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The second law of

Perspective
Future Cardiology
thermodynamics and the heart
Frank Lloyd Dini*1, Giacinta Guarini1, Doralisa Morrone1 & Mario Marzilli1
1
Cardiovascular Diseases Unit 1, Cardiac, Thoracic & Vascular Department, University of Pisa, Azienda
Universitaria Ospedaliera Pisana, Via Paradisa 2, 56100, Pisa, Italy
*Author for correspondence: Tel.: +39 050 995 307 n Fax: +39 050 995 308 n f.dini@ao-pisa.toscana.it

The second law of thermodynamics explains the phenomenon of irreversibility

and the increasing entropic trend of nature. Similar to human-made machines,
living structures are subjected to entropy generation, becoming ‘worn’ and
‘damaged’ from use. However, they have the possibility of eluding or deferring
these processes. According to nonequilibrium thermodynamics, the heart could
be considered as an open dissipative system, since it has the potential to offset
the body’s increasing entropic burden by using energy to export entropy to the
surroundings. By organizing the tissues’ molecules in order to perform external
work as a result of its ability to provide oxygen and nutrients and remove waste
products, the heart maintains the organization of the living structure and acts as
an open dissipative system. However, the increase in tissues’ randomness and
disorder as a result of a number of disease states may be responsible for the
intervening cardiac damage and entropy generation. This effect is known as the
‘Dorian Gray effect’ of the heart. Technical advances, including MRI and 3D
echocardiography, may provide a means to improve the understanding of
thermodynamic aspects of cardiovascular physiology and heart disease.

Thermodynamics is a branch of physics that
deals with energy and work of a system. The
term thermodynamics was originally applied
to the science dealing with the motive power
of heat, or the transformation of heat into
mechanical work or vice versa. Thereafter, the
subject was extended to the more generalized
concept of energy transformation. While this
subject is of very great importance to physicists
and engineers, it is rather unfamiliar in the field
of cardiovascular medicine. Like all pumps, the
heart requires a source of energy and oxygen
in order to function, that is, transferred from
the hydrolysis of ATP; thermodynamic con-
siderations should be addressed whenever we
consider resting ventricular performance and
its responses to physiological stresses, as well as
myocardial injury [1] .
Cardiac thermodynamics, metabolism
& external work
A widely accepted definition of energy is the
ability of a system to perform work. Everything
that happens is caused by an energy change.
The first law of thermodynamics establishes
the equivalence of the different forms of energy
(gravitational, kinetic, heat, elastic, electrical,
chemical, radiant, nuclear and mass energy);
energy can be converted from one form to
another but the total energy within the domain
remains fixed. This principle considers heat and
energy as two magnitudes of the same physical
nature. The mathematical expression of the first
law is:
DH = DG + DU
where DH is the total energy of a thermody-
namic system, DG is the amount of free energy
(that can be transformed into work) and DU is
the change of internal energy. Living organ-
isms must obey the laws of thermodynamics,
since they constantly need to expend energy to
perform vital life functions. Through aerobic
metabolism, that is the oxidation of organic
substrates, energy is obtained.
In a mechanical pump, the energy expended
in propelling fluids through pipes can be visual-
ized in terms of external (net) work. Certain fea-
tures of such mechanical devices are applicable
to the function of the heart as a pump [2] .
In the heart, the ejection of a volume under
pressure represents a form of mechanical work:
the pressure–volume (PV) work; this is because,
in a fluid system, work (force × distance) is equal
to pressure × volume. Stroke work, that is, the
PV work exerted by the left ventricle during each
beat, can be calculated as the product of stroke
Keywords
volume and the pressure at which the blood
is ejected. The total external work also com- n entropy n thermodynamics
n ventricular function
prises the kinetic work. The kinetic work (that
accounts for about 5% of the external work)
is spent to generate the energy that is needed
to move the column of blood through the left part of

