Serum and plasma as alternative sample types in analysis of cardiac markers in the clinical routine

There is an increasing demand for the results of cardiac markers (troponin I or T, creatine kinase MB mass and myoglobin) to be made available promptly after sample-taking. In order to shorten the turnaround time, the possibility of using EDTA- or heparin-plasma instead of serum was investigated. The study population comprised 391 patients with acute chest pain. Four different instruments and systems routinely used in Finland giving quantitative results were studied for the assays of creatine kinase isoenzyme MB mass, myoglobin, and troponin I or troponin T. In addition to serum samples, heparin-plasma seems to be useful for all three assays using the Access and Immulite systems, while EDTA-plasma seems to be useful for all three assays with the Access and Elecsys systems. For the AxSYM assays, serum samples seem to be the best alternative. In conclusion, it is possible to use a single EDTA- or heparin-plasma sample for Access, Elecsys and Immulite analysers, and thereby to shorten the turnaround time. In this way the quantitative analyses from plasma can be performed 30 min after taking the sample.     

Serum and plasma as alternative sample types in analysis of cardiac markers in the clinical routine

There is an increasing demand for the results of cardiac markers (troponin I or T, creatine kinase MB mass and myoglobin) to be made available promptly after sample-taking. In order to shorten the turnaround time, the possibility of using EDTA- or heparin-plasma instead of serum was investigated. The study population comprised 391 patients with acute chest pain. Four different instruments and systems routinely used in Finland giving quantitative results were studied for the assays of creatine kinase isoenzyme MB mass, myoglobin, and troponin I or troponin T. In addition to serum samples, heparin-plasma seems to be useful for all three assays using the Access and Immulite systems, while EDTA-plasma seems to be useful for all three assays with the Access and Elecsys systems. For the AxSYM assays, serum samples seem to be the best alternative. In conclusion, it is possible to use a single EDTA- or heparin-plasma sample for Access, Elecsys and Immulite analysers, and thereby to shorten the turnaround time. In this way the quantitative analyses from plasma can be performed 30 min after taking the sample.     

Myoglobin, creatine kinase MB, troponin T, and troponin I — rapid bedside assays in patients with acute chest pain

Three new rapid, qualitative bedside immunoassays were evaluated in the diagnosis of patients with acute chest pain. The subjects, 122 patients in group 1 (bedside tests for myoglobin, creatine kinase MB) and 233 patients in group 2 (bedside tests for troponin I and sensitive troponin T) were admitted to hospital with acute chest pain for less than 12 h. The bedside tests were performed on admission, and 2, 4, and 6 h later. The correlation between the two parts of the rapid creatine kinase MB/myoglobin test during the first 12 h after the onset of chest pain was moderate in all patients (κ=0.401, 95% confidence interval 0.321–0.483). The highest correlation was seen with the patients with definite and probable myocardial infarction. The correlations were smaller but significant also in other diagnostic groups (unstable angina pectoris, prolonged chest pain, and non-cardiac chest pain). The correlation between the rapid sensitive test for troponin T and rapid test for troponin I was significant in all groups (κ=0.776, 95% confidence interval 0.711–0.841). The myoglobin part of the rapid creatine kinase MB/myoglobin test may be too non-specific for clinical diagnostic purposes [in non-infarct patients the myoglobin part was significantly more often positive than creatine kinase MB or troponin tests (P<0.001)].     

