(Circulation. 1995;92:978-986.)
© 1995 American Heart Association, Inc.
Articles |
Hemodynamic Mechanisms Responsible for Reduced Subendocardial Coronary Reserve in Dogs With Severe Left Ventricular Hypertrophy
From the Departments of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, Mass, and the New England Regional Primate Research Center, Southborough, Mass.
Correspondence to Stephen F. Vatner, MD, New England Regional Primate Research Center, One Pine Hill Drive, PO Box 9102, Southborough, MA 01772.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Reduced subendocardial coronary reserve is a hallmark of left ventricular hypertrophy (LVH). The goal of this study was to determine whether hemodynamic, as opposed to structural, mechanisms were responsible for the reduced subendocardial coronary reserve.
Methods and Results The effects of near-maximal vasodilation with adenosine were examined in 10 conscious dogs with LVH (79% increase in ratio of LV weight to body weight) induced by aortic banding in puppies with and without preload reduction. At baseline, LV end-diastolic pressure, LV end-diastolic circumferential and compressive radial wall stresses, and LV myocardial blood flow were similar in dogs with LVH and sham-operated controls, while LV end-systolic circumferential wall stress tended to be greater in the LVH group compared with the control group. In control dogs, adenosine reduced LV circumferential end-systolic and end-diastolic wall stresses and compressive radial subendocardial wall stress; LV subendocardial blood flow increased (from 1.41±0.16 to 3.58±0.27 mL · min-1 · g-1) and the ratio of subendocardial to subepicardial blood flow decreased from 1.30±0.07 to 0.69±0.05. In dogs with LVH, during adenosine infusion, LV circumferential end-systolic and end-diastolic wall stresses and LV radial subendocardial wall stresses remained elevated, the increase in LV subendocardial blood flow was significantly smaller (from 1.11±0.11 to 2.27±0.24 mL · min-1 · g-1, P<.05), and the subendocardial/epicardial ratio fell to a lower level (from 1.22±0.17 to 0.35±0.03, P<.05). When LV wall stresses during adenosine were reduced in a subgroup of 5 dogs with LVH, the endocardium/epicardium ratio during adenosine infusion was no longer different from that in control dogs (0.63±0.11), nor was the level of subendocardial blood flow different (3.42±0.60 mL · min-1 · g-1).
Conclusions These data suggest that hemodynamic factors, eg, compressive forces, are an important component of the reduced subendocardial coronary reserve as opposed to structural alterations, even in the presence of severe LVH.
Key Words: vasodilation • blood flow • adenosine • myocardium • wall stress
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Reduced subendocardial coronary reserve in response to physiological stress such as pacing,1 2 3 4 5 exercise,6 7 8 9 10 11 or the coronary vasodilator adenosine1 2 12 is a hallmark of left ventricular hypertrophy (LVH). Increased vulnerability to abnormal perfusion in the hypertrophied heart has been ascribed to structural alterations, eg, vascular rarefaction or vascular hypertrophy,13 14 although a role for hemodynamic factors, eg, increased extravascular forces, has also been implicated.15 16 17 In dogs with severe LVH and heart failure, exhaustion of subendocardial blood flow reserve is associated with myocyte necrosis and fibrosis, suggesting that structural alterations play an important role in the development of heart failure.12 Furthermore, a recent study from our laboratory demonstrated in dogs with severe but compensated LVH that there were no transmural differences in vascular morphology and no reduction in volume percentage capillary space, suggesting that at this phase of the process of hypertrophy, structural alterations may not be the primary mechanism responsible for the reduced subendocardial coronary reserve.18 In support of this concept, it is well recognized that compressive forces across the myocardial wall affect the coronary circulation.15 16 17 18 19 20
Therefore, the goal of the present investigation was to examine the effects of near-maximal coronary vasodilation with adenosine infusion on regional myocardial blood flow in control dogs and in dogs with severe but compensated LVH under normal conditions and in dogs with LVH when preload was altered. In one set of experiments, preload was normalized in the dogs with LVH to match responses in sham-operated control dogs. In another set of experiments, preload was elevated further in dogs with LVH. It was considered important to calculate global circumferential and regional radial wall stresses because our hypothesis was that the compressive subendocardial radial stress, rather than structural changes, dictated the abnormal subendocardial blood flow response during near-maximal coronary vasodilation in dogs with LVH.
