Myocardial contraction is closely connected to
coronary flow and oxygen delivery, the balance
between oxygen supply and demand is a critical
determinant of the normal beat-to-beat function of
A knowledge of the regulation of coronary blood
flow, determinants of myocardial oxygen
consumption, and relationship between ischemia
and contraction is essential for understanding the
pathophysiologic basis and management of many
Determinants of myocardial oxygen consumption
Determinants of coronary vascular resistance
Extravascular compressive resistance
Resistance within microcirculation
Structure and funtion
Flow mediated resistance artery control
Neural control of resistance and conduit arteries
MYOCARDIAL OXYGEN CONSUMPTION
In contrast to most other vascular beds, myocardial
oxygen extraction is near-maximal at rest, averaging
approximately 75% of arterial oxygen content.
Increases in myocardial oxygen consumption are
primarily met by proportional
increases in coronary flow and
In addition to coronary flow, oxygen delivery is
directly determined by arterial oxygen content (Pao2).
Fick equation and the relationship between heart rate (HR)–systolic pressure (SBP) double
product and myocardial oxygen consumption . A, Increases in are primarily met by increases
in coronary flow and linearly related to the double product. Twofold increases in HR, SBP, or
contractility each result in approximately 50% increases in myocardial oxygen consumption.
The major determinants of myocardial oxygen consumption are
systolic pressure (or myocardial wall stress), and
left ventricular (LV) contractility.
A twofold increase in any of these individual determinants of
oxygen consumption requires an approximately 50% increase
in coronary flow.
The basal myocardial oxygen requirements needed to
maintain critical membrane function are low and the cost of
electrical activation is trivial when mechanical contraction
ceases during diastolic arrest and diminishes during ischemia.
Regional coronary blood flow remains constant
as coronary artery pressure is reduced below
aortic pressure over a wide range when the
determinants of myocardial oxygen consumption
are kept constant.
This phenomenon is termed
Autoregulatory relationship under basal conditions and following metabolic stress
Following stress (right panel), tachycardia increases the compressive determinants of coronary
resistance by decreasing the time available for diastolic perfusion and thus reduces maximum
vasodilated flow. In addition, increases in myocardial oxygen demand or reductions in arterial oxygen
content increase resting flow. These changes reduce coronary flow reserve, the ratio between dilated
and resting coronary flow, and cause ischemia to develop at higher coronary pressures.
Resting coronary blood flow under normal
hemodynamic conditions averages 0.7 to 1.0
mL/min/g and can increase between four- and
fivefold during vasodilation.
The ability to increase flow above resting values
in response to pharmacologic vasodilation is
Flow in the maximally vasodilated heart is dependent
on coronary arterial pressure.
Maximum perfusion and coronary reserve are reduced
when the diastolic time available for subendocardial
perfusion is decreased (tachycardia) or
the compressive determinants of diastolic perfusion
(preload) are increased.
anything that increases resting flow, including
increases in the hemodynamic determinants of oxygen
consumption (systolic pressure, heart rate,
contractility) and reductions in arterial oxygen supply
Thus, circumstances can develop that precipitate
subendocardial ischemia in the presence of normal
Subendocardial flow primarily occurs in diastole and
begins to decrease below a mean coronary pressure
of 40 mm Hg.
In contrast, subepicardial flow occurs throughout the
cardiac cycle and is maintained until coronary
pressure falls below 25 mm Hg.
This difference arises from increased oxygen
consumption in the subendocardium, requiring a
higher resting flow level, as well as the more
pronounced effects of systolic contraction on
subendocardial vasodilator reserve.
Transmural variations in coronary autoregulation and myocardial metabolism
The transmural difference in the lower
autoregulatory pressure limit results in
vulnerability of the subendocardium to
ischemia in the presence of a coronary
Endothelium-Dependent Modulation of
Epicardial arteries do not normally contribute
significantly to coronary vascular resistance,
arterial diameter is modulated by a wide variety
of paracrine factors that can be released from
platelets, as well as circulating neurohormonal
agonists, neural tone, and local control through
vascular shear stress.
Endothelium-dependent control of vascular tone.
CORONARY VASCULAR RESISTANCE
The resistance to coronary blood flow can be
divided into three major components,
R1 - epicardial conduit artery resistance
R2 - resistance secondary to metabolic and
autoregulatory adjustments in flow and occurs in
arterioles and resistance arteries
R3 - time-varying compressive resistance that is higher
in subendocardial than subepicardial layers
R1:Under normal circumstances, there is no
measurable pressure drop in the epicardial arteries,
indicating negligible conduit resistance.
