1384
Myocardial Oxygen Consumption and the Left
Ventricular Pressure-Volume Area in Normal
and Hypertrophic Canine Hearts
Gerald Izzi, MD; Michael R. Zile, MD; and William H. Gaasch, MD
Background. To assess and compare the energy demands of normal and hypertrophic hearts,
defined the relation between myocardial oxygen consumption (MVo2, an index of the energy
consumed by contraction) and the left ventricular pressure-volume area (PVA, an index of the
total mechanical energy generated by contraction) in eight normal and eight hypertrophic
(aortic band model) dog hearts; MVO2 was also measured in the nonworking (empty beating)
and basal (potassium arrest) states.
Methods and Results. The hearts were studied in an isolated, blood-perfused heart apparatus.
The slope of the MVo2-PVA relation (the inverse of which reflects myofibrillar efficiency) was
similar in normal and hypertrophic hearts (3.89±1.91 and 4.19±1.25 ml 02/mm Hg * ml' 105,
p=NS). The MVo2 in empty beating (0.038±0.006 and 0.041±0.015 mllbeat/100 g, p=NS) and
potassium-arrested (1.95±0.06 and 1.98± 0.20 ml/min/100 g,p=NS) hearts was likewise similar
in the two groups.
Conclusions. Basal and nonworking energy demands and working efficiencies of hypertrophic
hearts are equivalent to those of normal hearts. (Circulation 1991;84:1384-1392)
we
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C oncentric hypertrophy of the left ventricle is
generally considered an appropriate and beneficial physiological adaptation to high intracavitary pressures.1,2 This compensatory change, however, carries certain clinical risks that include a greater
cardiovascular morbidity and mortality caused by myocardial infarction, heart failure, and arrhythmias.3-7 In
addition, some clinical and experimental data indicate
a tendency for hypertrophic hearts to exhibit a decreased tolerance to ischemia.8 In an attempt to define
the mechanisms underlying such changes, we considered the possibility that abnormal energy demands or
inefficient energy metabolism could be responsible.
This notion was based on studies that indicate increased nonwork-related myocardial oxygen requirements in hyperthyroidism and under the condition of
inotropic stimulation.9,10 Not only does the hyperthyroid rabbit heart exhibit a decreased working efficiency and increased energy costs of excitationcontraction coupling, but there is also a tendency for
From the Departments of Medicine and Cardiology, The Baptist
Hospital, Boston (G.I.); the Medical University of South Carolina,
Charleston, S.C. (M.R.Z.); and The Medical Center of Central
Massachusetts, Worcester, Mass. (W.H.G.).
Supported by the American Heart Association, Massachusetts
Affiliate, Inc. G.I. is an American Heart Association PhysicianInvestigator.
Address for correspondence: William H. Gaasch, MD, The Med
Center/Memorial, 119 Belmont St., Worcester, MA 01605.
Received August 7, 1990; revision accepted May 14, 1991.
basal oxygen consumption to be higher than normal
in hyperthyroid hearts.9 Since nonwork-related energy demands can also be increased during inotropic
interventions,10 it would seem that such changes, if
present in hypertrophy, might contribute to an altered tolerance to ischemia. Accordingly, we compared the relative energy demands and efficiencies of
normal and hypertrophic dog hearts by measuring
oxygen consumption under working, nonworking
(empty beating), and basal conditions.
The heart derives essentially all of its energy from
aerobic metabolism; thus its oxygen consumption provides a measure of its total energy utilization.10-12
These energy requirements are influenced by a complex interplay among a variety of factors, all of which
were recognized by Suga and associates13,14 when they
developed what appears to be a reliable yet relatively
simple method to assess cardiac energetics. This
method is based on their demonstration of a direct
relation between the total mechanical energy (or work)
generated by the ventricle and the total energy utilization of the ventricle. This unique relation, formulated
in terms of a time-varying elastance model, used the left
ventricular (LV) pressure-volume area (PVA) as an
index of the mechanical energy generated by the ventricle and the myocardial oxygen consumption (MVo2)
as an index of energy utilization. Although this approach does not address underlying mechanisms, the
MVo2-PVA relation, like the relation between oxygen
Izzi et al Myocardial Oxygen Consumption and LVH
consumption and the force-length area,15 provides a
method to predict energy demands and allows a description of efficiency. Suga et al'6-18 and others have
used this method in normal hearts during a variety of
pharmacological and other interventions, but there is
little such information available in hypertrophic
hearts.10,19 Thus, within the framework of the
MVoz-PVA relation, we compared working, nonworking, and basal energy demands as well as efficiencies
among normal and hypertrophic hearts.
