Heart failure. Myocardial Infarction

1. Heart failure. Myocardial Infarction Ph.D., MD,Assistant ProfessorHanna Saturska

2. Functions of circulatory system • Stabilization of arterial pressure • Tissue provisionby О2

3. 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.

4. 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.

5. 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. conditions of high demand myocardial failure

6. Reasons Myocardiuminjury • Myocardium hypoxiaor ischemia • Infectional-toxicalmyocardiumdamage • Metabolism disorder • Nervous-trophical andhormonal influences on the organism Myocardiumoverload • Increase of heart outflow resistance (heart aperture stenosis, arterialhypertension) • Increase ofdiastolic inflow (hypervolemia, heart aperture insufficiency) Mixed

7. 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.

8. 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.

9. This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.

10. 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).

11. 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

12. 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

13. STAGES Compensation 1. Crash phase (main sense - compensative hyperfunction) 2. Stable adaptation phase (main sense - compensativehypertrophy) Decompensation 3. Exhaustion

14. Cardialmechanisms HB increase (in 2,5 time) 2. Systolic volume increase 3. Heart indexincrease 4. Heart workincrease Extracardialmechanisms 1. Increase of O2 utiliza-tionby the tissues 2. Reduce of peripheral vessels resistance Crash phase(St. of compensation)

15. Crash phase(St. of compensation) Reason increase of every cardiomyocytes load Physiologicalmechanisms * adequateexcitement *relation of excitementand shortening * adequateshortening *energy provision

16. Crash phaseImmediate adaptation mechanisms 1. Adequate excitement Is basedon selective penetration ofNa+, K+, Са2+due to difference between the extracellular ions concentration and intracellular one Result - depolarization

17. Crash phaseImmediate adaptation mechanisms 2.Relation of excitementand shortening *diffusion ofdepolarization wave inside the cardiomyocytes * Са2+penetration in to cytoplasma from SPR * Са2+connection with troponinand release of myosin 3. Shortening *actinand myosin interaction

18. Crash phaseImmediate adaptation mechanisms 4. Energy provision *Glycolisis activation *Mitochondria activation *CrPhreserve,glycogenreserve(are localized on SPR membrane) -most sensitive - depolarization ( Na,K-АТPаse and Са- АТPаse control of ions transpositionathwartconcentration gradient Excessive Са concentrationcauses its accumulation inmitochondrias and block of АТPsynthezise!!!

19. Crash phase (pathogenesis) Heart beat increase Functional changes • Increasedpenetration ofNaand Са cytoplasma inside • Decrease of depolarization interval Is possible if: • activity of Na,K-ATPaseand Са -ATPaseis high • CrPhreserve and ATP reserve is adequate • ATPsynthezisein mitochondrias is adequate • Na,Са-regulative mechanism is adequate

20. Crash phase (pathogenesis) Increase ofshorteningpower ( heterometricmechanism andhomeometric mechanism) • Activation of adenilatcyclase by catecholamines • cАМP synthesis • Increase of Са concentration in cytoplasma • Increase offree myosin fibers amount (Са blockades troponin) • Increased amount of myosin-actin interaction • Using of ATP, CrPh, glycogen

21. Crash phase (pathogenesis) Limitation mechanisms 1. Accumulation ofNa (because is limited Na,К-АТPase activity) 2. Violation ofNa,Са-exchanged mechanism 3. Са accumulation (because limitation of Ca-АТPase activity) after-effect:cardiomyocyte relaxation deficit (diasoledeficit) Са accumulation in mytochondrias (dissociationof oxidation and phocphorilation) 4. Energy deficit (deficitof АТP 40-60 % causes shortening depression) 5. Lactic acid accumulation (causes shortening depress ionbecause Н+ions interact with troponin)

22. Crash phase (pathogenesis) Resume Limitation mechanisms cause condition when heart load is more than heart work. It is the sense ofheart insufficiency. So, compensative hyperfunctionas an adaptation mechanism is depleted

23. 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 andSPR ones) * activationDNA and RNA synthesisin connective tissue cells of the heart (fibroblastsandendotheliocytes) *Controlled proliferationof the connective tissue cells (they are the donors ofRNAand structural proteins) Result: heart stable adaptationto load

24. Sickperson 1. Continuous heart load 2. Heart hypertrophy is inadequate to body weight 3. Decrease of capillaries amount in weight unit 4. Inadequateactivity of MCh 5. Inadequateactivity of SPR 6. Decreaseof nervous structures amountin weight unit (decrease of NA concentration) Sportsman 1. There are periods ofheart load and restoring 2. Heart hypertrophy is adequate to body weight 3. Increase of capillaries amount in weight unit 4. Adequateactivityof MCh 5. Adequateactivity of SPR 6. Increaseof nervous structures amountin weight unit (adequate concentration of NA) Signs of hypertrophy

