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Background
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Creatinine kinase (CK) is an enzyme, found primarily in muscle and brain tissue, which exists as three dimeric isoenzymes — CKMM (CK-3), CK-MB (CK-2), and CK-BB (CK-1) — built from subunits designated M and B. The CK-MB isoenzyme, which has a molecular mass of approximately 87,000 daltons, accounts for 5 to 50% of total CK activity in myocardium. In skeletal muscle, by contrast, it normally accounts for just 1% or less, CK-MM being the dominant form, though the percentage can be as high as 10% in conditions reflecting skeletal muscle injury and regeneration (e.g. severe exercise, muscular dystrophy, polymyositis).
Serial measurement of biochemical markers is now accepted universally as an important determinant in ruling in or ruling out acute myocardial infarction. CK-MB is one of the most important myocardial markers (in spite of not being altogether cardiac-specific), with well established roles in confirming acute myocardial infarction (AMI) and in monitoring reperfusion during thrombolytic therapy following AMI.
In AMI, plasma CK-MB typically rises some 3 to 8 hours after the onset of chest pains, peaks within 9 to 30 hours, and returns to baseline levels within 48 to 72 hours. The pattern of serial CK-MB determinations is more informative than a single determination. One CK-MB measurement, even when taken at an appropriate time, cannot definitively confirm or rule out the occurrence of AMI. High levels might reflect skeletal injury rather than myocardial damage. A value within the reference range might be significant if it represents an increase from the patient’s baseline levels. Accordingly it has been recommended that CK-MB be measured on admission to the emergency room, and at regulated intervals thereafter. The model described by Heart Emergency Room (ER) Program documented that serial testing for CK-MB isoenzyme (CK-MB, EC 2.7,3.2) mass on presentation and 3,6 and 9 hours later in patients with symptoms suggestive of acute ischemic coronary syndrome presenting with a non-diagnostic or equivalent electrocardiogram was more effective (100% sensitivity with 100% negative predictive value) than continuous serial electrocardiograms, electrocardiography and graded exercise testing. In this method, CK-MB calibrator, patient specimen or control is first added to a streptavidin coated well. Biotinylated monoclonal and enzyme labeled antibodies (directed against distinct and different epitopes of CK-MB are added and the reactants mixed. Reaction between the various CK-MB antibodies and native CK-MB forms a sandwich complex that binds with the streptavidin coated to the well. After the completion of the required incubation period, the enzyme-CK-MB antibody bound conjugate is separated from the unbound enzyme-CK-MB conjugate by aspiration or decantation. The activity of the enzyme present on the surface of the well is quantitated by reaction with a suitable substrate to produce color. The employment of several serum references of known (CK-MB) levels permits the construction of a dose response curve of activity and concentration. From comparison to the dose response curve, an unknown specimen's activity can be correlated with CK-MB concentration.
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