(Circulation. 1996;93:826-833.)
© 1996 American Heart Association, Inc.
Articles |
Assessment of Flow Events at the Ductus VenosusInferior Vena Cava Junction and at the Foramen Ovale in Fetal Sheep by Use of Multimodal Ultrasound
From the Division of Pediatric Cardiology and the Cardiovascular Research Institute, University of California at San Francisco.
Correspondence to Norman H. Silverman, MD, Room M 342A, Box 0214, University of California San Francisco, San Francisco, CA 94143. E-mail norman silverman@pedcardgateway.ucsf.edu.
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Abstract |
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Background Previous techniques for the study of the fetal circulation did not permit assessment of phasic events associated with the cardiac cycle. We used multimodal ultrasound techniques to examine flow events that occur in the major veins and across the foramen ovale in the circulation of the fetal lamb.
Methods and Results We studied eight fetal lambs instrumented with catheters in the superior and inferior venae cavae and a peripheral umbilical vein and performed ultrasound studies that included M-mode and two-dimensional imaging, pulsed and Doppler color flow ultrasound, and contrast echocardiography to evaluate flow in the ductus venosus, in both venae cavae, and through the foramen ovale. Two blood streams of different flow velocities were identified within the cephalic portion of the inferior vena cava. The stream that originated from the narrowed ductus venosus had a higher velocity than that from the caudal inferior vena cava (mean velocity, 57±13 versus 16±3 cm/s; P<.0002). Facilitated by the eustachian valve and the septum primum, the ductus venosus stream preferentially passed through the foramen ovale to the left atrium. This flow occurred during most of the cardiac cycle, except for 19.6±2.3% of the cycle when the foramen ovale was closed during atrial contraction. Superior vena cava flow passed almost exclusively into the right atrium and tricuspid valve; a small amount that was refluxed from the right atrium into the inferior vena cava subsequently passed through the foramen into the left atrium.
Conclusions Visualization of fetal circulatory streaming at the venous sites by ultrasound techniques aids in understanding the function of the fetal circulation and may be helpful in detecting the human fetus that is hemodynamically compromised.
Key Words: echocardiography, fetal • blood flow • ultrasonics • valves
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Introduction |
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The requirement for the fetus to obtain its oxygen and nutrient supply from the placenta instead of from the lungs and gastrointestinal tract, respectively, demands several morphological and functional features in the cardiovascular system that are distinct from the postnatal situation. Because of difficulties in gaining access to the fetus, most studies of the course of fetal circulation have been performed in fetal lambs. In the early studies of Lind1 and Barclay et al,2 contrast radiographic techniques were used, and more recently, the course and distribution of the circulation in the fetal lamb were examined by use of radionuclide-labeled microspheres.3 4 The disadvantage of these techniques is that it is difficult or impossible to examine phasic events during the cardiac cycle.
Oxygenated blood that returns from the placenta via umbilical veins mixes with venous blood in the inferior vena cava and atrium, but several investigators5 6 7 have described preferential streaming of venous blood flows in the lamb fetus, which would favor distribution of well-oxygenated blood to the heart and brain. Recently, considerable attention has been directed to the examination of patterns of venous blood flow in the major fetal channels, with the premise that analysis of the changes may be useful in the detection of fetal distress. Ultrasound examination with Doppler interrogation of the ductus venosus and inferior vena cava in the human fetus has been successful in defining flow patterns in the major venous returns in the human fetus, but it is difficult to correlate changes with specific fetal difficulties.
We examined the use of multimodal ultrasound techniques to define patterns of venous flow in lamb fetuses as a prelude to examining the effects of various types of fetal distress on phasic flows and velocity.
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Methods |
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Animal Preparation
We studied the fetuses of eight mixed Western breed ewes (weight, 3.5±0.5 kg) at a mean gestational age of 136±3 days (term, 150 days). The fetuses were surgically prepared before the ultrasound study in accordance with the guidelines of the Committee on Animal Research at our institution. Epidural anesthesia was achieved in the ewes with use of 1% tetracaine hydrochloride. Polyvinyl catheters (1.27-mm ID) were inserted into a maternal pedal artery and vein. Dextrose (10% in 0.9% NaCl) was infused at a rate of 3 mL/min, and ketamine hydrochloride (100 mg IV) was administered repeatedly every 10 to 15 minutes for sedation.