25. Sickperson 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 Signs of hypertrophy

26. Exhaustion (stage of decompensation) • Decrease of correlation between squarecardiomyocyte surface and cardiomyocyte volume (unbalance of ions pumps) • Decreased Na,K-АТPase activity (violation of repolarisation , appearanceof arrhythmias) • Decreasedactivityof SPR and Са-АТPase (heart relaxes slowly, some time arise diastole defect at Са accumulation)

27. Exhaustion (stage of decompensation) • Decreased MCh activityand energy deficit because Са is accumulated in MChand it causes dissociation of oxidation and phosphorilaion • Depression of contractilfunction • Exhaustion of connective tissue cellsdonors function • Decrease of coronary blood flow reserve • Decreaseof NА concentrationdecrease of maximal speed shortening of the heart and maximal force one

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

29. Pathological signs Violations of blood circulation • Reduce of systole output (increase of diastole excess blood volume, myogene dilation) • Decrease of heart output • Decreaseof systolearterial pressure • Increaseof diastolearterial pressure • Increase of veins pressure (causes the HR increase) • Slowdown of blood flow (main sign of decompensation) • Erythrocytosis (compensation)

30. Pathological signs Breathing violations • Dyspnoea (reflective irritation of breathingcenter by the СО2) • Attacks of cardiac asthma at night (bloodoverflow of the atriums and central veins, which causesbarro-receptors irritation and breathingcenter reflexes)

31. 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 (Naretention) andvasopressin (waterretention) • Hypervolemia, ascytes, edema

32. Myocardial infarction

33. 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.

34. Myocardial infarction Ischaemical necrosis of the myocardial tissue, whichis resulted from coronary blood supply insufficiency

35. 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 %)

36. 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).

37. ЕТHІОLOGY • Atherosclerosis of the coronary arteries (in 90-95 % died persons at section was found) • Trombosis of the coronary arteries: *at 4stage of atherosclerosis *arterial hypertension (because it causes blood coagulation hyperactivity) • Trombembolism (septicendocarditis, thrombus lyses) • Spasmof the coronary arteries

38. Risk factors 1. Stress (at trauma, operation, cold, negative emotions) BECAUSE IT CAUSES: • Increase of the heart activity • Stimulation of the heartmetabolism • Increase of О2using

39. Risk factors 2. Age(most often appears in 40 – 59 years old person). 3. Hypokinesia(activation of the sympathetic-adrenal system) 4. Obesity (hypercholesterolemia)

40. Risk factors 5. MAIL SEX • Morbidity of the men in 2-3 time more • Mortality of the men in 3-4time more Men 45-59 years old - mortality 37 % Woman 45-59 years old – mortality 17 % Men 60-74 years old - mortality 55 % Woman60-75years old – mortality 78,4 %

41. Risk factors 6. Heredity 7. Arterial hypertension 8. Diabetes mellitus 9. Infection (chlamydia pneumonia)

42. 1. Initial mechanisms As a result of atherosclerotic diseaseof the coronary arteries 2. Mechanismsof the cardiomyocites necrosis As a result of cardiomyocytes ischemia Pathogenesis

43. Initial mechanisms • Increase of the atherosclerotical plaque size: Vessel narrowing---ischemia---necrosogenicATP deficit vessels narrowing on 95 % (“criticalstenosis”) causes АТP deficit (less than 40-60 %) which results in cardiomyocytes necrosis

44. Initial mechanisms 2. Increase of injured vessel sensitivity to vasospastic effects Damage of endothelium ----- decrease ofNО-synthetase activity---- decrease ofNО concentration (which ispowerful vasodilator)

45. Initial mechanisms 3. Thrombosis • Anticoagulants blood activity decrease (heparin is used for activation of lipoprotein lipase athyperlipoproteinemia) • Decreased antithrombosis properties of the injured endothelium • Unmasked collagen fibers cause activation of the Villebrand’s factor

46. Cardiomyocytes necrosis mechanism 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 - ineffectiveNa,К-АТPase (fatalarrhythmias) - ineffective Са-АТPase (damage of the Mch)

47. Cardiomyocytes necrosis mechanism 2. Acidosis • Accumulation of Crebs-cycle metabolits • Accumulation ofAcetyl-Co-A • Accumulation offatty acids • Accumulation of piruvateacid • Accumulation of lactic acid

48. Cardiomyocytes necrosis mechanism Acidosis after-effects **depression of cardiomyocytes contractility (main sign of ischemical area) Mechanisms 1.Н+-ions interact withtroponin. It causes of myosin releasing impossibility. So, as a result, interaction of actin and myosin becomes impossible 2.Саdeficit in cytoplasma occurs because Ca can be accumulated in Mch very often it is complicated by the “reperfusion syndrome”

49. Cardiomyocytes necrosis mechanism 3. Са accumulation Reasons: • 1. Deficient of Ca return in to SPR (ATP deficit decreases Ca-ATPase activity) • 2. Violation ofNa,Са-exchange mechanism Consequences: • Ca deposit in Mch and АТP deficit • Damage of cardiomyocytes membranes

50. Cardiomyocytes necrosis mechanism 4. “Lipid triade” • 1. Phospholipase activation (is caused bycatecholamines 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)