. Forty infants studied between 4 and 28 days of age were divided into four groups: Control with no patent ductus or mechanical ventilation (n= 8); PDA + MV, with both patent ductus and mechanical ventilation (n=17); PDA, with patent ductus (n= 6); MV, with mechanical ventilation (n= 9). The groups PDA + MV and MV had significantly lower creatinine clearances and significantly higher fractional sodium excretions than controls. Mean arterial pressure was significantly lower in all groups compared to controls and correlated significantly with creatinine clearance (r = 0.47, p < 0.02). In conclusion, low renal function in these infants is further compromised by a patent ductus arteriosus and/or the use of mechanical ventilation.     

Left ventricular preload reserve in preterm infants with patent ductus arteriosus

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.     

Left ventricular preload reserve in preterm infants with patent ductus arteriosus

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.     

Left ventricle output and mean arterial blood pressure in preterm infants during the 1st day of life

The objective was to assess the contribution of left ventricular output (LVO) in determining low mean arterial blood pressure (MABP) in preterm infants admitted to the neonatal intensive care unit. Doppler echocardiography was prospectively performed on a cohort of 17 consecutive infants with low MABP (<30 mmHg) and on 17 consecutive control subjects (range: 600–1520 g; 27–30.7 weeks gestation). The median haematocrit was 42.5% in the low MABP group versus 49.4% in the control group (P < 0.01). The index of resistance to the LVO (RILV = MABP:LVO ratio) was lower in the low MABP group (98 vs 156 mmHg · l⁻¹ · kg⁻¹ · min⁻¹; P < 0.05). An analysis of the low MABP group regarding LVO revealed that a subgroup of four infants had LVO <10th percentile (185 ml · kg⁻¹ · min⁻¹) with a high RILV (>90th percentile: 226 mmHg · l⁻¹ · kg⁻¹ ·  min⁻¹) for three of the infants. The remaining 13 infants had LVO >10th percentile and a shortening fraction >25th percentile. In this subgroup, a high proportion of infants (9/13 vs 2/17, P < 0.01) had low RILV (<10th percentile: 96 mmHg · l⁻¹ · kg⁻¹ · min⁻¹) and the incidence of haemodynamically significant patent ductus arteriosus was higher than in the control group (10/13 vs 4/17, P < 0.01). Conclusion Left ventricular output, index of resistance to left ventricular output and patent ductus arteriosus status are important to consider in evaluating mean arterial blood pressure during early postnatal life in preterm infants. Low mean arterial blood pressure is frequently associated with normal or high left ventricular output, low index of resistance to left ventricular output and significant patent ductus arteriosus. Received: 10 November 1998 and in revised form: 8 February 1999 / Accepted: 9 February 1999     

Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress

We created a model for studying the cardiovascular and pulmonary effects of patent ductus arteriosus (PDA) in premature lambs with respiratory distress. In 47 fetal lambs at 129 to 133 days gestation (term, 145 days), we infiltrated the ductus arteriosus with formalin and placed a mechanical occluder about it so that its patency could be regulated. Two days later the lambs were delivered, given sheep surfactant, paralyzed, and their lungs mechanically ventilated. These premature lambs could more than double their left ventricular output when challenged with increasing degrees of left-to-right shunts through the PDA. This was accomplished by an increase in stroke volume, not by an increase in heart rate. During the 40-minute observation period, there was no change in dynamic compliance or functional residual capacity while the ductus was patent. When the ductus was patent, there was a significant increase in arterial PaO2 (even with small left-to-right shunts) and a decrease in PaCO2 (with large shunts). Despite the heart's ability to handle the increased volume load of a PDA, there were significant alterations in individual organ blood flows, resulting from a combination of decreased perfusion pressure and localized vasoconstriction. The abdominal organs had significant reductions in blood flow even with small PDA shunts. This decrease in organ blood flow may explain some of the pathophysiologic manifestations of PDA in preterm infants.     