With the ewe in the supine position, the uterus was exposed through a midline incision. A small hysterotomy was performed and a hindlimb exposed. All fetal surgery was performed under local anesthesia with 0.5% lidocaine hydrochloride. Polyvinyl catheters (0.76-mm ID) were inserted into the anterior tibial vessels and advanced to the lower inferior vena cava and descending aorta. Through a separate uterine incision, the neck was exposed and a catheter was placed into the jugular vein and advanced to the superior vena cava. The umbilical vein was cannulated via a peripheral cotyledonary vein and a catheter was advanced toward the fetus. A fetal ECG was obtained by placing electrodes on the uterus for monitoring of fetal heart rate and timing of events. All incisions were closed and the animal was prepared for the ultrasound study. Fetal relaxation was accomplished with succinylcholine 5 mg IV given every 20 to 30 minutes. Previous studies in our laboratory have shown the hemodynamic effects of succinylcholine to be minimal.
Ultrasound Studies
Ultrasound studies were performed with an
Acuson 128 XP-10
instrument with 3- and 5-MHz transducers placed directly on the closed
uterus as reported previously,8 9 thus providing the
opportunity for exquisite imaging and Doppler flow observations.
The following areas and vessels of the fetal circulatory system were
evaluated: the umbilical vein; the ductus venosus and hepatic veins;
the inferior vena cava; the right and left atrial area,
including the atrial septum and foramen ovale; the superior vena cava;
and the ventricles in four-chamber and short-axis planes.
Initially, sector scanning of all of these structures was performed to
identify clearly the intra-abdominal course of the umbilical vein,
the junction of the ductus venosus with the inferior vena
cava, and structures at the level of the foramen ovale.
Doppler interrogation was performed with the system set in the lower-frequency mode (3 MHz). For color flow imaging, the Nyquist limit was varied, and it was frequently lowered to the lowest possible limit to identify low-velocity flow signals and the temporal interrelation of the signals. Pulsed Doppler interrogation was performed at the specific sites mentioned above. In the ductus venosus and inferior vena cava area, the spectral Doppler display was recorded in the ductus venosus just proximal to the inferior cava, as well as in the caudal and cephalic inferior vena cava. In addition, we obtained umbilical venous signals within the umbilical cord and within the fetal abdomen. Pulsed Doppler interrogation was also performed within the left atrium at the site of the foramen ovale. For velocity measurement, an angle-correction factor, based on the cosine of the angle between interrogation and flow, was introduced when the angle was >15°.
M-mode signals were obtained from the region of the foramen ovale to define the venous valves and the nature of the valvar mechanism of the foramen ovale as clearly as possible. The modality of Doppler with M-mode and Doppler color flow (M-mode Doppler flow display) was used to attempt to define the spatial distribution as well as the velocity of flow and the timing of events.
Contrast echocardiography was performed through the umbilical venous and the inferior vena caval and superior vena caval catheters to examine the flow streaming patterns. As performed postnatally,10 we injected 0.25 to 2 mL of agitated 0.9% saline mixed with a small quantity of fetal blood that was withdrawn from the femoral arterial line. All studies were recorded on videotape (0.5-in Super VHS) for later playback and analysis.
Data Analysis and Statistics
Analysis of the ultrasound
studies was performed with a
Prism Imaging cardiac workstation. From pulsed Doppler
recordings, four to six consecutive cardiac cycles were used
and the measurements were averaged. Maximal velocities at systole,
early diastole, and late diastole (atrial
contraction) as well as mean velocity were measured and corrected for
angle of incidence when >15°. There was no attempt to account for
such deviations in the azimuthal plane. The cardiac cycle length was
measured from ECG recordings, and the periods of zero flow at
the foramen ovale were measured from Doppler recordings. To
define the phasic flow events at the junction of the ductus venosus and
inferior vena cava, pulsed Doppler, Doppler color
flow mapping, and contrast echocardiography proved
to be most valuable. All values are given as mean±SD. Velocities at
the ductus venosus and the inferior vena cava were compared
by paired Student's t test, and a value of
P<.05 was considered to indicate a significant
difference.
