Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction

We compared three current methods (immunoinhibition, "Isomune-CK" immunoprecipitation, and the Tandem-E CKMB II immunoenzymometric assay) for determination of creatine kinase (CK; EC 2.7.3.2) isoenzyme MB in serum. Although results inter-correlated well, the immunoinhibition assay gave higher activity values. Atypical CK forms did not interfere with the immunoprecipitation and immunoenzymometric methods. In acute myocardial infarction the catalytic properties of CK decreased with the enzyme's age, as reflected by a steady increase in activation energy of the catalyzed reaction. In septicemia patients with very low CK and CK-MB catalytic activity, mean CK-MB mass concentration exceeded the upper reference limit, suggesting an increased rate of loss of activity concentration in these patients' sera. Because of the assay's lesser susceptibility to conformational changes at the active site of the enzyme, we suggest that measurement of CK-MB mass concentration is better suited for infarct sizing than measurement of catalytic activity.     

Serum creatine kinase isoenzyme MB concentration after endomyocardial biopsy

Serum total creatine kinase (CK), CK-MB and myoglobin (Mb) were serially determined in 17 patients who underwent endomyocardial biopsy. Mean total CK levels increased from 36 +/- 27 U/l 30 min before biopsy to a maximum of 112 +/- 77 U/l 8 h following the procedure (p less than 0.05). Similarly, Mb concentrations rose from 57 +/- 55 micrograms/l to 119 +/- 57 micrograms/l 30 min after biopsy (p less than 0.05). Normalization of total CK and Mb levels occurred within 16 and 8 h, respectively. A new immunoenzymetric assay (IEMA) was used to measure the mass concentration of the CK-MB molecule. The initial CK-MB levels were 0.2 +/- 0.4 microgram/l; a small but significant elevation was recorded as early as 2 h after biopsy (1.6 +/- 1.5 micrograms/l, p less than 0.05). CK-MB returned to initial concentration 16 h after the beginning of the procedure. Comparison with the maximum CK-MB levels recorded in 16 myocardial infarction patients (258 +/- 172 micrograms/l, range 90-680 micrograms/l) indicated that the modest increase of CK-MB level detected after biopsy probably reflects a limited endomyocardium lesion at the sampling site, excluding any significant myocardial damage. Total CK and Mb, which showed more pronounced elevations than CK-MB, are likely to originate from other sources than the myocardium.     

Activities of mitochondrial aspartate aminotransferase and creatine kinase isoenzyme MB in serum following coronary bypass surgery

The mitochondrial isoenzyme of aspartate aminotransferase showed only slight increases in serum of twenty-seven patients after uncomplicated coronary bypass surgery, which contrasted the rapid and substantial increases in creatine kinase MB. In seven patients suffering perioperative infarction or serious complications, substantial increases in mitochondrial aspartate aminotransferase were detected and the elevations in creatine kinase MB were prolonged. Mitochondrial aspartate aminotransferase may appear as a specific marker of myocardial necrosis following coronary bypass surgery. The elevations of creatine kinase and creatine kinase MB were detected as early as 5 minutes after onset of coronary reperfusion and slightly higher activities were measured in coronary sinus blood than in systemic blood sampled simultaneously. Increases in mitochondrial aspartate aminotransferase, however, could first be measured 8 hours after reperfusion.     

Use of creatine kinase MB isoenzyme for diagnosing myocardial infarction when total creatine kinase activity is high

The usefulness of measuring creatine kinase MB isoenzyme for diagnosing myocardial infarction when activities of total creatine kinase are very high is unclear. We conducted a retrospective study in an urban hospital that serves a largely indigent population. We concentrated on 146 patients whose creatine kinase activity was greater than 1000 U/L (upper limit of normal: 165 U/L for women and 225 U/L for men), with MB isoenzyme greater than 10 U/L and less than 5% of total creatine kinase. The positive predictive value of MB isoenzyme (isoimmune method) values greater than 10 U/L was between 11.6% and 56.8% when the value for total creatine kinase exceeded 1000 U/L. Using different values (MB greater than 4% of total creatine kinase) as positive for myocardial infarction would have resulted in far fewer false-positives, but 10 cases of myocardial infarction would have been missed. The most appropriate cutoff value for MB isoenzyme in this population (total creatine kinase greater than 1000 U/L) was found to be greater than 2% of total creatine kinase.     

Relation of creatine kinase isoenzyme MB to postoperative electrocardiographic diagnosis in patients undergoing coronary-artery bypass surgery.

