(Circulation. 1997;96:1004-1011.)
© 1997 American Heart Association, Inc.
Articles |
Myocardial Contrast Echocardiography Can Be Used to Quantify Intramyocardial Blood Volume
New Insights Into Structural Mechanisms of Coronary Autoregulation
From the Division of Cardiology, Department of Medicine, University of Pittsburgh (Pa) School of Medicine.
Correspondence to Flordeliza S. Villanueva, MD, Division of Cardiology, University of Pittsburgh, 200 Lothrop St, Scaife Hall, Room S568, Pittsburgh, PA 15213.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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Background Changes in intramyocardial blood volume (IBV) mediate autoregulatory adaptations to coronary stenosis. This study investigated whether (1) myocardial contrast echocardiography (MCE) can quantify changes in IBV during coronary stenosis and (2) the relation between coronary resistance– and MCE-derived IBV could yield insight into structural mechanisms of IBV change.
Methods and Results A circulating in vitro model with constant flow and varying volume was used to determine whether indicator dilution theory could be applied to MCE. Contrast echo was performed with albumin microbubbles, and time-intensity data were fit to a gamma-variate function. With six different volumes, bubble transit time was linearly related to volume (r=.91). To determine whether changes in IBV could be quantified in vivo, the left anterior descending coronary artery in 12 dogs was instrumented with a flow probe, occluder, and intracoronary pressure catheter, and non–flow-limiting stenoses were created. IBV was derived by use of coronary resistance measurements applied to models that assumed autoregulation to occur via vasodilatation or microvascular recruitment. MCE-IBV was calculated from microbubble transit rates. At constant flow, MCE and resistance IBV increased with stenosis. Although MCE and resistance IBV were linearly related, MCE overestimated IBV derived from the vasodilatation model and underestimated IBV calculated from the recruitment model.
Conclusions MCE can quantify autoregulatory increases in IBV that maintain resting myocardial perfusion. These data suggest that both microvessel vasodilatation and recruitment are dual mechanisms of IBV change. MCE thus may be a clinically useful technique for the detection and quantification of coronary artery disease at rest.
Key Words: echocardiography • contrast media • coronary disease • stenosis
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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The myocardial microvasculature undergoes structural and functional modifications in response to different pathophysiological states. For example, microvascular rarefaction and remodeling occur in hypertension and diabetes.1 2 Conversely, the heart may adapt to coronary artery disease and chronic ischemia through angiogenesis.3 Coronary autoregulation, which maintains stable myocardial perfusion despite variations in perfusion pressure, is thought to be mediated by microvascular dilatation and/or recruitment.4 5 6 7 8 9 10 11 Such microvascular responses to altered physiological conditions result in changes in blood volume within the intramyocardial vasculature. Because such changes ultimately manifest as alterations in nutritive flow, quantifying IBV is of both basic physiological and clinical importance.
Current methods for quantifying IBV in vivo are limited. Digital angiographic impulse response analysis is limited in its spatial resolution.12 13 Dye or radioactive labeling techniques cannot be used in humans or performed repeatedly to assess dynamic changes.6 7 9 10 11 Furthermore, such methods do not yield insight into the mechanism of autoregulation, ie, vasodilatation versus vessel recruitment.
In the present study, we proposed that an intravascular tracer can characterize changes in IBV. MCE uses encapsulated gas microbubbles injected into the coronary circulation, which produce myocardial contrast enhancement during two-dimensional echocardiography.14 Because the bubbles remain entirely within the intravascular space, principles of indicator dilution theory applied to MCE give this technique the potential to quantify myocardial perfusion.15 Recent studies in dogs suggest that MCE can quantify increases in IBV during pharmacological hyperemia.15 Whether autoregulatory changes in IBV occurring with non–flow-limiting coronary stenoses can be quantified by MCE at rest, however, is unknown. Furthermore, no study to date has validated MCE against an independent measure of IBV.