With the development of hemodynamically
significant epicardial artery narrowing (more than
50% diameter reduction), the fixed conduit artery
resistance begins to contribute an increasing
component to total coronary resistance and, when
severely narrowed (more than 90%), may reduce
R2:The second component of coronary resistance is
dynamic and primarily arises from microcirculatory
resistance arteries and arterioles.
This is distributed throughout the myocardium across a
broad range of microcirculatory resistance vessel size
(20 to 200 μm in diameter) and changes in response to
physical forces (intraluminal pressure and shear stress),
as well as the metabolic needs of the tissue.
There is normally little resistance contributed by
coronary venules and capillaries and their resistance
remains fairly constant during changes in vasomotor
R3: The third component, or compressive resistance,
varies with time throughout the cardiac cycle and is
related to cardiac contraction and systolic pressure
development within the left ventricle.
In heart failure, compressive effects from elevated
ventricular diastolic pressure also impede perfusion
via passive compression of microcirculatory vessels
by elevated extravascular tissue pressure during
Increases in preload effectively raise the normal back
pressure to coronary flow above coronary venous
Extravascular Compressive Resistance (R3)
During systole, cardiac contraction raises extravascular
tissue pressure to values equal to LV pressure at the
This declines to values near pleural pressure at the
The increased effective backpressure during systole
produces a time-varying reduction in the driving
pressure for coronary flow that impedes perfusion to
Transmural Variations in Minimum Coronary
Resistance (R2) and Diastolic Driving Pressure
The subendocardial vulnerability to compressive
determinants of vascular resistanceis partially
compensated for by a reduced minimal resistance
from an increased arteriolar and capillary density.
Coronary vascular resistance in the maximally
vasodilated heart is also pressure-dependent,
reflecting passive distention of arterial resistance
Thus, the instantaneous vasodilated value of
coronary resistance obtained at a normal coronary
distending pressure will be lower than that at a
Structure and Function of the Coronary
Epicardial arteries (>400 μm in diameter) serve a conduit
artery function, with diameter primarily regulated by shear
stress, and contribute little pressure drop (<5%) over a wide
range of coronary flow.
Coronary resistance vessels can be divided into
resistance arteries (100 to 400 μm), which regulate their tone
in response to local shear stress and luminal pressure changes
(myogenic response), and
arterioles (>100 μm), which are sensitive to changes in local
tissue metabolism and directly control perfusion of the low-
resistance coronary capillary bed.
Capillary density of the myocardium averages 3500/mm2,
resulting in an average intercapillary distance of 17 μ m, and
is greater in the subendocardium than the subepicardium.
Transmural distribution of coronary resistance vessels—major vasodilatory and vasoconstrictor
mechanisms in epicardial conduit arteries and different sites of the microcirculation
Under resting conditions, most of the pressure drop
in the microcirculation arises in resistance arteries
between 50 and 200 μm in size, with little pressure
drop occurring across capillaries and venules at
normal flow levels.
Following pharmacologic vasodilation with
dipyridamole, resistance artery vasodilation
minimizes the precapillary pressure drop in arterial
At the same time, there is an increased pressure
drop and redistribution of resistance to venular
vessels, in which smooth muscle relaxation is limited
and the already low resistance is fairly fixed.
Microcirculatory pressure profile and local resistance changes to physiologic stimuli
in subepicardial vessels
Heterogeneous arterial microvessel response during autoregulation.
A reduction in pressure to 38 mm Hg elicited dilation in arterioles smaller than 100 um, whereas
larger arteries tended to constrict passively from the reduction in distending pressure.
Homogeneous vasodilation of resistance arteries during increases
in myocardial oxygen consumption.
There is dilation in all microvascular resistance arteries that is greatest in
vessels smaller than 100 um.
There is considerable heterogeneity in
microcirculatory vasodilation during physiologic
adjustments in flow.
For example, as pressure is reduced during
autoregulation, dilation is primarily accomplished by
arterioles smaller than 100 um, whereas larger
resistance arteries tend to constrict because of the
reduction in perfusion pressure.
In contrast, metabolic vasodilation results from a
more uniform vasodilation of resistance vessels of all
Similar inhomogeneity in resistance vessel dilation
occurs in response to endothelium-dependent
agonists and pharmacologic vasodilators.