The rationale for evaluating this additional wall stress component stems from the fact that radial wall stress is the only compressive stress; the other two components, namely circumferential and meridional, are tensile.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Model Development
Mongrel puppies of either sex 8 to 10 weeks of age were anesthetized with sodium thiamylal 12.5 mg/kg, maintained with halothane (1 vol%), and ventilated with a respirator (Harvard Apparatus). A right thoracotomy was performed through the fourth intercostal space with sterile surgical technique. The ascending aorta above the coronary arteries was isolated and dissected of surrounding tissue. A 1-cm-wide Teflon cuff was placed around the aorta and tightened until a thrill could be palpated over the aortic arch, and the chest was closed. In the littermates designated as controls, a right thoracotomy was performed, the aortic root dissected, and the chest closed without implantation of a band. The Teflon band created a fixed supravalvular aortic lesion, which became relatively more stenotic as the puppies grew.
Implantation of Instrumentation
At approximately 1 year of
age, 10 adult aortic-banded (LVH)
dogs, 6 additional nonbanded but sham-operated littermates, and 3
mongrel dogs were instrumented. After induction with sodium thiamylal
(12.5 mg/kg) and maintenance with halothane anesthesia (1 to 2 vol%),
an incision was made in the fifth left intercostal space by use of
sterile surgical technique. Tygon catheters (Norton Elastics and
Synthetic Division) were implanted in the descending thoracic aortas
and left atria of all the dogs and in the LV chambers of the banded
dogs. In all dogs, piezoelectric ultrasonic dimension crystals were
implanted on opposing anterior and posterior endocardial surfaces of
the left ventricle to measure LV ID. Full-wall thickness was also
measured in all dogs by implantation of piezoelectric ultrasonic
dimension crystals on opposing endocardial and epicardial surfaces in
the same equatorial plane as the ID crystals. Endocardial crystals were
placed through a stab wound in the epicardium and advanced obliquely
to, but not through, the endocardium. In addition, a piezoelectric
ultrasonic dimension crystal was advanced obliquely to the midwall of
the myocardium between the endocardial and the epicardial crystals for
assessment of LV regional wall motion. Placement of these crystals was
aided by intraoperative measurements of wall thickness. A solid-state
miniature pressure transducer (model P5, Konigsberg Instruments) was
implanted in the LV chamber to measure LV pressure in all dogs. Pacing
electrodes were implanted on the left atrium. The thoracotomy incision
was closed in layers, and the animals were allowed to recover for 2
weeks before study. The animals used in this study were maintained
according to the guidelines in "Care and Use of Laboratory
Animals" from the Institute of Laboratory Animal Resources, National
Council (Department of Health and Human Services publication [NIH]
No. 85-23, revised 1985).
Experimental Measurements
Statham strain-gauge manometers
(model P23ID, Statham
Instruments) connected to the chronically implanted catheters were
calibrated with a mercury manometer and used to measure aortic, left
atrial, and LV pressures. LV pressure was also measured with a
solid-state miniature pressure gauge calibrated in vitro with a mercury
manometer and in vivo with the LV catheter and Statham strain-gauge
manometer. The calibration for diastolic LV pressures, including zero
pressure, was obtained from the simultaneous left atrial pressure
measurement. In 1 dog, the LV pressure gauge did not operate properly.