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Methods
Left ventricular hypertrophy (LVH) was produced
by banding the aorta of puppies at 8 weeks of age.
One year later, when substantial hypertrophy was
present, the functional state of the ventricle was
described (combined echocardiographic and catheterization techniques). The hearts were then excised,
placed in an isolated blood-perfused heart apparatus,
and myocardial energetics were studied. Eight hypertrophied hearts and eight normal control hearts were
evaluated.
All animals received humane care in compliance
with the principles of laboratory animal care formulated by the National Society for Medical Research
and the Guide for the Care and Use of Laboratory
Animals prepared by the National Academy of Sciences and published by National Institutes of Health
(NIH Publication No. 85-23, reviewed 1985).
Left Ventricular Hypertrophy Model
At 8 weeks of age, puppies were anesthetized with
sodium pentobarbital (25 mg/kg i.v.) and ventilated
with a tnechanical respirator. A right thoracotomy
was performed through the third right intercostal
space, the pericardium was opened, and the aorta
was dissected free from the periaortic fat and connective tissue. A 5-mm-wide nonconstricting band
was placed around the aorta approximately 2 cm
above the aortic valve. After the banding procedure,
the pericardium was loosely approximated and the
thoracotomy was closed. The animals recovered and
were then allowed to "grow into" supravalvular aortic stenosis.20
At 12 months, when substantial LVH was present,
the banded animals underwent cardiac catheterization and echocardiography to define the functional
state of the left ventricle. The normal control dogs
did not undergo catheterization. The details of these
methods and techniques were published previously.20
Isolated Heart Preparation and Measurements
Our methods and a description of the isolated
blood-perfused dog heart preparation have previously been described in detail.21,22 Briefly, in each
experiment a support dog was anesthetized with
pentobarbital (15-20 mg/kg), anticoagulated with
intravenous heparin, and mechanically ventilated.
The heart from the experimental dog was placed on
cardiopulmonary bypass (perfused with blood from
the femoral artery of the support dog); the heart was
1385
then excised, placed in the isolated heart chamber,
and perfused at a constant pressure of 100 mm Hg.
The coronary venous blood from the isolated heart
was drained from the right atrium and right ventricle
(by a large-bore catheter with multiple side holes)
and returned to the femoral vein of the support dog.
This system provided empty right-heart chambers
throughout the experiment.
Ventricular fibrillation was induced and the left
atrium was opened. A balloon on a silastic mount was
placed in the left ventricle through the mitral annulus
and the heart was submerged in a blood bath maintained at 37°C. A heat exchanger system was used to
maintain the coronary perfusion temperature at
37°C. The heart was defibrillated and the preparation
was allowed to stabilize for 30 minutes before starting the experiment. All studies were performed at
constant heart rate (atrial pacing at approximately
120 beats/min).