A unique component of subendocardial coronary
resistance vessels are the transmural penetrating
arteries that course from the epicardium to the
These vessels are removed from the metabolic
stimuli that develop when ischemia is confined to
As a result, local control from altered shear stress
and myogenic relaxation to local pressure become
very critical determinants of diameter in this
“upstream” resistance segment.
Even during maximal vasodilation, this segment
creates an additional longitudinal component of
coronary vascular resistance that must be traversed
before the arteriolar microcirculation is reached.
Because of this greater longitudinal pressure drop,
the microcirculatory pressures in subendocardial
coronary arterioles are lower than in the
Intraluminal Physical Forces Regulating
- the ability of vascular smooth muscle to oppose
changes in coronary arteriolar diameter.
Thus, vessels relax when distending pressure is
decreased and constrict when distending
pressure is elevated
Although the cellular mechanism is uncertain, it is
dependent on vascular smooth muscle calcium
entry, perhaps through stretch-activated L-type Ca2+
channels, eliciting cross-bridge activation.
The resistance changes arising from the myogenic
response tend to bring local coronary flow back to
the original level.
Myogenic regulation has been postulated to be one
of the important mechanisms of the coronary
autoregulatory response and, in vivo, appears to
occur primarily in arterioles smaller than 100 um
Effects of physical forces on coronary diameter in isolated human coronary resistance arteries.
As distending pressure is reduced from 100 mm Hg, there is progressive vasodilation consistent
with myogenic regulation.
Flow-Mediated Resistance Artery Control
Originally demonstrated by Kuo and colleagues.
They found this to be endothelium-dependent
and mediated by NO, because it could be
abolished with an l-arginine analogue.
Flow-mediated vasodilation in cannulated human resistance arteries.
As the pressure gradient across the isolated vessel is increased, intraluminal flow rises
and causes progressive dilation that is abolished by removing the endothelium.
Similar flow-mediated dilation occurs in most arterial vessels, including the coronary
Neural Control of Coronary Conduit and
In normal arteries, acetylcholine elicits vasodilation but there is vasoconstriction in the
atherosclerotic artery, which is particularly pronounced in the stenosis.
Activation of sympathetic tone normally leads to net epicardial dilation but there is
vasoconstriction in irregular and stenotic coronary segments in patients with atherosclerosis.
PHYSIOLOGICAL ASSESSMENT OF
CORONARY ARTERY STENOSES
STENOSES PRESSURE FLOW RELATIONSHIP
The relationship between pressure drop across a
stenosis and coronary flow for stenoses between
30% and 90% diameter reduction can be described
using the Bernoulli principle.
The total pressure drop across a stenosis is governed
by three hydrodynamic factors—
separation losses, and
Fluid mechanics of a stenosis. The pressure drop across a stenosis can be predicted by the
Bernoulli equation. It is inversely related to the minimum stenosis cross-sectional area and
varies with the square of the flow rate as stenosis severity increases.
An = area of the normal segment; As = area of the stenosis; f1 = viscous coefficient; f2 =
separation coefficient; L = stenosis length; ΔP = pressure drop; = flow; u = viscosity of blood; ρ
= density of blood.
The single most important determinant of stenosis
resistance for any given level of flow is the minimum
lesional cross-sectional area within the stenosis.
Resistance is inversely proportional to the square of
the cross-sectional area.
Separation losses determine the curvilinearity or
steepness of the stenosis pressure-flow relationship.
Stenosis length and changes in cross-sectional area
distal to the stenosis are relatively minor
Stenosis resistance increases exponentially as
minimum lesional cross-sectional area decreases.
It is also flow dependent and varies with the
square of the flow or flow velocity.
As a result, the instantaneous stenosis resistance
increases during vasodilation.
Curvilinearity of the pressure-flow relationship as stenosis severity increases. The relationship
between pressure drop across the stenosis and flow for diameter narrowing of 30%, 50%, 70%,
80%, and 90% is calculated on the basis of a proximal reference internal diameter of 3 mm (area,
7.1 mm2). Measurements in parentheses are minimal lesional cross-sectional areas.
Instantaneous resistance is the slope of the pressure-flow curve (dashed red line) and, for a
given stenosis, increases as flow rate rises. At levels of resting flow (dashed vertical line), the
stenosis resistance increases exponentially as stenosis severity rises (solid red line in inset)
Interrelationship Among Distal Coronary
Pressure, Flow, and Stenosis Severity
Coronary blood flow reserve
Interrelationship among stenosis flow reserve
Very little increase in epicardial conduit artery
resistance (R1) develops until stenosis severity
reaches a 50% diameter reduction.