LV ID, LV full-wall thickness, and subendocardial and subepicardial
wall thicknesses were measured with an ultrasonic transit-time
dimension gauge, which was calibrated before, during, and after the
experiment. The positions of all catheters and crystals were confirmed
at autopsy. Full-wall thickness and subendocardial wall thickening were
measured directly from piezoelectric crystals in all dogs, whereas
subepicardial wall thickening could be measured in 7 of the LVH dogs
and 7 control dogs.
Blood Flow Measurements
Regional myocardial blood flow was
measured with isotopically
labeled microspheres (15±2 µm in diameter, New England Nuclear) in
9
control dogs and in 10 dogs with LVH. The radioactive label of the
microspheres (141Ce, 113Sn, 114In,
51Cr, 103Ru, 95Nb,
85Sr, or 46Sc) was chosen randomly. The
microspheres were suspended in 0.01% Tween 80 solution (10% dextran)
agitated by direct application of an ultrasonic probe to ensure
dispersion of the microspheres and placed in an ultrasonic bath for at
least 30 minutes before injection. Before the injection of
microspheres, 0.8 mL Tween 80 dextran solution (without microspheres)
was injected to determine whether the diluent for the microsphere
suspension would have an adverse effect on measurement of cardiac or
systemic hemodynamics. Approximately 1 to 2 million microspheres were
injected through the catheter implanted in the left atrium for
determination of blood flow. A reference sample of arterial blood was
withdrawn (7.75 mL/min) from the catheter in the descending thoracic
aorta. Reference sample withdrawal was initiated 15 seconds before
microsphere injection and continued for approximately 90 seconds after
the injection was completed. At the end of the experiments, the dogs
were killed with a lethal dose of sodium pentobarbital (50 mg/kg IV).
The atria and the right ventricular free walls were removed and
weighed. The LV free wall plus septum was also weighed. Samples of
myocardial tissue from the right ventricular (RV) free wall were
separated into subendocardial and subepicardial layers. Tissue samples
from the LV free wall, septum, and anterior and posterior papillary
muscles were subdivided into four equal transmural layers from
epicardium to endocardium, weighed, and placed in a gamma counter
(Canberra Industries) with appropriately selected energy windows. The
raw counts were corrected for background and crossover and compared
with the reference blood sample to obtain flow expressed in milliliters
per minute per gram of tissue. The blood flow data from the four LV
areas were averaged to yield one number for LV blood flow.
Endocardial/epicardial (Endo/Epi) blood flow ratios per gram were
obtained by dividing blood flow per gram in the subendocardial layer by
that in the subepicardial layer.
Experimental Protocol
Experiments were performed in a quiet
laboratory with the
unsedated, conscious dogs resting comfortably in the right lateral
position. Near-maximal coronary vasodilation was assessed in 9 control
dogs and 10 dogs with severe but compensated LVH by use of intravenous
administration of adenosine (4.7
µm · kg-1 · min-1).
Radioactive
microspheres were injected for measurement of regional myocardial blood
flow at baseline and during adenosine infusion. Because adenosine
altered LV end-diastolic pressure and wall stresses in dogs
with LVH, the adenosine infusion was repeated in 5 dogs with LVH after
preload was reduced with mild hemorrhage (14±2 mL/kg), and heart rate
was held constant with implanted left atrial electrodes. Radioactive
microspheres were again injected during near-maximal vasodilation.
Finally, to examine the relation between radial
end-diastolic subendocardial wall stress and myocardial
blood flow, end-diastolic pressure was further increased in
5 dogs with LVH by acute volume overload (42±8 mL/kg), with heart rate
held constant at approximately 150 beats per minute. Radioactive
microspheres were again injected during near-maximal vasodilation
induced by adenosine.
