Transcript Heart failure. Myocardial Infarction Ph.D., MD, Assistant Professor

Heart failure.
Myocardial Infarction
Ph.D., MD, Assistant Professor
Hanna Saturska
Functions of circulatory system
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Stabilization
of arterial
pressure
Tissue
provision by
О2
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The vital role of the circulatory system
in maintaining homeostasis depends
on the continuous and controlled
movement of blood through the
thousands of miles of capillaries that
permeate every tissue and reach every
cell in the body.
It is in the microscopic capillaries that
blood performs its ultimate transport
function.
Nutrients and other essential
materials pass from capillary blood
into fluids surrounding the cells as
waste products are removed.
Heart insufficiency (Heart failure)
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Heart failure is the pathophysiologic
state in which the heart, via an
abnormality of cardiac function
(detectable or not), fails to pump
blood at a rate commensurate with
the requirements of the metabolizing
tissues or is able to do so only with an
elevated diastolic filling pressure.
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Heart failure may be caused by
myocardial failure but may also
occur in the presence of nearnormal cardiac function under
conditions of high demand.
myocardial failure
conditions
of high demand
Reasons
Myocardium
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Myocardium hypoxia or ischemia
Infectional-toxical myocardium damage
Metabolism disorder
Nervous-trophical and hormonal influences on the
organism
Myocardium
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injury
overload
Increase of heart outflow resistance (heart aperture
stenosis, arterial hypertension)
Increase of diastolic inflow (hypervolemia, heart
aperture insufficiency)
Mixed
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Heart failure always causes
circulatory failure, but the converse
is not necessarily the case, because
various noncardiac conditions (eg,
hypovolemic shock, septic shock)
can produce circulatory failure in the
presence of normal, modestly
impaired, or even supranormal
cardiac function.
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To maintain the pumping function of
the heart, compensatory mechanisms
increase blood volume, cardiac filling
pressure, heart rate, and cardiac
muscle mass.
However, despite these mechanisms,
there is progressive decline in the
ability of the heart to contract and
relax, resulting in worsening heart
failure.
This chest radiograph shows an enlarged
cardiac silhouette and edema at the lung
bases, signs of acute heart failure.
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A 28-year-old woman
presented with acute
heart failure
secondary to chronic
hypertension. The
enlarged cardiac
silhouette on this
anteroposterior (AP)
radiograph is caused
by acute heart failure
due to the effects of
chronic high blood
pressure on the left
ventricle. The heart
then becomes
enlarged, and fluid
accumulates in the
lungs (ie, pulmonary
congestion).
Heart failure can be classified
into 4 classes
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Class I patients have no limitation of
physical activity
Class II patients have slight limitation
of physical activity
Class III patients have marked
limitation of physical activity
Class IV patients have symptoms even
at rest and are unable to carry on any
physical activity without discomfort
Heart failure can be divided into 4 stages, as
follows:
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Stage A patients are at high risk
for heart failure but have no
structural heart disease or
symptoms of heart failure
Stage B patients have structural
heart disease but have no
symptoms of heart failure
Stage C patients have structural
heart disease and have symptoms
of heart failure
Stage D patients have refractory
heart failure requiring specialized
interventions
STAGES
Compensation
1. Crash phase
(main sense - compensative hyperfunction)
2. Stable adaptation phase
(main sense - compensative hypertrophy)
Decompensation
3.
Exhaustion
Crash phase
(St. of compensation)
Cardial mechanisms
1.
HB increase (in 2,5
time)
2. Systolic volume
increase
3. Heart index increase
4. Heart work increase
Extracardial
mechanisms
1. Increase of O2
utiliza-tion by the
tissues
2. Reduce of
peripheral vessels
resistance
Crash phase
(St. of compensation)
Reason
increase of every cardiomyocytes load
Physiological
mechanisms
* adequate excitement
*relation of excitement and shortening
* adequate shortening
*energy provision
Crash phase
Immediate adaptation mechanisms
1. Adequate excitement
Is based on selective penetration of
Na+, K+, Са2+ due to difference between
the extracellular ions concentration and
intracellular one
Result - depolarization
Crash phase
Immediate adaptation mechanisms
2. Relation of excitement and shortening
*diffusion of depolarization wave inside the
cardiomyocytes
* Са2+ penetration in to cytoplasma from SPR
* Са2+connection with troponin and release of
myosin
3. Shortening
*actin and myosin interaction
Crash phase
Immediate adaptation mechanisms
4. Energy provision
*Glycolisis activation
*Mitochondria activation
*CrPh reserve, glycogen reserve(are localized on
SPR membrane)
-most sensitive - depolarization ( Na,K-АТPаse
and Са- АТPаse control of ions transposition
athwart concentration gradient
Excessive Са concentration causes its
accumulation in mitochondrias and block of
АТP synthezise!!!
