I. Introduction Myocardial infarction (MI) is also known as heart attack (Kumar, Abbas, Fausto, & Aster, 2010).

According to Kumar, Abbas, Fausto, and Aster (2010), MI is the most important form of ischemic heart disease, in which ischemia causes the death of the heart muscle. It is caused by an occlusion of the coronary arteries by a thrombus situated near an unstable atherosclerotic plaque that may have ruptured recently (Murray, Granner, Mayes, & Rodwell, 2010). The incidence and risk factors for MI are as follow: 1. Increasing age (10% of MI case occur in people under the age of 40; 45% occur under the age of 65) 2. When a person is predisposed to atherosclerosis 3. Blacks and whites are equally affected 4. Sex (greater risk in males than in females, which may be attributed to having unhealthy lifestyle and or bad vices; during reproductive stage of females, high estrogen level protects females from developing IHD) To have a better understanding of MI, a case from Harpers Illustrated Biochemistry 28th Edition by Murray, Granner, Mayes, and Rodwell shall be presented followed by an explanation of the pathophysiology, diagnostic measures and treatment of MI.

II. Case This case is taken from Harpers Illustrated Biochemistry 28th Edition by Murray, Granner, Mayes, and Rodwell.

A. History and Physical Examination We have a 46-year-old businessman admitted to the emergency department of the local hospital. His chief complaint was severe retrosternal pain lasting for about 1 hour. His blood pressure was elevated from 140/80 mmHg to 150/90 mmHg; this may be due to stress. His pulse was 60/min and he was sweating profusely. He had once been admitted to the hospital for treatment of a small MI. The patient was a heavy smoker despite having been advised to stop smoking. He was also advised to change his diet to vegetarian, low salt diet as well as to exercise regularly. He had been prescribed with HMG-CoA reductase inhibitor because his total cholesterol and low density lipoprotein (LDL) cholesterol had been elevated while his high density lipoprotein (HDL) cholesterol was depressed. He was also taking a combination of a thiazide diuretic and an angiotensin-converting enzyme (ACE) inhibitor for moderate hypertension as well as one aspirin (81 mg) per day. Regarding his family history, the patients father died of heart attack at the age of 52 while one of his siblings also had an MI at the age of 49. Although there was no evidence of cardiac failure, the admitting diagnosis was probable MI and for that he was given morphine, which has a coronary dilator effect, to relieve his pain and apprehension. He was immediately transferred to a cardiac care unit and was monitored continuously with electrocardiogram (ECG).

B. Laboratory Findings An S-T segment elevation and changes in the other leads was observed from the initial ECG which indicated an acute anterior transmural left ventricular infarction. The blood test showed an 8-fold increase in troponin T 6 hours after admission. Enzymatic

and protein diagnosis for MI was also used and showed the increased level of creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and other proteins and enzymes. Lastly, the levels of total cholesterol and the LDL/HDL cholesterol ratio were found to be within the normal limits (<5.17 mmol/L and 4:1, respectively) while the triacylglycerols were below the normal range, which was 1.50 mmol/L (normal level is <2.26 mmol/L).

C. Treatment The patient was given tissue plasminogen activator (t-PA) intravenously due to the diagnosis of anterior transmural MI. Chest pain was alleviated after 12 hours and he felt increasingly comfortable. The patient was then discharged 7 days later. He was instructed to continue his medication, to attend a cardiac rehabilitation program, and to stop smoking.

III. Discussion Myocardial Infarction (MI) is the death of cardiac muscle due to prolonged severe ischemia (Kumar, Abbas, Fausto, & Aster, 2010). Ischemia is brought about mainly by narrowing of the lumina of the coronary arteries by atherosclerosis leading to decreased blood flow to the heart. Other factors that cause ischemia are trauma to coronary arteries, emboli to coronary arteries, as well as congenital coronary artery anomalies. There are two main arteries in the coronary circulation: right and left coronary arteries. The left coronary artery branches off into: (1) circumflex artery, which encircles

