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1 Department of Cardiology, Intravascular
ultrasound (IVUS) has emerged as an important diagnostic method for
evaluating vessel diameter and vessel wall motion. To evaluate the
validity of IVUS in assessing changes in the pressure-diameter
relationship we compared measurements of abdominal aortic diameters
derived from IVUS with those simultaneously obtained at the same site
using implanted sonomicrometers in five chronically instrumented
conscious dogs and in seven acutely instrumented anesthetized dogs.
Five hundred eighty beats were analyzed to obtain peak systolic and
end-diastolic diameters and to calculate aortic compliance at different
blood pressure levels induced either by an aortic pneumatic cuff or by
intravenous injections of nitroglycerin or norepinephrine. IVUS agreed
closely with sonomicrometer measurements at different blood pressure
levels. However, IVUS slightly but significantly underestimated aortic
diameters by 0.6 ± 0.7 mm for systolic diameters
(P < 0.001) and by 0.7 ± 0.6 mm
for diastolic diameters (P < 0.001)
compared with the sonomicrometer measurements. We conclude that IVUS is
a feasible and reliable method to measure dynamic changes in aortic
dimensions and has the potential to provide ready access to assess
aortic compliance in humans.
aortic compliance; vascular ultrasound
COMPLIANCE OF THE ARTERIAL TREE has been shown to be
reduced in hypertension (4, 11, 15) and atherosclerosis (24, 25). An
increase of arterial compliance has been realized as an important
effect of antihypertensive therapy (29). Because of its size and its
structure the aorta contributes most to the distensibility of the
arterial system. Classical methods for assessing viscoelastic vessel
properties in humans are based on the analysis of the aortic pressure
decay in diastole (8) or on the calculation of systolic aortic input
impedance (18, 19). Measurements of pulse-wave velocity (10) and
impedance plethysmography (24) have been used as indirect, noninvasive
methods to estimate arterial compliance. The distension curve of
peripheral arteries can be assessed by Doppler signal processing of the
ultrasound radio-frequency signal (13). The mechanical behavior of the
aorta has also been studied using angiography (1), echocardiography
(7), sonometry (27), and magnetic resonance imaging (16). In
experimental settings central aortic compliance has been calculated
from pressure-diameter relationships using sonomicrometers (2, 6, 20,
22, 31). This method is considered the gold standard but cannot be
applied in humans. Recently, intravascular ultrasound (IVUS) imaging
has been used to visualize aortic cross sections with high resolution (9, 17). Initial studies have been published on the use of IVUS for
determining viscoelastic vessel properties in animals (26) and in
humans (12, 14, 30). However, IVUS has never been properly evaluated by
comparison with an established reference method in assessing aortic
wall mechanics. Therefore, the aim of this study was to investigate
whether IVUS can be used to reliably measure dynamic changes in aortic
dimensions. IVUS measurements of aortic cross-sectional areas were
compared with measurements derived from chronically and acutely
implanted sonomicrometers in conscious and anesthetized dogs at various
aortic pressures.
Aortic cross-sectional areas and diameters were measured using IVUS and
compared with simultaneously recorded measurements using implanted
sonomicrometer crystals in seven foxhounds (age 15-24 mo, body wt
21-32 kg). Measurements were performed in five experiments on five
of these dogs with chronically implanted sonomicrometers in the
conscious state and in seven experiments with acutely implanted sonomicrometers in all seven of these dogs under anesthesia. All experiments were done in accordance with the national law for the care
and use of animals in research and were approved by a state committee
(license no. 37-9185.81/45/96, Regierungspräsidium Karlsruhe).
Implantation Procedure
ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References
METHODS
Top
Abstract
Introduction
Methods
Results
Discussion
References
The abdominal aorta was exposed retroperitoneally through a left flank incision. A polyurethane catheter was inserted into the aorta 0.5 cm proximal to the renal arteries. An inflatable cuff was placed around the aorta just proximal to the renal arteries but distal to the tip of the catheter, to allow for mechanical pressure reductions. A pressure transducer (Konigsberg P5-S-N, Konigsberg, Pasadena, CA) was implanted 2-5 cm distal to the renal arteries into the aorta. Two ultrasound crystals (Sonomicrometer VD5-2, Triton, San Diego, CA) attached to Dacron patches were sutured 2-5 cm distal to the transducer onto the anterior and posterior aortic walls in a segment that was free of lumbar arteries. Adjacent tissue was attached loosely around the aorta to support a stable position of the sonomicrometer crystals. Connecting cables and catheters were led subcutaneously to the dog's neck, where they were brought out through the skin.
