Although a patent ductus arteriosus (PDA) can easily be visualized using ultrasound, the challenge is in differentiating a hemodynamically significant and potentially harmful ductus arteriosus from one which does not significantly affect the hemodynamics and therefore does not contribute to organ injury. Selection of the “right” PDA to treat is particularly important in this era when management of PDA has become even more controversial. Over the past decade, there has been an increased recognition of the need to better define the PDA that requires treatment and as such different classifications and scoring tools have been proposed. Attention to certain variables such as gestational and chronologic age, associated morbidities, and subpopulation characteristics with regard to the risk of complications attributable to the PDA can be helpful in the diagnosis of a pathologic PDA and subsequent selection for treatment.
Keywordsblood pressure, Doppler, echocardiography, near-infrared spectroscopy, patent ductus arteriosus, preterm neonate
Although presence of a patent ductus arteriosus (PDA) can easily be confirmed with ultrasound, diagnosis of a hemodynamically significant PDA is more challenging and not standardized.
Evaluation of a PDA for hemodynamic and clinical significance should include assessment of the magnitude of ductal shunt volume, the ability of the heart to accommodate and compensate for the shunt, and the impact of the shunt on the pulmonary and systemic circulations.
Clinical characteristics such as gestational and chronologic age, extent of cardiopulmonary support, and presence of other variables that may either enhance or mitigate the potential detrimental effects of a PDA can be useful in the evaluation of the hemodynamic and clinical significance of a PDA.
Scoring systems based on clinical characteristics, ultrasound measurements and other technologies such as near-infrared spectroscopy may be useful in evaluation and monitoring of a PDA in the future.
The diagnosis and management of a patent ductus arteriosus (PDA) with cardiorespiratory and thus clinical relevance in preterm neonates poses a major challenge in neonatal medicine. It is the most common cardiovascular abnormality in premature infants. The majority (∼70%) of infants born at a gestational age of less than 29 weeks will have a persistent PDA by the end of the first week of age. PDA is associated with several morbidities and mortality; however, a cause-and-effect relationship between the presence of a PDA and important short- and long-term clinical outcomes has never been definitively established. In addition, due to limitations in study design of randomized control trials and the retrospective nature of cohort studies reporting clinical outcomes, the impact of various approaches to treatment (conservative, medical, and surgical) on outcomes is unclear. As a result, treatment strategies (particularly modality and timing) vary between centers.
Developmental Role of the Ductus Arteriosus
The ductus arteriosus (DA) connects the main pulmonary artery to the descending aorta and is necessary for fetal survival. In the fetus the left ventricle receives oxygenated blood, returning from the placenta via the inferior vena cava and through the foramen ovale, and delivers it mainly to the upper part of the body. The right ventricle receives the majority of blood draining from the superior vena cava (SVC) and a proportionately lower amount of oxygenated blood from the umbilical venous system. Due to high pulmonary vascular resistance (PVR), the majority (80% to 90% depending on the gestational age of the fetus) of right ventricular output flows from the pulmonary artery to the descending aorta across the DA; hence the DA modulates flow to the lower part of the body. Similarly, the patent foramen ovale (PFO) is the route which modulates the delivery of oxygenated blood to the head and neck. Following birth, there is a sudden rise in left ventricular afterload, resulting from the loss of the low resistance placental circulation. This is accompanied by the aeration of the lungs, resulting in a fall in PVR and an increase in pulmonary blood flow. This results in a change in the organ of gas exchange from the placenta to the lungs. The DA eventually closes (first functionally and then anatomically) over the subsequent days in term infants. However, in preterm infants the DA can remain patent for a prolonged period of time for a variety of reasons.
Regulation of Ductal Tone and Constriction
In term infants, closure of the PDA occurs within the first 48 hours after birth. Closure of the DA occurs in two phases. The first phase, “functional closure,” involves narrowing of the lumen within the first hours after birth by smooth muscle constriction and the second phase, “anatomic remodeling,” consists of occlusion of the residual lumen by extensive neointimal thickening and loss of muscle media smooth muscle over the next few days.