Data Analysis
The data were recorded on a multichannel tape
recorder (model
101, Honeywell) and played back on a direct-writing oscillograph (Mark
200, Gould-Brush). A cardiotachometer (model 9857B, Beckman
Instruments) triggered by the LV pressure pulse provided instantaneous
records of heart rate, and LV dP/dt was derived from the LV pressure
signals by use of operational amplifiers connected as differentiators
with a frequency response of 700 Hz. A triangular wave signal was
substituted for the pressure signals to calibrate directly the
differentiator. LV end-diastolic dimensions were measured
at the onset of LV contraction, indicated by the initial increase in LV
dP/dt. LV end systole was defined as the point of maximum negative
dP/dt. LV circumferential end-diastolic and end-systolic
stresses were calculated with a cylindrical model: stress=1.36(PD/2h),
where P is LV pressure, D is short-axis ID, and h is wall
thickness.21 The average radial end-diastolic
subendocardial (
endo/ed) and subepicardial
(epi/ed) wall stresses were calculated with the
following formulas:
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where aed is end-diastolic radius (end-diastolic short axis diameterx0.5), hen and hep are the subendocardial and subepicardial wall thicknesses, respectively, at end diastole, and bed=aed+hen+hep (see the Appendix).
Statistical Analysis
Statistical analysis was performed by
use of SUPER
ANOVA (Abacus Concepts) on a Macintosh computer. The data are
reported as mean±SEM. The data were analyzed by ANOVA, with a
repeated-measures factor used for the administration of adenosine and a
grouping factor used to differentiate the normal group of animals from
the animals with LVH. Fisher's least-significant difference was used
as a post hoc test. When stresses were normalized, an ANOVA with two
repeated measures was used because the same animals were examined both
before and after normalization of stress and before and with
administration of adenosine. Significance was recorded for values of
P
.05.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Chronic pressure overload induced by aortic banding caused a 79% increase (P<.01) in the LV weight/body weight ratio in dogs with LVH compared with controls (Table 1
). There were no
major differences in either the body weights or the RV weight/body
weight ratio between groups (Table 1).
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Baseline Hemodynamics and LV Function
Table 2
shows baseline systemic hemodynamics. At
baseline, mean arterial pressure and heart rate were similar in both
groups, whereas diastolic arterial pressure was greater
(P<.05) in dogs with LVH compared with normal dogs.
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Table
3 lists baseline LV hemodynamics and dimensions.
At baseline, LV systolic pressure was significantly greater
(P<.01) in dogs with LVH compared with control dogs. LV
dP/dt, LV end-diastolic and end-systolic diameters, and LV
end-diastolic pressure were not significantly different in
the two groups. LV end-diastolic wall thickness was greater
(P<.05) in dogs with LVH compared with control dogs. Table
4 shows the LV wall stresses in both groups of animals.
Baseline LV circumferential end-systolic wall stress tended to be
greater in dogs with LVH compared with control dogs (107±14 versus
78±4 g/cm2), but the difference was not statistically
significant (P=.07). LV end-diastolic
circumferential stress and LV radial end-diastolic
subendocardial and subepicardial wall stresses were not different in
the two groups, but baseline values for radial subepicardial wall
stress were lower (P<.05) and relatively insignificant
compared with radial subendocardial wall stress (-6.4±0.7 versus
-7.8±0.7, control versus LVH subendocardial wall stress, and
-1.5±0.2 versus -1.6±0.2, control versus LVH
subepicardial wall
stress).
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Effects of Adenosine on Systemic LV Hemodynamics and LV Wall
Stresses
Table 2
shows the effects of near-maximal
vasodilation induced by
adenosine infusion on systemic hemodynamics. Both groups showed
significant decreases in mean and diastolic arterial pressures and
increases in heart rate. After adenosine infusion, systemic
hemodynamics were similar in the two groups. Table 3 gives the
responses of LV hemodynamics to adenosine infusion. In both groups, LV
systolic pressure and LV end-diastolic and end-systolic
diameters decreased (P<.05), although the decrease in LV
end-systolic diameter was less (P<.05) in dogs with LVH
compared with control dogs. Similar nonsignificant changes in LV dP/dt
were observed in both groups. However, in control dogs, LV
end-diastolic pressure decreased significantly
(P<.05) during adenosine infusion, but in dogs with LVH, LV
end-diastolic pressure remained elevated during adenosine
infusion, with the resultant responses being different
(P<.01). Table 4 shows the effects of adenosine on
LV wall
stresses. During adenosine infusion, the changes in LV circumferential
end-systolic wall stress were not different; however, LV
circumferential end-systolic stress was greater (P<.01)
during adenosine infusion in dogs with LVH compared with control dogs.