10.2217/FCA.12.45 © 2012 Future Medicine Ltd Future Cardiol. (2012) 8(5), 697–706 ISSN 1479-6678 697
 Perspective Dini, Guarini, Morrone & Marzilli
ventricular (LV) outflow tract into the circula-
tion [3] . Power is the rate of energy change per
length of time.
Myocardial mechanical events originate from
the conversion of chemical energy into mechani-
cal energy. For this process, myocardial tissue
requires a constant supply of oxygen and organic
fuels, which are delivered by the coronary circu-
lation. The major fuels that serve as an energy
supply for the myocardium are carbohydrates
(glucose and lactate) and free fatty acids.
Oxygen is utilized in the mitochondria by the
process of oxidative phosphorylation to gener-
ate high-energy phosphates, such as ATP and
phosphocreatine. The high rate of ATP turn-
over in the heart is reflected in the heart’s high
rates of oxygen consumption, the high cellular
density of mitochondria and the high capillary
density in the heart muscle. Of all muscles, the
myocardium contains the greatest number of
mitochondria. Thus, myocardial oxygen con-
sumption serves as a measure of the total energy
utilization of the heart [4,5] .
Cardiac efficiency as a thermodynamic
entity
Efficiency is a concept that was derived in the
19th century at the time of the industrial revolu-
tion when steam machines were the focal point.
It is common knowledge that only part of the
energy released by a machine is delivered as net
work. Such a machine converts concentrated
energy into less useful energy. Machines, engines
and so on, cannot transform all their energy input
into usable power; some of the energy will be used
up in the form of friction and heat. Similar to
mechanical engines, human bodies convert con-
centrated energy into less useful energy. Fuels like
gasoline and foods like carbohydrates and fats
have highly concentrated potential energy stored
in their chemical bonds. These substances con-
tain a high amount of energy in a small space. It is
cost effective for us to convert that concentrated
energy into net energy to keep our machines and
our bodies working.
The efficiency of the heart (external PV
work/oxygen utilization) to pump blood to supply
tissues’ needs ranges between 15 and 25% at rest-
ing outputs [6–8] . Mechanical efficiency is about
the same for all mammals and this efficiency
is similar to that of human-made engines. As a
result, a large mammal would provide a greater
amount of mechanical, external work in accor-
dance with the larger metabolism it generates [9] .
The efficiency of the heart is greater when
the stroke volume is high and the heart rate is
698 Future Cardiol. (2012) 8(5)
low. Cardiac efficiency declines as heart rate
increases. It has been suggested that efficiency
may be reduced at high heart rates because of the
increased amount of internal work performed in
order to deform the chamber wall at each beat:
less external work and more internal work is
performed per beat [10] .
In addition, for a given stroke volume, a
larger ventricle is characterized by a lower effi-
ciency because of the elevated energy cost due
to increased internal work and oxygen require-
ments of the myocardium. During dynamic
exercise, the efficiency may improve substan-
tially when the increase in net work is more than
the increase in myocardial oxygen consumption.
This is because stroke volume increases more
than arterial pressure. In pathophysiological dis-
ease states, such as heart failure, mechanical effi-
ciency is reduced; it has been hypothesized that
the increased energy expenditure relative to work
contributes to progression of the disease [11,12] .
The second law of thermodynamics
The second law of thermodynamics is arguably
the most important law in the whole of sci-
ence. It is based on human experience, since it
describes basic principles familiar in everyday
life. It is partially a universal law of decay; the
critical cause of why everything ultimately falls
apart and disintegrates over time. Even death
is a manifestation of this law, as it explains
why living structures become more and more
disorganized and finally perish. The effects of
the second law are visible all around, touching
everything in the universe.
There are many versions of the second law of
thermodynamics, but they all state the same,
that is to explain the phenomenon of the irre-
versibility in nature. Nicolas Leonard Sadi
Carnot established the foundation of this law
in 1824 [13] . Rudolf Clausius was then the first
to formulate the law in 1850 [14] . Over the next
century many other scientists have worked out
and tested the law.
To date, it is customary to use the term
‘entropy’ to state the second law that is there-
fore commonly known as the law of increased
entropy. Entropy has precise mathematical and
statistical definitions, but can be approximately
defined as the degree of disorder and unifor-
mity in a system. The mathematical expression
of the second law of thermodynamics is DS/Dt
≥0, where DS is the increase of entropy and Dt
is time.
The formula denotes that the change in
entropy in a thermodynamic system is always
future science group
 The second law of thermodynamics & the heart Perspective

