Heart failure.

Myocardial Infarction

Ph.D., MD, Assistant Professor Hanna Saturska

Functions of circulatory system

Stabilization of arterial pressure

Tissue provision by О2

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)

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.

Heart failure may be caused by myocardial failure but may also occur in the presence of near-normal cardiac function under conditions of high demand.

myocardial failureconditions

of high demand

ReasonsMyocardium injury

- Myocardium hypoxia or ischemia- Infectional-toxical myocardium damage- Metabolism disorder- Nervous-trophical and hormonal influences on the

organism

Myocardium overload- Increase of heart outflow resistance (heart aperture

stenosis, arterial hypertension)- Increase of diastolic inflow (hypervolemia, heart

aperture insufficiency)

Mixed

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.

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.

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 classifiedinto 4 classes

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:

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

Reason increase of every cardiomyocytes load

Physiological mechanisms * adequate excitement *relation of excitement and shortening * adequate shortening *energy provision

Crash phase (St. of compensation)

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

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 Immediate adaptation mechanisms

Crash phase (pathogenesis)

Heart beat increaseFunctional changes

Increased penetration of Na and Са cytoplasma inside

Decrease of depolarization interval

Is possible if: 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

Increase of shortening power( 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 mechanisms1. Accumulation of Na (because is limited Na,К-АТPase

activity)2. Violation of Na,Са-exchanged mechanism3. 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)

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 hypertrophySick person

1. Continuous heart load2. Heart hypertrophy is

inadequate to body weight3. Decrease of capillaries amount

in weight unit 4. Inadequate activity of MCh5. Inadequate activity of SPR6. Decrease of nervous

structuresamount in weight unit (decrease

of NA concentration)

Sportsman1. There are periods of heart

load and restoring2. Heart hypertrophy is

adequate to body weight3. Increase of capillaries

amount in weight unit4. Adequate activity of MCh5. Adequate activity of SPR6. Increase of nervous

structures amount in weight unit

(adequate concentration of NA)

Sick personResults

Heart insufficiency is compensated by the

hypertrophy (bigger heart mass). But this change limits maximal

heart work.

SportsmanResults

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

Signs of hypertrophy

Exhaustion (stage of decompensation) 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 Са-АТPase (heart relaxes slowly, some time arise diastole defect at Са accumulation)

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 (stage of decompensation)

Exhaustion (stage of decompensation) right-sided left-sided

Pathological signs

Violations of blood circulation 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)

Breathing violations

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)

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

Pathological signs

Myocardial infarction

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.

Ischaemical necrosis of the myocardial tissue, which is resulted

from coronary blood supply insufficiency

Myocardial infarction

Statistics

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 %)

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

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 Increase of О2 using

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 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. Heredity7. Arterial hypertension

8. Diabetes mellitus9. Infection (chlamydia pneumonia)

Risk factors

Pathogenesis

1.Initial

mechanisms

As a result of atherosclerotic disease of the

coronary arteries

2.Mechanisms of the

cardiomyocitesnecrosis

As a result of cardiomyocytes

ischemia

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

Initial mechanisms3. Thrombosis

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

1. ATP deficit 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

Mch)

Cardiomyocytes necrosis mechanism

2. Acidosis

Accumulation of Crebs-cycle metabolits Accumulation of Acetyl-Co-A Accumulation of fatty acids Accumulation of piruvate acid Accumulation of lactic acid

Cardiomyocytes necrosis mechanism

Acidosis after-effects

**depression of cardiomyocytes contractility

(main sign of ischemical area)

Mechanisms1. 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 accumulationReasons:

1. Deficient of Ca return in to SPR (ATP deficit decreases Ca-ATPase activity)

2. Violation of Na,Са-exchange mechanism

Consequences: Ca deposit in Mch and АТP deficit Damage of cardiomyocytes membranes

Cardiomyocytes necrosis mechanism

4. “Lipid triade” 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)

Cardiomyocytes necrosis mechanism

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)

Sings 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

FinishingSpontaneous recurrent process after blood supply restoring !!!

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)

Hibernal myocardium

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

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