The rate and degree of initial “functional” closure are determined by the balance between factors (mediators, second messengers and channels, among others) that favor constriction (oxygen, endothelin, calcium channels, catecholamines, and Rho kinase) and those that oppose it (intraluminal pressure, prostaglandins [PGs], nitric oxide [NO], carbon monoxide, potassium channels, cyclic adenosine monophosphate [AMP], and cyclic guanosine monophosphate). PGs play a key role in the regulation of ductal tone, especially during the first few postnatal weeks. PGE 2 is the most important factor in the regulation of DA tone during fetal development and acts on G protein–coupled E-prostanoid receptors to maintain ductal patency. It is generated from arachidonic acid by cyclooxygenase-1 (COX-1) and COX-2, the COX component of PG-H 2 synthase, followed by peroxidation by the same enzyme complex and, finally, by the action of PGE synthase (see Chapter 23 ). COX-2 plays a major role in maintaining ductal patency during fetal life. The current approach to medical therapy exploits this mechanism by the use of nonselective COX inhibitors such as indomethacin and ibuprofen and also by the use of acetaminophen, a peroxidase inhibitor, to close the DA postnatally.
Low oxygen tension in the fetus is another important factor for maintaining ductal patency. Following birth, the rise in oxygen tension promotes an oxygen-mediated constriction which is facilitated by the inhibition of the potassium voltage channels (Kv channels) present on the ductal smooth muscle cells and function to keep the cells in a hyperpolarized state. The presence of oxygen leads to depolarization, which in turn activates L-type calcium channels, allowing an influx of calcium into the smooth muscle cells causing constriction. A countermechanism via the mitochondrial electron transport chain serves as the intrinsic oxygen-sensing mechanism which regulates this constrictive effect via formation of reactive oxygen radicals which inhibit Kv channels. Interestingly, in vitro studies using rings of human DA tissue incubated in relatively low oxygen tension conditions (to mimic conditions of prematurity) for several days selectively fail to constrict in response to oxygen. This may explain, at least in part, failure of the DA to close in preterm infants.
The fall in PG levels following birth (due to the loss of placental PG production and increase in its removal by the lungs), accompanied by the rise in oxygen tension promotes the functional closure of the DA over the first 24 to 48 postnatal hours. After functional DA closure is achieved, the smooth muscle cells migrate from the media to the subendothelial layer, leading to neointimal formation. Expansion of the neointima (by hyaluron, migrating smooth muscle cells, and proliferating endothelia) forms protrusions, or mounds, that permanently occlude the already constricted lumen. This process results in an interruption of the blood supply to the innermost cellular layer, resulting in hypoxia and cell death. The presence of intramural vasa vasorum is essential to ensure adequate provision of oxygen and nutrition to the thicker wall of the DA at term. During postnatal constriction, the intramural tissue pressure obliterates vasa vasorum flow in the muscle media. The ensuing ischemic and hypoxic insult inhibits local PGE 2 and NO production, induces local production of hypoxia-inducible factors (HIF) like HIF-1α and vascular endothelial growth factor (VEGF) (which play critical roles in smooth muscle migration into the neointima), and produces smooth muscle apoptosis in the muscle media. In addition, monocytes/macrophages adhere to the ductus wall and appear to be necessary for ductus remodeling.
Resistance to Ductal Closure in Premature Infants
In contrast, in preterm infants the DA frequently fails to constrict or undergo anatomic remodeling after birth. The incidence of persistent PDA is inversely related to gestational age. This is due to several mechanisms. The intrinsic tone of the extremely immature ductus (<70% of gestation) is decreased compared with the ductus at term. This may be due to the presence of immature smooth muscle myosin isoforms, with a weaker contractile capacity, and to decreased Rho kinase expression and activity. Calcium entry through L-type calcium channels also appears to be impaired in the immature ductus. In addition, the potassium channels, which inhibit ductus contraction, change during gestation from K Ca channels not regulated by oxygen tension to K V channels, which can be inhibited by increased oxygen concentrations. The reduced expression and function of the putative oxygen-sensing K V channels in the immature ductus appear to contribute to ductus patency in several animal species.
In most mammalian species the major factor that prevents the preterm ductus from constricting after birth is its increased sensitivity to the vasodilating effects of PGE 2 and NO. The increased sensitivity of the preterm ductus to PGE 2 is due to increased cyclic AMP signaling. There is both increased cyclic AMP production, due to enhanced PG receptor coupling with adenylyl cyclase, and decreased cyclic AMP degradation by phosphodiesterase in the preterm ductus. As a result, inhibitors of PG production (e.g., indomethacin, ibuprofen, mefenamic acid, paracetamol) are usually effective agents in promoting ductus closure in the premature infant. Premature infants also have elevated circulating concentrations of PGE 2 due to the decreased ability of the premature lung to clear circulating PGE 2 . In the preterm newborn, circulating concentrations of PGE 2 can reach the pharmacologic range during episodes of bacteremia and necrotizing enterocolitis and are often associated with reopening of a previously constricted DA.
