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.     

Clinical and analytical evaluation of two immunoassays for direct measurement of creatine kinase MB with monoclonal anti-CK-MB antibodies

We examined the clinical and analytical performance of two immunoassays (Becton Dickinson CK-MB; Ciba-Corning Magic Lite CK-MB) in which monoclonal anti-CK-MB antibodies are used for directly measuring creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) in serum, and also one electrophoretic method (Ciba-Corning). Within- and between-assay precision for both immunoassays was good at the upper reference limits (less than 10% CV). Analytical recoveries ranged from 102 to 114%. Both immunoassays were free from interference by CK-BB, mitochondrial-CK, macro-CK, adenylate kinase, and CK-MM. Retrospectively, we evaluated four categories of patients, using both immunoassays and electrophoresis: normal controls, acute myocardial infarction (AMI) patients, severe skeletal muscle trauma patients, and acutely ill patients known not to have AMI. In general, there were excellent correlations among all three methods. CK-MB activity (U/L) measured by the Becton Dickinson immunoassay was approximately 50% of the mass concentration (microgram/L) of the Magic Lite immunoassay and 50% of the activity concentration (U/L) determined by electrophoresis. Both immunoassays were easy to perform and sensitive to the low CK-MB concentrations often found with low total-CK activities.     

Release patterns of CK-MB and mitochondrial CK following myocardial ischaemia

Following myocardial damage as in acute myocardial infarction (AMI) or open heart surgery, the tissue damage might result in a release of mitochondrial CK (CK-MIT). The presence of this CK isoenzyme in serum may be detected after chromatographic separation of CK-activity on Sephacryl S-200. By combining chromatographic separation of CK-MB with immunologic inhibition of CK-M, both CK-MB and CK-MIT can be estimated in serum. Using this procedure changes in enzyme activities were studied in ten patients with AMI and twelve patients subjected to open heart surgery using cardioplegia. Following AMI CK-MB peaked about 24 h after onset of ischaemic symptoms. CK-MIT increased similarly and reached a plateau after 24 h where it remained during an additional 24-36 h. At peak CK-MB concentration, the corresponding CK-MIT activity was about 22% of the CK-MB activity. Following cardiac surgery there was a rapid release of CK-MB with a peak about 5 h after release of aortic cross-clamping, and with a simultaneous CK-MIT activity amounting to 19% of the CK-MB activity. In conclusion, CK-MIT is released into serum following myocardial ischaemia. Its appearance has time characteristics similar to that of other mitochondrial enzymes. The CK-B method does not specifically determine CK-B, but non-CK-M, which in cardiac ischaemia at peak serum CK-MB concentrations includes about 20% CK-MIT.     

Serum and urinary human heart fatty acid-binding protein in acute myocardial infarction

A competitive enzyme immunoassay (C-EIA) was developed for the measurement of serum and urinary levels of human heart fatty acid-binding protein (hh-FABP), and the appearance and time-course changes of hh-FABP levels were evaluated in patients with acute myocardial infarction (AMI). Control serum and urinary hh-FABP levels, which were determined in 86 serum and 42 urine samples from 86 patients without AMI, were found to range between 0 and 2.8 ng/mL. Serial determinations performed on 11 patients with AMI demonstrated that hh-FABP levels were significantly elevated in the first serum and urine samples obtained within 14 h of the onset of clinical symptoms. Two serum and 2 urine samples obtained only 1.5 h after the onset of symptoms already showed elevated hh-FABP levels, while in the same serum samples the activity of the myocardial-specific isoenzyme of creatine kinase (CK-MB) was still normal. Maximal serum and urinary hh-FABP levels appeared between 5 and 10 h after symptoms developed, and fell sharply towards normal thereafter. The hh-FABP levels in serum and urine both peaked earlier than the elevation of CK-MB activity in serum. The presence of hh-FABP in serum and/or urine seems to be a marker for myocardial damage and could be used as a useful tool for the early diagnosis of AMI.     

