IMPORTANCE OF CARDIAC MARKERS IN MYOCARDIAL INFARCTION

01. INTRODUCTION

Myocardial injury can occur both in myocardial infarction and in unstable angina. Cardiac muscles can withstand ischemia up to about 20 minutes i.e. up to 20 minutes damage is reversible. With irreversible damage to the cardiac muscles, several types of chemicals are released to the blood stream. Therefore these chemicals are a good device to identify the cardiac injuries. There are many investigations available to detect these chemicals. Even though this is a good way of detecting cardiac injuries, there are some technical problems associated with measuring of these proteins.

02. CARDIAC MARKERS.

Certain proteins are released into the blood in large quantities from dying heart tissues following myocardial infarction. These proteins are called cardiac markers. The rate of liberation of specific proteins differs depending on their intracellular location, molecular weight and the local blood and lymphatic flow. This fact is exploited in diagnosing cardiac injuries such as myocardial infarction and unstable angina. The importance of measuring these cardiac markers is that a substantial number of patients with acute myocardial infarction do not have the typical ECG findings. Identified cardiac markers are;

I. Creatine kinase (CK)
II. Lactate dehydrogenase (LDH)
III. Aspartate transaminase (AST)
IV. Cardiac specific Troponin T & I (cTnT & cTnI)
V. Myoglobin

I. Creatine kinase

CK is a molecule made up of two polypeptide subunits (M and B) coded by different genes. Three major isoenzymes are available.
01. CK-MM is the major isoenzyme type available. This is present in skeletal and cardiac muscles
02. CK-MB is the isoenzyme which is primarily found in the cardiac muscles. A small amount is present in the skeletal muscles as well.
03. CK-BB is the isoenzyme which is mainly found in the brain matter. A small amount is also found in kidney, stomach, colon, and liver as well.

MM is the predominant CK type. Serum of a normal individual contains more than 97% of MM variety whereas rest consists of MB type. Normal CK level is 200-250 u/l There are several causes which can lead to the elevation of CK level in the blood .These include;
Ø Artefactual causes ( Hemolysis)
Ø Physiological causes(neonates, adult male> adult female, exercise)
Ø Pathological causes (e.g. shock & circulatory failure, Myocardial infarction, muscular dystrophy, Rhabdomyolysis, Hypothyroidism, Alcoholism, Head injury and strokes)

Most important aspect of the CK is it’s relevant with cardiac injury. The level of CK rises within 4 to 8 hours after the cardiac event and it returns to normal level by 48 to 72 hours. The peak level can be detected within 16 to 24 hours after the event. The main drawback of measurement of CK level is its lack of specificity for cardiac injuries as it elevates in above mentioned causes as well.
Since the CK-MB is more specific for the cardiac muscle, measurement of CK-MB level can be useful. But the skeletal muscles also contain some amount of CK-MB, which is very small when compare with the amount containing in the cardiac muscles (Table A). Usually in serum the fraction of CK-MB is about 3%. If this fraction is higher than the normal level it will indicate the cardiac injury. But sever skeletal muscles damage can give rise to the higher level of CK-MB therefore sever skeletal muscles damage can mimic acute myocardial infarction. To avoid this false positive scenario, series of ECG should be done with the measurement of CK level. There are some other causes which lead to the rise in CK-MB level such as crush syndrome, Major surgery, Defibrillation and Malignant Hyperthermia.

Table A
Isoenzyme % in heart muscles % in cardiac muscles

CK-MM 78 98
CK-MB 22 2


II. Lactate Dehydrogenase

This is a cytosolic enzyme. It is a tetramer of two subunits (H and M). There are five different types of isoenzymes available.