On the basis of classic indicator dilution theory, in which the transit of a tracer through a compartment is proportional to the ratio of flow to volume of the compartment,16 we theorized that microbubble transit rates could be used to calculate IBV at constant flow. Accordingly, this study tested the hypotheses that (1) MCE can quantify resting changes in IBV resulting from progressive non–flow-limiting epicardial coronary stenosis and (2) the relationship of resistance- and MCE-derived measures of blood volume can yield insight into structural mechanisms of autoregulation, ie, vasodilatation of existing versus recruitment of new microvessels. A twofold approach was used: First, an in vitro model was constructed to examine the applicability of indicator dilution theory to and the sensitivity of MCE for the detection of volume change. Second, a canine model was used to determine whether MCE could quantify resting changes in IBV in vivo during graded coronary stenosis. To validate the MCE data, an independent index of IBV was derived from simultaneous coronary resistance measurements.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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In Vitro Model
Six Plexiglas flow cells of identical lengths and varying radii (0.65, 0.95, 1.25, 1.6, 1.9, and 2.2 cm) were used to simulate different composite intravascular blood volumes. The proximal end of each cell was connected to an input reservoir and the distal end to an outlet drain, and the system was primed with 0.9% NaCl. Flow was controlled by a varistaltic pump (Mano-stat) and measured with a transit-time flow probe (Transonic Systems Inc). A port proximal to the flow cell was used for contrast injection, and an in-line mixer ensured homogeneous suspension of contrast.
Echocardiographic imaging of the flow cell was performed with a 5-MHz phased-array system (GE Medical Systems). Gain settings were optimized at the beginning of the experiment, and images were obtained in the short-axis plane. Sonicated 5% human albumin microbubbles (Albunex, Molecular Biosystems Inc) were used as the contrast agent (mean diameter, 4.3 µm).
The experimental protocol was as follows: With saline flowing at rate of 130 mL/min, a power injector (Medrad) was used to inject a bolus of 0.1 to 0.2 mL of Albunex into the system. MCE images were recorded continuously beginning immediately before the appearance and extending through washout of contrast. Volume was varied by fitting the system with different flow cells.
Animal Preparation
The in vivo protocol was approved by the Institutional Animal
Care and Use Committee of the University of Pittsburgh and conformed to
the American Heart Association Guidelines for Use of Animals in
Research. Twelve adult dogs were anesthetized with sodium
pentobarbital (30 mg/kg), intubated, and ventilated (Harvard
Apparatus). 7F catheters were placed in both femoral
arteries for recording of arterial pressure (Gould
Electronics) and withdrawal of radiolabeled microsphere
reference samples. The pressure signal was conditioned and displayed on
a physiological recorder (EVR-130, PPG
Biomedical Systems). Another catheter was placed in a femoral vein for
administration of fluids and drugs.
A left lateral thoracotomy was performed, and the heart was suspended in a pericardial cradle. A catheter was placed in the left atrium for radiolabeled microsphere injection. The midportion of the LAD and the proximal LCx were encircled by flow probes (Transonic Systems Inc). The proximal LAD was cannulated retrogradely with a 21-gauge catheter for microbubble injection, with the tip positioned in the aorta and the hub connected to a power injector. A variable occluder was placed around the proximal LAD, and the distal LAD was cannulated with a 25-gauge catheter for distal coronary pressure measurement. Hemodynamic data were digitally acquired and stored in a minicomputer.
Myocardial Blood Flow Measurements
Myocardial blood flow was measured by the radioactive
microsphere technique.17 Approximately
2x106 to 3x106 11-µm microspheres
(New England Nuclear) were injected into the left atrium during
simultaneous 90-second arterial blood
withdrawal. The short-axis slice of the left ventricle corresponding to
the MCE was cut into 16 transmural pieces, specimens were placed in a
Gamma counter (Packard Instruments), and corrections were made for
spillover of activity between neighboring windows. Flow
(mL·min-1·g-1)
to the risk bed (defined by use of india ink during premortem LAD
occlusion) was calculated for the centrally located
segments,17 excluding lateral borders.
Estimation of Intramyocardial Blood Volume by Coronary
Resistance Measurements
Because autoregulation is felt to largely involve the adjustment
of coronary arteriolar vessels to alter vascular
resistance4 5 by vasodilatation and/or recruitment of
microvessels, two models were developed for estimating IBV by
coronary resistance measurements.