LV pressure was measured with a Statham P23Db
pressure transducer. Systolic and diastolic pressures
were measured during incremental additions of saline to the ventricular balloon until systolic pressure
exceeded 100 mm Hg. The volume associated with
this peak systolic pressure was assigned a value of
100% (Vl,o) and all other volumes were related to the
100% volume. Thus, LV pressures were assessed
over a range of five volumes (i.e., V20, V40, V60, V80,
V100)4
Coronary blood flow was measured with an in-line
flowmeter. Blood was sampled from the arterial
(perfusion) and coronary venous catheters and pH,
Po2 and Pco2 were determined using a blood gas
analyzer (Instrumentation Laboratory, Watertown,
Mass.). Arterial and venous oxygen contents were
calculated from the blood oxygen saturation and the
measured hemoglobin concentration using the nomogram of Rossing and Cane.23
Pressure-Volume Area
In each heart, five coordinates of systolic pressure
and volume were obtained by incrementally filling
the LV balloon over a range of volumes from V20 to
Vloo. A volume equal to that of the plastic balloon
mount (4 ml) was added to each of the five saline
volume values so the pressure-volume plots reflected
total LV volume. The five pressure-volume coordinates were fit by a linear equation and the slope of
the systolic pressure-volume relation that represents
maximum systolic elastance (Em,,) was determined by
least-squares analysis. This systolic pressure-volume
line represents the upper border of the PVA. In a
similar fashion, the diastolic pressure-volume coordinates were fit by a linear equation; this line defined
the lower border of the PVA. Thus, at any volume,
the PVA is the area encompassed by the systolic and
diastolic pressure-volume lines and the vertical isovolumic pressure trajectory at that volume. The PVA
is expressed in millimeters of mercury times milliliters per beat per 100 g of myocardium; alternatively,
1386
Circulation Vol 84, No 3 September 1991
Normal
0)
0
0
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to
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E
0
W
z
0
cri
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r=0.95
(n
z
0
0.5z
X
0
0.02
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VOLUME (ml)
it may be expressed as joules per
mm Hg * ml=0.000133 J).
0.04
0.06
0.08
PVA (joules/beat/ 1 0Og)
beat
per
100
g
(1
Myocardial Oxygen Consumption
At each of the five volume states, total coronary
blood flow and coronary arteriovenous oxygen difference were measured. MVo2 of the entire heart was
calculated as the product of coronary blood flow
(milliliters per minute) and the arteriovenous oxygen
difference (milliliters of 02 per 100 ml of blood). The
MVo2 of the total heart was determined with the
right and left ventricles empty. The MVo2 of the right
ventricle was calculated as the product of the total
heart MVo2 and the ratio of the right ventricular
weight to the combined weight of both ventricles; this
ratio averaged 0.25+± 0.02 in the normal hearts and
0.19+0.02 in the hypertrophic hearts. Since the right
ventricle was empty throughout the experiments, we
assumed that the right ventricular contribution to
total MVo2 remained constant throughout each experiment. Thus, the LV MVo2 at any volume is equal
to the total heart MVo2 minus the (empty) right
ventricular MVo2. Oxygen consumption is expressed
in milliliters of 02 per beat per 100 g and in joules per
beat per 100 g of myocardium (1 ml of oxygen is
equivalent to 20 J).
Potassium Arrest
After baseline measurements of coronary blood
flow and arteriovenous oxygen difference in the
empty beating heart, potassium chloride (50 meq/l)
was infused into the arterial perfusion line at a rate
sufficient to produce asystole. After an initial bolus,
an infusion rate of approximately 35 mlmin was
sufficient to maintain an asystole state. Asystole was
confirmed by the absence of pressure development
and a flat EKG signal; manual palpation of the LV
0.10
0.12
FIGURE 1. Plots show representative
normal example of a pressure -volume
area (PVA) and the relation between
myocardial oxygen consumption and
PVA. Left panel: Five systolic and five
diastolic pressure-volume coordinates
define the PVA; note that the PVA does
not include the zone beneath the diastolic pressure -volume line. The slope
of the systolic pressure -volume line
represents maximum systolic elastance
(E,L); in this example E,,, equals 5.4
mm Hg/ml. Right panel: The relation
between myocardial oxygen consumption (MVo) and PVA is shown. Both
MVo2 and PVA are exvpressed in joules
per beat per 100 g. The solid line was
denrved from a least-squares best fit of
the five coordinates. The slope of this
relation is 5.44 and the intercept (i.e.,
the PVA -independent oxygen consumption) is 0. 97 J/beat/100 g.
confirmed a flaccid asystolic heart in all experiments.
Coronary blood flow and arteriovenous oxygen difference were measured at 1-minute intervals for 7
minutes and the MVo2 of the total heart was calculated from these data; as before, the LV MVo2 was
determined by subtracting the right ventricular contribution to total heart MVo,.