Serum creatine kinase and CK-MB isoenzyme responses to acute and prolonged swimming in trained athletes

Six highly-trained male swimmers completed a maximum work capacity tethered swim and a 1-h continuous tethered swim at approximately 70% VO2max in order to evaluate total serum creatine kinase and CK-MB isoenzyme changes. Venous blood obtained before, 5 min post-, 6 h post-, and 24 h post-exercise was analyzed for total serum CK (kinetic UV method, normal = less than 100 U/l) and CK-MB isoenzyme (quantitative electrophoretic technique, normal = less than 5 U/l). VO2max averaged 4.59 +/- 0.28 l/min, with a mean total work time of 24.5 min to achieve maximum capacity. Mean resting total CK was 100.5 +/- 15.8 U/l. Compared to rest, neither swim bout produced a significant (p greater than 0.05) elevation in mean total creatine kinase. No CK-MB isoenzyme was observed in any post-exercise blood sample. Swimming, performed by highly-trained swimmers at high levels of intensity or for prolonged durations, may not impose sufficient degrees of trauma producing muscular stress. Therefore, the structural integrity of the cell membrane is maintained and the loss of intracellular creatine kinase to the bloodstream prevented.     

An increase in creatine kinase secondary to acute pancreatitis: a case report

Creatine kinase (CK) activity is found in high concentrations in skeletal muscle, cardiac muscle and brain. Here, we describe a 64-year-old woman with acute pancreatitis and elevated serum CK activity. This association is extraordinarily rare. In particular, laboratory findings which were found to be abnormal were serum CK 4.150 U/l (peaked 1 day after admission) with the CK-MB fraction being less than 5%, lactate dehydrogenase (LDH) 424 U/l, serum lipase 1.265 U/I and serum amylase 1.105 U/l. Some data regarding the phenomenon of acute pancreatitis and elevated serum CK activity are given.     

Serum CK-MB isoenzyme after aortic and mitral valve replacements

A release of the MB fraction of creatine kinase (CK) enzyme into the serum due to myocardial manipulation and trauma occurs in patients undergoing cardiac surgery. Thus, the appearance of CK-MB activity as such is not sufficient to indicate of perioperative myocardial infarction. The mean (+/- SD) serum CK-MB isoenzyme level was 95 +/- 103 U/l 18 hours after aortic or mitral valve replacement in 76 patients. Thirteen patients undergoing closure of an atrial septal defect served as controls. They had a significantly lower (p less than 0.01) isoenzyme level postoperatively: 45 +/- 39 U/l. Two patients had the ECG changes of definite myocardial infarction after valve replacement and they also showed high CK-MB values, while the other patients with high enzyme level had no ECG signs suggesting acute infarction. CK-MB values correlated with the aortic cross-clamping time (r = 0.39, p less than 0.001) and weakly with the precordial ECG voltage of SV1 + RV5 (r = 0.25, p less than 0.01). While these findings may reflect the sensitivity of a thick myocardial wall to ischaemia during surgery, the postoperative recovery was not related to the serum CK-MB level.     

Response of serum indicators of myocardial infarction following exercise-induced muscle injury

The purpose of this investigation was to determine the response of three parameters used in the assessment of acute myocardial infarction (AMI) after a single bout of eccentric exercise designed to elicit skeletal muscle injury. Total creatine kinase (CK), CK-MB isoenzyme (CK-MB), and the leukocyte differential were determined after a 20-minute bench-stepping exercise in 21 men ranging in age from 30 to 45 years. Comparison of several criteria showed that the use of CK-MB or the relative lymphocyte percentage alone resulted in 11% and 1.8%, respectively, of data collection points exceeding cutoff values suggestive of AMI. However, the use of both parameters in combination completely eliminated false-positive results with no data collection points meeting the criterion. It is thus suggested that CK-MB activity in conjunction with the relative lymphocyte percentage may not only provide incremental value in the detection of AMI but also reduce the incidence of misdiagnosis associated with exercise.     

Creatinine-kinase-MB determination in non-cardiac trauma: its difference with cardiac infarction and its restricted use in trauma situations.