The role of beta-adrenoreceptor stimulation and contractile state in the preterm lamb's response to altered ductus arteriosus patency

A model of patent ductus arteriosus in premature lambs was created to study the relative importance of beta-adrenoreceptor stimulation and increased myocardial contractility. In 39 fetal lambs (133 +/- 2, +/- SD days gestation, term 145 days), the ductus arteriosus was infiltrated with formalin, and a snare was placed around it to regulate its patency. One day later, the lambs were delivered, given sheep surfactant, paralyzed, and mechanically ventilated. Microsphere measurements of left ventricular output were made between 4 and 6 h after delivery. When the ductus was opened, there was no change in heart rate, but there were significant increases in left ventricular output, stroke volume, left ventricular end-diastolic pressure, and peak dP/dt. The increase in peak dP/dt due to opening the ductus was greater than that due to an increase in left ventricular end-diastolic pressure alone and was accompanied by an increase in norepinephrine secretion from the left ventricle. Propranolol (1 mg/kg) was used to evaluate the effect of beta-adrenergic tone on left ventricular output and contractility. The left atrium was paced in both control and propranolol-treated lambs. When the ductus was closed, propranolol significantly decreased stroke volume and peak dP/dt without changing left ventricular end-diastolic pressure or systemic vascular resistance. During a saline volume load (50 ml/kg over a 3-min period), propranolol-treated lambs had a reduced stroke volume and peak dP/dt despite similar values of left ventricular end-diastolic pressure and resistance as those of control lambs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical aspects of very‐low‐birthweight infants showing reopening of ductus arteriosus

Background: Indomethacin is used to treat the hemodynamically significant patent ductus arteriosus in premature infants. Some infants show ductus arteriosus reopening after effective constriction by the drug. The purpose of this study was to examine the clinical characteristics of such infants. Methods: We studied 57 very‐low‐birthweight infants with effective constriction of patent ductus arteriosus by the initial course of indomethacin. They were classified into the reopened group if they developed hemodynamically significant patent ductus arteriosus again or into the closed group if they showed complete closure. Clinical characteristics were compared between the two groups. Results: Ductus arteriosus reopening was shown in 15 (26%) of the 57 infants. These 15 infants had successful clinical ductal closure after a subsequent course of indomethacin or oral mefenamic acid treatment or surgical ligation without any severe complications. Infants in the reopened group showed significantly higher rates of developing chronic lung disease at 36 weeks of gestation than those in the closed group (53% vs 18%; P= 0.009). Furthermore, multivariate logistic regression analysis revealed ductus arteriosus reopening was the only independent risk factor for developing chronic lung disease at 36 postconceptional weeks in this population (adjusted odds ratio, 6.1; 95% confidence interval, 1.4–31.2; P= 0.02). Conclusions: Incomplete closure of the ductus arteriosus is associated with recurrence of a clinically significant patent ductus arteriosus and reopening of the ductus after initial closure with indomethacin is associated with chronic lung disease.     

Echocardiographic systolic time intervals in premature infants with patent ductus arteriosus

Summary Thirty-six premature infants with respiratory distress syndrome and clinically significant patent ductus arteriosus (PDA) were studied by M-mode echocardiography before and after closure of the ductus. Before closure the ratio of left ventricular preejection period to left ventricular ejection time (LPEP/LVET) was .26±.03 (mean±SD). After closure of the ductus, LPEP/LVET was .38±.04 (mean±SD), significantly different from the value before closure but not significantly different from the value found in 21 control infants; also, a ratio < .30 was always associated with a clinically significant shunt. The combination of systolic time interval measurement with standard M-mode measurement of the left side of the heart enhanced echocardiographic detection of PDA in our series. Serial evaluation of systolic time interval measurements may provide a further index of left-to-right shunt through a PDA and be a valuable adjunct to the clinical management of these patients.Supported in part by grants from the Kentucky Heart Association.     

Pulsed Doppler measurement of left ventricular output as early predictor of symptomatic patent ductus arteriosus in very preterm infants

High left ventricular output (LVO) values are associated with symptomatic left-to-right ductal shunting in preterm infants. However, LVO data prior to the occurrence of symptomatic patent ductus arteriosus (SPDA) are lacking. To determine whether serial measurements could predict a SPDA, we measured LVO from day 1 until day 10 with pulsed Doppler echocardiography in 25 preterm infants with birth weights of less than 1,250 g and hematocrits of more than 0.40. Eleven infants never developed patent ductus arteriosus symptoms and had LVO values within the normal range (190-310 ml/min/kg) with only minimal daily variations. The remaining 14 infants developed SPDA which required treatment with indomethacin, ductal ligation, or fluid restriction on days 2-5. From day 1 until day 5 their mean LVO values were significantly higher compared to the group without left-to-right ductal shunt and this increase was secondary to higher stroke volume values. An increase in LVO of more than 60 ml/min/kg consistently preceded SPDA by at least 24 h. Serial measurements of LVO using a single-pulsed Doppler approach can be used for early prediction of SPDA.     