MV,2-PVA Relation
Each of the five PVAs was plotted against the
corresponding values for oxygen consumption, and
the slope of the MVo2-PVA relation was determined
by fitting the five coordinates by a linear equation.
The extrapolated y intercept is an index of the MVo2
of the empty beating heart. The MVo2 of the empty
beating heart (V0) was also measured directly. This
analysis is illustrated in Figures 1 and 2.
Myofibrillar efficiency was calculated as the ratio
of PVA to excess MVo2 (the excess MVo2 equals
total oxygen consumption minus that required for
basal metabolism plus activation).10 This ratio is
equivalent to the inverse slope of the MVo2-PVA
relation. To calculate efficiency, both PVA and
MVo2 are expressed in joules per beat per 100 g (see
above). Thus, the ratio of PVA (in joules) to excess
MVo2 (in joules) is a dimensionless parameter that
reflects the chemomechanical energy transduction
efficiency of the contractile machinery; we refer to
this as myofibrillar efficiency.
Data Analysis
Data in the table and text are presented as
mean+SD; mean+SEM is used in the figures. Differences in the slopes (Emax and MVo2-PVA relation)
and intercepts between normal and hypertrophic
groups were analyzed by using an analysis of variance
of regression and an analysis of covariance with a
Izzi et al Myocardial Oxygen Consumption and LVH
1387
LVH
C)
0
0
-,
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0
0
cm
1.5-
z
E
E
0
2
I-
W
a:
CO)
CO)
10-
Cl)
z
0
MV02= 6.72 PVA + 0.68
cc
a.
z
W
r =0.97
0.5-
0
Q02
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VOLUME (ml)
repeated-measures design. Differences in other parameters were assessed with an unpaired t test.
Differences were considered significant if p<0.05.
Results
As in our previous studies,20 the group of aorticbanded animals developed a substantial increase in
LV mass; the LV/body weight ratio was 9.2+1.6 g/kg.
The functional state of the LV assessed by echocardiography and cardiac catheterization remained normal; fractional shortening was 40±9% and LV enddiastolic pressure was 9+3 mm Hg. Thus, the eight
banded dogs in the current study are comparable
with those reported in our previous studies of LV
function, myocardial blood flow, and the tolerance to
ischemia in LVH.8,20 The LV/body weight ratio of the
normal control hearts was 5.2±1.2; these dogs did
not undergo cardiac catheterization.
Representative examples of the MVo2-PVA relations in normal and hypertrophic hearts are shown in
Figures 1 and 2. The data are presented in Tables 1 and
2, and a summary of the results is shown in Figure 4.
MVo2-PVA Relations
At Vlo (i.e., the volume required to produce a
systolic pressure of approximately 100 mm Hg) there
were no significant differences in LV systolic pressure, diastolic pressure, volume, or Em.x between the
two groups (Table 1). The average values for the
PVA in the normal and LVH groups (1,230+300 and
1,130+200 mm Hg times milliliters per beat) were
not significantly different. When expressed per 100 g
of LV, the PVA in the group with LVH was significantly less than normal (928±321 versus 565+±202
mm Hg times milliliters per beat per 100 g). The
MVo2 (expressed per 100 g of LV) was likewise lower
than normal in the LVH group, but this difference
did not achieve statistical significance.
0.04
I
0.06
I
008
FIGURE 2. Plots show representative example of pressurevolume area (PVA) (left panel)
and oxygen consumption data
from an animal with left ventricular hypertrophy (LVH) (right
panel). Maximum systolic
elastance is 5.4 mm Hg/ml. The
slope of the relation between oxygen consumption and PVA is
6.72 and the PVA-independent
oxygen consumption is 0.68
J/beatI100 g.
0.10
PVA (joules/beat/ 100g)
There was no significant difference in the slope of
the MVo2-PVA relation between normal and hypertrophic
groups
(3.89+1.91
versus
4.19+1.25
ml 02
millimeter of mercury times milliliters times 1O5).