Cardiac injuries can be life threatening. The possibility of late complications urges the practitioner to search for any evidence of cardiac trauma. But the diagnosis of cardiac injury remains difficult. Electrocardiography and cardiac enzyme determination are most widely used, because they are readily available. Many studies advocate creatine-kinase-MB (CK-MB) isoenzyme levels as a sensitive test for cardiac contusion. Others have discarded CK-MB testing as useless in trauma situations. An elevated CK-MB value in haemodynamically stable patients may confuse the individual practitioner. To better clarify its role we investigated the course of CK/CK-MB release after trauma, with no or only a very small chance of cardiac injury and compared it with patients with severe chest trauma having cardiac complications. A total of 25 trauma patients with only skeletal muscle injury were studied. Blood samples were taken during the first 4 days after trauma. These results were compared with those of a group of 91 consecutive patients with severe chest injury, including 10 with cardiac complications. Initial results in skeletal trauma patients were indicative of cardiac injury (CK > 5% of total CK and at least 20 U/l) in 10 patients. These findings were identical to those found in patients with severe chest injury having cardiac complications. CK/CK-MB tests are frequently positive after trauma without cardiac injury, even when selective criteria are used. The time each isoenzyme is released from muscle tissue after trauma greatly influences the outcome of the test. As this release does not occur at the same moment for each isoenzyme, the test result is very much time-dependent. As a result of these findings CK-MB testing tends to cause more confusion than clarification in trauma situations. We therefore eliminated CK-MB testing from our trauma protocol as a screening investigation for cardiac injury.     

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.     

Transient increase in serum creatine kinase isoenzyme BB activity after prostatectomy in a patient with massive benign prostatic hyperplasia

The activity of creatine kinase isoenzyme BB (CK-BB) in serum is rarely abnormally high (i.e., detectable). An increase in immunoreactive CK-BB or CK-BB activity in patients with prostatic disease has been proposed as an indication of prostatic adenocarcinoma. Here we report the case of an elderly man with massive benign prostatic hyperplasia but no clinical or pathological evidence of prostatic adenocarcinoma, whose serum CK-BB activity was found by agarose gel electrophoresis to be 1 U/L (normal: 0%), 10% of his total CK activity. Serum CK-BB activity was further increased to 16 U/L (20% of total CK activity) 1 h after prostatectomy, but became undetectable by the second day after the operation. The findings suggest that: (a) the source of the serum CK-BB activity was the enlarged prostate gland; (b) abnormally high CK-BB activity in serum of men with prostatic disease does not necessarily indicate the presence of prostatic adenocarcinoma; and (c) myocardial injury could be erroneously diagnosed postoperatively in prostatectomy patients if CK isoenzyme methods are used that do not consistently separate "heart-specific" CK-MB from CK-BB.     

肌酸激酶同工酶检测在急性心肌梗死中的临床价值

目的 探讨肌酸激酶（CK）MB和MM同工酶（CK-MB和CK-MM）亚型在急性心肌梗死（AMI）患者中的变化规律与其预后的关系,评价CK同工酶的亚型检测在AMI心肌早期再灌注、梗死延迟或再梗死诊断中的临床价值。方法 采用琼脂糖凝胶电泳系统将血清CK同工酶亚型分离为CK-MM3、CK-MM2、CK-MM1、CK-MB2和CK-MB1,并分析比较21例AMI患者血清CK同工酶亚型在发病后0～6小时、24小时和72小时的动态变化。结果 AMI患者血清CK-MB和CK-MM在发病后6h开始升高,其中以CK-MB2和CK-MM3升高为主,MB2／MB1〉1．36,MM3／MM1〉0．7;12-24小时达峰值,CK-MB／CK〉30％。15例早期再灌注的AMI患者血清CK、CK-MB和CK-MM在72小时下降至正常,但6例无早期再灌注患者仍处于较高水平,其中MB2／MB1〉1．29,MM3／MM1〉0．65。结论 CK同工酶的亚型检测能反映AMI患者心肌组织损伤的动态过程,可作为一项较灵敏的生化指标,有助于诊断AMI心肌早期再灌注、梗死延迟或再梗死。     