Crash phase (pathogenesis)
Heart beat increase
Functional changes
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Increased penetration of Na and Са cytoplasma
inside
Decrease of depolarization interval
Is possible if:
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activity of Na,K-ATPase and Са -ATPase is high
CrPh reserve and ATP reserve is adequate
ATP synthezise in mitochondrias is adequate
Na,Са-regulative mechanism is adequate
Crash phase (pathogenesis)
Increase of shortening power
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( heterometric mechanism and homeometric
mechanism)
Activation of adenilatcyclase by catecholamines
cАМP synthesis
Increase of Са concentration in cytoplasma
Increase of free myosin fibers amount (Са
blockades troponin)
Increased amount of myosin-actin interaction
Using of ATP, CrPh, glycogen
Crash phase (pathogenesis)
Limitation mechanisms
1. Accumulation of Na (because is limited Na,К-АТPase
activity)
2. Violation of Na,Са-exchanged mechanism
3. Са accumulation (because limitation of Ca-АТPase
activity)
after-effect: cardiomyocyte relaxation deficit (diasole
deficit)
Са accumulation in mytochondrias
(dissociation of oxidation and phocphorilation)
4. Energy deficit (deficit of АТP 40-60 % causes
shortening depression)
5. Lactic acid accumulation (causes shortening depress ion
because Н+ions interact with troponin)
Crash phase (pathogenesis)
Resume
Limitation mechanisms cause condition when
heart load is more than heart work.
It is the sense of heart insufficiency.
So, compensative hyperfunction as an adaptation
mechanism is depleted
Stable adaptation phase
(stage of compensation)
Gist: compensative hypertrophy
Mechanisms
* RNA synthesis activation in cardiomyocites
* Increase of ribosome quantity in cardiomyocites
* Structural proteins synthesis (at first mitochondrial
proteins and SPR ones)
* activation DNA and RNA synthesis in connective tissue
cells of the heart (fibroblasts and endotheliocytes)
* Controlled proliferation of the connective tissue cells
(they are the donors of RNA and structural proteins)
Result: heart stable adaptation to load
Signs of hypertrophy
Sick person
1. Continuous heart load
2. Heart hypertrophy is
inadequate
to body weight
3. Decrease of capillaries amount
in
weight unit
4. Inadequate activity of MCh
5. Inadequate activity of SPR
6. Decrease of nervous structures
amount in weight unit (decrease
of
NA concentration)
Sportsman
1. There are periods of heart
load and
restoring
2. Heart hypertrophy is
adequate to
body weight
3. Increase of capillaries
amount in
weight unit
4. Adequate activity of MCh
5. Adequate activity of SPR
6. Increase of nervous
structures
amount in weight unit
(adequate
concentration of NA)
Signs of hypertrophy
Sick person
Results
Heart insufficiency is
compensated by the
hypertrophy (bigger heart mass).
But this change limits maximal
heart work.
Sportsman
Results
Heart insufficiency, which is
compensated by the
hypertrophy,
increases of heart muscles
contraction power and speed
one.