Changes in left ventricular volume and systolic function before and after the closure of ductus arteriosus in full-term infants

Using echocardiographic techniques, the change in left ventricular (LV) volume and its effect on systolic function were studied before and after the closure of ductus arteriosus in 18 full-term infants. Examinations were performed twice in each infant, within 6 h after birth and on day 5, and the patency of the ductus with left-to-right shunt was confirmed at the first examination by Doppler echocardiography. A biplane Simpson's rule method was used for volume measurements. The LV end-diastolic volume, stroke volume, and cardiac output were more than 1.3-fold before the ductal closure, and the ejection fraction showed the similar change. However, the mean normalized systolic ejection rate, an index of contractility, and heart rate showed no significant difference. The Frank-Starling curve was obtained from the relationship between the LV end-diastolic and stroke volumes, and the LV performance was operated at a higher level on that curve when the ductus was open. Our data indicated that LV cardiac output was significantly higher during the patency of the ductus arteriosus and that this high cardiac performance might depend more on the Frank-Starling response to the volume load through the ductus arteriosus than on the increase of LV contractility and heart rate.     

Angiographic evidence of absent ductus arteriosus in severe right ventricular outflow obstruction

Summary The angiocardiograms of 5 newborn infants with autopsy and/or surgically-proven congenital absence of the ductus arteriosus (ADA) and right ventricular outflow obstruction (Group A), and of 14 neonates with pulmonary atresia complex and patent ductus arteriosus (Group B) were reviewed. Aortic size was similar in both groups; however, the diameters of the right and left pulmonary arteries were much smaller in Group A than in Group B (right pulmonary artery: 2.6 vs 4.5 mm,P<0.005; left pulmonary artery: 2.5 vs 4.3 mm,P<0.005). Extensive bronchial collaterals were observed in Group A but not in Group B. Tricuspid aortic valve stenosis was present in 2 patients in Group A but in none in Group B. The diagnosis of ADA may be made in newborn infants with severe right ventricular outflow obstruction if the angiocardiograms reveal hypoplasia of the pulmonary arteries, extensive bronchial collaterals, and nonvisualization of the ductus arteriosus. Other suggestive features include aortic valve stenosis and/or right aortic arch with aberrant left subclavian artery.Supported in part by Grant RR-305 from the General Clinical Research Centers Program of the Division of Research Resources and by Grant HL-07605 from the National Heart, Lung and Blood Institute. National Institutes of Health, Bethesda, Maryland     

Pulmonary vasculature changes associated with idiopathic closure of the ductus arteriosus and hydrops fetalis

Summary Antenatal closure of the ductus arteriosus has been considered as a potential risk factor for the development of hydrops fetalis and persistent fetal circulation of the newborn. We present an infant with antenatal ductal closure who had not received prenatal prostaglandin synthetase inhibitors. The pulmonary vascular morphological findings are described and compared to three additional infants in whom the ductus arteriosus was known to be patent; one with neonatal sepsis and two others with hydrops fetalis.The infants with fetal hydrops, regardless of etiology, had increased muscularization of the acinar pulmonary arteries. In addition, the infant with antenatal closure of the ductus arteriosus also had both a significant decrease in preacinar arterial external diameter and an increase in medial wall thickness. Antenatal closure of the ductus arteriosus appears to enhancein utero pulmonary blood flow and this may be the cause of pulmonary vascular remodeling.     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

Comparison of effects of 95% and 90% oxygen saturations in respiratory distress syndrome.