Thus, the relation between energy used (i.e., MVo2)
and energy generated (i.e., PVA) is essentially equal
in normal and hypertrophic hearts; myofibrillar efficiency is similar in normal and hypertrophic hearts
(21+ 9 versus 19 +1 1, p = NS).
per
Nonworking and Basal MVo2
At zero PVA, the MVo2 was almost equal in the
two groups (0.040±0.006 versus 0.043±0.012 ml/
beat/100 g); these extrapolated values are similar to
those obtained by direct measurement (0.038+0.006
versus 0.041+0.015 ml/beat/100 g). During potassium
arrest (Figure 3), MVo2 was essentially equal in the
normal and hypertrophic groups (1.95+0.06 and
1.98+0.20 ml/min/100 g); thus, basal oxygen requirements in this model of LVH is not significantly
different from normal. Our interpretation of these
data is that the nonwork-related energy demands
(basal plus activation) are normal in concentric LVH.
These results are summarized graphically in Figure 4.
Discussion
The uniquely aerobic character of myocardial metabolism underlies the use of MVo2 as an index of the
heart's total energy utilization. The factors that influence conversion of chemical energy into mechanical work (i.e., the factors governing MVo2) are well
described, and several indexes have been proposed as
major and minor determinants of MVo2.12 Prominent
among the major factors are those related to the
development of systolic force; changes in force development or the time integral of force exhibit strong
positive correlations with MVo2.24 27 An essential
limitation of these indexes is that the MVo2 is related
1388
Circulation Vol 84, No 3 September 1991
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TABLE 1. Left Ventricular Energetics in Normal and Hypertrophied Hearts
Normal
(n =8)
Left ventricular pressure at V1l+
110±9
Peak systolic (mm Hg)
End diastolic (mm Hg)
5.6+2.5
Left ventricular volume (Vl0 in ml)
24.9+4.2
Left ventricular mass (g)
132.7+20.4
Emax (mm Hg/ml)
5.36±+1.17
Total mechanical energy at Vloo
PVA (mm Hg * mlfbeat)
1,230+296
928+321
(mm Hg. ml/beat/100 g)
Myocardial oxygen consumption
0.073±+0.015
Working LV (ml 02 /beat/100 g at Vloo)
0.038±0.006
Empty beating LV (ml 02/beat/100 g)
1.95+±0.06
Potassium arrest (ml 02/min/100 g)
MVo2-PVA relation
3.89± 1.91
Slope (ml 02/mm Hg * ml 105)
5.83±3.03
(dimensionless)
0.040±0.006
Intercept (ml 02/beat/100 g)
0.80±0.13
(joules/beat/100 g)
21±9
Myofibrillar efficiency (%)
Hypertrophy
(n=8)
112+6
8.8+3.1
22.6+9.0
205.0+44.5*
5.97±2.96
1,130±200
565-+202*
0.067±0.019
0.041+0.015
1.98±0.20
4.19± 1.25
6.25±2.01
0.043±0.012
0.89+0.30
19± 11
LV, left ventricle; PVA, pressure-volume area.
*p<O.05.
to factors other than force development and external
work. Recognizing that myocardial energy requirements are determined by the sum of external and
internal work, Britman and Levine28 used a model of
the myocardium consisting of a contractile element in
TABLE 2. Regression Equations for the MVo2-Pressure-Volume
Area Relations in Normal and Hypertrophied Hearts
Regression equation
r
Normal
1
2
3
4
5
6
7
8
MVo2=5.23 PVA+0.82
MVo2=4.99 PVA+0.58
MVo2=5.44 PVA+0.97
MVo2=12.06 PVA+0.82
MVo2=2.96 PVA+0.69
MVo2=4.54 PVA+0.77
MVo2=8.39 PVA+0.93
MVo2=3.01 PVA+0.84
0.97
0.97
0.95
0.95
0.99
0.99
0.99
0.83
Hypertrophy
MVo2=6.11 PVA+0.73
MVo2=9.36 PVA+0.85
MVo2=5.42 PVA+ 1.51
MVo2=2.17 PVA+0.74
MVo2=6.72 PVA+0.60
0.99
0.97
0.99
0.86
0.97
0.89
MVo2=7.06 PVA+0.92
0.87
MVo2=6.72 PVA+0.92
0.96
MVo2=6.44 PVA+0.91
Linear regression analysis was used to determine the correlation
coefficient (r). The MVo2 and pressure-volume area (PVA) are
expressed in joules per beat per 100 g; thus, the slope of the
MVo2-PVA relation is dimensionless and the intercept is given in
joules per beat per 100 g.