During adenosine infusion, LV circumferential end-diastolic
wall stress and LV compressive radial end-diastolic
subendocardial stress decreased significantly in control dogs but
remained elevated in dogs with LVH, with the resultant responses being
significantly different (P<.01). This was most apparent for
the compressive radial subendocardial wall stress (-3.9±0.6
versus
-9.1±0.9 g/cm2, respectively, Fig 1).
Radial end-diastolic subepicardial
stress demonstrated a qualitatively similar pattern, but the changes
with adenosine infusion were minor because of the relatively low
baseline values.
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, dotted line) and dogs
with LV hypertrophy (LVH) (
, solid line). At baseline, wall
stresses were not different, but with adenosine, wall stresses were
significantly greater (*P<.05) in dogs with LVH. Note that
radial wall stresses (
Effects of Adenosine Infusion on Regional Myocardial Blood
Flow
Table 5 describes the transmural myocardial blood
flows in the left ventricle at baseline and during near-maximal
vasodilation induced by adenosine infusion. At baseline, values were
not different in the two groups. In response to adenosine infusion, the
increase in blood flow in the subendocardium was less
(P<.01) and the increase in the subepicardium was greater
(P<.05) in dogs with LVH compared with control dogs. The LV
Endo/Epi ratio fell to a greater extent (P<.01) in dogs
with LVH (0.35±0.03) compared with control dogs (0.69±0.05).
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Effects of Alterations in Preload
To determine whether
compressive forces could play a role in the
impairment of subendocardial myocardial blood flow during near-maximal
vasodilation induced by adenosine, additional experiments were
performed in a subgroup of 5 dogs with LVH. In the first set of
experiments, heart rate was kept constant, and LV
end-diastolic pressure was decreased by mild hemorrhage
(14±2 mL/kg) to simulate the hemodynamics observed both at baseline
and during adenosine infusion in control dogs (Table 6).
At baseline, mild hemorrhage did not affect mean arterial pressure, LV
subendocardial and subepicardial blood flows, and the Endo/Epi ratio.
LV systolic pressure, LV end-diastolic pressure (5.8±1.5
versus 9.1±2.0 mm Hg), and LV radial subendocardial wall stress
(-4.4±1.1 versus -7.0±1.5) were less
(P<.05) at
baseline during preload reduction than before preload reduction. After
preload reduction during near-maximal vasodilation with adenosine, LV
circumferential end-systolic and end-diastolic wall
stresses and LV radial subendocardial wall stress decreased in dogs
with LVH (Fig 2). LV subendocardial blood flow increased
to the level observed in control dogs (3.42±0.60
mL · min-1 · g-1 versus
3.58±0.27
mL · min-1 · g-1, Fig
3,
right), and the LV Endo/Epi ratio (0.63±0.11) was no
longer different from that observed in control dogs (0.69±0.05, Fig
4).
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, solid line)
preload reduction in dogs with LV hypertrophy (LVH). Significantly
different responses (P<.05) are noted by asterisks. After
preload reduction, wall stresses fell with adenosine, as was observed
with control dogs (Fig 1
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In another set of experiments, preload was increased
by use of volume
load. Fig 5 displays the relation between radial
end-diastolic subendocardial wall stress and
subendocardial blood flow (top) and Endo/Epi ratio (bottom) during
adenosine infusion under all three conditions studied. A good
correlation was observed between LV radial end-diastolic
stress and subendocardial blood flow (r=.69) and Endo/Epi
ratio (r=.71).