higher or equal to zero, and time is the funda-
mental dimension in which the system is doing
work. Entropy exists in all systems, nonliving and
living, that have free energy for doing work [15] .
Entropy is the measure of the amount of
energy unavailable for work that manifests itself
as irretrievable heat. When energy is dispersed or
widely distributed in a system, the possibility to
use that energy for mechanical work decreases
and entropy rises. Increases in entropy corre-
spond to an increase of disorder and to irrevers-
ible changes in a system. As usable energy is irre-
trievably lost, disorganization, randomness and
chaos increase. There is a tendency that over time
differences in temperature, pressure and chemi-
cal potential equilibrate. Any physical system
will spontaneously approach equilibrium. The
physicists call this the state of thermodynamic
equilibrium, or of maximum entropy. In a state
of thermodynamic equilibrium, there are no net
flows of matter or of energy, no phase changes
and no unbalanced potentials (or driving forces),
within the system.
It is important to fully understand which
might be the effective constituents that take part
in entropy production. Entropy measures the
degree to which energy is mixed up inside a sys-
tem, that is, the degree to which energy is spread
or shared among the components of a system.
Entropy is large when the small microscopic
components of the system are disorganized
and move completely independently. Friction,
that is, the transformation of mechanical (i.e.,
ordered) energy into (disordered) thermal
energy, is the first source of the entropy of the
living body. Although the second law is simple
in principle, applying it to a living being could
be difficult due to the challenge of determining
probabilities at the microscopic level. In addi-
tion, it should be argued that a system could be
steadily or ­temporally confined in a metastable
equilibrium.
The cardiac cycle as a thermodynamic
cycle
The function of the heart as a pump consists of
pressure generation and LV volume changes to
the end that blood flow can distribute oxygen and
nutrients and retrieve carbon dioxide and waste
products. The cardiac cycle can be analyzed as
a thermodynamic cycle. A PV diagram or PV
loop is used in thermodynamics to describe a
thermal cycle involving changes in volume and
pressure in a system. A key feature of the dia-
gram is that the amount of energy expended or
received by the system as work can be estimated
as the area enclosed by the curve. In cardiovas-
cular physiology, the diagram is often applied
to the left ventricle, and it can be mapped to
specific events of the cardiac cycle (Figure 1) . The
configuration and geometry of the left ventricle
differ among individuals. Nevertheless, when
pressure, volume and flow curves obtained
from two normal individuals are superimposed

SW = P × SV + 1/2 + mv2

3
c
Pressure

Pressure

4 2
d b
External
work
Internal
work
1
a
Volume Volume

Figure 1. Pressure–volume diagrams in thermodynamics (steam engine) and in

cardiovascular physiology. (A) A pressure–volume diagram is used in thermodynamics to describe
a thermal cycle involving changes in volume and pressure in a system. (B) The cardiac cycle can be
analyzed as a thermodynamic cycle. 1: expansion (work out); 2: heat in (combustion); 3: compression
(work in); 4: heat out (exhaust); a: isovolumic contraction; b: ejection phase; c: isovolumic relaxation;
d: filling.
m: Mass; P: Pressure; SV: Stroke volume; SW: Stroke work; v: Velocity.