Little is known about the factors responsible for the changes that occur with advancing gestation. A recent study showed advancing gestation alters gene expression in pathways involved with oxygen-induced constriction, contractile protein maturation, tissue remodeling, and PG and NO signaling. Prenatal administration of glucocorticoids significantly reduces the incidence of PDA in premature humans and animals. Although postnatal glucocorticoid or corticosteroid administration also reduces the incidence of PDA, glucocorticoid (dexamethasone) or corticosteroid (hydrocortisone) treatment, especially if it is given in the immediate postnatal period or combined with administration of COX inhibitors, respectively, has been associated with increased incidence of several other neonatal morbidities. The patient’s genetic background also seems to play a significant role in determining persistent ductus patency. Several single nucleotide polymorphisms in candidate genes have been identified that are associated with PDA in preterm infants: angiotensin receptor (ATR) type 1, interferon γ (IFN-γ), estrogen receptor-alpha PvuII, transcription factor AP-2B (TFAP2B), PGI synthase, and TRAF1. Studies suggest that an interaction between preterm birth and TFAP2B may be responsible for the PDAs that occur in some preterm infants: TFAP2B is uniquely expressed in ductus smooth muscle and regulates other genes that are important in ductus smooth muscle development. Mutations in TFAP2B result in patency of the DA in mice and humans and TFAP2B polymorphisms are associated with the PDA in preterm infants (especially those that are unresponsive to indomethacin). Expression of SLCO2A1 and NOS3 genes (involved with PG reuptake/metabolism and NO production, respectively) is decreased in the DA from non-Caucasians. This may lead to an increase in PG and decrease in NO concentrations, thereby making ductal patency more PG dependent and possibly explaining the clinical finding of a better response to indomethacin in non-Caucasians.
Neointimal mounds are less well developed and often fail to occlude the lumen in preterm infants (especially those born before 28 weeks’ gestation). The preterm ductus is a much thinner vessel than the full-term ductus; therefore there is no need for vasa vasorum because the vessel wall is nourished with oxygen via diffusion through luminal blood flow (vasa vasorum first appear in the outer ductus wall after 28 weeks’ gestation when the vessel wall thickness increases beyond 400 μm). As a result, unless the ductus lumen is completely obliterated, the preterm ductus is less likely to develop profound hypoxia as it constricts after birth. Without a strong hypoxic signal, neointimal expansion is markedly diminished, resulting in mounds that fail to occlude the residual lumen.
Pathophysiologic Continuum of the Ductal Shunt in Preterm Infants
During fetal life, low systemic vascular resistance (SVR) due to the low resistance placenta, combined with elevated PVR result in pulmonary artery–to-aorta (“right-to-left”) flow across the DA. During normal neonatal transition, increased SVR associated with umbilical cord clamping occurs in parallel to a longitudinal decrease in PVR precipitated by ventilation and increase in pulmonary blood flow. The degree of right-to-left ductal shunt decreases to equally bidirectional within 5 minutes of birth, becomes mostly left to right by 10 to 20 minutes, and entirely left to right by 24 hours of age.
In preterm neonates the size and direction of the ductal shunt will have a variable impact on pulmonary and systemic hemodynamics. The shunt may be conceptualized within a physiologic continuum between life-sustaining conduit, neutral bystander, and pathologic entity. In infants with critical congenital heart disease, patency of the DA may be necessary to support pulmonary (e.g., tricuspid atresia) or systemic (e.g., critical aortic stenosis) blood flow. In severe persistent pulmonary hypertension of the newborn (PPHN), the postnatal failure of pulmonary arterioles to relax (e.g., due to asphyxia, respiratory distress syndrome) results in high PVR and persistence of a right-to-left ductal shunt. The latter shunt may reduce right ventricular afterload and support postductal systemic blood flow, albeit with deoxygenated blood. A bidirectional shunt in milder cases of PPHN may play a neutral role, merely permitting the noninvasive estimation of the systemic-pulmonary pressure gradient.