As a result, there is no significant pressure drop
across a stenosis or stenosis-related alteration in
maximal myocardial perfusion until stenosis severity
exceeds a 50% diameter reduction (75% cross-
As stenosis severity increases further, the
curvilinear coronary pressure-flow relationship
steepens and increases in stenosis resistance are
accompanied by concomitant increases in the
pressure drop (ΔP) across the stenosis.
This reduces distal coronary pressure, the major
determinant of perfusion to the microcirculation,
and maximum vasodilated flow decreases.
Above a value of 70% diameter reduction, small increases in
stenosis severity are accompanied by further increases in
stenosis pressure drop that reduce distal coronary pressure
and result in progressive reductions in maximal vasodilated
perfusion of the microcirculation.
A critical stenosis, one in which subendocardial flow
reserve is completely exhausted at rest, usually
develops when stenosis severity exceeds 90%.
Under these circumstances, pharmacologic
vasodilation of subepicardial resistance vessels
results in a reduction in distal coronary pressure that
actually redistributes flow from the
subendocardium, leading to a transmural steal
Concept of Maximal Perfusion and
GOULD originally proposed the concept of
There are currently three major indices used to
quantify coronary flow reserve—
Absolute flow reserve
It is expressed as the ratio of maximally vasodilated flow
to the corresponding resting flow value in a specific
region of the heart and quantifies the ability of flow to
increase above the resting value.
Clinically important reductions in maximum flow
correlating with stress-induced ischemia on SPECT
are generally associated with absolute flow reserve
values below 2
Absolute flow reserve is altered not only by factors
that affect maximal coronary flow but also by the
corresponding resting flow value.
Resting flow can vary with hemoglobin content,
baseline hemodynamics, and the resting oxygen
As a result, reductions in absolute flow reserve can
arise from inappropriate elevations in resting
coronary flow and from reductions in maximal
Absolute flow reserve can be quantified using
intracoronary Doppler velocity or
thermodilution flow measurements, as well as by
quantitative approaches to image absolute tissue
perfusion based on PET
In the absence of diffuse atherosclerosis or LV
hypertrophy, absolute flow reserve in conscious
humans is similar to measurements in animals, with
vasodilated flow increasing four to five times the
value at rest.
There is also fairly good reduplication of the
idealized relationship between stenosis severity and
absolute flow reserve in patients with isolated one-
or two-vessel CAD with intracoronary vasodilation.
In contrast, in patients with risk factors such as
hypercholesterolemia and no significant coronary
luminal narrowing, values of absolute flow reserve
using PET are lower than in normals, reflecting
microcirculatory impairment in flow or attenuated
Abnormalities in the coronary microcirculation and
uncertainty in stenosis geometry or diffuse
atherosclerosis lead to considerably more variability
of the observed relationship between stenosis
severity and absolute flow reserve in patients with
more extensive disease.
A significant limitation of absolute flow reserve
measurements is that the importance of an
epicardial stenosis cannot be dissociated from
changes caused by functional abnormalities in the
microcirculation that are common in patients
(e.g., hypertrophy, impaired endothelium-dependent vasodilation).
Relative Flow Reserve
Measured using nuclear perfusion imaging .
In this approach, relative differences in regional
perfusion are assessed during maximal
pharmacologic vasodilation or exercise stress and
expressed as a fraction of flow to normal regions of
This compares relative perfusion under the same
hemodynamic conditions and thus is relatively
insensitive to variations in mean arterial pressure
and heart rate.
An alternative invasive approach uses absolute flow
reserve measurements and derives relative flow
reserve by dividing measurements in a stenotic
vessel by those in remote normally perfused
First, conventional SPECT imaging requires a normal
reference segment within the left ventricle for
Because of this, relative flow reserve measurements
cannot accurately quantify stenosis severity when diffuse
abnormalities in flow reserve related to balanced
multivessel CAD or impaired microcirculatory vasodilation
Large differences in relative vasodilated flow are
required to detect SPECT perfusion differences
because nuclear tracers become diffusion-limited
and their myocardial uptake fails to increase
proportionally with increases in vasodilated flow.
As a result, differences in tracer deposition underestimate
the actual relative difference in perfusion.
