Blood velocity wave form characteristics of superior mesenteric artery and anterior cerebral artery before and after ductus arteriosus closure

EUROPEANJOURNAL OF

ELSEVIER

European Journal of Ultrasound 2 (1995) 183-189

Clinical paper

Blood velocity wave form characteristics of superior mesenteric artery and anterior cerebral artery before and after ductus arteriosus closure Frank van Bel *a Jaap Schipper b, Gerard L. Guit b, Margot van de

Bor a

aDepartment of Pediatrics, University Hospital of Leiden, Leiden, The Netherlands bDepartment of Diagnostic Radiology, University Hospital of Leiden, Leiden, The Netherlands Received 22 October 1994; revision received 29 March 1995; accepted 7 April 1995

Abstract

Objective: To investigate the blood supply to intestines and brain in the preterm newborn with hemodynamically important patent ductus arteriosus (PDA), and to assess its change after proven ductal closure using color Doppler imaging. Methods: Velocity wave forms of the anterior cerebral artery (ACA) and the superior mesenteric artery (SMA) were obtained before and 12 h after closure of PDA in 14 preterm infants. Results: During PDA, abnormal high peaksystolic blood flow velocities (PSFV) were found in the SMA but not in the ACA, with mostly negative or abnormally low end-diastolic flow velocities (EDFV) in both investigated arteries. In the six infants whose ductus eventually closed, PSFV and EDFV of the SMA normalized to reference values which was not the case in the eight infants whose ductus remained open. PSFV and EDFV values of the SMA were not different compared to pre-indomethacin levels. Temporal mean blood flow velocities of SMA and ACA, used as a relative measure of intestinal and cerebral blood flow, respectively, did not differ before and after ductus closure. Conclusion: These results suggest a compensatory increase of PSFV of SMA during PDA to maintain an adequate intestinal blood supply. Keywords: Neonate; Blood velocity; Cerebral artery; Mesenteric artery; Patent ductus arteriosus

1. Introduction Preterm infants who have a hemodynamic important left-to-right shunt through a patent ductus * Corresponding author, University Hospital Leiden, Department of Pediatrics, Neonatal Unit, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 262909; Fax: +31 71 248199.

arteriosus (PDA) are more likely to develop necrotizing enterocolitis (Kitterman 1986; Kliegman et al. 1993). This may result from a decreased blood flow due to a ductal run-off phenomenon which causes a retrograde blood flow during the diastolic phase of the cardiac cycle in the descending aorta and the limited ability of the intestinal vascular bed of these babies to respond

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F. van Bel et al./ European Journal of Ultrasound 2 (1995) 183-189

to this cardiovascular stress (Serwer et al. 1982, B6melburg and Jorch 1989; Kliegman et al. 1993). The main objective of the present study was to investigate the blood supply to the intestines during PDA and to assess its change after proven ductal closure. It is suggested that left-to-right shunting through a PDA predominantly orginates from the descending aorta (Rudolph et al. 1964; Spach et al. 1980). We therefore also simultaneously estimated cerebral blood flow. For investigation of changes in intestinal and brain blood supply, we used Color Doppler Imaging (CDI) which provides reliable depiction of the arterial vessels supplying these organs. This enabled reliable serial measurements of absolute blood flow velocity in these vessels for proper assessment of changes in actual blood flow (van Bel et al. 1993). 2. Patients and methods 2.1. Patients

Fourteen preterm infants consecutively admitted to our neonatal intensive care unit, of gestational age less than 33 weeks as determined by maternal dates of Ballard score (Ballard et al. 1979), were included in the study after informed parental consent. All infants were appropriate for gestational age and all had PDA. Infants with abnormalities, which could possibly alter blood flow velocity to brain and/or intestines other than PDA, or who used vasoactive drugs, were not included in this study. PDA diagnosis was based on clinical signs, radiographic characteristics and Doppler/echocardiographic evidence. All infants had the characteristic murmur, bounding pulses and hyperdynamic precordium, and Doppler echocardiographic investigation showed a diastolic reverse flow in the main pulmonary artery with a predominantly left-to-right flow through the ductus arteriosus. Body weights of the 14 infants ranged from 900 to 2030 g (mean + S.D.: 1161 ± 406); and gestational age ranged from 26 to 32 completed weeks (mean ± S.D.: 28.3 ± 2.5). The postnatal age ranged from 4 to 17 days; median 7 days. Twelve infants were artificially ventilated during the study period and could not be weaned from the ventilator. The ventilator set-