Systemic short-term fibrinolysis with high-dose streptokinase in acute myocardial infarction: time course of biochemical parameters

The course of plasma catalytic activities of total creatine kinase, creatine kinase isoenzyme MB, total, cytoplasmatic and mitochondrial aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, glutamate dehydrogenase and concentrations of myoglobin, urea, acidic alpha 1-glycoprotein and creatinine were followed in 33 patients suffering from acute myocardial infarction. All patients were randomized in a double-blind, prospective study. One group (18 patients) was infused with streptokinase 1.5 X 10(6) units/90 minutes; the control group received routine continuous i.v. heparin treatment (1000 units/h). Ten hours after completion of the study protocol, treatment of both groups of patients was continued with heparin, 1000 units/h and Aspisol, 1 g/day2). Streptokinase treatment induced earlier wash-out and therefore earlier peak levels of several enzymes: total creatine kinase (11 hours), creatine kinase isoenzyme MB (6 hours), total and cytoplasmatic aspartate aminotransferase (6 hours) and lactate dehydrogenase (9 hours). Total creatine kinase peak catalytic activity and myoglobin peak concentration were higher in the group receiving thrombolytic therapy. A significantly different course of catalytic activity between both treatment groups was found for total creatine kinase and creatine kinase isoenzyme MB, total and cytosolic aspartate aminotransferase, lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase. The course of mitochondrial aspartate aminotransferase catalytic activity was different only 12 hours after the beginning of treatment. The shift of several catalytic activities to an earlier peak level in plasma may indicate reperfusion of ischaemic myocardium due to thrombolytic therapy.     

Normal Myocardial Enzymes and Normal Echocardiographic Findings During Noninvasive Transcutaneous Pacing

Noninvasive transcutaneous pacing was performed for 30 minutes in 10 healthy volunteers. The pace rate was from 85 to 115 min-1, and the threshold for pacing was from 38 to 70 mA, median 59 mA. Echocardiography before and during pacing showed no changes in left ventricular end-diastolic diameter, in fractional shortening nor in contraction pattern. Also, blood pressure remained unchanged. Blood samples for determination of myoglobin, creatine phosphokinase, creatine kinase MB and lactate dehydrogenase were drawn prior to pacing and 1,2,3,4,6,8 and 24 hours after pacing. The serum concentrations were the same before and after pacing for all enzymes and myoglobin. We conclude that non-invasive transcutaneous pacing for 30 minutes causes no muscular or myocardial injury and that the left ventricular function remains normal.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Study of a myoglobin test in patients hospitalized for suspected myocardial infarction

An immunoagglutination latex test was studied in comparison with a plasma myoglobin radioimmunoassay in 103 subjects with suspected myocardial infarction. The test provided an early and reliable indication of raised plasma myoglobin (greater than 85 micrograms/l), a biochemical marker for the early phase (12 h) of myocardial infarction. The diagnostic values (sensitivity and specificity) studied over a 36 h period were the same as those for the plasma myoglobin assay. The sensitivity was similar to that of creatine kinase activity and better than that of the creatine kinase MB/creatine kinase ratio; the lower specificity was due to false-positive results in some subjects with angina. The myoglobin test, which provides rapid results, may be substituted in early diagnosis of myocardial infarction for the plasma myoglobin assay which is unsuitable for emergency analysis.     

Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up

OBJECTIVE: Creatine kinase and myoglobin are markers of muscular damage in rhabdomyolysis. Whereas myoglobin is considered to be the principal compound causing tubular damage, serum creatine kinase level is presently guiding therapeutic interventions in clinical practice to prevent acute renal failure. Because differences in elimination kinetics of these two compounds may influence therapeutic decisions, we studied elimination kinetics of myoglobin and creatine kinase in patients with rhabdomyolysis. DESIGN: Open, noncomparative study. SETTING: Intensive and intermediary care units in a university hospital. PATIENTS: A total of 13 consecutive patients with rhabdomyolysis whose baseline serum creatine kinase exceeded 5000 IU/L. Ten of 13 patients were treated with forced alkaline diuresis, and none were dialyzed. RESULTS: Myoglobin had faster elimination kinetics than creatine kinase (p <.01), and the average times to reach the 50% level of initial values were 12 hrs for myoglobin and 42 hrs for creatine kinase. Elimination of myoglobin was not affected by glomerular filtration rate. Compared with creatinine clearance (mean, 102 mL/min), myoglobin clearance was low (mean, 3 mL/min), both in patients with preserved renal function (n = 11) and in those with acute renal failure (n = 2). CONCLUSION: Serum myoglobin has faster elimination kinetics than creatine kinase in patients treated with forced alkaline diuresis for rhabdomyolysis. Considering the etiologic role of myoglobin, our data suggest that serum myoglobin level, rather than that of creatine kinase, should be used to guide therapy in patients with rhabdomyolysis.     