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Results |
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Ductus Venosus–Inferior Vena Cava Junction
All fetuses were in a stable condition at the beginning of the study, with an arterial pH of 7.36±0.05 and a heart rate of 185±17 beats per minute. In several fetuses, two or, less frequently, only one venous valve was identified at the junction between the inferior vena cava and ductus venosus (Fig 1
). In
addition, occasional venous valves were seen
within the inferior vena cava that were separate from the
eustachian valve (valve of the inferior vena cava) within
the right atrium. These venous valves were not rigid but rather moved
with the flow and facilitated separation of the streams of blood flow
that originated from the ductus venosus and the inferior
vena cava, respectively.
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The flow in the intra-abdominal part of the
umbilical vein had a
flat profile and a mean velocity of 30±3 cm/s (Fig 2).
Two separate streams within the cephalic inferior vena cava
were observed in all animals and could be identified by pulsed
Doppler, Doppler color flow mapping, and contrast
echocardiography (Figs 2 through
4). The stream that originated
from the
ductus venosus entered the inferior vena cava on its left
and posterior aspect and tended to spiral in the vena cava in such a
way that it encountered the eustachian valve and the crista dividens
(superior crest of the foramen ovale) and was then preferentially
directed toward the left atrium (Fig 3). Contrast
echocardiograms with
saline administered into the inferior vena cava or the
umbilical vein defined a much higher proportion of blood arriving in
the left atrium from the ductus venosus than from the
inferior vena cava, although there was some distribution to
both atria from both of these sources. Blood flow in the left hepatic
vein was identified in five animals by pulsed Doppler ultrasound;
the flow velocity was similar to that in the caudal
inferior vena cava before the ductus venosus entry. Caudal
inferior vena caval flow had a pulsatile nature, with a
nadir just after the A wave and a mean velocity that averaged 16 cm/s
(Fig 4) (Table). The flow within the ductus
venosus was
also pulsatile, but its velocity was significantly higher, especially
in late diastole (Table), whereas the flow profile within
the intra-abdominal part of the umbilical vein was flat and the
mean velocity was lower than in the ductus venosus (Table).
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Phasic Atrial Events
The functional mechanism of the foramen
ovale was characterized by
a parallel movement of the septum primum (flap valve of the foramen
ovale) and of the eustachian valve noted on two-dimensional
echocardiography in all animals (Figs 5 and 6).
The temporal and topical
relationships between these two structures was displayed best with
M-mode echocardiography. With the onset of
ventricular systole, the flap valve of the foramen ovale
moved into the left atrial cavity and rapidly reached a peak distance
away from the atrial septum during early systole, whereas the
eustachian valve moved toward the atrial septum and remained apposed to
it throughout ventricular systole (Figs 5 and
7). Together with the crista dividens, the eustachian
valve appeared to form a conduit within the right atrium that directed
inferior vena caval blood directly into the left atrium and
prevented the flow from the superior vena cava from crossing into the
left atrium. The extension of this conduit within the left atrium was
formed by the foramen ovale and septum primum flap valve (Figs
5 and 8). However, late in ventricular
diastole, in association with atrial contraction, the flap
valve moved to apposition with the foramen, functionally closing it for
a period that lasted for 19.6±2.3% of the entire cardiac cycle length
(Fig 8), while the eustachian valve moved toward a position
against the
right atrial wall (Figs 5 and 6). M-mode color
flow mapping at the
region of the oval fossa also displayed the abrupt cessation of flow
into the left atrium during atrial contraction but with recommencement
of flow across the foramen early in systole (Fig 8).
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From analysis of the saline contrast injections, it was evident
that most of the superior vena cava flow was directed to the right
ventricle, but a small portion also reached the left atrium. The atrial
septum–eustachian valvar mechanism was overcome by a reflux of
blood from the superior vena cava into the inferior vena
cava and by its subsequent shunting across the foramen ovale together
with the inferior vena caval flow (Fig 9).