tings in these infants were not significantly changed during the study period. All infants were stable and did not develop necrotizing enterocolitis. The study was approved by the Scientific Board of the Department of Pediatrics. For bedside investigation of the blood supply to the organ systems to be investigated, a Philips Quantum I CDI System (Quantum Medical Systems, Issaquah, WI) with a 5 or 7.5 MHz transducer was used. The CDI system used in this study employs linear phased array transducers. Red cells moving toward the transducer were depicted as red; red cells moving away from the transducer were depicted as blue. The velocity scale was usually set at high or medium values because a low value leads to excessive frequency shifts, resulting in aliasing (Switzer and Nanda 1985). When possible the 7.5 MHz transducer was used because of the higher definition and more realistic images of the vascular anatomy. Changes in cerebral blood flow were derived from the blood flow velocity wave form of the anterior cerebral artery (ACA), a major intracranially situated artery (Batton et al. 1983). The ACA was visualized in the parasagittal plane using the anterior fontanelle as an acoustic window. The Doppler sample volume was then placed where the ACA curves around the genu of the corpus caUosum. In this case the angle between ultrasound beam and flow direction of the blood (angle of insonation) is negligible (Fig. 1A). Changes in intestinal blood flow were derived from the blood flow velocity wave form of the superior mesenteric artery (SMA), the artery predominantly supplying the intestines. Changes in blood flow in this vessel have been considered indicative for changes in bowel perfusion (van Bel et al. 1990a). The SMA is the second major branch of the abdominal aorta - - its origin is just below the celiac axis, from the ventral wall of the aorta. The proximal segment of the SMA usually has an anterior course, which allows Doppler insonation under a small angle of insonation when using a longitudinal abdominal approach (Fig. 1B). In both arteries the position of Doppler sample volume was further optimized by acoustic and visual control and the angle of insonation was

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185

measured by the angle menu. This enabled us to obtain a blood flow velocity wave form of maximal quality and to correct the signal for the cosine of the angle of insonation. During all Doppler investigations of the arteries, a minimum of 5-10 sequential homogeneous cardiac cycles of optimal quality were subjected to real-time spectral analysis. Peaksystolic flow velocities (PSFV), end-diastolic flow velocities (EDFV) and temporal mean flow velocities (TMFV - - the time-mean of the maximum flow velocity envelope curve) were determined and averaged in cm/s. The acoustic output of the CDI system was below 100 mW/cm 2 (spatial peak temporal average intensity) in all instances, but it was almost always much lower. During CDI investigations the infants were in a resting state, and positioned in anti-Trendelenburg. To exclude the possible influence of postprandial changes on intestinal blood supply, the infants were not fed orally (Quamar et al. 1984). The TMFV of the SMA and ACA were used as relative measures of blood supply to intestines and to the brain, respectively. Neonatal data were collected prospectively, pH and PaCe2 were obtained from an indwelling arterial catheter or from arterializexi blood samples. Arterial oxygen tensions were derived from continuous TcPO 2 measurements. Blood pressure measurements were made directly by an arterial pressure transducer or indirectly by an oscillometric method (Dinamap ®, Critikon, Tampa, Fl). When necessary, packed cell transfusions were given to keep the hematocrit above 40%.

A

2.2. Study design o

Fig. 1. CDi images of the investigated arteries. (a) Parasagittal CDI image of the brain depicting the anterior cerebral artery (ACA) and pericallosal artery (PCA). (b) Longitudinal CDI image through the upper abdomen depicting the descending abdominal aorta (DAo), the celiac axis (CA) and superior mesenteric artery (SMA). The arrowheads indicate the locations where the Doppler sample volume was placed in the arteries.

CDI investigations of the SMA and ACA were done just before and at 12 h after indomethacin treatment (0.1 mg/kg, iv). The rationale of this scheme was based upon earlier work, in which we found that an indomethacin-induced decrease of PSFV, EDFV and TMFV of ACA and SMA was not longer apparent at 12 h after indomethacin therapy (van Bel et al. 1989; van Bel et al. 1990b). Mean arterial blood pressure, hematocrit, pH and P a C e 2 were determined simultaneously with the CDI studies and heart rate and TcPO2 registered.

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At 12 h after indomethacin treatment, the attending pediatric cardiologist, who was unaware of the study results, assessed ductal closure using clinical signs and Doppler/echocardiographic examination. 2.3. Statistical analysis

Results are reported as means 4-S.D. Comparisons between two values were made using Student's t-test for paired or unpaired observations as appropriate. P-values of less than 0.05 were considered statistically significant.

3. Results In six infants the ductus eventually proved to be closed after treatment and in eight infants the ductus remained open. Mean arterial pressure, heart rate, pH, PaCO2, TcPO 2 and hematocrit were stable and showed no significant differences before and at 12 h after treatment with indomethacin. CDI gave instantaneous information of the flow direction in the investigated arteries. This revealed that before treatment a color conversion from red to blue occurred during the diastolic phase of the

A

B

Fig. 2. CDI imagesof the brain and upper abdomen of an infant with PDA. (a) CD1 revealed a color conversion from red during the systolicphase (SP) to blue during the diastolic phase (DP) in the anterior cerebral artery (ACA), indicating a retrograde blood flowwhich was confirmedby the velocitywaveform(seearrowheads). (b) CDI revealeda color conversionfrom red during the systolic phase (SP) to blue during the diastolic phase (DP) in the super mesenteric artery (SMA), indicating a retrograde blood flow which was confirmed by the velocitywaveform(see arrowheads).