future science group www.futuremedicine.com 699

 Perspective Dini, Guarini, Morrone & Marzilli
in preset hemodynamic conditions, the curves
almost perfectively coincide.
The cardiac cycle includes both electrical
(e.g.,  myocardial cellular depolarization) and
mechanical events. The electrical events precede
and initiate the mechanical events. The excita-
tion–contraction coupling is the term used to
define the events that connect the depolarization
of the cell membrane to the contraction of the
muscle fibers. While a steam engine is a system
that performs the conversion of heat or thermal
energy to mechanical work, the heart uses sub-
strates to convert chemical energy into mechani-
cal work to propel the blood in the circulation (it
is not a thermal machine but is rather a chemi-
cal-dynamic machine). The graphic depiction of
ventricular volume and pressure during the car-
diac cycle plays a key role in understanding the
mechanics of normal and abnormal ventricular
contraction. Inscription of the PV loop begins at
end-diastole and is inscribed in a counter-clock-
wise direction passing through four phases. The
stroke work is reflected by the size of the PV loop
and is proportional to both the pressure gener-
ated by the ventricular contraction and the stroke
volume [16] .
To relate work to oxygen consumption, account
must be taken of both external and internal work;
the latter is sometimes called the potential energy,
being the work generated in each cardiac cycle
that is not converted in external work. The inter-
nal work (potential energy) is represented by the
PV triangle obtained by joining the end-systolic
PV point to the origin. The heart uses a large
amount of energy to perform internal work. The
energy expended as internal work contributes to
the heart’s inefficiency because it is degraded
into heat during diastole. This includes energy
used to overcome the inertia of elastic and vis-
cous elements. Most of the energy expended in
cardiac metabolism that does not contribute to
the propulsion of blood appears in the form of
heat. The area subtended by the PV curve corre-
lates closely to the myocardial oxygen consump-
tion. However, there is a component of the initial
energy unavailable for work that contributes to
the malfunction of the system. This compo-
nent reflects the natural tendency of things to
approach the state of maximum entropy.
Entropy generation & the heart
Like human-made machines, the more inten-
sively we use them, the more rapidly they will
malfunction. In addition, also the increase in
inefficiency of the cardiac cycle brings about
an entropy generation. In mammals, an inverse
700 Future Cardiol. (2012) 8(5)
linear relationship has been found between rest-
ing heart rate and lifespan [17] . Smaller mam-
mals have higher heart rates and higher metabo-
lism per gram of tissue than larger mammals,
although the overall metabolic rate is higher in
larger animals than in smaller ones according
to Kleiber’s law [18,19] . At first sight, the fact that
large animals live longer than small ones appears
to contradict the second law. An elevated heart
rate is likely to bring about a higher entropy gen-
eration as well as a lower metabolic efficiency.
The inefficiency of the heart might account for
the shorter lifespan of small animals.
The recognition that things wear out with
use, and the more we use them the faster they
wear out, is very old. The processes of ‘wear
and tear’ are intrinsically associated with the
second law and are governed by the concept of
entropy. In an energetic process, like in human-
made engines, part of the energy ends up as
heat and is dissipated in the environment, the
remainder is spread out within the system as
degraded energy or irretrievable heat and con-
tributes to compromise its organization on a
molecular level.
A reversible process is defined as a process that
can be reversed without leaving any trace on its
surroundings. That implies that both system and
surroundings are returned to their initial states
at the end of the process. Processes that are not
reversible are called irreversible processes. The
irreversible processes involve heat and result in
entropy generation, which tends to accumulate
within the system. For example, friction heats
up and slows down moving parts. Reversible
processes do not actually occur in nature. They
are present only in those systems characterized
by the absence of friction and the dispersion of
energy and therefore do not produce entropy;
they are merely idealized phenomena. However,
some processes can reasonably approach the
reversibility criterion. The ana­lysis of a num-
ber of natural processes can be facilitated by
assuming that they are in fact reversible. These
processes are called quasi-reversible.
In some respects, the cardiac cycle might be
considered a quasi-reversible process; in fact,
myocytes turn chemical energy into mechanical
energy, which is subsequently transformed into
heat, but at the end of each cardiac cycle the heart
tends to return to the initial volume and pressure
conditions [20] . However, part of the potential
energy that is stored in chemical bonds ends up
in less organized forms of energy that contribute
to the entropy generation within the system. The
possibility of minimizing the entropy production
future science group