Saline contrast injections performed through a peripheral
umbilical vein catheter showed that a far greater amount of
microcavitations reached the left than the right atrium, indicating a
separation of streams and site of delivery of the inferior
caval blood (Fig 2
). The contrast method, although it delimits
specific
flow streams, does not provide a precise quantitation of flow.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Patterns of blood flow in the fetus have been defined by angiographic studies1 2 and, more recently, by the use of radionuclide-labeled microspheres.3 These studies confirmed that almost all of the superior vena caval blood is directed through the tricuspid valve into the right ventricle, and inferior vena caval blood is partly distributed through the foramen ovale and partly through the tricuspid valve. Because the inferior vena cava receives blood from the umbilical veins through the ductus venosus and hepatic circulation, it had been thought that these patterns of flow explained the higher oxygenation of blood in the ascending aorta derived from the left ventricle as compared with blood in the descending aorta derived from the right ventricle via the ductus arteriosus. Subsequently, with the labeled microsphere technique, it was shown that ductus venosus blood, which is derived almost exclusively from the umbilical venous return, is distributed preferentially through the foramen ovale, whereas blood from the caudal inferior vena cava is directed preferentially through the tricuspid valve.5 6 11 This would tend to increase the oxygen content of ascending aortic blood. The mechanisms whereby both the selective streaming of superior vena caval blood and the preferential streaming of inferior vena caval and ductus venosus blood result have not been defined.
With ultrasound techniques, it had been suggested that in the human fetus, ductus venosus blood first enters the right atrium and then crosses into the foramen ovale by transatrial flow.12 13 14 However, Kiserud et al15 clearly showed by Doppler color flow techniques that ductus venosus blood streams directly through the inferior vena cava and into the left atrium through the foramen ovale in the human fetus. In our studies in the sheep fetus, we have shown clearly, both by contrast echocardiography and by Doppler color flow, that there are two distinct flow streams in the intrathoracic portion of the inferior vena cava. The ductus venosus stream follows the posterior and left aspect of the vena cava and is predominantly directed through the foramen ovale, whereas the caudal inferior vena cava stream passes anteriorly and to the right in the thoracic segment of the vena cava and preferentially allows flow into the right atrium.
The mechanisms that account for this streaming in the inferior vena cava have not yet been identified. We reported11 16 the presence of a membranous valve over the joint orifice of the ductus venosus and left hepatic vein at their entrance into the inferior vena cava and postulated that this valve deflected ductus venosus blood in such a way as to direct it toward the foramen ovale. It had been proposed by Kiserud et al17 from studies of human fetuses that the streaming of ductus venosus blood was related to the very high velocity observed in the ductus venosus. They recorded peak velocities of 65 to 75 cm/s and suggested that this high velocity permitted the stream to remain separated from the low-velocity caudal inferior vena caval stream for the short distance to the foramen ovale.17 Indeed, we also noted the high velocity of ductus venosus flow in the sheep fetus, with a peak velocity of 69 cm/s compared with a caudal inferior vena cava velocity of 22 cm/s.
The high velocity of ductus venosus flow cannot be explained by the magnitude of flow alone. In the sheep, about 50% of umbilical venous blood, or about 100 mL/kg body wt per minute, flows through the ductus, whereas caudal inferior vena caval flow is about 80 mL·kg-1·min-1.3 Two other explanations have been provided. First, the ductus venosus is considerably more narrow than the caudal inferior vena cava; and second, the presence of a sphincter has been proposed to account for the high velocity. The presence of a sphincter had been postulated18 but was questioned,19 20 although some investigators had noted a sphincter in fetal lambs.21 Edelstone22 did not consider that an active contractile mechanism was present in the ductus venosus but felt that it adapted passively to flow changes. We clearly demonstrated,16 by means of silicone rubber injection into the veins, the presence of a circumferential constriction in the ductus venosus immediately adjacent to its origin from the common umbilical venous channels, and this could well account for the high velocity in the ductus venosus.