Table B
Isoenzyme subunits Sites % in normal person
LD1 HHHH Heart, red cells, kidney 20-30
LD2 HHHM Heart, red cells, kidney 30-40
LD3 HHMM Lung, spleen, platelets 20-30
LD4 HMMM Liver, skeletal muscles 5-15
LD5 MMMM Liver, skeletal muscles 5-15

There are several causes which can lead to the elevated level of LDH. These include;
Ø Artefactual causes ( Hemolysis)
Ø Physiological causes (neonates)
Ø Pathological causes (circulatory failure, myocardial infarction, megaloblastic anemia, renal infarction)

The LDH has been supplanted by other tests. It begins to rise in 8 to 12 hours following MI, and peaks in 3 to 6 days, gradually dissipating in 8 to 14 days. Measurement of LD isoenzymes is necessary for greater specificity for cardiac injury. There are five isoenzymes. Ordinarily, concentration of isoenzyme LD2 is greater than LD1, but with myocardial injury, this pattern is "flipped" and LD1 is higher than LD2. LD5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury.2-hydroxybutrate is a substrate for the LD1 therefore this substrate is used to measure the level of LD1.
The molecular size of the LGH is larger than that of CK therefore it takes time to appear.


III. Aspartate transaminase

This is an enzyme which is found in cardiac muscles, skeletal muscles, liver, kidney and red cells. This enzyme is present both in the mitochondria and cytosol .Action of this enzyme is to catalyze the transfer of an amino acid group from Aspartate to alpha ketoglutarate to form oxaloacetate and glutamate.
Causes which lead to the elevation of AST are;
Ø Artefactual causes (Hemolysis)
Ø Physiological causes (neonates)
Ø Pathological causes (circulatory failure, myocardial infarction, and viral hepatitis.)

This is not a reliable test to diagnose cardiac injury since it is not specific for the cardiac muscle.


IV. Troponin

Troponin is a contractile protein found in the smooth, skeletal and cardiac muscles. It consists of three components.
Troponin C ( calcium binding site)
Troponin I ( inhibitory component)
Troponin T ( tropomycin binding site)

Cardiac specific Troponin T (cTnT) and cardiac specific Troponin I (cTnI) are important in cardiac injury. The amino acid sequences of cardiac specific Troponin are different from those of skeletal Troponin. These differences permitted the development of quantitative assays for cTnT and cTnI with highly specific monoclonal antibodies. Since cTnT and cTnI are not normally detectable in the blood of healthy individuals but may increase after myocardial infarction to levels 20 times higher than the upper reference limit.
. The level of cardiac specific Troponin begins to rise 4 to 6 hours after the cardiac injury (myocardial infarction).it reaches the peak value within 24 hours and it tends to persist 10 to 14 days.
Cardiac specific Troponins are very sensitive. They rise in micro infarcts and in unstable angina as well. Cardiac specific Troponin can be used as prognostic indicators. If the cTnT is positive in unstable angina, it will indicate poor prognosis. The degree of Troponin is proportionate to the degree of cardiac injury.
There is no significant difference in cTnT and cTnI in diagnosing myocardial infarction except in chronic renal failure where the cTnT shows false positive test. In that condition cTnI should be measured.
When comparing cardiac specific Troponin with cardiac specific CK, there is no significant advantage over CK-MB in early diagnosis of acute myocardial infarction. Since Troponin has a longer half life than CK, it has an advantage over CK in diagnosis of late presentation. Troponin is also more sensitive and specific than CK.

VI. Myoglobin

Myoglobin is component of muscles. It can be detected in serum following muscles injury. It can be detectable within 2 hours after the myocardial infarction. Since there are no reliable methods detecting cardiac specific Myoglobin from other types of Myoglobin, this is not usually used as a cardiac marker.

03. SUMMARY

Cardiac markers are an important tool in diagnosis of myocardial infarction. But facilities are not widely available as these investigations are expensive.

Table C
Cardiac marker Begins to rise Peak Duration
CK-MB 4 to 8 hours 16 to 24 hours 48 to 72 hours
LD1 8 to 12 hours 3 to 6 days 8 to 14 days
cTnT & cTnI 4 to 6 hours 16 to 24 hours 10 to 14 days