1
2
3
4
5
6
7
8
series with an elastic element. With knowledge of the
elastic element stiffness, it was possible to calculate
contractile element work (CEW) and to relate this
variable to MVo2 over a wide range of altered
hemodynamics in anesthetized dogs. They found a
high correlation between CEW and MVo2, and they
demonstrated that this relation was significantly better than that found between oxygen consumption and
pressure-time per minute, force-time per minute, or
fiber shortening. This model of a contractile element
in series with an elastic element has significant
shortcomings29 and partly for this reason, CEW is not
widely used as an index of energy utilization. However, the principle that MVo2 is influenced by mechanical factors other than external work is of major
physiological importance.
Using a time-varying elastance model of the left
ventricle, Suga et al3,14 recognized a positive linear
relation between the MVo2 and the total PVA of the
working left ventricle. Thus, the energy used by the
left ventricle was found to be closely related to the
size of the area defined by the end-diastolic and
end-systolic pressure-volume lines (and the systolic
trajectory of pressure-volume between end diastole
and end systole). In the ejecting heart, this area
consists of the systolic pressure-volume loop (external work) plus the triangular area to the left of this
loop (potential energy); in the nonejecting (isovolumic) condition, there is no external work and the
total mechanical energy is represented by the triangular area to the left of a vertical line defined by the
systolic pressure development. Importantly, MVo2 is
linearly related to the PVA regardless of whether the
Izzi et al Myocardial Oxygen Consumption and LVH
1389
6
CJ
0
0
c
5-
2
4 - Baseline
44
E
FIGURE 3. Plot showing left ventricular
consumption during potassium arrest in normal hearts and hearts with left
ventricular hypertrophy (LVH). Baseline
data were obtained in the empty beating
(nonworking) state. The oxygen consumption fellfrom baseline values of 4. 7and 5.1
in normal and LVH to approximately 2 ml
02/min/100 g during arrest. There was no
significant difference in oxygen consumption between the two groups.
Normal
A LVH
*
oxygen
z
3-
2
CL
U) 2z
z
W
I
-
11
Infusion
-KCI
1
00
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0
2
1
3
6
5
4
7
TIME (minutes)
soned that an assessment of myocardial energetics
within the MVo2-PVA framework would be more
relevant to the clinical problem of altered tolerance
to ischemia in hypertrophic hearts.8 Therefore, we
determined the slope of the MVo2-PVA relation and
used the inverse of this relation as an index of
efficiency. To date, only hyperthyroidism (in rabbits)
has been shown to affect the slope; this is thought to
be mediated through a change in the V1/V3 isomyosin
ratio9; such changes are apparently not seen in
dogs.35 Although basal and nonwork-related oxygen
requirements are affected by the inotropic state, the
slope of the MVo2-PVA relation is remarkably in-
heart is freely ejecting, auxotonic, or isovolumic; it is
not determined by the time course of the isovolumic
pressure-volume coordinates.30
MVo2-PVA Relation and Efficiency
It is generally accepted that, when systolic wall
stress and inotropic state are considered, MVo2 is
normal in human hypertrophic hearts.2627,31 Such
studies, however, do not dissect out the relative
contributions of basal and activation energy requirements, nor do they provide information on myofibrillar efficiency. Other more basic studies are important
in terms of underlying mechanisms,32-34 but we rea-
.Z
.0
od
/ormal
LVH
0i
CDE0
0
0.06
1.2.