Although it is attractive, the hypothesis that the high velocity of ductus venosus blood is responsible for its preferential flow through the foramen ovale is not supported by other observations in fetal lambs. Experimental compression of the umbilical cord reduces umbilical venous return; although the proportion of umbilical venous blood that enters the ductus venosus versus the hepatic circulation is drastically increased, actual ductus venosus flow falls. Despite this reduction in flow, the difference in oxygen saturation between ascending and descending aorta is maintained.23 Even more striking is the fact that complete occlusion of the ductus venosus in fetal lambs had no effect on oxygen saturation in the ascending and descending aorta, indicating that a high velocity in the ductus venosus is not necessary to maintain fetal ductus venosus flow patterns.24
The difference in velocity of ductus venosus and caudal inferior vena caval blood in the cephalic portion of the inferior vena cava raises serious questions about the use of phasic or mean velocity in this region to assess alterations in fetal circulatory dynamics.25 The velocities are so heterogeneous, depending on position within the vessel, that changes may be recorded unrelated to flow. In fact, different velocities have been noted at various positions within the ductus venosus26 that may account for changes in ductus velocity unrelated to changes in flow.27 The use of Doppler color flow mapping should make it possible to measure each stream individually.
The other important mechanism that facilitates a higher oxygen
saturation in ascending compared with descending aortic blood is the
selective passage of superior vena caval blood through the tricuspid
valve into the right ventricle. Previously, it had been
proposed28 that superior vena caval blood is deflected by
Lower's tubercle toward the tricuspid valve. This tubercle resides on
the lateral aspect of the right atrium at the superior vena
cava–right atrial junction. We describe a novel mechanism that
accounts for the flow pattern and that relates to the dynamic
interaction between the eustachian valve and the flap valve of the
septum primum during the cardiac cycle. At the onset of
ventricular systole, in association with rapid
inferior vena caval blood flow, the septum primum valve
rapidly moves into the left atrium. Simultaneously, the
eustachian valve moves parallel with the septum primum valve in a
manner that tends to deflect the superior vena caval stream away from
the foramen ovale and thus to the tricuspid valve. This movement of the
eustachian valve in the same direction as the septum primum valve could
possibly be explained on the basis of a Bernoulli effect, because
velocity of blood flowing through the foramen ovale is high
(Table).
These positions of the eustachian and foramen ovale valves are
maintained throughout ventricular systole and most of
diastole but are reversed by atrial systole. With the onset
of atrial systole, forward flow in both the superior and
inferior venae cavae is curtailed, and there may even be a
momentary reversal in flow.25 In association with this,
the eustachian valve and septum primum flap move rapidly in parallel,
so that the septum primum tends to close the foramen ovale and the
eustachian valve moves away from the foramen ovale to a position closer
to the right atrial wall. This phase, which starts with the onset of
atrial systole and ends with the onset of ventricular
systole, occupies 
20% of the cardiac cycle.
Although most superior vena caval blood passes through the tricuspid valve, studies with microspheres have shown that a very small volume does cross the foramen ovale to the left atrium. The mechanism of this phenomenon has been defined by our study of contrast echocardiography with injections into the superior vena cava. During ventricular systole, superior vena caval blood flows exclusively through the tricuspid valve, but during atrial systole, we noted that some microbubbles that had been injected into the superior vena cava passed through the right atrium to the cephalic portion of the inferior vena cava and then, with the onset of ventricular systole, flowed through the foramen ovale into the left atrium.
Our studies have defined venous flow patterns and foramen ovale dynamics in the normal fetal lamb. From limited observations in the human fetus, it is apparent that the streaming of ductus venosus and caudal inferior vena caval blood is similar. Because the flow patterns are closely related to circulatory dynamics, they would almost certainly be influenced by cardiac arrhythmias and congenital cardiac anomalies, as well as by fetal conditions that influence the volumes and velocities of venous return in the major venous channels. Efforts should be directed to detailed analysis of these mechanisms in normal human fetuses and in fetuses with cardiovascular abnormalities.
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Acknowledgments |
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Dr Silverman was supported in part by Grant 900931 from the American Heart Association, Dallas, Tex.
Received May 31, 1995; revision received August 24, 1995; accepted October 6, 1995.
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