AIMS: To determine if decreasing arterial blood saturation from 95% to 90% could cause vasoconstriction of the pulmonary vasculature and dilatation of a patent ductus arteriosus in preterm newborn infants with respiratory distress syndrome (RDS). METHODS: Doppler echocardiographic studies were compared at 95% and 90% pulse oxygen saturation (SpO2) in 13 preterm infants aged 61.7 (4.3) hours with RDS and Doppler echocardiographic evidence of tricuspid regurgitation. RESULTS: The mean (SD)Doppler echocardiographic indices determined at 95% were heart rate (146 (3.60) beats per minute), acceleration time of the velocity wave forms of the pulmonary artery (PAAT) (51.8 (2.5) milliseconds), ratio of PAAT to right ventricular ejection time (ET) (0.26 (0.02)), diameter of the ductus arteriosus (2.6 (0.6) mm), pulmonary blood flow (0.33 (0.03) l/minute) and the left ventricular shortening fraction (SF)(0.4 (0.02)%). The ascending aorta flow velocity wave form was used for the calculation of pulmonary blood flow. The right ventricular to right atrial systolic pressure gradient calculated using the peak velocity of the tricuspid regurgitation jet was 26.7 (7.4) mm Hg. CONCLUSIONS: A decrease from 95% to 90% SpO2 did not have any effect on the pulmonary circulatory haemodynamics nor the ductus arteriosus.     

Outcome following patent ductus arteriosus ligation in premature infants: a retrospective cohort analysis

Background  

The patent ductus arteriosus (PDA) is an important problem in premature infants. Surgical PDA ligation is usually only be considered when medical treatment has either failed or was contraindicated. The aims of our study were to determine the mortality and morbidity following patent ductus arteriosus ligation in premature infants, and whether prostaglandin synthetase inhibitor (PSI) use prior to ligation affects outcome.     

Cardiac adaptation in small for gestational age neonates after prenatal hemodynamic disturbances

BACKGROUND: Small for gestational age neonates with prenatal hemodynamic disturbances are at increased risk for neonatal morbidity. Investigations of fetal cardiac function have proved some functional impairments. The aim of the study was to investigate postnatal cardiac adaptation in these neonates in comparison with neonates without prenatal hemodynamic impairments. METHODS AND RESULTS: Forty-one neonates with prenatal hemodynamic disturbances and 40 neonates with undisturbed prenatal hemodynamics were observed during the first 5 days of life. Doppler sonographic measurements of left ventricular time intervals, stroke volume, cardiac output and the incidence of patent ductus arteriosus were obtained in all neonates of both groups. Heart rate and blood pressure were recorded simultaneously. RESULTS: A higher incidence of patent ductus arteriosus and a diminished stroke volume, but increased cardiac output, based on a significantly increased heart rate, were determined in SGA neonates with prenatal hemodynamic disturbances. In contrast, systolic left ventricular time intervals were not changed in these neonates, as expected. CONCLUSIONS: The described findings could be signs of persistent hemodynamic impairments in growth-retarded neonates with prenatal disturbed hemodynamics. The neonates revealed a reduced ability to compensate the prenatal hemodynamic disturbances. This aspect should be included in the discussion of perinatal management in cases of severe growth retardation.     

Preoperative left ventricular internal dimension in end-diastole as earlier identification of early patent ductus arteriosus operation and postoperative intensive care in very low birth weight infants

Patent ductus arteriosus (PDA) is common in premature infants. In very low birth weight infants (VLBWI), PDA requires surgical therapy in many cases. It is unclear to know at-risk infants showing cardio-dysfunction after PDA surgery. The purpose of this study was to identify at-risk infants showing cardio-dysfunction after surgery for patent ductus arteriosus (PDA). We examined the relationship between left ventricular (LV) performance before and after PDA ligation in a retrospective observational cohort study. We studied 64 preterm neonates with symptomatic PDA before and after surgical ligation. Echocardiographic examinations were performed pre- and postoperatively. M-mode measurements included left ventricular internal dimension in end-diastole (LVIDd) and LV fractional shortening (FS). All cases showed decreased LVFS after PDA closure. Most cases (49/64, 77%) showed postoperative FS decreased to below normal (< 28%). Preoperative relative LVIDd was significantly larger in abnormal FS infants (137 ± 18%) than in normal FS infants (118 ± 11%; p < 0.01). A cut-off value of preoperative relative LVIDd (absolute LVIDd/normal value) for predicting postoperative cardio-dysfunction was 127.4% (sensitivity, 0.735; specificity, 0.933; area under curve, 0.817). Determination of preoperative LVIDd might facilitate earlier identification of infants needing early PDA surgery and postoperative intensive care.