S-100ao protein in serum during acute myocardial infarction

Concentrations in serum of S100ao protein (alpha alpha form of S-100 protein, which is present at high concentrations in heart muscle) were successively measured by enzyme immunoassay in 21 patients with acute myocardial infarction (AMI) and six with angina pectoris (ANP). Results were compared with measurements of creatine kinase isoenzyme MB (CK-MB) concentrations in the same specimens. Mean S100ao concentrations in sera from 100 healthy adults were 0.12 (SD 0.08) microgram/L. In patients with AMI, S100ao concentrations were 4.74 +/- 5.27 micrograms/L at admission, peaked 8 h after admission (23.5 +/- 27.7 micrograms/L), then decreased gradually. Among nine AMI patients who were admitted within an hour after their attack, eight showed abnormally high concentrations of S100ao in serum (greater than 0.5 microgram/L), whereas only four showed abnormally high CK-MB concentrations (greater than 5 micrograms/L) in sera at the time of admission. Serum S100ao concentrations remained within the normal range in all six patients with ANP; however, serum CK-MB concentrations were increased in two of them. Therefore, serum S100ao is useful not only for detection of AMI but also for differentiating AMI from ANP.     

Evaluation of a new automated system for the determination of ck-mb isoforms

We evaluated a new analyzer (Cardio REP) specifically designed for cardiac CK-MB isoenzyme and isoforms activity, with a performance time of 24 minutes. Ten AMI patients, with times elapsed between the onset of chest pain and admission to hospital ranging from 30 minutes to 4 hours, were monitored every 3–4 hours until the 16th hour of hospitalization. In each serum sample, in addition to total CK-MB and CK-MB isoforms measured by the Cardio REP analyzer, we also assayed total CK activity, CK-MB activity by immunoinhibition method, CK-MB mass concentration, CK-MB isoforms by REP method, troponin T, and myoglobin. The precision study demonstrated acceptable within assay and between assay CVs% for total CK-MB (8.1 and 10.4), MB₁ (9.1 and 14.2), and MB₂ (9.1 and 8.2) isoforms. The method was found to be linear up to 371 U/L for MB₂ isoform fraction and up to 516 U/L for total CK-MB. Results for CK-MB obtained with the Cardio REP correlated well with those for CK-MB activity obtained with the immunoinhibition method (r = 0.869) and those of CK-MB mass concentration (r = 0.923). The sensitivity of the Cardio REP CK isoforms method was found to be greater than that of the REP CK isoforms method. Time to first increased value of MB₂/MB₁ ratio and MB₂ isoform was earlier in comparison to that for CK-MB mass concentrations and similar to that for myoglobin, a marker that, however, lacks specificity. The diagnostic efficiency of CK-MB isoforms and the availability of a real-time, fully automated method for their measurement suggest the utilization of this biochemical marker in emergency for the early diagnosis of AMI.     

Creatine kinase (EC-No.2.7.3.2) and creatine kinase isoenzymes during pregnancy and labor and in the cord blood

Total CK and CK isoenzyme activity in serum was investigated during pregnancy, labor and after delivery as well as in cord blood. Total CK was decreased in the second trimester of pregnancy but increased in late pregnancy. Low CK-MB activity in serum was found in patients with early labor pains. CK-BB activity could never be detected during pregnancy. Total CK and isoenzyme activity increased after delivery. The rise of total CK and CK-MB in maternal serum is directly correlated with the following: type of delivery, duration of labor, parity of the mother, and birth weight. From this it can be deduced that postpartum CK levels depend on skeletal muscle activity as well as on the activity of uterine muscle. Prematures and infants "small for date" have significantly lower total CK and slightly more elevated CK-BB activity in cord blood than children of normal maturity. CK-BB activity is much more pronounced in high risk patients with low Apgar score.     

Differentiating muscle damage from myocardial injury by means of the serum creatine kinase (CK) isoenzyme MB mass measurement/total CK activity ratio

We immunoenzymometrically measured creatine kinase (CK) isoenzyme MB in extracts of myocardium and in homogenates of five different skeletal muscles. CK-MB concentrations in the former averaged 80.9 micrograms/g wet tissue; in the skeletal muscles it varied widely, being (e.g.) 25-fold greater in diaphragm than in psoas. CK-MB in skeletal muscles ranged from 0.9 to 44 ng/U of total CK; the mean for myocardium was 202 ng/U. In sera from 10 trauma and 36 burn patients without myocardial involvement, maximum ratios for CK-MB mass/total CK activity averaged 7 (SEM 1) ng/U and 18 (SEM 6) ng/U, respectively. Except for an infant (220 ng/U), the highest ratio we found for serum after muscular damage was 38 ng/U. In contrast, the mean maximum ratio determined in 23 cases of acute myocardial infarction exceeded 200 ng/U. Among seven determinations performed 8 to 32 h after onset of symptoms, each infarct patient demonstrated at least one ratio greater than or equal to 110 ng/U. Ratios observed after infarct were unrelated to treatment received during the acute phase. We propose a CK-MB/total CK ratio of 80 ng/U as the cutoff value for differentiating myocardial necrosis from muscular injury.     

