Mechanism
of Heart Failure: Adaptive and maladaptive Mechanisms.
A Number of mechanisms aid the heart faced with an increased hemodynamic
burden (such as pressure or volume overload) or one that has sustained loss of
myocardium or contractility.
On a short –term basis many of these
responses are adaptive. How ever, on a long term basis these responses are often
maladaptive.
The
Frank
Starling Mechanism operates through an increase in preload.
As outlined above, an increase in the end diastolic volume of the ventricle is
associated with stretching of the sarcomeres, which increases the interaction
between actin and myosin filaments and their sensitivity to there by enhancing
contraction.
How ever, ventricular dilation may become maladaptive when
it becomes excessive, as may occur in sever valvular regurgitation, dilation increase
wall stress through the operation of Laplace’s law and there by reduces shortening
.
Compensatory hypertrophy occurs in hemodynamic overload, which in
turn restores elevated ventricular wall stress to normal. If the hypertrophy is
insufficient to restore wall stress further, leading to a vicious circle. Also,
serve ventricular hypertrophy may impair ventricular filling and cause myocardial
ischemia .
In ventricular remodeling there are change in the size, mass,
and configuration of the ventricle as a consequence of hemodynamic changes following
mechanical over load, hypertension, cardiomyopathy, and myocardial infraction.
Remodeling is triggered by myocyte growth, interstitial fibrosis and apoptosis
ischemia, vasoactive peptides, and fibrosis. A change to a more spherical shape,
which decreases the effectiveness of ejection, is common in the remodeled ventricle.
Redistribution of a subnormal cardiac output away from the skin, skeletal
muscle, and kidneys with maintenance of blood flow to the most vital organ, i.e.
the brain and the heart, occurs. The vasoconstriction, how ever, may increase
after load, thereby reducing cardiac output further.
Reduction
in Cardiac Efficiency The common forms of low output systolic HF, secondary to
coronary atherosclerosis, Hypertension, cardiomyopathy, and certain valvular and
congenital lesions, are characterized by a reduction in the external work performed
by the heart.
while
myocardial oxygen consumption remains normal or nearly so, there fore the external
efficiency i.e. the ratio of external work performed to energy consumed, is often
depressed.
Alterations
In Energy Metabolism When HF occurs in the presence of acute or chronic ischemia,
it can be attributed to reduced supply or oxygen with a resultant reduction of
ATP generation.
Severe ventricular hypertrophy and dilatation from any
etiology can contribute to ischemia, especially in the subendocardium, and this
can impair both ventricular contraction and filling.
In some form of
HF with out ischemia, myocardial energy stores in the form of creatine phosphate
are decreased, as is the activity of the enzyme creatine kinase required for the
shuttling of high energy phosphate between creatine phosphate and ADP,
Suggesting that reductions in myocardial energy reserves may play a role in nonischemic
conditions as well.
Abnormal
of Excitation Contraction Coupling :
Substantial evidence support
the view in may forms of heart failure the delivery of CA2+ to the contractile
sites is disturbed, there by impairing cardiac performance.
How ever,
the molecular basis of this abnormality in deed of the sub cellular structure
involved the sarcolemma, T tubules, and SR has yet to be defined .
There
is, however, evidence for a reduction in the activity of the ca2+ release channel
in the SR and of messenger RNA’s of the proteins regulating ca2+ channels,
and the activity of the SR ca2+ between the SR and the cytoplasm.
Impaired
expre3ssion of the genes encoding these proteins can impair both myocardial contraction
and relaxation and there by contribute to the development of HF.
Neurohumoral
and Cytokine Adjustments: A reduction in cardiac performance evokes a series of
Neurohumoral adjustments. Which may at different times be adaptive or maladaptive.
These adjustment are adaptive when they maintain arterial perfusion
pressure in the face of a sudden reduction of cardiac output.. However, they are
maladaptive when they increase the hemodynamic burden and oxygen required of the
failing ventricle and when they exacerbate injury.
The
Adrenergic Nervous System : In patients with HF the levels of circulating norepinephrine
may be markedly elevated, reflecting the increased activity of the adrenergic
nervous system.
This increased activity supports ventricular contractility
in acute HF that is intensified when large doses of B- adrenergic blocking agents
are administered acutely, providing evidence for the proactive action of adrenergic
nervous activation.
However , the chronic adrenergic stimulation that
occurs in HF may increase after load by raising vascular resistance, cause cardiac
arrhythmias, and may damage myocytes further, perhaps by increasing myocardial
energy expenditures and ca2+ overload.
Gradually increasing doses of
B Blockers are of benefit in patients with chronic HF. The Renin Angiotensin Aldosterone
system When cardiac output declines, the Renin Angiotensin Aldosterone system
is activated.
Concentrations of the both circulating angiotensin II
and aldoster one are increased, the former contributing to excess vasoconstriction
and the latter to the retention of salt and water perhaps to cardiac fibrosis.
The local tissue systems is also activated in HF and angiotensin II
exerts a local cardiotoxic effect activates protein kinase C. The latter stimulates
cardiac hypertrophy and causes ventricular remodeling .
Patients with
HF are usually improved by blocking this system with angiotensim converting enzyme
ACM inhibitors, angiotensin II receptor blocked, and Aldosterone antagonists.