Raised CK-MB isoenzyme after exercise in a patient with alcoholic myopathy

The relation between exercise, total serum creatine kinase activity, and serum creatine kinase MB isoenzyme in a patient with alcoholic myopathy was investigated. After a short-term exercise the serum values of creatine kinase MB isoenzyme rose to high levels within hours. This finding is important for obvious differential diagnostic reasons.     

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.     

Myoglobin concentration, creatine kinase activity, and creatine kinase B subunit concentrations in serum during thyroid disease

Changes in values for myoglobin, total creatine kinase (EC 2.7.3.2), and creatine kinase B-subunit in the serum of patients with thyroid disease are compared with values for these during the 24-h after myocardial infarction. Concentrations of all three of these muscle-derived proteins were significantly higher than normal in patients with primary hypothyroidism, and declined with treatment. Values for total creatine kinase activity were below-normal in hyperthyroid patients, but increased after treatment. Values for total creatine kinase and, to a lesser extent, myoglobin in hypothyroidism extend into the range of values observed after myocardial infarction. The mechanism of the changes in these analytes in hypothyroidism may be related to increased leakage from skeletal-muscle cells or diminished clearance from the circulation, or both.     

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.     

Asystole and increased serum myoglobin levels associated with ‘packing blackout’ in a competitive breath‐hold diver

Many competitive breath‐hold divers use ‘glossopharyngeal insufflation’, also called ‘lung packing’, to overfill their lungs above normal total lung capacity. This increases intrathoracic pressure, decreases venous return, compromises cardiac pumping, and reduces arterial blood pressure, possibly resulting in a syncope breath‐hold divers call ‘packing blackout’. We report a case with a breath‐hold diver who inadvertently experienced a packing blackout. During the incident, an electrocardiogram (ECG) and blood pressure were recorded, and blood samples for determinations of biomarkers of cardiac muscle perturbation (creatine kinase‐MB isoenzyme (CK‐MB), cardiac troponin‐T (TnT), and myoglobin) were collected. The ECG revealed short periods of asystole during the period of ‘packing blackout’, simultaneous with pronounced reductions in systolic, diastolic, and pulse pressures. Serum myoglobin concentration was elevated 40 and 150 min after the incident, whereas there were no changes in CK‐MB or TnT. The ultimate cause of syncope in this diver probably was a decrease in cerebral perfusion following glossopharyngeal insufflation. The asystolic periods recorded in this diver could possibly indicate that susceptible individuals may be put at risk of a serious cardiac incident if the lungs are excessively overinflated by glossopharyngeal insufflation. This concern is further substantiated by the observed increase in serum myoglobin concentration after the event.     

Creatine kinase isoenzyme MB determination on the ACA: dependence on serum matrix and other effectors

Creatine kinase isoenzyme MB catalytic activities in human serum, determined by ACA ion exchange chromatography and immunoinhibition, differ significantly, the correlation coefficient being 0.88. The reasons for this variation are interference of antibodies with the creatine kinase B subunit in the immunoinhibition assay, nonreproducible elution of creatine kinase isoenzyme MB from the ion exchange resin in the ACA pack, due to varying protein concentrations in the serum samples and increasing elution of creatine kinase isoenzyme MM from the ion exchange column caused by a preceding partial inactivation of creatine kinase isoenzyme MM. Pretreatment of serum samples with a solution containing magnesium sulphate, maleate and 2-oxoglutarate (solution A) prior to determination of creatine kinase isoenzyme MB catalytic activities on the ACA significantly improves the sensitivity and specificity of the method; the correlation coefficient for the values from the ACA and immunoinhibition then becomes 0.92. Dilution of serum samples with bovine serum albumin solution is now practicable.     