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), and during increased preload with volume load
( |
Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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With the development of LVH, baseline myocardial function is generally preserved without major changes in baseline levels of myocardial perfusion across the LV wall.1 2 9 12 22 However, reduced subendocardial coronary reserve in response to near-maximal vasodilation has been a hallmark of LVH.1 2 3 4 5 6 7 8 9 10 11 12 Our current results confirm this with adenosine, as near-maximal vasodilation induced selective impairment in subendocardial blood flow in dogs with LVH. Our hypothesis was that the abnormal levels of LV end-diastolic wall stresses in dogs with LVH during near-maximal vasodilation are particularly responsible for the impairment in subendocardial blood flow. Indeed, when the elevated LV wall stresses during adenosine infusion were normalized by preload reduction in dogs with LVH, subendocardial blood flow and the Endo/Epi ratio were actually no longer different from values observed in sham-operated control dogs.
These data suggest that the reduced subendocardial reserve in this
model of LVH cannot be explained by structural alterations. This is
consistent with morphologic data obtained recently from our laboratory
in dogs with LVH.18 In that study, no transmural
differences in capillary or arteriolar density were observed in the
hypertrophied hearts; in fact, the volume percentage of capillary space
was not reduced in this model of LVH.18 We also showed
previously that in dogs with compensated LVH, subendocardial fibrosis
is only modestly elevated,12 making it improbable that
this structural alteration is responsible for the reduced coronary
reserve. Finally, when preload was elevated during adenosine infusion
in dogs with LVH in the present study, there was further compromise
of subendocardial coronary reserve (Fig 5), supporting the
concept of
the critical role of subendocardial compressive forces in dictating
coronary blood flow distribution in LVH. Because perfusion of the
subendocardial layer is related to the diastolic coronary pressure
minus the back pressure, which is reflected by the subendocardial
compressive forces, it follows that perfusion of the subendocardial
layers would be enhanced when the increased compressive forces
characteristic of LVH were alleviated. This is indeed what we observed
in the dogs with LVH when preload was reduced.
These data also argue against the possibility that there is impaired smooth muscle vasoactivity, potentially caused by perivascular fibrosis or other factors, in this model of severe hypertrophy. It is also well recognized that preload plays a primary role in the transmural distribution of myocardial blood flow; eg, in healthy dogs, an increase in preload selectively reduces myocardial blood flow in the subendocardial layers. For example, Ellis and Klocke23 showed that an increase in preload from 6 to 20 mm Hg reduced subendocardial blood flow from 1.40 to 1.10 mL · min-1 · g-1. Recently, Duncker et al17 examined the role of extravascular compressive forces during near-maximal coronary vasodilation with adenosine using the coronary pressure-flow relation in anesthetized dogs with LVH induced by aortic banding. Their results demonstrated an increase in minimum coronary resistance and an increase in extravascular compressive forces during near-maximal vasodilation,17 consistent with the findings in the present study. In that study, however, the effects of the extravascular compressive forces on regional myocardial blood flow were not assessed. Interestingly, in a study by Jeremy et al,24 when intracoronary adenosine was delivered to dogs with renovascular hypertension–induced LVH, the reduction in coronary reserve was more prominent at higher pressures in the hypertrophied heart.