If the DA remains patent after birth, preterm infants who experience the expected fall in PVR may be susceptible to the effects of a large systemic-to-pulmonary (left-to-right) shunt. Blood flows across the PDA continuously in systole and diastole, resulting in volume overload of the pulmonary artery, pulmonary veins, and left heart. Shunt volume (Q) is directly proportional to the fourth power of the ductal radius (r) and the aortopulmonary pressure gradient <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='(ΔP)’>(??)(ΔP)
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Increased pulmonary blood flow (termed pulmonary overcirculation) may lead to alveolar edema, reduced pulmonary compliance, and increased need for respiratory support. Increased blood flow to the left heart results in dilatation and increased end-diastolic pressures in the left ventricle and atrium. In the setting of immature diastolic function present in preterm infants, the increase in end-diastolic pressure can significantly contribute to the evolution of pulmonary venous hypertension and pulmonary hemorrhage (see later discussion). The increase in pulmonary blood flow occurs at the expense of systemic blood flow. Left-to-right shunting across the PDA (referred to as ductal steal) will lead to systemic hypoperfusion that may result in organ dysfunction. In addition, ductal steal from the descending aorta associated with a PDA, shorter diastolic (and coronary perfusion) times due to tachycardia, and increased myocardial oxygen demand may result in subendocardial ischemia. This pathophysiologic cascade is thought to explain, at least in part, the relation between a PDA and adverse outcomes.
Myocardial Adaptation in Preterm Infants to Patent Ductus Arteriosus
Cardiac output is the result of the interactions between preload, afterload, intrinsic myocardial contractility, and heart rate. Under normal conditions and in the absence of a PDA, the left cardiac output of a neonate is in the range of 150 to 300 mL/kg/min. The presence of a PDA results in increased pulmonary blood flow and left atrial (LA) volume and a resultant increase in left ventricular preload. Studies have consistently shown a higher left ventricle end-diastolic volume (preload) when the DA is open with a predominantly left-to-right shunting pattern. According to the Starling curve, the increase in myocardial muscle fiber stretch from higher preload augments stroke volume. Indeed, most studies have demonstrated a significantly increased left ventricular output (LVO) in the presence of a PDA with predominantly left-to-right shunting. In the presence of a PDA, the low-resistance pulmonary vascular bed is in parallel with the systemic vascular bed. This results in a reduction of left ventricle afterload, which, in combination with the increased preload, enhances the myocardium’s ability to increase its stroke volume. However, in the clinical setting the presence of a PFO alters the effects of a PDA on left ventricular stroke volume by decompressing the left atrium.
There are significant differences in both the structure and function of the myocardium between preterm and term neonates, and older children and adults. These differences place the immature myocardium at a disadvantage as far as contractility is concerned. Furthermore, because coronary blood flow takes place primarily during diastole, myocardial performance might be adversely affected if diastolic blood pressure is low in the presence of a PDA. Some early studies suggested that myocardial ischemia may occur in the presence of a hemodynamically significant PDA (hsPDA). More recently, studies have demonstrated compromised coronary artery perfusion and the presence of high cardiac-specific troponin levels (indicative of myocardial damage) in the presence of a PDA, suggesting a detrimental effect on myocardial perfusion and potential ischemia.
Some authors have suggested that because higher preload is associated with a greater stretch of myocardial fibers, myocardial contractility should increase in the presence of a PDA, along with the increased LVO. They speculate that a lack of change in myocardial contractility, in the presence of a PDA, indicates deterioration of myocardial function. However, using a relatively load-independent measure of myocardial contractility, Barlow et al. showed that hsPDA had no effect on contractility. More recent studies, using more advanced functional parameters such as strain, have also failed to demonstrate worsening function in the presence of the PDA. Preservation of left ventricular function occurs despite significant changes in left ventricle morphology over the first 4 postnatal weeks. This includes an increase in LA volume, left ventricle end-diastolic volume, left ventricle sphericity index (indicating a more globular heart), and left ventricle filling pressure.
The potential impact that a PDA has on right ventricular function remains poorly understood. Changes seen in the left ventricle are a consequence of pulmonary overcirculation described previously. Conversely, systemic hypoperfusion may result in a reduction in the right ventricle preload (even in the presence of a left-to-right PFO shunt). In addition, prolonged exposure to increased pulmonary blood flow may promote an increase in PVR and a resultant increase in right ventricular afterload. Recent studies have demonstrated reduced right ventricular function evident as early as day 7 in infants with a large PDA. The clinical relevance of these changes to left or right ventricle function and morphology and their potential impact on the evolution of PDA-associated morbidities is currently unknown.