Our approach to measuring IBV premises that resistance of microvessels
(R) such as arterioles or capillaries can be approximated on the basis
of Poiseuille's law.18 Assuming that coronary
blood flow during acute stenosis is maintained by
vasodilatation alone, IBV at a stenosis (IBVs) with
respect to baseline (IBVb) can be calculated as (see
"Appendix A"):
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If IBV changes due to vessel recruitment, then IBV at a
stenosis relative to baseline can be calculated (see
"Appendix "):
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Myocardial Contrast Echocardiography: In
Vivo Studies
With the echocardiographic system described
above, MCE imaging with Albunex was performed at the mid–papillary
muscle short-axis level. In vivo, Albunex has an intravascular rheology
similar to that of red blood cells14 and causes no changes
in systemic and coronary hemodynamics at the
intracoronary doses required to achieve myocardial
opacification.20
Off-line Analysis of MCE Images
MCE images were analyzed off-line by use of previously
described methods.21 22 23 Briefly, images were digitized in
real time (Mipron, Kontron Electronics), and consecutive
end-diastolic frames were aligned by use of computer
cross-correlation techniques.23 Regions of interest were
drawn manually. For the in vitro experiment, the entire internal
cross-sectional area of the flow cell was selected. For the animal
studies, a region of interest corresponding to the LAD bed (determined
during the experiment by MCE performed during transient LAD occlusion)
was drawn, excluding the lateral 25% of borders of the bed to avoid
areas of overlap between LAD and LCx territories. Average pixel video
intensity within the region of interest was measured for each frame,
time-intensity data were transferred to another computer (VAXstation
4000/90, Digital Equipment Corp), and background-subtracted
time-intensity plots were fit to a gamma-variate function
(y=At
e-
t), where A is a
scaling factor, t is time, and is a parameter of tracer
transit rate14 equal to the ratio of flow (Q) to the
volume of distribution of a tracer (Vd)16 :
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Experimental Protocol: In Vivo Study
The increment in stenosis gradient required for each of
three to five progressive stenoses was initially determined so
that a range of non–flow-limiting gradients could be evaluated. The
occluder was tightened until a maximal non–flow-limiting
stenosis occurred, and the gradient across this
stenosis divided by the number of stenoses was set as
the target increase in gradient for each successive
stenosis.
MCE was performed by power-injecting 0.5 to 1.5 mL of Albunex into the aorta. The injection volume yielding the best visual result was used for subsequent stages. Baseline arterial and distal LAD pressure and epicardial flow were recorded, followed by MCE and radiolabeled microsphere measurements. The occluder was tightened to create the first stenosis based on the target gradient as defined above, followed by a brief waiting period to permit hemodynamic stabilization, and hemodynamic, MCE, and microsphere measures were repeated. A total of 5 stenoses were created in 5 dogs and 3 stenoses in 7 dogs. To adjust for possible bias resulting from creating stenoses in incremental fashion, the order in which stenoses were created was randomly varied in 4 dogs.
At the completion of data collection, the proximal LAD was ligated, MCE was performed, and 20 mL of india ink was injected into the left atrium to define LAD bed borders. The dog was immediately killed by KCl and pentobarbital overdose, the heart was excised, and the cross section corresponding to the MCE image was processed to determine radiolabeled microsphere blood flow.
Statistical Methods
Data are expressed as mean±SEM. Data were compared by
repeated-measures ANOVA (SAS Institute). Paired t testing
(two-tailed) with Bonferroni criteria for significance was used when a
significant difference was found by ANOVA. The relation between MCE-
and resistance-derived IBV was assessed by linear regression.
Statistical significance was defined as P<.05.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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In Vitro Studies
Flow cell volumes were expressed as a function of cross-sectional area. At constant flow, there was a linear correlation between mean microbubble transit time (1/
) and flow cell cross-sectional area
(r=.91, P<.01) (Fig 1
). These
data indicate that at constant flow, microbubble transit rates vary
with volume and confirm the applicability of indicator dilution theory
to the measurement of volume using MCE.