the heart muscle supplying blood to the lateral side of the back of the heart and (2) left anterior descending artery, which supplies blood to the front of the left side of the heart. On the other hand, the right coronary artery branches off into: (1) right posterior descending artery, which supplies the right and the left ventricles, posterior part of the ventricular septum, and the atrioventricular (AV) node; (2) artery of the sinoatrial (SA) node, which supplies the SA node; and (3) acute marginal arteries, which supplies the anterior portion of the right ventricle and coastal surface reaching the apex (snell, date?). Blood supply to the heart lessens when the coronary arteries are partially occluded by an atherosclerotic lesion, or any of the aforementioned factors. As blood supply to the heart diminish the nutrients and oxygen delivered to the heart also diminishes. Diminishing oxygen supply to the cardiac muscles, also known as ischemia, may progress and lead to cell death, also known as infarction. Patients experiencing MI may experience any of the following symptoms: 1. Intense chest pain that may radiate into the neck, jaw or arms 2. A sense of substernal heaviness, squeezing or pressure 3. Shortness of breath (dyspnea) 4. Fatigue 5. Fainting (syncope) 6. Nausea 7. Sweating (diaphoresis) 8. Anxiety 9. Sleeplessness 10. Hypertension

11. Tachycardia and arrhythmias In addition to the patients clinical history, physical examination and electrocardiogram interpretation, cardiac biomarkers, due their high sensitivity and high specificity, are also used to diagnose MI. These cardiac biomarkers are enzymes and other non-enzymatic substances (i.e. proteins) that appear in the plasma or serum in the presence of MI. Cardiac biomarkers must be detected within the diagnostic window and must also be subjected to automated assay for accuracy in preliminary diagnosis of MI (Murray, Bender, Botham, Kennelly, Rodwell, Weil et al, 2009). Timing in determination of these cardiac biomarkers is of importance since immediate intervention is necessary to alleviate the signs and symptoms of MI and to prevent permanent myocardial tissue damage. In line with that, cardiac biomarkers are subject to conformational changes upon extraction from the patients blood plasma or serum mainly by proteolytic cleavage of peptide bonds as well as phosphorylation of amino acids and oxidation of sulfhydryl groups, which normally occur in ischemic diseases (Gillard, 2008) . The following are used as cardiac biomarkers in diagnosing MI: 1. Lactate dehydrogenase (LDH) LDH is a cytoplasmic enzyme found in almost all cells of the body. It is a tetrameric enzyme made up of two monomeric subunits, H (for heart) subunit and M (for muscle) subunit (Murray, Bender, Botham, Kennelly, Rodwell, Weil et al, 2009). These subunits combine to form five LDH isozymes namely: HHHH (I1), HHHM (I2), HHMM (I3), HMMM (I4), and MMMM (I5). Isozyme I1 is found mostly in heart tissues; isozym I2 is primarily associated with lymphatic system; isozyme I3 is found in lungs and other tissues; isozyme I4 is found in the kidneys, placenta, and pancreas; and lastly, isozyme I5

is found mostly in liver tissues (Ophardt, 2003). In the presence of any type of tissue damage release of the a defined pattern of LDH isozymes that can be determined first by separating these isozymes through electrophoresis and then using a coupled assay for detection of the specific isozymes present. In MI LDH initially rises 8 to 12 hours, peaks at 48 to 72 hours, and goes back to the baseline by 7 to 10 days (Ehrman, date?). Since LDH takes a longer time before it is present in the blood plasma or serum, it is not much of a preference in detecting MI nowadays because other cardiac biomarkers appear more rapidly at the onset of MI. 2. Aspartate Aminotransferase (AST) Aspartate aminotransferase, also known as serum glutamate oxaloacetate transaminase, is a member of the transaminase family of enzymes (Technical Bulletin, p.14). AST catalyzes reversible transfer of the -amino group between aspartate and glutamate. It is found in the heart, muscle, kidney, brain, lung and liver. Although increased AST levels indicate tissue damage, its specificity is low as it may also be elevated in tissue damage other than the heart. In MI, AST level rises 6 to 12 hours, peaks at 24 to 36 hours and goes back to the baseline within 3 to 4 days. 3. Creatine kinase MB (CK-MB) Creatine kinase also known as creatine phosphokinase is an enzyme that catalyzes phosphorylation reaction of creatine and ADP to form ATP and creatine in the muscle cells (Guyton, find the page). Creatine kinase has two monomeric subunits, M (muscle) subunit and B (brain) subunit. The presence of two monomeric subunits enables creatine kinase to have three (3) isozymes. Creatine kinase BB (CK-BB) is found in the brain, creatine kinase MM (CK-MM) is found in the skeletal muscle, and creatine kinase