F. van Be/et al./ European Journal of Ultrasound 2 (1995) 183-189

cardiac cycle in two patients in both investigated arteries, and only in the SMA and descending aorta in another three patients, indicating a retrograde blood flow during diastole (Fig. 2). After indomethacin treatment, the SMA and descending aorta still showed a color conversion during the diastolic phase in one patient. Fig. 3 shows the individual blood flow velocities (PSFV, TMFV and EDFV) in the ACA and SMA

ACA

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187

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Fig. 3. Peak-systolic (PSFV), temporal mean (TMFV) and enddiastolic (EDFV) blood flow velocities in the anterior cerebral artery (ACA) and superior mesenteric artery (SMA) before and at 12 h after treatment with indomethacin. Individual velocities (and means ± S.D.) of infants whose ductus closed are indicated by the closed circle, and those of infants whose ductus remained open are indicated by the open triangles.

60-

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30

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50-

403O

20

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I

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~I~ p < 0 . 0 5

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before and at 12 h after treatment with indomethacin. In the ACA, PSFV did not differ before and after ductal closure or between subgroups (closed ductus vs. open ductus). However, PSFV of SMA was significantly lower in infants whose ductus eventually closed, compared to their pre-indomethacin values. TMFV did not differ in any artery before or after treatment, nor were there differences between subgroups. EDFV values of both arteries in the infants whose ductus closed were significantly higher compared to pretreatment values, although the EDFV values of the infants whose ductus did not close also tended to increase. 4. Discussion

a

S

[

I

BEFORE

AFTER

In the present study, CDI enabled fast vessel identification, instantaneous information of flow

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direction and greatly facilitated Doppler sample volume placement. Regarding the use of pulsed Doppler ultrasound to assess true blood flow through the vessel under investigation, it must be stated that true artery blood flow can not be determined with this technique. However, both investigated vessels are large arteries and the internal diameters of these vessels will be relatively constant. Changes in resistance of their respective vascular beds will primarily occur in the more distally situated arterioles. TMFV values of the investigated arteries are therefore indicative for changes in their blood volume. In fact, Doppler ultrasound-derived measurements of volume blood flow in the SMA have been reported and validated in adults (Sato et al. 1987). Moreover, experimental and clinical studies in the ACA show a good correlation between Doppler derived TMFV and true cerebral blood flow (Batton et al. 1983; Greisen et al. 1984). Mandatory, however, for the calculation of the absolute blood flow velocity, is knowledge about the angle of insonation. The CDI technique provides reliable depiction of the vessel under investigation which enables proper Doppler insonation of the vessels and calculation of the angle of insonation. With these considerations in mind, we assumed that changes in TMFV of the SMA and ACA reflected changes in intestinal blood flow and brain blood flow, respectively. The abnormally high PSFV values during PDA in the SMA compared to reference values (van Bel et al. 1990b) and their subsequent normalization in those infants whose ductus eventually closed, confirmed earlier findings (Rudolph et al. 1964; Spach et al. 1980; van Bel et al. 1990). In an earlier study we found similar results investigating the renal arteries of preterm babies suffering PDA (van Bel et al. 1990c). We speculate that the high PSFV values represented a compensation mechanism. Diastolic run-off during the diastolic phase from the SMA to the descending aorta during PDA had been compensated by an increase in compliance of the vascular bed of the SMA, permitting a higher capacitance of the vessel. This speculation has been further supported by distinct patterns of the PSFV of the ACA. PSFV did not significantly change after ductal closure, as compared to the

