H1 \ lil^ľL FAUÍUIi^ ÜF Ml r: j.^ r ígfll '< j r v ^11 m ge (> 45 c?, > 55 ?); sex (#) hypertension (STK > 120) DM 1 positive family anamnesis (<55(5\<45 $) LDL chol > 2.6 mmol/1 HDLchol<1.3m TG > 1.14 mmol/1 AJJ metabolic sy CHRI smoking, phys. inactivity left ventricle hvnertroülr NEW CRP and other iTiiHllllllHlMítlIMlTFm ers '94* iliJihulUM markers of AS plaque unstability atherosclerosis nonatherosclerotic coronary artery disease (inflammation, autoimmune processes) coronary artery spasm coronary trombosis (<— platelet deposition) coronary embolism increased myocardial oxygen demand F«k stable angina pectoris variant angina pectoris silent myocardial ischemia arrhythmias cardiac insufficiency unstable angina pectoris acute myocardial infarction sudden cardiac death WHO äiagfW3Í3 ujÄŕ/11 two of the following must be present: severe chest pain longer than 20 minutes (crushing chest pain perhaps radiating to the arm, back, jaw or abdomen) ■ changes indicať cardiac markers relea ■^■;i; ■ angaa ial di VII: another form of myocardial ischemia villHPgiiiaBKľ nary disease musculoskeletal pain abdominal pain (ulcers, pancreatitis, cholelithiasis etc.) AMI can be clinically silent, particularly in elderly, and the ECG changes may not always be typical (previous infarction, arrhythmias, pacemaker). pid and reversible changes in the cellular membrane. Anaerobic glycolysis becomes the major source of energy. It is not sufficient to meet the needs of ATP. Subsequent metabolic derangement causes functional and structural lesions of membranes and leakage of soluble molecules from the cytosol to interstitiu This reversible phase of ischemic injury lasts 5 hours. If reperfusion of the injured myocardium does not take place —► lysis of cellular structures and a rise of structurally bound markers in plasma. All these substances found in blood in increased amounts are called cardiac markers. old markers enzymes AST CK CK-MB HBD new markers CK-MB mass myoglobin troponins >j •i 1 Tropü-üix Togeher with actin and tropomyosin is one of proteins making up the cardiac muscle fibre. It is a complex of three polypeptides - Tn C, Tn T and Tn I. acim tropomyosin Ca" Tni Mg2+ TiiC TfiT lOŮOnm Tn T binds the troponin complex to tropomyosin molecule Tn I is the ATPase inhibitor Tn C binds Ca2+ beeing highly specific and sensitive for myocardial damage. Their greatest use is to exlude cardiac damage in a patient with chest pain: AMI is highly unlikely if there is no increase in troponins. The soluble fraction of Tn I and T is released together with the other cytosolic markers during the reversible phase of my cardial injury. The insoluble fraction o Tns is released after the irreversible necrosis when there is a decline in the concentration of cytosolic markers. cardiac-specific isoform cTnT different from riated muscle cells degenerative changes in skeletal muscles (dermatomyositis/polymyositis, Duchene muscular dystrophy, post-traumatical regeneration of muscles) dialysed patients (t cTnT in 30%) TnT start of plasma level elevation in 3.5-10 h leak around 18 hours post infarction (free troponin present in cytosol) ?mains elevated for 2-3 weeks due to it continued release from contractile maratus more specific for myocardium than Tnr cardiac-specific isoform cTnl (31 AA) is not produced by fetal cross-striated muscle cells increase of cTnl in dialysed patients is less often than cTnT ■»—■——■ start of elevation in 3.5-10 h, peak in 9-18 h , remains elevated for 2-3 weeks Dynamic of Tni and TnT release at patients with AMI 1504 3 | ioo4 0) DC 50 + 0 50 100 150 200 250 300 Time to symptom's origin /h the method for assessment of TnT is identical worldwide a variety of kits for different methods for assessment of Tnl represent the major disadvantage of its clinical use (different cut off values, difficulties in comparison) Tnl - more specific for myocardium TnT - problem with increase interpretation in patients with renal failure and systemic degenerative processes If this therapy is succesful in restoring perfusion, there is a rapid rise in plasma cardiac markers (wash-out phenomenon). The rises are slower and last longer if occlusion remains. : fibrinolysis start - plasma value peak; < 14 h in successful reperfusion, > 14 h if occlusion remains c^Cq (slope) or cx/c0 (ratio): concentration increase steepness in l^í h of therapy; crc0 > 0.2 jig/1 in successful reperfusion troponin T [pg/l] 4(H 30 A 20 A A / 10 J 7 / ft/ 50 100 lVJ/üglübiü cytosolic protein, sensitive indicator of cardiac damage, but is non-specific, being pre muscles as well ^^g^gU^TOmJ^^^mt^R released early following infarction. It4s the earlies AMI indicator and, as such, is useful for decisions on thrombolytic