We compared (a) the frequency of detection of isoenzyme MB of creatine kinase (CK; EC 2.7.3.2) in serum of patients undergoing coronary-artery bypass surgery, (b) the interval during uhich its activity was supranormal in serum, and (c) an index of the amount of CK released into blood ("CK-MB area") with postoperative electrocardiographic changes in 80 patients. The frequency of detection of CK-MB is a function of frequency of sampling during the early postoperative period. Because the duration of appearance and the calculated CK-MB area increased as the electrocardiogram became more specific for infarction (p less than 0.01), a twice-daily sampling schedule proved clinically relevant. Only 5.4% of patients had electrocardiographic evidence of infarction when CK-MB was absent by the second postoperative morning. When CK-MB was still detected at that time, 69.6% of patients had persistent new Q waves, consistent with infarction. In three patients who died postoperatively, significant myocardial necrosis was demonstrated. All three had had persistently increased values for CK-MB, related to electrocardiographic changes of infarction in one patient and ischemic changes in two. Evidently CK-MB is a more sensitive indicator of myocardial necrosis than the electrocardiogram and CK-MB area should be a useful criterion in evaluating methods of intra-operative myocardial protection.     

Comparison of catalytic activity and mass concentration of serum creatine kinase MB isoenzyme in the detection of coronary reperfusion in acute myocardial infarction after therapeutic thrombolysis

Serum creatinine kinase MB isoenzyme time-activity curves are useful for the assessment of coronary reperfusion after acute myocardial infarction. The purpose of this study was to compare serum creatine kinase MB catalytic activity with mass concentration for the determination of coronary reflow after therapeutic thrombolysis. Creatine kinase MB mass was determined immunoenzymometrically. Creatinine kinase MB catalytic activity concentration was determined by electrophoresis. Serum was collected every 4 hours for 96 hours in two groups of myocardial infarction patients: A (n = 10), urokinase induced reperfusion; B (n = 10), conventional therapy without urokinase. Peaks of mass and activity occurred at similar times in groups A and B. Both were significantly earlier in the urokinase treated patients. The maximal rate of increase of creatine kinase MB (based on either mass or catalytic activity) was threefold greater in the urokinase group. There are no important differences between the behaviour of creatine kinase measured as catalytic concentration or as mass concentration. Mass concentration is therefore equally useful as an indicator of coronary reperfusion.     

Interpretation of changes in the activity of creatine kinase MB isoenzyme in serum after coronary artery bypass grafting

Measurement of CK-MB in the sera of patients undergoing coronary artery bypass grafting shows a significant increase above pre-operative levels in all cases. However, the timing of the peak post-operative activity and its level allow criteria to be proposed which differentiate between two classes of patients: those with myocardial infarction or lesser myocardial damage, in whom peak activities are seen in specimens taken 21 hours after operation; and those in whom peak activities are found in specimens taken 4-7 hours after operation, presumably reflecting reversible myocardial changes. Activity peaks of more than 50 U/l occurring at 21 hours are considered to support a diagnosis of myocardial infarction.     

Troponin T and creatinine kinase isoenzyme MB mass in the diagnosis of myocardial infarction

The aim of this study was to compare troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) with conventional enzymes, ie CK, CK-MB activity and lactate dehydrogenase isoenzyme 1, in the diagnosis of myocardial infarction (MI). 624 patients (351 men and 273 women, median age 69 years) were admitted to hospital with suspicion of an acute coronary heart disease event. TnT was elevated (> 0.10 μg/L) in 100%, CK-MBm (> 5.0 μg/L) in 99%, and both markers in 99% of the 89 patients with the diagnosis of a definite MI according to modified FINMONICA criteria. In the 60 patients with the diagnosis of a probable MI, TnT was elevated in 65%, CK-MBm in 67% and both markers in 60%. In the patients with unstable coronary artery disease (unstable angina or prolonged chest pain attack) and conventional enzymes within normal limits, TnT was elevated in 14%, CK-MBm in 17% and both markers in 9%. The use of TnT and CK-MBm did not lead to a major change in the diagnostics of definite MI. However, TnT and CK-MBm did not confirm the diagnosis of probable MI in one-third of the events. These new markers revealed a myocardial injury in about 15% of those patients who had unstable coronary artery disease and conventional enzymes within normal limits.     