CD
c)0.
z
0
E
0.04
0.-
NORMAL
Emax 5.0
CD)
z
-
0
MV02
0.02
1.2
LVH
z
W
±
5.8 PVA+ 0.80
0.4_
0
----
BASAL-
-
-
-
Emax -5.4 ± 2.8
MV02 6.3 PVA+0.89
-
0
0.625
250
0.05
0.075
500
0.J0
(joules/beat)
750
(mmHg.mI/beat)
PRESSURE VOLUME AREA (per 100
gm
LV)
FIGURE 4. Plot showing summary of the
relations between myocardial oxygen consumption and the left ventricular pressurevolume area (PVA) in normal hearts and
hearts with left ventricular hypertrophy
(LVH). Oxygen consumption is expressed in
milliliters of 02 per beat per 100 g and in
joules per beat per 100 g (1 ml of oxygen is
equivalent to 20 J). The PVA is expressed in
millimeters of mercury times milliliters per
beat per 100 g and in joules per beat per 100
g (1 mm Hg ml is equivalent to 0.000133 J).
Symbols indicate oxygen consumption at a
working volume of Vioo; see text for details.
Basal and nonworking (zero PVA) energy
requirements and myofibrillar efficiencies of
normal and hypertrophic hearts are essentially
equal.
1390
Circulation Vol 84, No 3 September 1991
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sensitive to pharmacological and other acute interventions that affect contractility.10
The inverse slope of the MVo2-PVA relation can
be taken to represent the efficiency of chemomechanical energy conversion.10 This is not merely the
efficiency of performing external work; rather, it
reflects a total efficiency of performing external work
plus a residual "potential energy" that remains after
end systole. With each cardiac cycle some of this
potential energy is converted to internal work, but
most of it is dissipated as heat.14 Suga30 has emphasized several differences between the potential energy in his PVA analysis and the internal work in
Britman and Levine's CEW analysis; recognizing and
comparing the differing energy costs of potential
energy and internal work may provide a better understanding of ventricular energetics.
Myofibrillar efficiencies calculated from the inverse slope of the MVo2-PVA relation were essentially the same in our normal and hypertrophic hearts
(21% and 19%, respectively). These data are consonant with those of Starling et al,36 who studied
normal in situ dog hearts and reported MVo2-PVA
slopes of 3.15 and 3.48 ml 02 per millimeter of
mercury times milliliters times 105; thus, the dimensionless slope was approximately 5 and myofibrillar
efficiency was approximately 20%. Nozawa et al37
reported a similar efficiency in normal in-situ hearts.
There is no obvious reason why these efficiency
values are lower than those reported by Suga et al,
but a common feature of our methods and those of
Starling et al is the use of calculated oxygen contents
of coronary arterial and venous blood. Suga measured oxygen content directly, and it is possible that
the differences in the MVo2-PVA slope (and efficiency) is somehow related to the oximetry method.
These considerations, however, have little bearing on
our comparisons between normal and hypertrophic
hearts; our data indicate that myofibrillar efficiency
in pressure-overload hypertrophy is not significantly
different from normal.
MVo2 in Empty Beating Hearts
The energy demands of a nonworking heart can
be estimated by extrapolation of the MVo2-PVA
relation to zero PVA or by directly measuring
MVo2 in the empty beating condition. The extrapolated values for MVo2 in our normal (0.040 ml/
beat/100 g) and hypertrophic hearts (0.043 ml/beat/
100 g) were essentially equal; these extrapolated
values were not significantly different from those
measured directly (Table 1). In an extensive review
of this topic, Suga reported values ranging from
0.017 to 0.047 ml/beat/100 g; the average value from
his five most recent studies was 0.028 ml/beat/100 g
in empty beating hearts'0; this is equivalent to
approximately 3-4.5 ml/min/100 g. Due in part to
the wide range of heart rates in published experiments, 24,28,38-40 the MVo2 of nonworking hearts
reportedly ranges from 2.5 to 5.5 ml/min/100 g. In
our experiments, the normal and hypertrophic
hearts (nonworking) consumed approximately 5 ml
02/min/100 g.