This limitation can be overcome with PET tracers of
perfusion and appropriate kinetic modeling.
Finally, whereas prognostic data related to the
perfusion deficit size are available, there are no
imaging studies evaluating the quantitative severity
of the stress or vasodilated flow reduction as a
continuous outcome measure.
Fractional Flow Reserve
This technique, pioneered by PIJLS, is based on the
the distal coronary pressure measured during
vasodilation is directly proportional to maximum
Fractional flow reserve (FFR) is an indirect index
determined by measuring the driving pressure for
microcirculatory flow distal to the stenosis (distal
coronary pressure minus coronary venous pressure)
relative to the coronary driving pressure available in the
absence of a stenosis (mean aortic pressure minus
coronary venous pressure).
The approach assumes linearity of the vasodilated
pressure-flow relationship, which is known to be
curvilinear at reduced coronary pressure, and usually
assumes that coronary venous pressure is zero.
This results in the simplified clinical FFR index of mean
distal coronary pressure/mean aortic pressure (Pd/Pao).
Although derived, the measurements are conceptually
similar to those of relative coronary flow reserve
because they rely only on minimum mean coronary
pressure measurements during intracoronary
vasodilation and compare stenotic with normal regions
(assumed to equal 1) under similar hemodynamic
They are attractive in that they can immediately assess
the physiologic significance of an intermediate stenosis
to help guide decisions regarding coronary intervention
and are unaffected by alterations in resting flow.
Similarly, because they only require vasodilated coronary
pressure measurements, FFR can be used to assess the
functional effects of a residual lesion after PCI.
Routine measurement of FFR in patients with
multivessel coronary artery disease who are
undergoing PCI with drug-eluting stents
significantly reduces the rate of the composite
end point of death, nonfatal myocardial
infarction, and repeat revascularization at 1 year.
As an initial management strategy in patients
with stable coronary artery disease, PCI did not
reduce the risk of death, myocardial infarction, or
other major cardiovascular events when added to
optimal medical therapy.
In patients with stable coronary artery disease and
functionally significant stenoses, FFR-guided PCI plus
the best available medical therapy, as compared
with the best available medical therapy alone,
decreased the need for urgent revascularization.
In patients without ischemia, the outcome appeared
to be favorable with the best available medical
• Fractional Flow Reserve, calculated from
coronary pressure measurement, is an accurate,
invasive, and lesion-specific index to demonstrate
or exclude whether a particular coronary stenosis
can cause reversible ischemia.
• FFR can be determined easily, in the cath-lab,
immediately prior to a planned intervention
DEFER study: background
FFR based strategy for PCI in equivocal stenosis
( DEFER – Study)
The DEFER Study: Objectives
• to test safety of deferring PCI of stenoses
not responsible for inducible ischemia as
indicated by FFR > 0.75 ( “outcome” )
• to compare quality of life in such patients,
whether or not treated by PCI
(CCS-class, need for anti-anginal drugs)
DEFER Group REFERENCE Group PERFORM Group
The DEFER Study: Flow Chart
Patients scheduled for PCI without
Proof of Ischemia (n=325)
performance of PTCA (158)deferral of PTCA
FFR < 0.75
FFR < 0.75
No. at risk
Defer group 90 85 82 74 73 72
Perform group 88 78 73 70 67 65
Reference gr 135 105 103 96 90 88
0 1 2 3 4 5
(FFR < 0.75)
Years of Follow-up
event – free survival (%)
Cardiac Death And Acute MI After 5 Years
DEFER PERFORM REFERENCE
FFR > 0.75 FFR < 0.75
baseline 1month 1 year 2 year 5 year
Defer group Perform group Reference group
freedom from chest pain
FFR > 0.75 FFR > 0.75 FFR < 0.75
Five-year outcome after deferral of PCI of an
intermediate coronary stenosis based on FFR
0.75 is excellent.
The risk of cardiac death or myocardial infarction
related to this stenosis is <1% per year and not
It can only assess the functional significance of
epicardial artery stenoses and cannot assess
physiologic contributions caused by abnormalities in
microcirculatory flow reserve in resistance vessels.
The measurements are also critically dependent on
achieving maximal pharmacologic vasodilation.
In addition, ignoring the backpressure to coronary
flow by assuming that venous pressure is equal to
zero and ignoring curvilinearity of the diastolic
pressure-flow relationship will cause the FFR to
underestimate the physiologic significance of a
This is particularly problematic at low coronary
pressures and when assessing the functional
significance of coronary collaterals where venous
pressure needs to be accounted for.