Myoglobin,creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain

OBJECTIVES: Measurements of myoglobin and creatine kinase (CK)-MB isoforms have been suggested to be sensitive tests for the early diagnosis of myocardial infarction (MI). We have investigated the utility of myoglobin, creatine kinase (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS: The study population comprised 440 patients who had had chest pain for less than 12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+) patients (concentration of cTnT >0.1 microg/L at two different time points during 72 h). RESULTS: At the time of admission to the emergency department receiver operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not better than that of myoglobin. Six hours after admission CK-MB isoforms and CK-MBm provided statistically significantly larger areas under the curve (AUC) than myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (< 3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac markers studied. CONCLUSIONS: According to the present findings, CK-MB isoforms or myoglobin offer no advantage over CK-MBm as early markers of myocardial infarction.     

Troponin T levels in detection of perioperative myocardial infarction after coronary artery bypass surgery

OBJECTIVES: The present study was designed to evaluate the clinical relevance of serum cardiac troponinT (cTnT) assay in detection of perioperative myocardial infarction (PMI) after coronary artery bypass grafting (CABG). MATERIALS AND METHODS: The clinical utility of cTnT was compared to that of total CK, CKMB mass, CKMB activity and myoglobin. Serial venous blood samples were obtained before surgery and 4, 8, 16, 24, 48 and 72 hours after aortic unclamping (AU) in 42 patients who underwent CABG. We had 6 PMI patients, 24 patients with minor myocardial damage (MMD) and 12 without ischemic myocardial changes (no IMC). RESULTS: In discriminating no IMC from PMI the diagnostic sensitivity, specificity and the predictive values of cTnT were superior to that of CKMB mass, CKMB activity, myoglobin and total CK during 72 hours after AU. In discriminating MMD from PMI the diagnostic performance for CKMB mass and CKMB activity was superior to that of cTnT during the first 24 hours. After 24 hours the diagnostic performance for cTnT was improved but began to decline for CKMB isoenzymes. The discriminatory power of myoglobin measurements was lower than that of cTnT and CKMB mass. CONCLUSION: Our results indicate that troponin T is an accurate marker for the detection and monitoring of perioperative myocardial damage, especially 24 hours after AU.     

Serum isoenzyme pattern of creatine kinase and lactate dehydrogenase in various animal species

The creatine kinase and lactate dehydrogenase isoenzyme pattern were determined in the serum of normal and untreated rats, rabbits, dogs, monkeys and pigs. The relative distribution of all isoenzymes in the serum and an electrophoretic pattern for each animal species are presented. The isoenzyme serum pattern showed a great variation between the species. The diagnostic value of serum creatine kinase isoenzyme MB and lactate dehydrogenase isoenzymes 1 and 2 in predicting cardiac lesions in different animal species is briefly discussed.     

Immunochemical extraction and automated measurement of plasma creatine kinase MB isoenzyme and creatine kinase MB2 isoform

Measurement of creatine kinase MB (CK-MB) and its isoforms CK-MB₂ and CK-MB₁ are now applied in the diagnosis of acute myocardial infarction (AMI). The most common approach for analysis includes RIA, IRMA, and electrophoresis, all of which may be time-consuming. This study examines determination of CK-MB and CK-MB₂ by a rapid immunochemical extraction method followed by an automated measurement for both analytes. The automated method was sensitive to 2 U/L, linear to 180 U/L, and gave excellent interassay precision (<10% CV). Interference studies indicated that bilirubin, hemolysis, and lipemia caused analytical problems as did the presence of high activities of other CK isoenzymes, notably CK-MM and CK-BB, requiring dilution of samples prior to analysis. Application of immunochemical extraction gave a reference interval of CK-MB (0–2.5 U/L) and CK-MB₂ (0.1–1.4 U/L) for blood donors (20–60 years), peak levels for ruled-out AMI patients of CK-MB (0.5–7.3 U/L) and CK-MB₂ (0.3–4.9), peak levels for ruled-in AMI patients of CK-MB (80–174 U/L) and CK-MB₂ (80–155 U/L). Coronary artery bypass patients (n = 24) and all trauma patients (n = 14) also demonstrated elevations in CK-MB and CK-MB₂, whereas only five of the trauma patients demonstrated increased CK-MB by IRMA. In patients (n = 7) having increased total CK and normal CK-MB by IRMA, the extraction assay for CK-MB and CK-MB₂ yielded increased values in all patients. This new approach to CK-MB and CK-MB₂ analysis can be performed within 30 minutes of sample receipt. J. Clin. Lab. Anal. 11:163–168, 1997. © 1997 Wiley-Liss. Inc.     