MB (CK-MB) is found mostly in the heart but may also be released when the skeletal muscles are injured (Murray, Bender, Botham, Kennelly, Rodwell, Weil et al, 2009); (Gillard, 2008). Detection of CK isozymes is possible through separation by electrophoresis. In MI CK-MB initially rises 4 to 6 hours, peaks at 24 hours, and goes back to the baseline by 48 to 72 hours (Murray, Bender, Botham, Kennelly, Rodwell, Weil et al, 2009). To establish an accurate diagnose of MI utilization of CK-MB may present false positive since it may also be released during skeletal muscle injury. For that reason, CK-MB is used to diagnose MI alongside with other cardiac biomarkers that are more specific to MI. 4. Cardiac Troponin Troponin is a complex of three loosely bound protein subunits, each having a specific role in muscle contraction (Guyton & Hall, year? p76). It is present both in skeletal muscles as well as in cardiac muscles and is lacking in smooth muscles. It has three components: troponin I, troponin C, and troponin T. Troponin I is the inhibitor subunit that keeps troponin C and troponin T tightly bound to actin in the absence of calcium ions, thus covering the myosin active binding site of actin. Troponin C is the calcium binding site of troponin and is also bound to troponin T. Lastly, troponin T acts as cement that holds tropomyosin and the other two troponins intact with the actin. Only troponins T and I differ structurally and antigenically in cardiac muscles compared with skeletal muscles; therefore, their presence in the blood plasma or serum is a strong indicative of myocardial disease. Cardiac troponins rise 2 to 6 hours after MI, peaks at 12 to 16 hours, and goes back to baseline after 4 to 10 days. 5. Myoglobin

Myoglobin is a protein found in all muscle cells. It is a monomeric protein that stores oxygen in muscle cells. It is a very sensitive indicator of muscle injury. However, since it is found all muscle types, it is not specific for myocardial disease. Despite its low specifity, the rise in myoglobin can still help determine the size of an infarction while negative myoglobin can help rule out myocardial infarction. Myoglobin rises 2 hours after MI, peaks at 6 to 8 hours, and goes back to baseline a little more than 12 hours (Gillard, 2008) Treatment of MI includes change in lifestyle and administration of drugs that removes occlusion of the coronary arteries. The following are examples of thrombolytic drugs: 1. Heparins Heparins, either unfractionated (UFH) or of the low molecular weight type (LMWH). Reduce the incidence of thrombosis by about 50%. They have the drawback of parenteral administration... They may cause anti-thrombin (AT) deficiency, thrombocytopenia bleeding and a few more rare side-effects. The methods for laboratory control of heparin dosage, notably the aPTT, are inadequate. The question of whether adapted doses of heparin would do better than current practice remains unsolved because control methods to guide the adaptation are not available. Prolonged heparin treatment, in particular with UFH is not favored. 2. Oral Anti-Coagultion Oral anticoagulation (oAC) is maintained with coumarin congeners, i.e., anti-vitamin K drugs' They inhibit the oxidation reduction cycle of vitamin K;-i

the liver, required for the normal y-carboxylation of the clotting Factors II, VII, IX and X, protein C and protein S. 3. Aspirin A-spirin is the only antiplatelet drug in general use. It irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA2. 4. Tissue plasminogen activator (t-PA) Tissue plasminogen activator is a protein that is involved in the breakdown of blood clots. Reperfusion of the

IV. Definition of Terms Ischemia Ischemic Heart Disease Unstable atherosclerotic plaque Thrombus Retrosternal Anterior Transmural MI

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