makes the heart move towards a quasi-reversible
condition. In some respect, the cycles of the heart
may be referred to as the coupled cycles that
actually appear in dissipative structures arising
in systems maintained far from thermodynamic
equilibrium by energy flow [21,22] .
The general system theory & the
nonequilibrium thermodynamics
The general systems theory is the cornerstone
to elucidate the interaction between thermo-
dynamics and living organisms. This theory
was introduced by Ludwig Von Bertalanffy to
explain the apparent disagreement between clas-
sical thermodynamic laws and the development
of complex structures of living organisms [23] .
In thermodynamics, one usually considers
both the thermodynamic system and its environ-
ment. In a physical sense, a system is anything
that we wish to analyze and distinguish from its
surroundings or environment; we could use the
term system for any pattern of relationship, from
an atom to a galaxy, from a cell to an ecosystem.
The environment of a thermodynamic system
includes the other thermodynamic systems that
can interact with it. An isolated system is one
so completely sealed off from its environment
that neither matter nor energy passes through
its boundaries. This is an imaginary construct,
however, an idea rather than a reality, because
it is impossible to create a situation in which no
energy is exchanged between the system and the
environment [24] .
There is a profound difference between a
human-made machine and a biological system;
the latter tends to evade the decay to equilib-
rium with the possibility of a longer lifespan.
Like other natural systems, human living is
an energetic process. The two principal laws
of thermodynamics apply only to closed sys-
tems, which are entities that can exchange
energy (as heat or work) but not matter with
their surroundings. The second law states that
entropy in a closed system will increase as time
advances until it reaches a maximum value.
According to classical thermodynamics, a liv-
ing organism continually increases its entropy
and tends to approach the state of maximum
entropy. Nonetheless, biological systems tend
to evolve toward higher levels of order in terms
of differentiation and organization. This is
one of the most outstanding aspects of cellu-
lar life and represents the exact opposite of the
entropy principle. It is by avoiding the rapid
decay into the inert state of the equilibrium that
an organism appears so enigmatic.
future science group
The second law of thermodynamics & the heart Perspective
An open system is a system that continuously
interacts with the environment. The interaction
can take the form of energy, or material transfers
into or out of the system boundary. Open sys-
tems maintain themselves in a continuous inter-
change with their environment, importing and
exporting matter and energy. Living systems are
open systems; they import complex molecules
high in free energy. At any level, living systems
are composed of interacting subsystems, which
in turn are also systems, albeit on a smaller scale.
Classical thermodynamics, the dynamics of
Carnot, Clausius, Boltzmann, Gibbs, Joule,
Kelvin and Helmholtz, is often called equilib-
rium thermodynamics. In the 1950s, the Russian
chemist Ilya Prigogine worked to establish the
view that life is a far-from-equilibrium phenom-
enon that is able to be studied in nonequilibrium
thermodynamics, rather than in classical ther-
modynamics [25] . Nonequilibrium thermody-
namics is a branch of thermodynamics that deals
with systems that are far from thermodynamic
equilibrium. Most systems found in nature are
moving away from thermodynamic equilibrium.
A dissipative system is a thermodynami-
cally open system, which has the capability of
continuously importing free energy from the
environment and, at the same time, exporting
entropy. It requires that a portion of the energy
flowing through it is used to maintain the
system far from thermodynamic equilibrium.
Consequently, the entropy of an open system
either can be maintained at the same level or can
decrease, unlike the entropy of a closed system,
which tends to increase. In this perspective, the
second law of thermodynamics takes the form
of a continuity equation, in which the change
in entropy of the system (DS/Dt) consists of the
sum of entropy production due to irreversible
processes in the system (DS1/Dt) and the entropy
that flow across the system boundary (DSE /Dt).
The latter term of this equation has been named
negative entropy or negentropy:
DS/Dt = DS1/Dt + DSE /Dt
While DS1/Dt is always ≥0, the external com-
ponent or negentropy may be either positive or
negative. Therefore, if DSE /Dt is negative, the
total entropy DS/Dt may either be stationary
(DS/Dt = 0) or decrease (DS/Dt<0). While at
first glance this statement might appear to be
counterintuitive and in violation of the second
law, it is not [26] .
Dissipative structures not only maintain them-
selves in a stable state far from equilibrium, but
www.futuremedicine.com 701
 Perspective Dini, Guarini, Morrone & Marzilli