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In Vivo Studies
Hemodynamic measurements. The
Table depicts the mean hemodynamic and
blood flow measurements at baseline and during the experimental stages
in the 7 dogs with 3 stenoses and during stenoses 1, 3,
and 5 in the 5 dogs with 5 stenoses. Heart rate and aortic and
left atrial pressures remained constant. Similarly,
microsphere-derived LAD flow was unchanged despite
stenosis gradients ranging from 11±1 mm Hg at the
mildest to 39±3 mm Hg at the most severe stenosis.
Although microsphere-derived LCx flow changed by ANOVA, the
difference between baseline and the final stenosis was
insignificant by Bonferroni criteria. Total coronary flow (sum
of LCx and LAD flow-probe measurements) remained stable.
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Relationship between stenosis severity and IBV. Fig 2A summarizes the resistance-derived volume measurements
in all dogs. At constant flow, IBV calculated from the vasodilatation
model significantly increased as stenosis severity progressed,
with a 20±3% increase between baseline and the maximum
non–flow-limiting stenosis (P
.0001). Likewise,
when the recruitment model of autoregulation was used, there was an
increase in IBV with progressive stenosis amounting to a
64±7% increase with the maximum stenosis
(P.0001). Because right atrial pressure has also been used
to approximate distal coronary pressure,19
resistance-derived IBV was also calculated with an assumed right atrial
pressure of 5 mm Hg. IBV derived by this approach was not
significantly different from the values derived by use of left atrial
pressures.
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Fig 2B
illustrates mean MCE-derived IBV at each stenosis. Like
the resistance-based calculations, MCE measures of IBV increased
significantly with progressive stenosis
(P.0002).
Relationship between resistance- and MCE-derived measures of
IBV. MCE-determined IBV measurements were compared with those
derived from coronary resistance data and are shown in Fig 3, which also includes the data from all stages in the 5
dogs undergoing 5 stenoses. There was a significant linear
relationship between the vasodilatation model and MCE estimates of IBV
(y=1.84x-0.40, r=.66,
P<.0001) (Fig 3A). MCE measurements, however, overestimated
the coronary resistance–derived IBV, predicting an 84%
greater change in IBV at any given stenosis.
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As shown in Fig 3B, there was a linear relationship between MCE- and
recruitment model–derived measurements of blood volume
(y=0.81x+0.13, r=.70,
P<.0001). Unlike the relationship when the vasodilatation
model was used, MCE underestimated IBV when recruitment was assumed to
be the mechanism of autoregulation, with a 19% smaller change in blood
volume at a given degree of stenosis than that predicted by
coronary resistance measures.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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This study used measures of coronary resistance to evaluate the accuracy of MCE for IBV assessment. The three major findings were as follows: (1) At constant resting flow, IBV increases with progressive coronary stenosis; (2) MCE is capable of quantifying changes in IBV in response to non–flow-limiting stenosis; and (3) both microvascular vasodilatation and recruitment concurrently participate in coronary autoregulatory increases in IBV.
Basis for Using MCE to Quantify IBV
The theoretical underpinnings for measuring volume by use of MCE
are shown in Fig 4. This figure illustrates three
scenarios in which constant resting flow despite progressive
stenosis is maintained by microvascular vasodilatation of
existing vessels or recruitment of new vessels, resulting in an
increase in the composite IBV (boxes). On the basis of a
two-compartment model and indicator dilution theory, the transit rate
() of a tracer will decrease as volume enlarges, providing that the
input function and flow are constant.16
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Before this approach was applied in vivo, an in vitro model was used to
determine whether microbubble transit rates would detect changes in
volume. The in vitro experiment demonstrated that at constant flow,
there was a linear relationship between volume and mean transit time
(1/), thus confirming predictions of indicator dilution theory and
validating the theoretical basis for using MCE to assess changes in
microbubble distribution volumes.