Direct measurements of the energy demands of
empty beating hearts theoretically overestimate those
of a pure nonworking state (i.e., activation plus basal
requirements) for at least two reasons. First, our
experimental preparation precludes measurement in
a truly empty condition (the LV contains a plastic
balloon mount); thus, some isometric force is developed in the area of the mitral annulus. Second, low
levels of crossbridge cycling (even in a totally empty
heart) require energy; ideally, such an unmeasured
contribution to the energy demands should be considered. Thus, to assess accurately the energy demands of a true nonworking state (i.e., basal plus
activation) it would be necessary to inhibit all crossbridge cycling; this could be accomplished with 2,3
butenedione (BDM), a cardioplegic agent that (at
low doses) selectively inhibits crossbridge cycling in a
reversible manner.41-43 Such studies would be necessary to avoid an overestimation of the nonworking
(i.e., basal plus activation) requirements. However,
our observation that the extrapolated value for MVo2
is similar to the measured value suggests that any
such error is probably small.
Basal Oxygen Consumption
The resting or basal metabolic rate of the intact
LV is difficult to assess because the heart does not
normally exhibit sufficiently long diastolic intervals
to permit measurements of oxygen consumption in
the absence of contraction. In our experiments, we
rendered the heart inactive by infusing potassium
into the coronary arterial perfusion line and thus we
were able to measure an asystolic MVo0 during a
continuous, stable coronary perfusion. Within 2
minutes of asystole, the MVo2 fell to approximately
2 ml/min/100 g and remained constant for the
duration of the potassium infusion; the results were
essentially equal in the normal and hypertrophic
hearts (Figure 3). Our average values are similar to
the basal MVo2 (1.9 ml/min/100 g) that Britman and
Levine derived from their calculations of contractile
element work in the intact working heart.28 The
results are also similar to the normal basal requirements (1.5-2.0 ml/min/100 g during potassium arrest) reported by Suga et al16 and others.38,39,44 Sink
et a145 found a slightly lower value in hypertrophied
hearts (1.3 ml/min/100 g), and they also concluded
that this was the same as that seen in normal hearts.
Within the range of data reported here, basal requirements are approximately 40% of that required by
empty beating hearts and 20% of that required by
working hearts (Figure 4). Since basal MVo2 may
increase as a function of myocardial fiber length,46 it is
possible that the relative contribution of basal to total
MVO, might increase as the chamber is filled. If this
were the case, the myofibrillar efficiencies might be
greater than we calculated.
Izzi et al Myocardial Oxygen Consumption and LVH
Downloaded from http://circ.ahajournals.org/ by guest on July 31, 2017
Implications
During cardiac surgery, the left ventricle is subjected to ischemic arrest, potassium arrest, and on
occasion the empty beating state is maintained for
variable periods of time. During these periods, any
increased oxygen requirement (basal or activation)
might lead to increased ischemic injury. The current
results indicate that oxygen requirements are normal
in our model of concentric LVH. Therefore, any
reduced tolerance to such surgical procedures is not
likely to be due to increased oxygen demands per se.
It is possible, however, that heightened sympathetic
tone or the administration of positive inotropic
agents might augment basal or activation-related
oxygen demands and in this manner contribute to an
impaired tolerance to ischemia, independent of
work-related demands. In the absence of such increased "basal plus activation" oxygen demands,
abnormal myocardial perfusion or depressed baseline energy stores are likely responsible for the
increased sensitivity to ischemic injury seen in some
hypertrophic hearts.8
The MVo2-PVA relation that we applied in these
studies of isolated dog hearts might have potential in
clinical studies of myocardial energetics. The
echocardiogram is ideally suited to measure LV
cavity size or volume and wall mass. Coupled with
measurements of intracavitary pressure, a PVA is
relatively easy to obtain. Methods to measure coronary blood flow and MVo2 in humans are likewise
available. Thus, LV energetics and efficiency in patients with and without heart disease can be described; such methodology might be particularly useful in the evaluation of new pharmacological
therapies for patients with heart disease.
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KEY WORDS * left ventricular hypertrophy * left ventricular
pressure-volume area
myocardial oxygen consumption
myocardial energetics
Myocardial oxygen consumption and the left ventricular pressure-volume area in normal
and hypertrophic canine hearts.
G Izzi, M R Zile and W H Gaasch
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Circulation. 1991;84:1384-1392
doi: 10.1161/01.CIR.84.3.1384
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1991 American Heart Association, Inc. All rights reserved.
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