Finally, inserting the guidewire across a stenosis can
artifactually overestimate stenosis severity caused by
the reduction in effective intralesional area when
there is diffuse disease, when it is placed in small
branch vessels, or in assessing a severe stenosis.
Despite these limitations and its invasive nature,
FFR is currently the most direct way to assess the
physiologic significance of individual coronary lesions.
Pathophysiologic States Affecting
Microcirculatory Coronary Flow Reserve
Abnormalities in coronary flow reserve and
endothelium-dependent vasodilation are common in
women with insignificant coronary disease and can
be accompanied by metabolic ischemia, assessed by
magnetic resonance spectroscopy and they
negatively affect prognosis.
The two most common factors affecting
microcirculatory resistance control independently of
coronary stenosis severity in patients are
LV hypertrophy and
impaired NO-mediated resistance vessel vasodilation.
Left Ventricular Hypertrophy
Effects of left ventricular hypertrophy (LVH) on maximal coronary flow
The effects of hypertrophy on coronary flow reserve are
complex and need to be thought of in terms of the absolute
flow level as well as the flow per gram of myocardium.
With acquired hypertrophy, resting flow per gram of
myocardium remains constant, but the increase in LV mass
necessitates an increase in the absolute level of resting flow
through the coronary artery.
In terms of maximal perfusion, acquired hypertrophy does
not result in vascular proliferation and coronary resistance
vessels remain unchanged.
Because maximum absolute flow remains unchanged,
maximum perfusion per gram of myocardium falls.
The net effect is that coronary flow reserve at any given
coronary arterial pressure is reduced and inversely related to
the change in LV mass
Some degree of LV hypertrophy is common in patients with
CAD and it likely contributes to reductions in coronary flow
reserve that are independent of stenosis severity.
The actual coronary flow reserve in hypertrophy will be
critically dependent on the underlying cause of hypertrophy
and its effects on coronary driving pressure.
A similar degree of hypertrophy caused by untreated systemic
hypertension will have a higher coronary flow reserve than in
aortic stenosis, in which mean arterial pressure remains
Similarly, when hypertrophy is from systolic hypertension and
increased pulse pressure caused by reduced aortic
compliance, the accompanying reduction in diastolic pressure
can lower coronary reserve
Impaired Endothelium-Dependent Vasodilation
Measurements of coronary flow reserve in humans with risk
factors for atherosclerosis are systematically lower than
normals without coronary risk factors and underscore the
importance of abnormalities in microvascular control in
determining coronary flow reserve.
KUO and colleagues have demonstrated that experimental
hypercholesterolemia markedly attenuates the dilation of
coronary arterioles in response to shear stress and
pharmacologic agonists that stimulate NOS in the absence of
This was reversed with l-arginine, suggesting that it reflects
impaired NO synthesis or availability.
Although resting blood flow is not altered, there is a
marked increase in the coronary pressure at which
intrinsic autoregulatory adjustments become
exhausted, with flow beginning to decrease at a
distal coronary pressure of 60 versus 45 mm Hg,
approximately similar to the shift occurring in
response to a twofold increase in heart rate.
In vivo microcirculatory studies have demonstrated
that there is an inability of resistance arteries to
dilate maximally in response to shear stress.
This likely reflects excess resistance in the transmural
penetrating arteries, which are upstream of
metabolic stimuli for vasodilation and extremely
dependent on shear stress as a stimulus for local
These abnormalities amplify the functional effects of
a coronary stenosis, resulting in the development of
subendocardial ischemia at a lower workload
Impaired microcirculatory control with abnormal NO-
mediated endothelium-dependent resistance artery dilation
Transmural perfusion before
and after blocking NO-
mediated dilation with LNNA in
exercising dogs subjected to a
These observations in animals with impaired NO production
appear to be relevant to pathophysiologic states associated
with impaired endothelium-dependent vasodilation in
For example, coronary flow reserve is markedly reduced in
the absence of a coronary stenosis in familial
hypercholesterolemia, and improving endothelial function
by lowering elevated LDL levels with statins produces a
delayed improvement in coronary flow reserve in normal
and stenotic arteries and also ameliorates clinical signs of
Impaired NO-mediated vasodilation likely affects the
regulation of myocardial perfusion in other disease states in
which endothelium-dependent vasodilation is impaired.