We then sought to determine whether MCE could detect IBV changes in response to non–flow-limiting stenoses. We quantified IBV change using two models derived from coronary resistance measurements to validate the MCE findings. The in vivo study demonstrated that over a broad range of stenoses and at constant flow, IBV measured by use of MCE and the resistance models increased as stenosis severity progressed. Furthermore, MCE and resistance measures of relative volume were linearly related, confirming the applicability of MCE for quantifying volume change in the beating heart.
Discrepancies Between MCE- and Resistance-Derived IBV
Although MCE volume calculations were linearly related to
resistance-derived measurements when autoregulation was assumed to
occur via vasodilatation, they systematically overestimated
resistance-derived volumes by 
84%. There are several possible
reasons for this discrepancy. One explanation may be related to the
fact that the two techniques interrogate slightly different vascular
compartments. Coronary resistance measurements reflect changes
predominantly in coronary microvessels (arterioles <170
µm and venules <150 µm in diameter), in which 70% of
resistance resides,24 and are less sensitive to changes in
veins. Microbubbles, on the other hand, traverse not only the
arterioles, capillaries, and small venules but also larger
intramyocardial vessels that contribute less to coronary
resistance. Hence, the microbubble transit could theoretically become
prolonged by an increase in venous capacitance, which would not be
"detected" by our resistance measurements. It is unlikely,
however, that isolated increases in venous volume occurred that would
have been singularly detected by MCE; others have shown that even in
the presence of maximal dipyridamole-induced
hyperemia, coronary venous resistance is not
significantly changed.24
The second reason for the discrepancy could be phasic changes in IBV. Liu et al25 showed that IBV varies throughout the cardiac cycle. Because our time-intensity data were derived from end-diastolic frames, the MCE volume probably represents IBV at end diastole, which is at its maximum. On the other hand, the resistance-based IBV was computed from mean coronary resistance and most likely represents mean IBV for the entire cardiac cycle. Conceivably, the larger IBV detected by MCE compared with the vasodilatation model may be due to differences in the specific phase of the cardiac cycle that was sampled. On the basis of Liu's data, however, the difference between the mean and the peak IBV was between 10% and 20%, which accounts for only one fifth to one third of the additional volume detected by MCE. Cyclic changes in blood volume are therefore unlikely to fully account for our observations.
A third possible explanation for the discrepancy in MCE and resistance measurements of volume with the vasodilatation model may be that vasodilatation is not the sole structural correlate to coronary autoregulation. Considerable evidence suggests that vasodilatation is a major mechanism for regulating coronary perfusion. Using intravital microscopy, Kanatsuka et al5 observed that arterioles <100 µm in diameter dilated in response to a mild coronary stenosis. Similarly, Chilian and Layne4 showed that coronary arterioles <150 µm in diameter vasodilated when perfusion pressure was reduced to 40 mm Hg. Such data support the prevailing notion that a primary mechanism of autoregulation is vasodilatation of already patent resistance arterioles and lend credence to the vasodilatation model on which our resistance-derived IBV calculations were based.
Vasodilatation, however, may not fully account for the entire IBV
increase. Recruitable vessels may exist in the coronary
microvasculature.7 8 9 10 11 Measuring the intercapillary
distance in rat hearts, Henquell and Honig8 concluded that
21% to 37% of capillaries were not perfused under normoxic
conditions. Crystal et al7 demonstrated in dogs a twofold
increase in small-vessel blood volume (index of open capillaries)
during asphyxia. Weiss and Conway9 reported that 36% to
45% of capillaries and 46% to 49% of arterioles in rabbits were not
perfused or were underperfused at rest. Furthermore, these arterioles
appear to be functional and recruitable by vasopressin or chemical
sympathectomy.10 11
Measurement of microbubble transit rates would not necessarily
have discriminated between vasodilatation and recruitment as mechanisms
of volume change. Resistance measures of volume, however, would be
affected by microvessel recruitment. A resistance model was developed
that assumed the primary mechanism of autoregulation to be recruitment
("Appendix B"). Fig 5 illustrates the regression
lines (from Fig 3) for MCE estimates of IBV versus resistance-derived
measures when the mechanism of autoregulation is assumed to be
vasodilatation only or recruitment only. The bold solid line
represents the line of identity, which would theoretically
represent the data had either model completely accounted for
the observations. Although MCE overestimated IBV derived with the
vasodilatation model, it underestimated volumes when recruitment was
assumed to be the primary mechanism of autoregulation. Fig 5 thus
suggests that both vasodilatation and recruitment of microvessels
contributed to the observed increases in IBV.