may also develop new patterns of organization.
When highly ordered complex systems emerge,
they develop and grow at the expense of increas-
ing disorder at higher levels of hierarchy. They
may go through new instabilities and transform
themselves into new structures of increased com-
plexity. Convection cells, hurricanes, autocata-
lytic chemical reactions and living systems are
all examples of far from equilibrium dissipating
structures [27] .
Organization maintained by extracting
order from the environment
While in the past, observable phenomena were
explained by reducing them to an interplay of
elementary units investigable independently of
each other, contemporary general systems theory
explores phenomena in terms of dynamic pat-
terns of relationship. Every living system is made
up of open dissipative interactive systems and
subsystems (according to nonequilibrium ther-
modynamics), whose organization is established
upon a number of hierarchical networks [28] .
To maintain organization, a biological system
needs high energy as well as dissipation fluxes
that can be achieved via frequent interactions
with the surroundings. Every component in turn
holds membership in one or more larger systems
forming a set of connections with the outside
world. They give rise to couplings that entail
vast ranges of processes from the cycle of oxy-
gen, to the cycles of carbon and that of nitrogen,
but the ultimate source of energy is the Sun. In
these coupled human and natural systems, living
beings and nature interact reciprocally and form
complex feedback loops.
By 1905, on the basis of the second law of ther-
modynamics, Boltzman realized that the intrin-
sic organization of living systems could only be
understood as a part of the whole Earth system
[29] . Erwin Rudolf Josef Alexander Schrödinger,
an Austrian physicist and theoretical biologist,
who was one of the fathers of quantum mechan-
ics, theorized that entropy produced by every
cell can be transferred but not eliminated. He
hypothesized that organisms preserve their
internal order and prevent their natural degra-
dation by feeding on the amount of order that an
organism sucks from the external environment
as negentropy [30] . Biological systems preserve
their internal order by taking energy from the
Sun: during the day approximately 1400  J/s
reaches every square meter of the Earth’s surface.
A similar quantity of energy is radiated away into
space from the Earth as thermal radiation. As the
physicist and mathematician Roger Penrose has
recently pointed out, what is really important for
life on Earth is the ability of the Sun to reduce
the excess entropy in the biosphere [31] .
Energy from the Sun is taken up by plants,
which absorb that energy in their chloroplasts.
Chloroplasts are the sites in which, through a
series of metabolic reactions that require the
Sun’s energy, called photosynthesis, ordered

The ‘Dorian Gray effect’

Figure 2. The ‘Dorian Gray effect’. (A) Cardiac work is an orderly energy transfer that organizes
the body’s molecules to do work. The heart’s ability to offset the increasing tissues’ entropic burden
by the energy flow can be threatened by the increase of tissues’ randomness and disorder as a result
of various disease states; the heart may become a vulnerable target of a number of attacks either
from the internal environment (metabolic) or from the external environment. (B) This effect is known
as the ‘Dorian Gray effect’ of the heart.

702 Future Cardiol. (2012) 8(5) future science group

 The second law of thermodynamics & the heart Perspective

Flushing out of entropy Cardiac work

through lungs and kidney Energy organizes
molecules to do work

Energy
Flushing out of entropy
through muscular work

Organic fuels, oxygen

Biosphere

Carbon cycle Water and Nitrogen cycle

energy cycle

Figure 3. Negative entropy. The ability of flushing out the excess of entropy is one of the most
outstanding features of cellular life. The function of the heart is to organize body’s the molecules to
do work and this energy flow helps to offset the increasing body’s entropic trend primarily through
the external work made by the skeletal muscles. With the aid of application of the general system
theory, the heart could be viewed as a connection between surroundings (biosphere) and the
metabolism of the body.

energy-rich carbohydrates and oxygen molecules
are produced from carbon dioxide and water.
Animals use carbohydrates to produce high-
energy phosphates through the mitochondria
and are therefore dependent on photosynthe-
sizing species. The interaction between systems
and the resulting new supersystem properties,
which do not exist when the components are
isolated, constitutes a mechanism of exchange
of energy and entropy that is able to maintain
the living organism far from thermodynamic
equilibrium. The role of sunlight as the indis-
pensable source of energy and negentropy is
coupled with the photobiogenesis of vitamin D
from 7-dehydrocholesterol.
Many cycles of living organisms are irrevers-
ible if we consider them apart from the environ-
ment or surroundings, but they approach the
quasi-reversible status if we contemplate them
in a context that includes the world outside the
system boundaries. For instance, plants take
energy from disorganized molecules, such as
carbon dioxide and water, to produce organized
substances, like carbohydrates and oxygen that
are then utilized as energy by other organisms.
It is by a continuous exchange of energy and
matter with the adjacent systems and subsystems
that the cycles of a composite living being will
approach reversibility. Cycles that are composed
of processes that move towards reversibility will
give the maximum net work with an increase
in efficiency. The so-called Gaia hypothesis
proposes that all organisms and their inorganic
surroundings on Earth are closely integrated to
form a single and self-regulating complex sys-
tem, maintaining the conditions for life on the
planet [27,32,33] . In this perspective, the cardio-
vascular, respiratory and renal systems should
be considered as parts of this hierarchy of sys-
tems and subsystems tightly coupled with the
biosphere.
The heart as an energy converter & its
antientropic function
The ability of ‘flushing out’ the excess of entropy
is one of the most outstanding features of cellular
life. For unicellular organisms the problem is a
simple one. Surrounded by water, cells can take
up nutrients directly from and eliminate waste
directly into the environment; in this way they
ensure the constancy of intracellular conditions
(homeostasis) necessary for their proper func-
tion. In multicellular organisms, all cells must
receive nutrients and eliminate their waste prod-
ucts. To achieve this goal there must be a contin-
uous stream of nutrients from the environment
to the cells and a continuous stream of waste
products from them to the environment [34] .
Maintenance of the complex, high-energy
condition like that of a multicellular organism