At least 10 days of recovery were allowed before experiments were performed in conscious dogs. At postoperative days 1, 3, 6, and 9 the dogs received a combination of bencylpenicillamine and sulfatolamide (Tardomycel, 3 ml sc, Bayer) for antibiotic prophylaxis. The catheter was flushed every second or third day and filled by a solution of heparin (1,700 IU/ml) and cephtazidim (Fortum, Glaxo, Bad Oldesloh, Germany).
IVUS Measurements in Conscious Dogs With Chronically Implanted Sonomicrometers
The dogs were lying on their right side on a padded bench throughout the experimental period as they had been trained before without using sedation. After disinfection and local anesthesia with 5 ml mepivacaine (Scandicaine, Astra, Wedel, Germany), the right femoral artery was punctured transcutaneously and a 5-Fr sheath was inserted using the Seldinger technique. After application of 1,000 IU of heparin, the IVUS catheter (3.2 Fr, CVIS System, Sunnyvale CA) was inserted through the sheath and positioned into the abdominal aorta just next to the sonomicrometer crystals. Catheter position was verified by the appearance of artifacts in the sonomicrometer signals when the ultrasound crystals at the tip of the IVUS catheter were between the opposing sonomicrometers. Correct catheter positioning was assumed when the artifacts disappeared after the IVUS catheter was introduced or pulled back for a distance of ~5 mm. Additionally, in some experiments the sonomicrometers could be detected on the IVUS image. To minimize measurement errors caused by oblique catheter positions, we placed the IVUS catheter coaxial and centered over a distance as long as possible and confirmed the position by performing a manual pullback of the ultrasound crystal up to the aortic bifurcation with the catheter sheath remaining in the same place.IVUS Measurements in Anesthetized Dogs With Acutely Implanted Sonomicrometers
Premedication and anesthesia were performed as described in Implantation Procedure. After laparotomy and preparation of the aorta two sonomicrometers were loosely fixed on opposite positions on the right and left wall of the aorta. The arterial sheath and the IVUS catheter were positioned in the same way as described for the experiments in conscious dogs.Experimental Protocol
Simultaneous measurements by IVUS and sonomicrometer were made under resting conditions and after intravenous bolus injections of nitroglycerin (1.0 mg in 10 ml NaCl, Nitrolingual, Pohl-Boskamp, Hohenlockstedt, Germany) and norepinephrine (Arterenol, Hoechst, Frankfurt am Main, Germany, 8 µg in 5 ml NaCl) to study the agreement over a wide range of aortic pressures. Mechanical pressure reduction was achieved by a controlled inflation of the aortic cuff, causing a pressure reduction down to 40-60 mmHg within 60 s. A period of at least 5 min was allowed for recovery after each test. After completion of the experiments in the dogs with chronically implanted sonomicrometers, we removed the arterial sheath after renewal of local anesthesia and manually compressed the femoral artery for 20 min. After the experiments in the dogs with acutely implanted sonomicrometers the animals were killed by an overdose of pentobarbital.Data Acquisition
Recording of aortic pressures and electrocardiogram. Aortic pressures were measured using the implanted and precalibrated Konigsberg transducer, connected to an amplifier (Pressure Amplifier SP1400, Gould, Valley View, OH). To account for offset errors of the Konigsberg transducer, blood pressure was also measured via the implanted aortic catheter, which was connected to an extracorporeal pressure transducer (Statham P23 XL, Spectramed, Oxnard, CA) with a calibrated amplifier that was zero-adjusted to atmospheric pressures immediately before the experiment (Pressure Processor, Gould). Pressure signals and amplified electrocardiogram (ECG) signals (ECG/Biotach, Gould) were recorded on an IBM-compatible computer after analog-to-digital conversion (DAS-16, Keithley-Metrabyte, Taunton, MA) at a sampling rate of 100 Hz.
Sonomicrometer measurements. Aortic diameters were derived from ultrasound transit times between implanted sonomicrometer crystals (Sonomicrometer 120, Triton). To improve electrical isolation, the backs of the crystals were covered with a small drop of silicone (RTV118Q, GE-Silicones, Bergen op Zoom, The Netherlands) and the connecting cables were inserted into Silastic tubing. Sonomicrometer crystals were calibrated before implantation by placing them on two thin glass platelets (0.15 mm) in blood at 38.5°C and recording the millivolt output while the platelets were held at 12 defined distances (accurate within 10 µm) ranging from 8 to 15 mm. During the experiments, the millivolt output of the sonomicrometer device was recorded at a rate of 100 Hz simultaneously with the pressure and ECG signals on the computer. The sonomicrometer measurements were converted off-line from millivolts into millimeters by using the linear regression coefficients from the calibration measurements and the offset of the sonomicrometer output determined immediately before the experiment.