Increased creatine kinase MB in the absence of acute myocardial infarction

Although measurement of CK-MB is a very sensitive, specific, and cost-effective test for use in diagnosis or exclusion of acute myocardial infarction, it should not be used as the sole diagnostic indicator, and all positive values must be critically analyzed to exclude other causes of increased values in serum. This is particularly important when the population being tested consists of patients with multiple medical problems, with low to medium probability of myocardial infarction, and without clinical or other biochemical (i.e., LDH 1) evidence of acute myocardial infarction. When the temporal pattern and absolute CK-MB values are considered together with the patient's clinical status, the diagnostic specificity is dramatically increased. In addition, one must be familiar with the limitations of individual assay systems in order to exclude method-related artifactual values.     

Comparison of enzyme immunoassay and immunoprecipitation for creatine kinase MB in diagnosis of acute myocardial infarction

We compared the clinical performance of measuring creatine kinase (EC 2.7.3.2) isoenzyme MB by use of an enzyme immunoassay (Enzygnost CK-MB, Behring Diagnostics) with an immunoprecipitation method (Isomune-CK, Roche Diagnostics) for the diagnosis of acute myocardial infarction. Sera from 80 patients admitted to the coronary care unit because of chest pain were examined: 40 who had this diagnosis of myocardial infarction, and 40 in whom it was ruled out. In addition, sera from 40 apparently healthy individuals were examined. The clinical sensitivity and specificity of these methods were evaluated by use of receiver operating characteristic curves. We conclude that for clinical efficiency, this enzyme immunoassay is slightly superior to the immunoprecipitation assay we used, because of its greater analytical sensitivity and precision for measuring the mass of the isoenzyme.     

At what level of serum total creatine kinase activity can measurement of serum creatine kinase MB isoenzyme activity be omitted in suspected myocardial infarction?

The purpose of this study was to establish a discriminatory limit for serum total creatine kinase activity (CK activity) below which CK isoenzyme fractionation is unnecessary. We looked at 2610 serum samples from 1077 consecutive patients with suspected acute myocardial infraction (AMI). The CK activity was determined according to the Scandinavian recommended method. Isoenzymes of CK were separated by agarose gel electrophoresis, followed by fluorometric scanning. When the threshold for CK activity was 150 U/l, none of the samples had a creatine kinase MB isoenzyme activity (CK-MB activity) equal to or higher than 30 U/l (the diagnostic level), which has been found to differentiate between patients with AMI and those without AMI. Only 14 patients (1.3% of all patients investigated) had CK-MB activity peaks between 10 U/l (detection limit) and 30 U/l. Of these, AMI was only diagnosed in one. We recommend that CK-MB activity should be measured only when CK activity is higher than 150 U/l. This would make about 50% of all CK-MB measurements unnecessary.     

Analytical and clinical evaluation of creatine kinase MB mass assay by IMx: comparison with MB isoenzyme activity and serum myoglobin for early diagnosis of myocardial infarction.

We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin.     

Comparison of serum creatine kinase and creatine kinase MB activities post marathon race versus post myocardial infarction

Serial total creatine kinase (CK) and CK MB activities were determined in the serum of seven runners following a marathon race and compared to enzyme activities in the sera from five patients following acute myocardial infarction (AMI). In the runner's sera, total CK and CK MB activities were significantly elevated at 1, 24, 48 and 72 hours post marathon race when compared to the 1 hour pre-marathon samples (p < 0.01). Serum CK MB activities peaked at 24 hours in both groups of subjects. The MB activities 24 hours following the marathon were substantially higher (91 ± 30 U/l; mean ± SD) than the MB activities 24 hours following AMI (46 ± 38 U/l). However, the percentages of CK MB 24 hours following the marathon and AMI were almost identical (7.0 ± 2.4% and 7.2 ± 2.3%, respectively). Furthermore, CK and CK MB clearances were significantly prolonged (p < 0.02 and p < 0.001, respectively) following the marathon race (T $\text{1}\text{2}$ CK, 49 hours; T $\text{1}\text{2}$ CK MB, 29 hours) as compared to following AMI (T $\text{1}\text{2}$ CK, 27 hours; T $\text{1}\text{2}$ CK MB, 12 hours). These results suggest release of CK MB from the skeletal muscle of marathon runners. Therefore, we recommend that elevation of CK MB in the range indicative of myocardial damage be interpreted with caution in long-distance runners.