future science group www.futuremedicine.com 703

 Perspective Dini, Guarini, Morrone & Marzilli
requires a means of converting this energy into
the necessary net work. At the same time, it is
necessary to maintain constant internal condi-
tions despite large changes in the external envi-
ronment. Therefore, similar to an automobile
that has an internal combustion engine, trans-
mission and drive chain to provide the necessary
mechanism for converting the energy of gasoline
into transportation, complex organisms need a
transport system (cardiovascular system and
blood) as well as exchange systems (lungs, gut
and kidneys) to couple the available energy to
the necessary work and to sustain the system far
from the equilibrium.
All of the organ systems in the body contribute
to homeostasis, but the cardiovascular system is
especially important. Myocardial viability and
function depend on the accessibility of energy
to maintain intracellular homeostasis, biosyn-
thesis and to perform the biological work. A
fundamental function of the heart is to orga-
nize the body’s molecules to do work and this
energy flow helps to keep the system far from
thermodynamic equilibrium (Figure 2) .
The description of the heart as a dissipative
structure was first made by Dirk Brutsaert [35,36] .
Brutsaert introduced the concept that the inter-
actions among different levels of complexity at
molecular, cellular and tissue levels may induce
the development of emerging new features that
are not apparent when the heart is only consid-
ered as the sum of the properties of the cells of
which it is composed [37] . The heart’s interact-
ing systems, from the cycles of attachment and
detachment of contractile proteins to the muscle
pump function, create a means of converting the
potential energy stored in chemical bonds in the
external work for the transport of oxygen, carbo-
hydrates, fatty acids, amino acids, vitamins and
water to all the tissues and wash out of meta-
bolic waste products like carbon dioxide, urea
and creatinine.
Extending this concept to a more systemic
view [38] , the heart may be interpreted not only
as a part of the cardiovascular system and a con-
nection with the other organs and tissues, but
also as a link with the outer environment forming
a network for the development of new patterns of
order that ultimately moves living beings away
from thermodynamic equilibrium. The flush-
ing out of entropy requires work by the living
system on the external environment, which is
produced by the conversion of chemical energy.
Consequently, the more efficient the energy
transfer from the heart to the muscles, the more
entropy is dissipated in the surroundings.
704 Future Cardiol. (2012) 8(5)
Conclusion
Contemporary entropy theory presents the
concept of entropy not as merely a thermody-
namic issue whose utility is primarily limited to
the study of heat transfer, but rather a broader
concept that is inversely related to the amount
of external work done. In physics, entropy is
opposed by work, which is defined as an orderly
application of energy. Work is needed to create
order and oppose the tendency towards increased
entropy. Biological work seems to play a pivotal
role in dissipating the excess entropy. Dissipative
structures grow more complex by exporting, or
dissipating, entropy into their surroundings.
The heart could be viewed as an open dissipa-
tive system that connects the biosphere with the
metabolism of the body. Such an interaction gives
rise to emerging new properties that confer the
necessary means to export the excess entropy in
the surroundings. Particularly, this maintains a
state of low entropy by discarding high-entropy
fluxes out of the body’s system because of the
ability of muscles to perform external work. The
awareness of the importance of nonequilibrium
thermodynamics in the interpretation of the car-
diovascular system in physiology as well as of dis-
ease states may be valuable in the implementation
of new strategies of treatment and prevention.
Clinical implications & future perspective
A living system is more than a conglomerate of
carbon, oxygen and water, but comprises a num-
ber of interactive dissipative structures (mol-
ecules, cells and tissues) in which the heart and
the circulation represent the core of the mecha-
nisms of vital support. The heart and the circula-
tion may be considered life-supporting structures
that use energy to keep the body’s molecules to
remain organized and have a potential to offset
the increasing entropic burden in co-operation
with the respiratory, excretory and skeletal muscle
systems. In doing so, the cardiovascular system is
central in controlling the adaptation processes to
the surroundings changes and explains the resil-
ience of the internal conditions to a number of
perturbations, which might affect the living sys-
tem as a whole or the heart itself. Small perturba-
tions lead to small changes and thus homeostatic
conditions can be preserved, but greater threats
may substantially compromise the equilibrium.
The role of the heart as a connection between the
inner and outer environments makes it the vul-
nerable target of a number of attacks, either from
the internal environment (metabolic) or from the
external environment. During lifetime, cardiac
entropy tends to increase to offset the increasing
future science group
 The second law of thermodynamics & the heart Perspective