Effects of Patent Ductus Arteriosus on Blood Pressure
Blood pressure is the product of the interaction between cardiac output and peripheral vascular resistance (see Chapter 3 ). In general, systolic blood pressure is primarily affected by changes in stroke volume, whereas diastolic blood pressure is mainly reflective of changes in peripheral vascular resistance. Traditionally, low diastolic blood pressure has been considered the hallmark of an hsPDA and many studies have supported this notion. Studies that specifically looked at the relationship between blood pressure and PDA have shown similar decreases in both systolic and diastolic blood pressure (and therefore no change in the pulse pressure), at least during the first postnatal week. Infants born at weights between 1000 and 1500 g with a PDA have slight, but nonsignificant, decreases in systolic, diastolic, and mean blood pressures. In contrast, infants born at less than 1000 g and with a PDA have significantly lower systolic, diastolic, and mean blood pressures but no change in pulse pressure. Because stroke volume increases and vascular resistance decreases in the presence of a PDA, one might expect that systolic blood pressure be maintained despite the decrease in diastolic pressure. Unfortunately, cardiac output, ductal shunt volume, and peripheral resistance were not measured in any of these studies, making it difficult to determine the cause for the lack of a wide pulse pressure. In immature animals a decrease in the diastolic and mean blood pressure occurs even when the shunt is small, whereas a significant decrease in systolic blood pressure occurs only when the PDA shunt is moderate or large. In a more recent cohort of 141 preterm infants less than 29 weeks’ gestation, systolic blood pressure in infants with a PDA by the first postnatal week was only slightly lower than those without a PDA. However, diastolic and mean blood pressure were lower by the end of the first postnatal week, which translates into a higher pulse pressure ( Fig. 22.1 ). In this group, LVO was higher and diastolic flow in systemic vessels was lower, possibly explaining those findings ( Fig. 22.2 ). PDA may also contribute to development of hypotension, even during the transitional period, a time period when high-volume ductal shunts are thought to be uncommon. A study found evidence for a possible role of a moderate-large PDA in vasopressor-dependent hypotension. Similarly, PDA is reported to be an independent risk factor for refractory hypotension.
Effects of a Hemodynamically Significant Patent Ductus Arteriosus on Organ Perfusion
Despite the ability of the left ventricle to increase its output in the face of a left-to-right ductus shunt, organ blood flow distribution is significantly altered. Interestingly, redistribution of systemic blood flow occurs even with small shunts. Blood flow to the skin, bone, and skeletal muscle is most likely to be affected first by the left-to-right ductal shunt. The organs affected thereafter are the gastrointestinal tract and kidneys, due to a combination of decreased perfusion pressure (ductal steal) and localized vasoconstriction (compensatory measure). Indeed, mesenteric blood flow is decreased in both fasting and fed states in the presence of a PDA. Significant decreases in blood flow to these organs may occur before there are signs of left ventricular compromise. In addition, treatment strategies used to facilitate closure of the PDA, such as indomethacin, may have an effect on organ blood flow independent of the hemodynamic changes associated with the presence of an hsPDA.
Although cerebral blood flow (CBF) has also been assessed by near-infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI) (see later and Chapter 16 ), blood flow velocity, measured by the Doppler technique, has been the most frequently used technique to assess changes in organ blood flow in the human neonate. In animal models, organ blood flow has also been measured by the microsphere technique or direct flow measurements. As discussed in Chapter 16 in detail, each of these techniques has significant limitations. Unfortunately, it is not currently feasible to continuously measure absolute blood flow to different organs in human neonates.
Using the Doppler technique with ultrasonography, the amount of blood flowing through a vessel is a function of the vessel diameter (cross-sectional area) and mean blood flow velocity. Because of the small size of the neonatal vessels (e.g., anterior cerebral artery [ACA] or middle cerebral artery [MCA]), accurate measurement of vessel diameter is not possible. In addition, the Doppler technique assumes that the diameter of the vessel remains constant during the cardiac cycle, a notion that has been repeatedly challenged. Despite these limitations, Doppler velocity measurements and velocity-derived indices have been shown to have acceptable correlations with more invasive measures of organ blood flow. The most commonly used Doppler indicators of organ blood flow are systolic, diastolic, and mean blood flow velocities, velocity time integral, pulsatility index (PI), and resistive index (RI). Because the PI and RI are inversely related to flow, and directly related to vascular resistance, an increase in the PI or RI indicates a reduction in organ blood flow and/or an increase in the vascular resistance of the organ.