IVUS imaging.
For IVUS imaging a commercially available ultrasound system (Vingmed
CFM 800 A/CVIS, Sonotron, Cologne, Germany) was used. Images were
recorded at a frame rate of 30/s and stored on videotape (S-VHS,
Panasonic AG 7350). A representative example of systolic and diastolic
images is shown in Fig. 1. Blood pressure
signals, and in some experiments the ECG, were also recorded on the
videotape. To synchronize signals recorded on videotape to those stored
on the computer, brief electrical marks were superimposed on the blood
pressure signal in intervals of 30 s. The IVUS system was calibrated in
blood at 37-38°C using tubular Plexiglas phantoms (diameters
2-14 mm; accurate within 10 µm).
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Data Analysis
From the digital recordings of pressure and sonomicrometer output, the systolic, diastolic, and mean values were determined off-line beat by beat including the time marks in the pressure signal, using a specifically designed computer program. This program also converted the sonomicrometer output into millimeters as described in Sonomicrometer measurements. To correct for a possible zero-offset of the Konigsberg transducer, the mean value of its pressure signal was adjusted by direct comparison to the mean value of the pressure signal recorded by the extracorporeal transducer.Analysis of the IVUS images was performed off-line by manually tracing the border between lumen and vessel wall. We planimetrically measured systolic and diastolic areas from continuous recordings of aortic cross sections using the blood pressure signal to identify systolic and diastolic frames. Because of the small aortic pressure amplitude during pressure reduction with the inflatable aortic cuff for analysis of these experiments, we compared the diameter measurements at the time of the maximum of the R wave in the ECG to be sure that IVUS and sonomicrometer measurements were derived at the same time. Each measurement value is given as the mean of three single measurements. Diameters were calculated as
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Arterial compliance was calculated as the ratio of the systolic to diastolic amplitude of the diameter to the amplitude of the pressure. Pressure elastic modulus (Ep) was calculated according to the following equation proposed by Peterson et al. (21)
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Statistical Analysis
For statistical analysis the SAS system for personal computers was used (23). Continuous variables are indicated as means ± SD. Measurements of aortic cross-sectional areas were made in triplicate to reduce measurement error. IVUS and corresponding sonomicrometer measurements were compared using the Student's t-test. Agreement between IVUS and sonomicrometer measurements was tested by comparing mean differences with their corresponding averages, a statistical method proposed by Bland and Altman (5). Changes of the same variable under different experimental conditions were compared using analysis of variance for repeated measurements. A P value <0.05 was considered statistically significant.| |
RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Aortic pressure-diameter relationships were analyzed in 294 beats in
acutely instrumented dogs, in 121 beats in chronically instrumented
animals after pharmacological interventions (Fig. 2), and in 165 beats during mechanical
pressure reduction. Systolic IVUS parameters could not be measured in
one dog with chronically implanted sonomicrometers because of
insufficient image quality caused by motion artifacts. Data of
hemodynamic variables at rest and under different experimental
conditions are shown in Table 1.
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Validation of IVUS Measurements
IVUS significantly overestimated diameters in phantoms with diameters between 2 and 14 mm. Therefore, the IVUS measurements in vivo were corrected using a linear regression equation (Fig. 3). Intra- and interobserver measurement variability assessed by IVUS was <5% for systolic and diastolic aortic diameters. The correlation coefficients of diameter measurements were 0.94 (P < 0.001) for interobserver variability and 0.97 (P < 0.001) for intraobserver variability.
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Diameter Measurements
When all single beats were analyzed as a group, IVUS slightly but significantly underestimated systolic and diastolic aortic diameters compared with the sonomicrometer measurements (P < 0.05, Fig. 4). There was better agreement in measuring systolic diameters than in measuring diastolic diameters (P < 0.05). The difference between IVUS and sonomicrometer diameter measurements after injection of nitroglycerin and norepinephrine was equal to that under resting conditions (Table 1).
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Compliance and Pressure Elastic Modulus
In experiments using acutely implanted sonomicrometers, IVUS agreed closely with sonomicrometer measurement when compliance was determined at different blood pressures (Fig. 5A). Compliance measurements had an upper limit of agreement (+2 SD) of 2.9 µm/mmHg and a lower limit of agreement (
2 SD) of 8.7
µm/mmHg (Fig. 5B). With
chronically implanted sonomicrometers we also found a linear correlation between the two methods with a slightly higher correlation coefficient (Figs. 5A and
6A),
although overall agreement was less close (Fig.