therapy. start of elevation 0.5 - 2 h, peak in 6 -12 h, return to normal values in 14 -18 h AST (aspartate ammoiramferase) 1st marker used for AMI dg aspar xalacetate + glutamate non-specific for myocardium, | in skeletal muscle diseases, haemolysis, liver or pulmonary diseases etc, in AMI ratio AST/ALT >1 non recommended f or AMI dg types of isoenzymes formed by 2 subunits: B (brain) ■ and [ (muscle) • each isoenzyme is a combination of 2 subunits : CK-BB ■ ■ typical for brain CK-MB • ■ myocardium CK-MM • • muscles and myocardium myocardium: 42% MB, 58% MM skeletal muscles: 97% MM, 3% MB CK-MB previously used for AMI dg imunochemical assessment of concentration in mg/1, no activity reaction with specific antibody — determination of partly destroyed molecules without enzymatic activity higher sensitivity than CK-MB 5 isoenzymes formed by 4 subunits, 2 types of subunits isoenzyme LD, tissu myocardium, eres, kidneys myocardium, eres, kidneys muscles, lymphatic tissue, leukocytes liver, muscles liver, muscles myocardium typical isoenzymes LDj and LD2 are called HBD (2-hydroxy utýrate ehydrogenase (f substrate afinity to 2-OHbutyrate than lactate) ^^^^ra meSEí ^H M H H 100 Time; Days after Onset of AMI Physiological or cut off values of cardiac markers TnT Tnl from < 0.01 to < 1.5 \ig/\ (different methods) Mb S 16-76 ng/1 $ 7-64 jug/1 CK-MB mass < 5 ug/1 HBD 6 $ 0.7 |xkat/l $ < 0.6 |xkat/l S 0.41-3.16 (Xkat/1 $ 0.41-2.83 (Xkat/1 < 0.4 (xkat/1, or 6% of total CK S 3.3-7.5 |xkat/l ? 3.3-6.3 |xkat/l < 3.0 |xkat/l OTHER MARKERS IN DG OF ACUT CORONARY SYNDROMES G'FĽ'Ľ (eimllae^ peeífw ĽB isoenzyme of glycogen Phosphorylase, glycogen Phosphorylase - enzyme of glycogenolysis 3 isoenzymes formed by 2 subunits, 3 types of subunits- B, M, isoenzyme BB IfflMl brain and myocardium skeletal muscles liver very sensitive and early indicator of myocarial injury I in 0.5-2 h, return to normal values in 2 days peak about 20times the amount of the physiological value OTHER MARKERS IN DG OF ACUT CORONY SYNDROMES modifie very early non-specific marker - in serum occurs minutes after attack, peak in 1 or more h, return to normal values in 6-12 h xXFAür fiiöfirx Tsťíív iiľläij biiiáhiv or o í £xü common marker as GPB »•gCTiTnřinřiTffifgiTnrtTi] WBC considering the risk of AS plaque destabilisatio I in liver and renal failure and tumors h( HO-CHo-CHo-NNCH research ŕlíimm'mc pBvfiííBJ d L I síDľuiuiib^ sviiLiibuľZiiLí* Tiaren üüü ľbibiiubu o D Y ^ílľLÍlUlííVDl ■£J asorelaxation and natriuretic effects secretion stimulated by: atrial distension or hypertrophy, ventricle overload, myocardial ischemia, blood volume expansion, glucocorticoids, hypoxia, thyroideal dis. 28 AA peptide with a 17 AA ring formed by a disulfide bond in the middle of the molecule produced, stored and released by atrial myocytes in response to: atrial distention stretching of the vessel walls sympathetic stimulation of ß-rec. hypernatremia ANGT-II endothelin (vasoconsrtictor) Physiological effe Renal | the glomerular filtration rate (GFR), resulting in greater excretion of Na+ and water I Na+ reabsorption inhibits renin secretion, thereby inhibiting the RA system í aldosterone secretion Cardiovascular relaxes vascular smooth muscle by: | of vascular smooth muscle cGMP and inhibition of the effects of catecholamines inhibits maladaptive cardiac hypertrophy Adipose tissue | the release of free fatty acids from adipose tissue I intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase ^5 in the blood are used as a ire and may be usefu markers are higher in patients with worse outcome. Both BNP and NT-proBNP have been approved as a marker for acute congestive heart failure. The plasma/serum concentrations are incr in patients with asymptomatic am symptomatic ular dysfunction. originally identified in extracts of porcine brain, but in humans it is produced mainly in the cardiac ventricles 32 AA polypeptide secreted in response to excessive synthesized as pre-pro-hormone —► proBNP (AA 1-108) - cleavage -► BNP (AA 77-108) and inactive NTproBNP (AA 1-76) Binds to and activates NP receptor system in a similar fashion to ANP but with 10-fold lower affinity; its biological half-life is, however, twice as lon^ Effects: I in systemic vascular resistance and central venous pressure I in natriuresis 4 in cardiac output and J, in blood volume renin and aldosterone synthesis inhibition cut off =100 ng/1 = 28,90 pmol/1 (1 pmol/1 = 3.460 ng/1; 1 ng/1 = 0.289 pmol/1) r n i 11 prolil \r [n-iznmmú 76 AA N-terminal fragment co-secreted with BNP synthesized as pre-pro-hormone —► proBNP (AA 1 108) - cleavage -+ BNP (AA 77-108) and inactive cut off = 125 ng/1 = 14.75 pmol/1 (1 pmol/1 = 8.457 ng/1; 1 ng/1 = 0.1182 pmol/1)