Cerebral Blood Flow
Although some studies suggest that CBF is maintained in the presence of an hsPDA, most studies have shown a decrease in flow and a disturbance in cerebral hemodynamics. Furthermore, indomethacin, one of the drugs used for pharmacologic closure of the PDA, has a direct, albeit, transient vasoconstrictive effect on the cerebral circulation, which is likely independent of the drug’s effect on the COX enzyme.
Using the Doppler technique, Perlman et al. demonstrated a decrease in diastolic blood flow velocity in the ACA of preterm infants in the presence of hsPDA. Similarly, Lemmers et al. reported that an hsPDA had a negative impact on cerebral oxygenation that resolved after treatment with indomethacin. Investigators have also observed retrograde diastolic flow and increased PI in the ACA in the presence of a PDA. In contrast, Shortland et al. found no difference in ACA CBF velocity between infants with or without a PDA ; however, they did report that there was a higher incidence of periventricular leukomalacia (PVL) in the subgroup of infants with retrograde blood flow in the ACA. A study showed progressive reduction in MCA end-diastolic flow velocity during the first postnatal week in extremely preterm infants. These changes sharply contrasted to those without a PDA in whom the velocity progressively increased. Correlations between a hsPDA (assessed by the left atrial-to-aortic (LA:AO) ratio) and both end-diastolic velocity and RI in the ACA have also been made in very low birth weight (VLBW) infants. These data suggest that CBF progressively decreases as left-to-right shunts across the PDA become larger. In preterm lambs and humans, CBF is maintained at a constant level in the presence of a PDA, as long as LVO is increased. It appears that the increase in cardiac output, at least to a certain point, ensures adequate cerebral perfusion (albeit with an altered pattern) in patients with a PDA. Indeed, Baylen et al. reported a decrease in CBF when cardiac output was compromised in preterm lambs with a PDA.
Furthermore, a significant PDA is an independent predictor of low SVC flow (a surrogate for systemic blood flow and perhaps CBF) in preterm infants. The effect of a PDA on SVC flow appears isolated to the first 12 hours after birth (when the myocardium has not yet adjusted to the postnatal increase in afterload). Even in the term neonate during the first few minutes after birth, the rapid change in ductal shunting to a left-to-right pattern may affect CBF, as suggested by the strong inverse relationship between net left-to-right ductal shunting and MCA mean velocity. This finding supports the notion that absence of a compensatory increase in cardiac output may be, at least in part, responsible for the low CBF associated with a PDA in preterm neonates.
Superior Mesenteric and Celiac Artery Blood Flow
Intestinal hypoperfusion is a known risk factor for necrotizing enterocolitis (NEC). Studies evaluating blood flow to the abdominal organs in general, and to the superior mesenteric artery (SMA) in particular, have uniformly demonstrated a decrease in blood flow in the presence of a hsPDA. Diastolic flow reversal in the descending aorta has been reported as early as 4 hours after birth; flow reversal can be seen in 34% and 46% of very preterm infants with a large PDA, at 12 and 24 hours after birth, respectively. In addition, administration of indomethacin appears to directly reduce not only CBF but also intestinal blood flow.
Studies using preterm lambs, during the first 10 hours after delivery, demonstrate that even small ductal shunts (those <40% of the LVO) cause significant reductions in blood flow to the abdominal organs. The decrease in organ blood flow occurs despite significant increases in cardiac output and is due to the combined effects of decreased perfusion pressure and localized vasoconstriction. Similar findings were also reported by other investigators. In premature primates, mesenteric blood flow is decreased in both fasting and fed states in the presence of a PDA. Despite the changes in blood flow, oxygen consumption in the terminal ileum appears to be unaffected by the presence of a PDA in preterm lambs.
Similar findings have been reported in premature human infants. Martin et al. reported retrograde diastolic flow in the descending aorta of preterm infants with a large PDA, which resolved after closure of the DA. Similarly, Deeg et al. and Coombs et al. demonstrated a decrease in both the systolic and diastolic blood flow velocities in the SMA and celiac artery in preterm infants with a PDA. The diastolic blood flow abnormalities appeared to be greater in the SMA. Using ultrasound, Shimada et al. assessed left cardiac output and abdominal aortic blood flow in VLBW infants before and after ductal closure and compared the findings with those obtained in patients without a PDA ( Fig. 22.3 ). Despite a higher left ventricular cardiac output in the PDA group, blood flow in the abdominal aorta was lower in the PDA group than in the controls. Abdominal aortic blood flow increased significantly after ductus closure. These changes in intestinal perfusion have led to concerns when feeding infants with a PDA.