A new immunoassay for the measurement of myoglobin in serum

Because the concentration of serum myoglobin (Mb) increases within 2 to 4 hours after the first sign of acute myocardial infarction, it has been proposed as an early marker of the condition. Our aim was to evaluate a new assay that provides a rapid, quantitative determination of Mb (Baxter Stratus Myoglobin) based on the radial partition technique. We compared the results obtained by this technique with those from nephelometric and radioimmunoassay methods. A significant agreement was observed, the correlation coefficients (r) being 0.999 and 0.996, respectively. The method evaluated provided good reproducibility with CVs between 3.14% and 4.87%, and its linearity and analytical sensitivity were satisfactory. The clinical evaluation of this assay demonstrates that Mb increases in serum of patients with acute myocardial infarction before total creatine kinase and creatine kinase MB isoenzyme. Mb concentration shows an early peak and earlier return to normal values after the necrosis compared to enzymatic activities. Moreover the assay is rapid and fully automated. The method is therefore considered appropriate for contributing to the early diagnosis of AMI in clinical laboratories. © 1994 Wiley-Liss, Inc.     

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.     

Screening for acute myocardial injury: creatine kinase is comparable to myoglobin.

During the last decade, there have been many studies comparing myoglobin and the troponins to creatine kinase MB. Myoglobin was introduced as an early marker, but most studies have not directly compared it to total creatine kinase in any detail. We retrospectively (9/98-5/99) examined 1772 paired samples from 1572 patients drawn in the emergency department to assess the optimum decision limits, sensitivity, specificity, positive predictive values (PPV), and negative predicitve value (NPV) for creatine kinase and myoglobin in predicting acute myocardial injury. Of the admitted patients, 114 had acute myocardial injury, 166 had angina and 89 had non-cardiac chest pain; 1203 patients were discharged. Initially low creatine kinase (<100 IU/l; minimum 19 IU/l) and myoglobin (<100 microg/l; minimum 9.5 microg/l) results were identified in 63.5% and 88.3% of patients, respectively, emphasizing the importance of serial sampling. Receiver operator characteristic analysis demonstrated optimum decision limits at 100 IU/l and 70 microg/l, respectively. These levels were associated with sensitivity/specificity/PPV/NPV of 66/66/13/96 for creatine kinase and 54/85/22/96 for myoglobin. We conclude that both tests are comparable for initial screening of patients with chest pain in the emergency department. Since creatine kinase is faster, cheaper, and more widely available, it is the test of choice for our institution.     

Evaluation of the optimized bioluminescent assay for the determination of total creatine kinase and creatine kinase MB activities

A very sensitive, optimized bioluminescent assay for certain kinase and creatine kinase MB activities is tested. We evaluated reagent blanks, sensitivity, precision and compared the results with those of the spectrophotometric immunoinhibition test. The main advantage of the new method is a detection limit of less than 1 U/l which, together with a high precision (s = 0.1 at detection limit), allows determinations of the creatine kinase MB activity even in normal sera in about 20 minutes. A disadvantage of the manual procedure is that it may be necessary to include up to five pipetting steps.     

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.     

Secretion of creatine kinase MB isoenzyme by an immature teratoma with predominant rhabdomyosarcomatous elements

A 37-year-old man with metastatic immature (malignant) teratoma with prominent rhabdomyosarcomatous elements had markedly increased activity of creatine kinase (EC 2.7.3.2) MB in serum. There was no electrocardiographic evidence of infarction or ischemia, and autopsy revealed no myocardial infarction, significant coronary atherosclerosis, myocarditis, or invasion of the heart by tumor. A high proportion of the creatine kinase activity in a homogenate of the tumor was attributable to the MB isoenzyme. Persistent increases of creatine kinase-MB and an unusually high MB isoenzyme activity, out of proportion to total creatine kinase activity, may indicate a nonmyocardial origin of this isoenzyme.