The impaired subendocardial coronary reserve in dogs with LVH was observed in the presence of increased LV circumferential end-diastolic and end-systolic wall stresses and subendocardial radial stress. During adenosine infusion in dogs with LVH, subendocardial wall stress actually increased; in sham-operated control dogs, it decreased. These data paralleled those for LV diastolic pressure, which can be discerned from inspection of the model used for radial subendocardial wall stress, which is influenced most heavily by the LV pressure measurement. The observed alteration in subendocardial blood flow in association with increases in LV end-diastolic radial wall stress in the present study extends to the hypertrophied heart the findings from previous studies in normal preparations that demonstrated the influence of the distribution of myocardial stress on coronary blood flow19 23 and the effects of vascular compression on the diameters of subendocardial and subepicardial microvessels.25
In contrast to the present study where the emphasis is on diastolic stresses, other investigators examined the effects of strain on the regulation of blood flow. However, this interest has been concentrated on systole. Downey et al26 concluded from their studies that although myocardial fiber shortening strain contributed to extravascular compression, this effect was evenly distributed. However, they did not study diastolic flow patterns as a function of diastolic pressure. On the other hand, Williams et al27 compared flow distributions with perfusion limited to systole and with coronary perfusion during the whole cardiac cycle in unloaded, beating hearts. Using adenosine to maximally dilate the arteries and obviate autoregulation, they found a gradient of extravascular compression across the LV wall attributable to strain changes. This result is qualitatively similar to what one might expect for the radial stress distribution, which decreases from the endocardium to the epicardium. Unfortunately, the data available in the present study were insufficient to evaluate radial strains accurately. On the other hand, it must be noted that strain results from the application of a stress that is not only a function of strain but also the elasticity of the material, which varies with load; therefore, stress might be a more sensitive parameter than strain.
In summary, the present study demonstrates that hemodynamic, rather than structural, factors are critical in mediating the reduced subendocardial blood flow reserve observed in dogs with chronic pressure-overload LV hypertrophy. The elevated LV end-diastolic pressure and wall stresses, particularly in the subendocardial region, play a primary role in mediating the abnormal subendocardial coronary reserve because when LV end-diastolic pressure and circumferential and radial subendocardial wall stresses were normalized, subendocardial blood flow responses to near-maximal vasodilation in dogs with LVH were normal. These conclusions may not be extrapolated to all models of hypertrophy, particularly models associated with significantly reduced subendocardial capillary density. Importantly, however, similar findings were observed in experimental cardiomyopathy, which is characterized by a dilated heart, increased wall stress, and no hypertrophy.28 In that model, reducing the increased load to control levels also normalized the deficit in subendocardial coronary reserve.28
Clinical Implications
LVH is a major risk factor for
cardiovascular morbidity and
mortality29 ; LV wall stress is increased at rest at the
stage of heart failure and increased further during the stress of
catecholamine infusion30 or
exercise.9 10 11
Chronic treatment with vasodilators, eg, angiotensin-converting enzyme
inhibitors, can improve the morbidity and mortality of heart
failure.31 32 Reduction in loading conditions is part
of
the rationale for the use of vasodilators in the therapeutic regimen in
heart failure.33 Their beneficial effects are usually
explained by the blockade of the renin-angiotensin and the sympathetic
systems. However, as demonstrated in the present study, elevated
compressive forces during episodes of vasodilation reduce
subendocardial perfusion, whereas reduction of compressive forces
improves perfusion. This mechanism could also play a role in the
pathogenesis of heart failure34 35 and in the
salutary
action of vasodilator and converting enzyme inhibitor therapy.
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Acknowledgments |
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This work was supported in part by US Public Health Service grants HL-38070, HL-33107-11, and HL-33065-08, as well as RR-00168 and INSERM. We wish to thank Amy Kerdok for her technical assistance.
Evaluation of Subendocardial and Subepicardial Radial
Wall
Stresses
Assuming a cylindrical annulus at the site where geometric
measurements are made, the radial wall stress (r) at any
radius r is given by
 |
where
P is the LV cavity pressure and a and b are the inner and
outer radii respectively.21 In particular, the average
subendocardial (ren) and superepicardial
(rep) radial wall stresses take the form
 |
 |
and
 |
 |
where hen and hep are the subendocardial and subepicardial wall thicknesses, respectively, and b=a+hen+ hep.
If the full LV wall thickness is given by h=hen+ hep and ID by D, the above expressions for radial wall stresses may be written in the form
 |
and
 |
Received January 3, 1995; revision received March 8, 1995; accepted March 9, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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