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Cardiovascular Research 48 (2000) 4–7
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Editorial
Cardiac work and efficiency
N. Westerhof*
Laboratory for Physiology, Institute for Cardiovascular Research, ICaR-VU, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam,
The Netherlands
Received 11 July 2000; accepted 13 July 2000
See article by Kiriazis and Gibbs [1] ( pages 111 – 119)
in this issue.
1. Work output and efficiency of the heart
1.1. Pressure–volume relation and oxygen consumption
Many researchers have tried to relate cardiac energy
metabolism in terms of oxygen consumption or heat
production to mechanical performance. One now popular
and accepted mechanical parameter is based on the pressure–volume relations found in the intact heart where
pressure is plotted as a function of volume over the cardiac
cycle [2]. The curve that is followed during the heartbeat
consists of the following four parts (Fig. 1, top). Starting at
end-diastole (right bottom corner) ventricular pressure
increases while volume remains constant (isovolumic
contraction), during the ejection phase volume decreases
but pressure changes little, and, after closure of the aortic
valves isovolumic relaxation ensues, which is followed by
the filling phase. The area circumscribed is external
mechanical work per beat. The triangular area between the
systolic and diastolic pressure–volume relations and
bounded by isovolumic relaxation is ‘potential energy’.
The sum of the two areas, shaded in Fig. 1 top, is called
the pressure–volume area (PVA).
It was shown that the oxygen consumption per beat
(VO 2 ) is linearly related to the PVA (Fig. 1, bottom). To
derive oxygen consumption per minute, VO 2 may be
multiplied by heart rate. The intercept with the VO 2 axis is
the ‘unloaded’ oxygen consumption, found when the heart
is not allowed to develop pressure so that the PVA is
negligible. The ‘unloaded’ oxygen consumption consists of
*Tel.: 131-20-444-8111; fax: 131-20-444-8255.
E-mail address: [email protected] (N. Westerhof).
two parts, activation and basal oxygen consumption. The
first depends on excitation–contraction coupling and is
proportional to cardiac contractility. For the quiescent
muscle the PVA and the oxygen cost of activation both are
zero. The remaining part results from all other processes
requiring oxygen such as ion pumps. With increased
cardiac contractility the oxygen cost of activation (Fig. 1,
bottom) is increased in a proportional manner but the slope
of the relation between PVA and oxygen consumption is
not affected.
The relation between PVA and VO 2 holds for all types of
contractions, from isovolumic to isobaric (‘unloaded’)
contractions. Isovolumic contractions correspond to the
largest PVA and thus the largest oxygen consumption [3].
We see that external work is not a good measure of oxygen
consumption.
Many other relations between oxygen consumption and
mechanical or hemodynamic parameters have been proposed. The two best known are the rate pressure product
(RPP) and the tension time index (TTI).
The RPP is the product of systolic pressure (Ps ) and
heart rate and is used as a measure of oxygen consumption
in many biochemical studies. When these studies are
performed in isolated hearts in Langendorff perfusion, i.e.
no external work is performed, the PVA(0.5Ps (Ved 2
V0 )(0.5P 2s /Es , with Ved is end-diastolic volume, and V0
and Es are the volume axis intercept and the slope of the
systolic the pressure–volume relation (Fig. 1, top). In other
words, for constant contractility (constant Es ) the Ps relates
in a quadratic way to the PVA. With an increase in
contractility but constant filling (constant Ved ) the PVA
increases in a linear way with Ps but the intercept of
relation between PVA and oxygen consumption is altered.
Thus the RPP, as a measure of cardiac metabolism should
be used with care.
The use of the TTI [4], the averaged pressure over the
ejection period, is also limited because for an isovolumic
contraction the TTI is negligible (ejection time negligible).
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N. Westerhof / Cardiovascular Research 48 (2000) 4 – 7
5
verted to heat. In terms of the above diagrams (Fig. 1,
bottom [3]) the myocardial conversion efficiency is defined
as PVA / total VO 2 . The contractile efficiency or myofibrillar
efficiency is defined the inverse of the slope of the VO 2
–PVA relation. This contractile efficiency is in the order of
40–50%. Economy of contraction is often used when no
muscle shortening takes place (presumably approached in
isovolumic beats) and is usually defined as the amount of
energy (oxygen consumption, ATP-usage or contraction
related heat rate) used for isovolumic contraction [6].
Work and efficiency depend on the load and the heart
[7]. Isovolumic (isometric) contraction, i.e. no ejection (no
shortening) and unloaded contractions, i.e. no pressure
(force) development, do not produce mechanical work and
efficiency is therefore also negligible. This means that
when plotting work or efficiency as a function of pressure
or cardiac output [7], at the extremes work and efficiency
are negligible and that in between a maximum exists. It
was shown that the heart under control resting conditions
pumps at these maxima [7].
1.3. Heat production
Heat production of the heart has been measured [5].
Measurements show that heat is transported by convection
by the coronary circulation and by diffusion to thorax and
ventricular lumen in about equal amounts, and that convection transport increases with increasing perfusion. These
measurements agree with the observation that the heart is
about 25% efficient. However, accurate measurements are
extremely difficult to carry out.
Fig. 1. Top: diastolic and systolic pressure volume relations of the heart
and the force length relations of (linear) heart muscle for a single
contractile state. The intercept with the volume axis is V0 . The sum of
external work and potential energy, pressure volume area (PVA) or force
length area (FLA) is a measure of cardiac oxygen consumption. Bottom:
relation between oxygen consumption or enthalpy with PVA or FLA. The
intercept with the vertical axis can be obtained by unloaded contraction
(no pressure or force developed). The slope of the line is independent of
contractility. The unloaded oxygen consumption consists of two parts:
activation related oxygen consumption, which is proportional to contractility, and a basal part, the oxygen consumption used for all other
processes.