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Comparison With Other Studies
Assessment of IBV during autoregulation has been attempted by
others using different techniques in animal models. Measuring digital
angiographic impulse response, Schuhlen et al13 reported a
74% increase in IBV with subcritical stenosis, which is higher
than the maximum MCE-derived IBV. Wu et al26 used
high-speed computed tomographic scanning and estimated an 11% increase
in IBV at a stenosis gradient of 9 mm Hg, which increased
to 25% at a gradient of 40 mm Hg, which is lower than our
MCE-derived IBV. Because both these studies applied indicator dilution
theory, we might have expected MCE approximations of IBV to be
comparable to that reported by these investigators. Although the
increase in MCE-IBV is within an order of magnitude roughly comparable
to that found by these authors, there are important differences between
these two studies and ours. The first relates to possible differences
in stenosis severity in each study, which are difficult to
precisely compare on the basis of the information provided. Second,
these studies used iodinated angiographic agents, which are
coronary dilators.26 Schuhlen et al injected ionic
dye, which could have accounted for the larger IBV increase in that
study. Third, angiographic dyes are not pure intravascular tracers, and
15% extravasation occurs during the first pass.27
Extravasation of dye would result in an overestimation of IBV by
time-intensity curves, whereas subtraction of this effect by
mathematical correction techniques as done by Wu et al26
could potentially underestimate IBV. In this regard, MCE offers a
distinct advantage over angiographic techniques, because the
microbubbles are purely intravascular and
physiologically inert.
Using atrial injection, Skyba et al15 performed MCE during hyperemia in dogs with stenosis and showed that the peak myocardial video intensity can detect presumed changes in IBV. However, Skyba et al did not confirm an actual increase in IBV or validate MCE against other independent indices of volume change. The use of coronary resistance as an independent measure of IBV is thus an important differentiation of our present study. Also, our study used microbubble transit rate, a parameter less influenced by variations in bubble concentration and dose, instead of peak intensity, to measure IBV. Furthermore, unlike Skyba et al, we assessed IBV in the absence of pharmacological stress.
Critique of Our Methods
The determination of is subject to the limitations inherent to
MCE. Analysis of time-intensity curves presumes a linear
relationship between microbubble concentration and video intensity, and
comparisons among curves are optimized by reproducible microbubble
doses. The use of a commercially prepared agent should have minimized
microbubble injection variability. Other limitations include image
attenuation,15 28 and conversely, thresholding for
detecting backscatter.28 The dose of contrast agent was
chosen to achieve optimal opacification while avoiding attenuation.
Furthermore, a linear signal-to-video postprocessing algorithm was
used.
Serial comparison of is valid only if the input function is
constant; variability in the input function would affect tracer transit
time independent of changes in flow or volume.16 A power
injector was used to standardize the injection method. Additionally,
since total coronary flow stayed constant, the contribution of
left main artery flow to the input function should have remained
unchanged.
The method for deriving coronary resistance is in itself controversial because multiple parameters affect small-vessel resistance, and the true backpressure to coronary inflow is difficult to quantify. We used a generally accepted measure of coronary resistance, in which coronary driving pressure was calculated as the difference between distal LAD pressure and left ventricular end-diastolic pressure.19
An independent measure of IBV based on Poiseuille's equation was
derived, and it is important to understand the limitations related to
its application in vivo. Poiseuille's equation was derived from
steady-state fluid flow through small rigid tubing,18
whereas larger arteries are elastic and flow through them is pulsatile.
