This paper is a review of Doxorubicin:
a anti-cancer drug and the adverse effects on the heart such as dilated cardiomyopathy
(DCM) which result in further complications like Heart Failure (HF). In
addition, the use of the hormone Melatonin as a potential “antagonist” and a reducing
factor for the progression of the disease.
The NHS spends about 60-70% of
their finance for the service of treating HF, and more than 20% of cases
regarding HF is due to DCM. Hence understanding this epidemic can support to
improve the NHS service and reduce the percentage of patients suffering from
HF is the dysfunction of the
cardiac system therefore the strength to provide the body tissue with the
necessary amounts of blood is compensated or the volume of blood to the heart
is reduced. Therefore, if the equilibrium of the volume of blood entering and
leaving the heart is unbalanced, the dynamics are disturbed. DCM causes the performance
of the cardiomyocytes to degenerate due to a poor length-tension relation, as
it expands the myocytes and potentially weakens it too, thus the cardiac rhythm
will become unsteady. Common HF symptoms are associated with Dyspnoea (breathlessness),
Oedema in the ankles and feet, fatigue, poor physical activity and wheezing.
The extent of how serious the patient’s symptoms at rest and exercise are
organised into four classes.
Systole is the duration in which the ventricles contract, this
force enables the movement of blood into the pulmonary artery and the Aorta.
Starling’s law states the length-tension relation of the muscle, when the
sarcomeres are lengthened there is more opportunities for the formation of
myosin-actin cross-bridge formations, hence there is more tension generated.
However, the ventricles do not operate with long sarcomeres instead they tend
to be shorter than skeletal muscle fibres, but as the blood flows into the
ventricles this enable the sarcomeres to stretch and this generates an ejection
Therefore, preload induces
troponin C to bind to calcium, exposing the myosin-binding sites present on the
actin filaments hence allowing this cross-bridge formation which uses ATP and
releases ADP and a phosphate. This causes a conformation change in myosin and
the filaments slide past each other, ATP then rebinds to myosin releasing it
from actin. The calcium unbinds from troponin C and the cardiac muscle relaxes.
Although when the fibres length
increases in DCM, this makes the ventricle walls thinner, remodelling the chambers
making them excessively hollow. This will reduce the ejection fraction (EF) from
the normal of 55%.
In this study, out 89 patients 59
had Idiopathic-DCM, 1.61 (median valve) was recorded as a low Peak Filling Rate
for the End Diastolic Volumes, and 75% of these patients had an EF value below
45%. Hence when EDV is reduced the tissues receive less blood and therefore
preload is decreased too, this cycle continues until the hearts supply of blood
is completely inadequate and the EF value is below normality.