entropy of body’s tissue unless this entropy bur-
den is conveyed to the surroundings (Figure 3) . A
so-called ‘Dorian Gray effect’ might reflect the
intervening cardiac damage that emerges from
the limitations in the process of adaptation in
the face of perturbations that, for the most part,
come from outside the heart (Figure 2) .
Technical advances applicable to the assess-
ment of the cardiovascular system have pro-
vided new means to improve the understanding
of the thermodynamic aspects of cardiovascu-
lar physiology and disease states. Visualization
of blood flow and the emergence of dissipative
vortical structures may be obtained by contrast
echocardiography [39] . MRI is the most reliable
and accurate technique to assess morphological
disarray and scarring within the myocardial tis-
sue that reflects an increased entropic burden.
Although a number of attempts have been made
to assess cardiac efficiency, most of them rely on
a definition of efficiency as of quantity of the
work performed to the oxygen consumption of
the heart. The value of this approach is question-
able, since in the failing heart myocardial scarring
may reduce both external work and myocardial
oxygen consumption. For the heart as a pump, an
ideal definition of the efficiency of energy release
would be the ratio between the net work and the
maximal work possible. The evaluation of the
peak power of the left ventricle, with respect to
the potential energy stored in LV mass can pro-
vide insights on the amount of the inefficiency,
as well as the entropic burden of the heart [40] .
When irreversible scarring is present within LV
myocardial tissue, the system tends to approach a
state of maximum entropy and the ability of the
heart to generate power with respect to mass will
be reduced. Energy starvation and the accumula-
tion of by-products have been indicated as major
factors, which are capable of compromising LV
function in patients with heart disease.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial
involvement with any organization or entity with a
financial interest in or financial conflict with the sub-
ject matter or materials discussed in the manuscript.
This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony, grants or
patents received or pending, or royalties.
No writing assistance was utilized in the production
of this manuscript.

Executive summary
„„The term thermodynamics was originally given to the science dealing with the motive power of heat, or the transformation of heat into
mechanical work or vice versa. Thereafter, the subject was extended to the more generalized concept of energy transfer.
„„The second law of thermodynamics describes basic principles familiar in everyday life. It is partially a universal law of decay; the ultimate

cause of why everything ultimately falls apart and disintegrates over time. Even death is a manifestation of this law. The effects of the
second law are everywhere, touching everything in the universe.
„„In thermodynamic terms, living beings must function as open systems.

„„From a biological standpoint, energy is the capacity to increase order.

„„Entropy can be thought of as a measure of the randomness of a system. It is related to the various modes of motion in molecules.

„„The arrow of time: time goes from the past to the future where the entropy is greater than it was before.

„„Nonequilibrium thermodynamics is a branch of thermodynamics that deals with systems that are far from near equilibrium conditions

studied in classical thermodynamics.

„„Living beings, contrary to the general tendency dictated by the second law of thermodynamics, preserve their internal order and

prevent their natural degradation by feeding on the amount of order that an organism sucks from the surroundings as negative
entropy.
„„Cardiac energy organizes body’s molecules to perform work, creating what physicists call order. The lack of order to do work is called

entropy, which physicists call a disorder.

„„According to the theory of dissipative systems, the heart might be considered a life-supporting structure with a potential to offset the

increasing entropic burden of the body.

„„The heart works as an open dissipative system, since it has the capacity to exchange heat and matter with the surroundings, thus

maintaining the living system far from equilibrium as a result of an entropy decrease.
„„During one’s lifetime, cardiac entropy tends to increase to offset the increasing entropy of body’s tissues. A so-called ‘Dorian Gray

effect’ might reflect the intervening cardiac damage.

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