CK-MM Isoforms Research Articles

Creatine kinase isoforms in ischemic heart disease.

The MM and MB isoenzymes of creatine kinase exist in serum as a collection of at least three major MM and two major MB isoforms. Each of these are derived from single tissue MM and MB isoforms, which are converted to these other forms by carboxypeptidase N after their release from necrotic skeletal and myocardial tissue. Measurement of the MM isoforms in ischemic heart disease is useful for early diagnosis of acute myocardial infarction and for the noninvasive determination of coronary artery reperfusion for infarction patients receiving thrombolytic therapy. Because MM is also released in acute skeletal-muscle disease, MB isoform measurements may have the highest clinical sensitivity. These determinations are important for providing objective information to cardiologists who need to make critical decisions concerning the management of these patients. I review the procedures for treating patients with myocardial infarction, the potential role of CK isoforms, and the methods currently available for isoform analysis, including high-resolution electrophoresis, isoelectric and chromatofocusing, and liquid chromatography. Rapid and highly sensitive methods are needed for implementation of CK-MM and MB isoforms for prospective emergency determinations for patients with acute myocardial infarction.

Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise.

We could detect skeletal muscle injury early after an acute exercise bout by measuring creatine kinase (CK, EC 2.7.3.2) MM isoforms in serum. Eleven men performed 120 alternating-arm, eccentric (muscle lengthening) biceps contractions with the intensity of each contraction being 110% of maximal concentric strength--a form of exercise previously shown to cause significant increases of CK in serum at 24 h and muscle soreness 48 h after exercise. Total CK and CK-MM isoform activities in serum were determined before and at 0.5, 0.75, 1, 1.5, 2, and 6 h after exercise. Using thin-film agarose gels and a rapid isoelectric focusing technique, we separated the MM isoforms into MM3 (skeletal muscle form), MM2, and MM1 (in vivo conversion forms). The isoforms reflected the MM form released into the serum from tissue as well as the conversion of one form to another. There were no significant increases in total CK from before to 6 h after exercise: 75 (SD 36) vs 91 (SD 33) U/L. However, CK MM3 in serum increased significantly (P less than 0.01) within 2 h after exercise from 22 (SD 6)% to 28 (SD 6)%. The MM3 to MM1 ratio also increased significantly (P less than 0.05) during this time, from 0.6 (SD 0.3) to 0.9 (SD 0.4). Thus, quantification of CK MM isoforms permitted very early detection of skeletal muscle enzyme release.

Creatine kinase MM isoforms in serum after cardiac surgery.

We evaluated creatine kinase (CK; EC 2.7.3.2) MM3:MM1 isoform ratios in the serum of cardiac patients immediately after cardiac surgery for the diagnosis of perioperative myocardial injury. The mean ratio was 4.8 (range, 1.4-10.7) in 22 patients who had postoperative myocardial complications and 4.6 (1.3-9.6) in 66 patients who did not. By the first postoperative day the ratio had decreased substantially in both groups of patients. The isoform ratio did not correlate with the concentration of total CK, CK-MB, total lactate dehydrogenase (LD), or the incidence of LD1:LD2 or LD5:LD2 ratio reversal. Of these measurements, CK-MB and LD concentrations differed most between the groups of patients; parallel testing of CK-MB and LD showed an optimized sensitivity and specificity of 77% and 87%, respectively. We conclude that analysis for CK-MM isoforms does not add information in the period immediately after cardiac surgery; concentrations of CK-MB and LD correlate with myocardial injury, but the sensitivity and specificity of these measurements may not be high enough for clinical utility.

Serum isoforms of creatine kinase MM and MB in myocardial infarction. An appraisal of quantitative, clinical and pathophysiological information

Using an electrophoretic method, the changes in the catalytic activities of three CK-MM isoforms (MM1, MM2, MM3) and two CK-MB isoforms (MB1, MB2) in the serum of 13 patients with acute myocardial infarction (AMI) have been monitored for 3 days after the onset of chest pain. In post-AMI period, MM3 reaches a peak first, 17 h after infarction (394 U/l), followed by MB2 (17.3 h, 190 U/l), MB1 (20.6 h, 82 U/l), MM2 (28.7 h, 637 U/l), and MM1 (32 h, 780 U/l). According to their faster decay from circulation, MB2 and MM3 have higher fractional disappearance rates (-0.035 and -0.026 per hour, respectively). The MM3/MM1 activity ratio rises beyond the upper limit found in healthy subjects within about 3 h after onset of symptoms and peaks 9.3 h after AMI, even earlier than peaks of isoforms. These characteristics make the ratio an earlier and more sensitive indicator of acute enzyme release from necrotic myocardium.