Heart work is increased and
human endurances is
increased too
Exhaustion (stage of decompensation)
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Decrease of correlation between square
cardiomyocyte surface and
cardiomyocyte volume (unbalance of
ions pumps)
Decreased Na,K-АТPase activity
(violation of repolarisation ,
appearance of arrhythmias)
Decreased activity of SPR and СаАТPase (heart relaxes slowly, some
time arise diastole defect at Са
accumulation)
Exhaustion (stage of decompensation)
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Decreased MCh activity and energy deficit
because Са is accumulated in MCh and it causes
dissociation of oxidation and phosphorilaion
Depression of contractil function
Exhaustion of connective tissue cells donors
function
Decrease of coronary blood flow reserve
Decrease of NА concentration decrease of
maximal speed shortening of the heart and
maximal force one
Exhaustion
right-sided
(stage
of
decompensation)
left-sided
Pathological signs
Violations of blood circulation
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Reduce of systole output (increase of diastole
excess blood volume, myogene dilation)
Decrease of heart output
Decrease of systole arterial pressure
Increase of diastole arterial pressure
Increase of veins pressure (causes the HR
increase)
Slowdown of blood flow (main sign of
decompensation)
Erythrocytosis (compensation)
Pathological signs
Breathing violations
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Dyspnoea (reflective irritation of breathing
center by the СО2)
Attacks of cardiac asthma at night (blood
overflow of the atriums and central veins,
which causes barro-receptors irritation and
breathing center reflexes)
Pathological signs
Violation of water-electrolyte balance
(edema)
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Blood circulation violation (slowdown blood flow in
capillaries, intravenous blood pressure increase)
Reflexes of blood circulation dumping (blood retention
in depot : liver, veins)
Deficit of blood circulation in the arteries
Irritation of the vessels volume receptors
Hypersecretion of aldosteron (Na retention) and
vasopressin (water retention)
Hypervolemia, ascytes, edema
Myocardial infarction
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Ischemic heart disease occurs when
there is a partial blockage of blood
flow to the heart. When the heart
does not get enough blood it has to
work harder and it becomes starved
for oxygen. If the blood flow is
completely blocked then a myocardial
infarction (heart attack) occurs.
Myocardial infarction
Ischaemical necrosis of the
myocardial tissue, which is resulted
from coronary blood supply
insufficiency
Statistics
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Morbidity increases
Patients which suffer from
myocardial infarction are younger
year by year
Mortality of the patients which suffer
from myocardial infarction increases
year by year
(30-40 %)
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Coronary artery disease is currently the
leading cause of death in the United
States. Despite the increasing
sophistication of surgical techniques, the
introduction of new techniques such as
balloon angioplasty, and a number of new
drugs (e.g. beta blockers, calcium
antagonists), it is estimated that over 1
million heart attacks will occur this year,
resulting in 500,000 deaths. In short, we
do not have an adequate therapeutic
solution to the problem of myocardial
infarction (heart attack).
ЕТHІОLOGY
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Atherosclerosis of the coronary
arteries (in 90-95 % died persons at
section was found)
Trombosis of the coronary arteries :
*at 4 stage of atherosclerosis
*arterial hypertension (because it
causes blood coagulation
hyperactivity)
Trombembolism (septic endocarditis,
thrombus lyses)
Spasm of the coronary arteries
Risk factors
1. Stress
(at trauma, operation, cold, negative emotions)
BECAUSE IT CAUSES:
Increase of the heart activity
Stimulation of the heart metabolism
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Increase of О2 using
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Risk factors
2. Age (most often appears in 40 – 59
years old person).
3. Hypokinesia (activation of the
sympathetic-adrenal system)
4. Obesity (hypercholesterolemia)
Risk factors
5. MAIL SEX
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Morbidity of the men in 2-3 time more
Mortality of the men in 3-4 time more
Men 45-59 years old - mortality 37 %
Woman 45-59 years old – mortality 17
%
Men 60-74 years old - mortality
55 %
Woman 60-75 years old –
mortality 78,4 %
Risk factors
6. Heredity
7. Arterial hypertension
8. Diabetes mellitus
9. Infection (chlamydia pneumonia)
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Pathogenesis
1.
2.
Initial
mechanisms
Mechanisms of the
cardiomyocites
necrosis
As a result of
atherosclerotic
disease of the
coronary arteries
As a result of
cardiomyocytes
ischemia
Initial mechanisms
1.