Nonetheless, Baez et al29 and others30 have
found that the diameter of capillaries and small arterioles varied
little despite large changes in internal pressure. Thus, the
relationship most likely still pertains to the resistance measurements
in small arterioles and capillaries. In larger arterioles, where flow
is still pulsatile, it has been suggested31 that
resistance is proportional to the third instead of the fourth power of
the radius. However, even if most coronary resistance resided
in these larger arterioles, however, which dilate by 5% to 20%
during moderate to severe stenosis,4 5 the error
in volume estimation would be only between 2.5% and 10%.
Another assumption made in deriving the coronary resistance–IBV relationship was that the response from the coronary microvessels is homogeneous, ie, that the degree of vasodilatation is uniform among vessels. There is, however, both spatial and temporal heterogeneity to myocardial perfusion,32 and microvessels also respond heterogeneously to hypoperfusion.4 5 Like all models, ours simplify the complexities of the physiological situation under study. Nonetheless, these models do provide a first-order approximation of the minimum (vasodilatation) and maximum (recruitment) IBV increments that correspond to changes in measured coronary vascular resistance. However simplified, the models appear to provide a useful conceptual structure for understanding the dual mechanisms of coronary autoregulation.
Clinical Implications
The quantification of IBV can be applied to the clinical
evaluation of patients with suspected coronary artery disease.
There are advantages to measuring myocardial blood volume rather than
coronary blood flow, which is the current standard used by
stress scintigraphy.33 In the presence of
pharmacologically induced maximal vasodilatation, for example,
coronary flow can be affected by alterations in aortic pressure
independently of the microvascular responses under investigation. The
measurement only of changes in flow may thus not fully encompass the
microvascular events that more truly reflect the
physiological sequelae of a coronary
stenosis. Measuring IBV with MCE, therefore, may provide a
better approach to measurement of coronary vascular
reserve.
Quantification of IBV by use of MCE could obviate the need for performing exercise or pharmacological stress to detect coronary stenoses noninvasively. Because most patients with coronary artery disease have normal perfusion at rest, current noninvasive techniques to diagnose coronary disease require some form of stress to elicit flow heterogeneity between normal and stenosed beds. As shown here, in regions subserved by stenosed arteries, normal flow at rest is maintained by an increase in IBV, and the magnitude of increase is proportional to the severity of stenosis. Assessing blood volume, therefore, yields information about the severity of and microvascular response to stenosis, without having to elicit an increase in flow. As such, measuring IBV heterogeneity with MCE may enable detection of coronary stenosis in the resting state.
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Selected Abbreviations and Acronyms |
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Appendix A |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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Calculation of IBV Using Coronary Resistance Measurements: Model of Coronary Autoregulation by Vasodilatation
Our approach to calculating IBV is based on Poiseuille's law. Coronary vascular resistance and blood volume reside largely in the arterioles and capillaries. Resistance of these microvessels, R, can be estimated by Poiseuille's equation18 :
 |
 | (1) |
 | (2) |
:
 |
Ks=K. On
the basis of these assumptions, the vasodilatation model (vaso)
predicts that IBV at a stenosis relative to baseline IBV can be
estimated:
 | (3) |
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Appendix B |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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Calculation of IBV From Coronary Resistance Measurements: Model of Coronary Autoregulation by Microvessel Recruitment
If coronary autoregulation occurs solely by recruitment of microvascular units and these recruited vessels are modeled as a composite compartment parallel to the existing microvascular bed, the total coronary resistance at each stenosis is expressed as
 |
,
then Rs can be expressed as
 |
Krecruit=K. Coronary
resistance at a given stenosis can therefore be expressed
as
 | (4) |
, and 4, in this recruitment model, IBV at
each stenosis compared with baseline can be derived:
 | (5) |
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Acknowledgments |
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This study was supported by Grants-in-Aid from the National Center of the American Heart Association and the Pennsylvania Affiliate of the American Heart Association (Dr Villanueva) and a FIRST Award from the National Institutes of Health (R29-H247046-01) (Dr Feldman). Dr Mills is the recipient of a fellowship training grant from the Pennsylvania Affiliate of the American Heart Association. Albunex was provided by Molecular Biosystems, Inc.
Received August 19, 1996; revision received February 3, 1997; accepted February 11, 1997.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix AAppendix BReferences |
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