When the TTI is calculated as the pressure–time integral
for isovolumic beats it is a measure of cardiac economy
(see below).
1.2. Efficiency and economy
External (mechanical) efficiency is defined in analogy to
that of motors and equals the ratio of external work and
oxygen consumption. Cardiac efficiency is normally about
20–25% [5]; the remainder of the oxygen used is con-
2. Papillary muscle
Papillary muscle is used as a model of the whole heart
with the main advantages that (blood) perfusion is not
required and geometry is relatively simple. When a (complex) geometric model of the left ventricle is used, wall
stress (F, tension) can be related to ventricular pressure (P)
and muscle length (L) to ventricular volume (V ). The PVA
becomes force length area (FLA, see Fig. 1), which can be
related to oxygen consumption per contraction.
In the tradition of the measurement of heat in skeletal
muscle many studies have been performed on isolated
cardiac muscles using thermopiles [8,9]. The temperature
of the muscle is measured, and heat production derived.
Many aspects of the heat production and their meaning
have been published [8,10,11]. However, for the present
discussion it is sufficient to state that the measurement of
temperature and mechanical performance allows the calculation of enthalpy, a measure of oxygen consumption
[1,12].
The model relating PVA and VO 2 , as suggested by Suga
and coworkers [2,3], based on (isolated) blood perfused
N. Westerhof / Cardiovascular Research 48 (2000) 4 – 7
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heart studies, did not seem to agree with the accepted
concepts on (skeletal) muscle contraction. Fenn’s experiments [13], on skeletal muscle, disproved the notion that
with each contraction, a predetermined amount of energy
was liberated either in the form of work or heat, or their
combination. This ‘all or none’ phenomenon is not supported by the model relating FLA with VO 2 , because the
PVA depends on the load. In other words the FLA concept
is not supporting the long discarded ‘all or none’ behavior
of muscle energetics. The major argument that appeared to
disprove the concept of FLA, was also given by Fenn [13]
who reported that, for skeletal muscle, a contraction with
shortening (thus smaller FLA) generated more heat (used
more oxygen) than an isometric contraction (with larger
FLA). However, this so-called Fenn effect is difficult to
show in cardiac muscle, and is only found under very
special experimental conditions [11].
Most studies on isolated cardiac muscle did not use the
pattern of contraction the muscle encounters in the heart
and thus also did not allow for determination of the FLA.
This approach was started relatively late [14,15] but makes
it possible to study if the findings in the heart are based on
cardiac muscle behavior. It took until 1990 [16] to show
that the FLA of isolated heart muscle was a good measure
of relaxation heat (oxygen consumption). This was shown
also by Gibbs et al. [12]. In other words there appeared to
be basic differences between skeletal muscle and heart
muscle in terms of the Fenn effect. It also implies that the
PVA approach to cardiac metabolism finds its basis in the
behavior of the cardiac muscle.
3. Cardiac aging
Because of the interaction of regulatory systems in the
intact human and animal, it is extremely difficult to obtain
a dependable measures of intrinsic contractile and energetic behavior. Therefore studies on isolated cardiac
muscle, where conditions can be accurately controlled, are
required to obtain the effects of aging on cardiac muscle
mechanics and energy.
The changes taking place in the cardiovascular system
with age have been extensively discussed by Lakatta [17].
Although studies on the mechanics and efficiency of
cardiac muscle in normal and diseased conditions have
been performed [6,12], very little has been done with
respect to aging. It has been reported that with age the rate
of contraction is decreased, electrical performance is
altered, changes take place in the isoenzymes of the
contractile apparatus and calcium handling is affected
[17,18].
3.1. Study by Kiriazis and Gibbs
In the study of Kiriazis and Gibbs [1], mechanical
performance and efficiency are studied in the isolated
cardiac muscle of aging rat. The basal metabolism (Fig. 1),
measured in the quiescent muscle, was found to be
decreased with age. This could have resulted from fewer
membrane pumps in the somewhat hypertrophied
myocytes where cellular area–volume ratio is decreased.
Active metabolism (Fig. 1) was not different between the
muscles from young and old rats.
With senescence both shortening and force generation
decreased, leading to a smaller external work. Also energy
consumption was decreased, but mechanical efficiency (in
terms of work over enthalpy) remained the same. Contractile efficiency and economy did not change either with age.
Thus force and shortening change with age but all indicators of efficiency stay the same. The authors found
similar results in muscles of the rabbit with long-term
volume overload [12].
In guinea-pigs the effects of aging were found to be a
shift myosin heavy chains (MHC) from the alpha to the
beta type resulting in a slower but more economical
myocardium [18]. The difference may result from the
difference in experimental animal because in the rat mostly
b-MHC is present. In pressure overloaded hearts [17] and
in the transition to failure in the rat [12] efficiency and
economy appear to be increased as well. Aging is thus in
terms of contraction speed not unlike the overloaded
condition but efficiency and economy seem to stay the
same while in overload these parameters increase.
It is possible to study energetics in human muscle strips
from biopsies [10]. This approach gives the opportunity to
study patient groups in terms of mechanics and efficiency.
This type of study should be encouraged.
3.2. Clinical aspects
With the use of ultrasound techniques (Doppler and
echo) much information on cardiac pump function can be
obtained. Also magnetic resonance imaging gives much
functional information. The mechanical parameters required to obtain work, in combination with oxygen consumption and the derivation of efficiency, are presently not
part of the standard diagnostic procedures. This is in large
part because a series of contractions with different filling is
required to obtain at least some accuracy in the determination of the PVA. Also oxygen consumption is rather
complex to measure in the human. The use of magnetic
resonance spectroscopy and positron emission tomography
may change this.
References
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