Increase of the atherosclerotical
plaque size:
Vessel narrowing---ischemia---necrosogenic ATP
deficit
vessels narrowing on 95 % (“critical stenosis”) causes
АТP deficit (less than 40-60 %) which results in
cardiomyocytes necrosis
Initial mechanisms
2. Increase of injured vessel sensitivity to
vasospastic effects
Damage of endothelium ----decrease of NО-synthetase activity---decrease of NО concentration (which is
powerful vasodilator)
Initial mechanisms
3. Thrombosis
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Anticoagulants blood activity decrease
(heparin is used for activation of lipoprotein lipase at
hyperlipoproteinemia)
Decreased antithrombosis properties of the injured
endothelium
Unmasked collagen fibers cause activation of the
Villebrand’s factor
Cardiomyocytes necrosis mechanism
1. ATP deficit
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Decrease of the cytochromoxydase
activity
Violation of electrons transfer in MCh
Violation of Krebs-cycle
Accumulation of acetylcoensime-A, fat
acids
Deficit of ATP and CPh causes
- ineffective Na,К-АТPase (fatal
arrhythmias)
- ineffective Са-АТPase (damage of the
Cardiomyocytes necrosis mechanism
2. Acidosis
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Accumulation
Accumulation
Accumulation
Accumulation
Accumulation
of
of
of
of
of
Crebs-cycle metabolits
Acetyl-Co-A
fatty acids
piruvate acid
lactic acid
Cardiomyocytes necrosis mechanism
Acidosis after-effects
**depression of cardiomyocytes contractility
(main sign of ischemical area)
Mechanisms
1. Н+-ions interact with troponin. It causes of
myosin releasing impossibility. So, as a result,
interaction of actin and myosin becomes
impossible
2. Са deficit in cytoplasma occurs because Ca can
be accumulated in Mch
very often it is complicated by the “reperfusion
syndrome”
Cardiomyocytes necrosis mechanism
3. Са accumulation
Reasons:
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1. Deficient of Ca return in to SPR (ATP deficit
decreases Ca-ATPase activity)
2. Violation of Na,Са-exchange mechanism
Consequences:
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Ca deposit in Mch and АТP deficit
Damage of cardiomyocytes membranes
Cardiomyocytes necrosis mechanism
4. “Lipid triade”
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1. Phospholipase activation (is caused by
catecholamines and Ca)
2. Lipids peroxidation (accumulation of
the free radicals, relative insufficiency of
the antioxidants)
3. Fat acids (damage of the membrane’s
lipids and violation of the ion channel’s
functions)
Hibernal myocardium
Especial condition of the heart which is
characterized by the sharply decreased pump
function of the heart (at human absolute rest)
without cardiomyocytes cytolysis as a result of
blood supply reducing
(protective reaction)
Hibernal myocardium
Sings
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Decreased left ventricle output at increased O2
need of the organism (physical activity, fever,
hyperthyroidism)
Decreased using of ATP
Retardation of the cardiomyocytes necrosis
Renewal of Н+ concentration, creatinphosphate
level, рСО2 (during 1-3 hour)
Hibernal myocardium
Finishing
Spontaneous recurrent process
after blood supply restoring !!!
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1 stage – hypokinetic and asynchronous
cardiomyocytes contruction
2 stage – renewal of synchronous
cardiomyo-cytes contruction and left
ventricle output rising at increased O2
need of the organism (physical activity)
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The chronic but reversible myocardial dysfunction seen
in patients with severe coronary artery disease is a
complex, progressive, and dynamic phenomenon that
is initiated by repeated episodes of ischemia. In the
early stages, resting perfusion is usually preserved, but
flow reserve is significantly reduced. With time, and
probably also increases in the physiological significance
of the underlying coronary narrowing, some of the
dysfunctional segments which initially appeared
“chronically stunned” may eventually become
underperfused, probably in response to the decrease in
myocyte energy demand. This transition from chronic
stunning to chronic hibernation is associated with
several morphological alterations, which include
myofibrillar disassembly, myofibrillar loss, and
increased glycogen content. Interestingly, these
changes take place similarly in dysfunctional and in
normally perfused remote regions of the dysfunctional
heart, which suggests that they may be more a
response to chronic elevations in preload or stretch
than the direct consequences of ischemia.
(Panel A): Light micrograph of a normal myocardium. (Panel B):
Representative light micrograph of hibernating myocardium. The myolytic
cytoplasm is filled with PAS-positive material typical of glycogen.
Magnification ´320.
Myocardial Infarction Prevention
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Strophanthin comes from an extract
of an African plant called
strophanthus gratus. Since 1991 it
was discovered as an endogenous
substance that research shows can
prevent angina pectoris and
myocardial infarction by 80-100
percent without major side effects.
strophanthus gratus