1. Biochemical Markers for Diagnosis of Myocardial Infarction Cardiovascular Block Medical Biochemistry Course Dr. Reem M. Sallam, MD, PhD.

2. What is Myocardial Infarction? Myocardial ischemia results from the reduction of coronary blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs ---this is defined as: myocardial infarction is the death & necrosis of myocardial cells as a result of coronary prolonged & irreversible ischemia

3. Biochemical Changes in Acute Myocardial Infarction (mechanism of release of myocardial markers) ischemia to myocardial muscles (with low O 2 supply) anaerobic glycolysis increased accumulation of Lactate decrease in pH activate lysosomal enzymes disintegration of myocardial proteins cell death & necrosis release of intracellular contents to blood BIOCHEMICAL MARKERS clinical manifestations (chest pain) ECG changes

4. Diagnosis of Myocardial Infarction SHOULD depend on THREE items (as recommended by WHO) 1- Clinical Manifestations 2- ECG 3- Biochemical Markers

5. criteria for ideal markers for myocardial infarction 1- Specific: to myocardial muscle cells (no false positive) 2- Sensitive: - rapid release on onset of attack (diagnose early cases) - so, can detect minor damage - no miss of positive cases (no false negative) 3- Prognostic: relation between plasma level & extent of damage 4- Persists longer: so, can diagnose delayed admission 6- Reliable: procedure depends on evidenced principle 5- Simple, inexpensive: - can be performed anywhere by low costs - no need for highly qualified personnel 7- Quick: low turnaround time

6. Types of Biochemical Markers for Myocardial Infarction 1- Cardiac Enzymes (isoenzymes): Total CK CK-MB activity CK-MB mass 2- Cardiac proteins: Myoglobin Troponins

7. Cardiac Enzymes Total CK (sum of CK-MM, CK-MB & CK-BB) non specific to cardiac tissue (available in skeletal ms.) CK-MB (CK-2) activity more specific than total CK BUT: less specific than troponin I (available in sk. Ms) appears in blood: within 4-6 hours of onset of attack peak: 12 - 24 hours returns to normal: within 2 - 3 days (no long stay in blood) Advantages: - useful for early diagnosis of MI - useful for diagnosis reinfarction Disadvantages: not used for delayed admission (more than 2 days) not 100% specific (elevated in sk.ms damage)

8. CK-MB mass - appears one hour earlier than CK-MB activity (more sensitive) - So, useful for diagnosis of early cases & reinfarction - BUT: not for diagnosis of delayed admission cases & less specific than troponin I Relative index = CK-MB mass / Total CK X 100 more than 5 % is indicative for MI

9. Cardiac Proteins Myoglobin cytosolic protein - not specific for cardiac tissue (also in sk.ms. & renal tissue) - appears in blood EARLIER than other markers (within 1-4 hours) So, with high sensitivity - BUT: Returns to normal in 24 hours So, not for delayed admission cases (after one day of onset of attack)

10. Cardiac Troponins Protein complex located on the thin filament of striated muscles consists of 3 subunits: cTn T, cTnI & cTn C with different structures & functions cTnI & cTnT are used are biomarkers for MI diagnosis Cardiac troponins (cTn) are different from skeletal muscle tropnins So, more specific for MI diagnosis cTnI: 100 % cardiac specific With greater sensitivity for diagnosing minor damage of MI Appears in blood within 6 hours after onset of infarction peak: around 24 hours Disappears from blood after about one week (stays longer) So, useful for diagnosis of delayed admission cases Prognostic marker (relation between level in blood & extent of cardiac damage)

11. Recommendations for use of biochemical markers for diagnosis of myocardial infarction 1- Recommended for all patients complaining of chest pain (with clinical examination & ECG) 2- Sample Type: plasma Timing: i. on admission ii. serial ( at least every one hour in a period 6-9 hours) should be referenced to admission & onset of pain 3- Test should be with low turnaround time less than one hour (accepted) less than half an hour is preferred 4- Types of Markers used: two types early markers: as Myoglobin: appears in blood early (within less 4 fours) BUT not specific & not persists for long period (less than 2 days) definitive markers: Troponin: appears in blood later than myoglobin (within 6 hours) BUT 100% specific, prognostic & stays longer (one week) 5- Troponin is currently the marker of choice should be available in all cardiac & emergency centers (if not, CK-MB mass is the second choice)

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