6B). In this group the range of
compliance values was higher and IVUS underestimated small and
overestimated larger compliance measurements. Overall, IVUS
overestimated aortic compliance under resting conditions and after
injection of nitroglycerin but not after application of norepinephrine
(Table 1). Both methods showed a significant increase in aortic
compliance after injection of nitroglycerin and a significant decrease
after application of norepinephrine. Accordingly,
Ep significantly
decreased after nitroglycerin and significantly increased after bolus
injection of norepinephrine (Table 1).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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The results of this study show that IVUS can be used to evaluate dynamic changes in aortic dimensions under various pressure conditions. To our knowledge, this is the first in vivo study comparing IVUS with a standard reference method for measuring dynamic changes of vessel dimensions. Several studies on measurements in vitro (9, 17, 28) have shown a good accuracy of IVUS. Our data show that aortic diameters and consequently aortic compliance correlated well with the reference values but that IVUS slightly underestimated diameters and overestimated aortic compliance compared with measurements with sonomicrometers under dynamic in vivo conditions in chronically and acutely instrumented dogs. Because IVUS measures internal aortic diameters whereas sonomicrometers measure external aortic diameters, this underestimation a priori was to be expected. Nevertheless, in some experiments IVUS overestimated aortic diameter compared with sonomicrometry. The most likely explanation for this finding is that it cannot be excluded that small deviations of the catheter axis might have resulted in oblique cross sections leading to overestimation of the aortic diameter. However, care was taken to position IVUS catheters in the center of the vessel as parallel to the aorta as possible.
Overall, systolic measurements were more concordant than diastolic values. This may be explained by a higher aortic wall thickness in diastole than in systole. With regard to compliance there was a better agreement between the two methods in those experiments with acute implantation compared with those using chronic implantation of sonomicrometers. A reason for this finding may be the postoperative development of scar tissue, which might have impaired aortic wall motion and could account for our finding that IVUS showed a progressive overestimation of compliance at higher values. Gross inspection of histological specimens of the aortic segments in which the sonomicrometers had been implanted showed an increase of fibrous tissue surrounding the aorta. Although IVUS probably underestimates diameters because it measures internal diameters, the method is useful, especially when evaluating changes in diameter and compliance secondary to pharmacologically or mechanically induced pressure changes. Abdominal aortic diameter values measured by sonomicrometry in this study are in accordance with those reported previously in dogs of comparable weight (20). In addition, our data of pressure elastic modulus were in the same range as measurements using IVUS in the abdominal aorta of pigs (26).
Another important point is the overestimation of phantom diameters by IVUS, which warrants the use of a correction algorithm. This has been related to ultrasound equipment factors such as signal processing time (3).
Study Limitations
There are several potential limitations of the study that should be considered. First, IVUS and sonomicrometer measurements were not derived from exactly identical positions because of artifacts interfering with the sonomicrometer signal when the devices were in the same cross section. Because care was taken to keep the distance between the two devices to <5 mm, we do not expect this to be a relevant factor regarding the interpretation of our results. Second, sonomicrometers were implanted periadventitially and not within the inner vessel boundary where IVUS measurements were made. Finally, another limitation of the method is that aortic wall thickness, which would be necessary to calculate wall stress, could not be adequately derived using IVUS.Implications
IVUS is a feasible and reliable method for the investigation of dynamic changes in aortic wall mechanics. In experimental settings it may alleviate the need for implantation of sonomicrometer crystals and may instead be used in conscious dogs. However, the fact that at present IVUS images cannot be recorded with the same time resolution as sonomicrometer measurements must be taken into account. As a potential advantage compared with sonomicrometers and noninvasive ultrasound methods IVUS allows for a mapping of the viscoelastic behavior of multiple aortal segments and may thus help in the understanding of the underlying mechanisms in changes of viscoelastic properties in arterial hypertension and in atherosclerosis.| |
ACKNOWLEDGEMENTS |
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This work was supported in part by a grant of the Medical Faculty, Ruprecht-Karls Universität Heidelberg (project no. 22/94).
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FOOTNOTES |
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This work was presented in part at the 69th Scientific Sessions of the American Heart Association, November 1996, New Orleans, LA.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: S. E. Hardt, Dept. of Cardiology, Ruprecht-Karls Universität, Bergheimer Strasse 58, 69115 Heidelberg, Germany.
Received 6 August 1998; accepted in final form 4 November 1998.
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