Creatine kinase MB isoforms in patients with skeletal muscle injury: ramifications for early detection of acute myocardial infarction.

We measured total creatine kinase (CK), CK-MB isoenzyme, and the MB isoforms in 202 serum and plasma samples from nine groups of patients and normal individuals: 39 with acute myocardial infarction (MI), divided according to time between the onset of chest pain and blood collection (1-6 h, 7-12 h, and 13-48 h); 26 with chest pain for whom an MI was ruled out, sampled at admission; 17 undergoing bypass surgery or cardiac catheterization, sampled within 6 h after either procedure; 17 with acute skeletal muscle injury, sampled within 8 h after injury; 30 marathon runners immediately after a race; 17 runners and other athletes > 12 h after training or a race; 12 with cerebral injury or seizures, sampled at admission; 8 with closed head injury, sampled at admission; and 38 normal subjects. CK-MB (relative index) and MB isoforms (MB2/MB1) were respectively increased in 15% and 75% of MI patients 1-6 h after onset, 94% and 94% after 7-12 h, and 88% and 8% after 12 h, and in 87% and 82% of cardiac surgery patients. MB isoforms were increased in most patients with acute skeletal muscle trauma and in subjects examined after exercise, but were within normal limits in patients for whom MI was ruled out, patients with cerebral trauma, and normal individuals. The relative index of MB/total CK was normal in essentially all individuals in the last groups, including those with acute skeletal muscle trauma. We concluded that the CK-MB isoform ratio is increased in both acute skeletal muscle injury and MI. The isoform ratio is most useful for distinguishing recent from old (> 12 h) injury.     

AMI患者早期CK同工酶亚型的高压电泳图谱分析

目的探讨CK同工酶亚型在AMI胸痛发作后24h内的变化规律,为AMI患者的早期诊断提供依据。方法采用REP全自动高压电泳仪检测AMI胸痛发作后不同时间以及对照组的CK-MM1、CK-MM2、CK-MM3、CK-MB1、CK-MB2等指标并进行荧光扫描,同时在Olympus2700全自动生化分析仪上测定CK、CK-MB的总活性,对所得数据进行恰当的统计分析。结果在AMI患者胸痛发作24h内,CK同工酶亚型有一特殊的变化规律:4~6h内,CK-MB2、CK-MM3开始升高,8~12h达高峰,92%的病人CK-MB2/CK-MB1>1.5,同时91%的病人CK-MM3/CK-MM1>0.5。结论CK同工酶亚型CK-MM3/CK-MM1、CK-MB2/CK-MB1的检测可作为AMI早期诊断的指标。     

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.     

Change in concentrations of myogenic components of serum during 93 h of strenuous physical exercise

Effects of 93 h of long, strenuous ranger training on activities of creatine kinase (CK) and lactate dehydrogenase (LD), along with their isoenzymes, and on concentration of myosin light chain were examined in sera of young soldiers. Total CK activity in serum was measured before, during, and after the training. Throughout, total CK activity in serum increased steadily. At the end of the training, activity of CK-MB was increased but its activity ratio to total CK remained unchanged; the activity ratio of LD1/LD2 also was not increased, although total LD activity was increased. Myosin light chain was increased by about fourfold at the end of the training and remained high for three days thereafter. However, its concentration was much lower than in myopathies such as polymyositis and Duchenne muscle dystrophy. The increased activities in serum of total CK and CK-MB isoenzyme on strenuous physical exercise evidently were of noncardiac origin. Although CK activity was comparable with that seen in myopathies accompanied by disintegration of skeletal muscle, the relatively low concentration of myosin light chain in serum suggests minimal skeletal muscle damage.