PSFV during ductal patency. As demonstrated by several investigators, the blood shunting left-toright through a PDA predominantly originates from the descending aorta, resulting in a marked reduction of net flow down the descending aorta (Rudolph et al. 1964; Spach et al. 1980). The mechanism responsible for this phenomenon, favouring flow from the descending aorta, is thought to have been the orientation of the PDA and the higher vascular impedance in the trunk and lower extremities than in the head and arm (Spach et al. 1980). However, not all ductal steal originated from the descending aorta, which is demonstrated by abnormal low or even negative diastolic flow velocities (two patients) in the ACA during PDA. The tendency to higher EDFV values, in both SMA and ACA, in the infants whose ductus remained open, indicates a decrease in left-to-right shunt, probably because of an (incomplete) indomethacin-induced constriction of the ductus arteriosus. That indomethacin itself influenced the velocity values measured at 12 h after treatment is less likely. Earlier investigations showed that indomethacin had indeed a transient negative impact on cerebral blood velocity (van Bel et al. 1989), and on blood velocities in the SMA (van Bel et al. 1990b), but also that all velocities were not significantly different anymore at 2-4 h after the indomethacin medication. The present study using the CDI technique revealed that ductal steal, reflected in TMFV and EDFV, is similar in the SMA and ACA. But ductal steal seemed to influence PSFV of the two vascular beds differently. This may suggest that ductal steal predominantly occurred from the descending aorta. The increased PSFV values of the SMA demonstrated during PDA probably represented a compensation mechanism to warrant sufficient blood supply to the intestines. Although our data do not support the assumption that a PDAinduced ischemia of the intestines is related to the reported increased incidence of neonatal necrotizing enterocolitis, it is important to realize that all our patients were stable and were treated early to achieve quick closure of the ductus. A prolonged existence of PDA with cardiac decompensation and/or the influence of enteral feeding on intesti-

F. van Bel et al./ European Journal o f Ultrasound 2 (1995) 183-189

nal hemodynamics may affect compensatory mechanisms with respect to intestinal perfusion and may explain the reported increased evidence of necrotizing enterocolitis during PDA. References Ballard JL, Kazmaier-Novak K, Driver M. A simplified score for assessment of fetal maturation of newly born infants. J Pediatr 1979; 95: 769-774. Batton DC, Hellmann J, Hernandez MJ, Maisels MJ. Regional cerebral blood flow, cerebral blood velocity, and pulsatility index in newborn dogs. Pediatr Res 1983; 17:909-91 I. B6melburg, Joreh G. Abnormal blood flow patterns in renal arteries of small preterm infants with patent ductus arteriosus detected by Doppler ultrasonography. J Pediatr 1989; 148: 660-664. Greisen G, Johansen K, Ellison PH, Fredriksen PS, Mall J, Friss-Hansen B. Cerebral blood flow in the newborn infant: Comparison of Doppler ultrasound and t33Xenon clearance: J Pediatr 1984; 104:411-418. Kitterman J. Effects of intestinal ischemia. In: Moore TD, ed. Necrotizing enterocolitis in the newborn. Report of the 68th Ross Conference on Pediatric Research. Ross Laboratories, Columbus, Ohio, 1986; pp 38-40. Kliegman RM, Walker WA, Yolken RH. Necrotizing enterocolitis: Research Agenda for a disease of unknown etiology and pathogenesis. Pediatr Res 1993; 34: 701-708. Quamar MI, Read AE, Mountford R, Skidmore R, Wells PNT. Effect of carbohydrate, fat and protein on superior mesenteric artery blood flow in man. Gut 1984; 25:1154 (Abstr.). Rudolph AM. Scarpelli EM, Golinko R J, Gootman NL.

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Hemodynamic basis for clinical manifestations of patent ductus arteriosus. Am Heart J 1964; 68: 447-453. Sato S, Ohnishi K, Sugitas S, Okuda K. Splenic artery and superior mesenteric artery blood flow: Non surgical Doppler US measurement in healthy subjects and patients with chronic liver disease. Radiology 1987; 164: 347-352. Serwer GA, Armstrong BE, Anderson PAW. Continuous wave Doppler ultrasonographic quantitation of patent ductus arteriosus flow. J Pediatr 1982; 100: 297-299. Spach MS, Serwer GA, Anderson PAW, Canent RV Jr, Levin AR. Pulsatile aorto-pulmonary pressure flow dynamics of patent ductus arteriosus in patients with various hemodynamic states. Circulation 1980; 61: 110-122. Switzer DF, Nanda NC. Doppler color flow mapping. Ultrasound Med Biol 1985; 11: 403-416. van Bel F, van de Bor M, Stijnen T, Baan J, Ruys JH. Cerebral blood flow velocity changes in preterm infants after a single dose of indomethacin: The duration of its effect. Pediatrics 1989; 84: 802-807. van Bel F, van Zwieten PHT, Guit GL, Schipper J. Superior mesenteric artery blood flow velocity and estimated volume flow: Duplex Doppler US study of preterm and term neonates. Radiology 1990a; 174: 165-169. van Bel F, van Zoeren D, Schipper J, Guit GL. Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants. J Pediatr 1990b; 116: 965-970. van Bel F, van de Bor M, Guit GL, Schipper J. Indomethacininduced renal blood flow disturbances in premature infants: Assessment with color Doppler flow imaging. Pediatr Res 1990c; 27: 229A. van Bel F, Schipper J, Guit GL, Visser MOJM. The contribution ofcolour Doppler flow imaging to the study of cerebral haemodynamics in the neonate. Neuroradiology 1993; 35: 300-306.