Creatine kinase and myoglobin determination in myocardial infarction

Summary In order to evaluate the diagnostic and prognostic impertance of serum myoglobin (Mb) determination during acute myocardial infarction (AMI) we determined the time of first rise of both CK and Mb, that is the time in hours between the onset of pain and the last normal myoglobin and enzyme determination (TFR for Mb=2.2±1.5 h; TFR for CK=4.0±2.5 h). We also attempted to evaluate infarct size by mathematical analysis of the serum concentrations of Mb. The average percentage difference between the infarct size calculated from the CK concentrations and Mb concentrations was 35.8±35.2%. The results show that the determination of serum myoglobin is a useful and sensitive test for the early diagnosis of AMI. On the other hand, the serum myoglobin cannot be utilized to evaluate infarct size. The main limitation in the determination of infarct size from the serum Mb concentrations lies in the extreme variability of the disappearance rate (Kd), mainly resulting from the renal elimination of the substance.     

Activity of serum aspartate aminotransferase isoenzymes in patients with acute myocardial infarction

Activities of aspartate aminotransferase (AST) isoenzymes were determined in serial serum samples from 40 cases of acute myocardial infarction, and compared with activities of creatine kinase, CK-MB isoenzyme, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase for temporal changes. Cytosolic (soluble) AST (s-AST) and mitochondrial AST (m-AST) respectively increased 6.6 and 9.0 h after onset of chest pain. The median time at which serum m-AST activity peaked (15.8 U/L, range 6.4-53.5 U/L) was 47.8 h after the onset of infarction, 19.8 h later than the peak s-AST activity (171 U/L, range 53-517 U/L) and m-AST also disappeared from the serum more slowly than s-AST (p less than 0.001). Serum m-AST values were above normal for at least six days after the infarct. The ratio of m-AST to total AST in serum increased after myocardial infarction, being greatest (20%, range 11-32%) on the third day after onset. For individuals, peak activities of s-AST correlated well with total CK (r = 0.91) and CK-MB (r = 0.86) peak activities, indicating that s-AST also reflects the infarct size. However, m-AST correlated poorly with the enzymes commonly used in infarct diagnosis; it apparently provides different biological information.     

心肌坏死标志物联合检测在急性心肌梗死早期诊断及鉴别中的意义

目的探讨心肌坏死标志物联合检测在急性心肌梗死早期诊断及鉴别中的意义。方法选取20lO年12月至2013年5月我院收治的90例患者,其中45例被确诊为急性心肌梗死,设为观察组,其余45例疑似急性心肌梗死的患者经过心电图、彩色多普勒超声心动图检查未见异常,最终确定为非急性心肌梗死患者,设为对照组。对两组患者进行酶活性、心肌蛋白及同工酶电泳检查。采用免疫抑制法测定肌酸激酶（CK）、肌酸激酶同工酶（CK—MB）,采用电化学发光法检测肌钙蛋白l（cTnI）和肌红蛋白（MYO）,记录CK、CK—MB、cTnI和MYO等含量,比较观察组患者心肌标志物不同时间的变化并进行统计学分析。结果与对照组比较,观察组患者血清CK、CK—MB、cTnI及MYO含量升高明显,其中CK、MYO含量升高最为显著（P〈0．05）。CK、CK—MB在发病3-6h后快速升高,均于24h左右达高峰,经治疗3-5天后恢复;cTnI前24h与CK—MB同步,但在血中维持时间较长;MYO在发病后12h发生异常,12h内达到峰值（P〈0．05）。结论心肌坏死标志物联合检测可以提高急性心肌梗死检出率,有助于急性心肌梗死早发现、早诊断和早治疗。     

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.     

Prediction of myocardial infarct size from early serum myoglobin observations

Different possibilities to predict infarct size were analysed. The basic method was the fitting of a mathematical model to serial serum myoglobin concentration values from the very early phase of infarction. Correlation was performed with infarct size estimated from the complete serum curves of 53 patients. An observation period up to and including the serum peak value (on the average 6.8 h after onset) was required in order to give a well-determined value of infarct size. A correlation coefficient of r = 0.85 (n = 38) was then obtained. The serum peak concentration value of myoglobin correlated even better (r = 0.89). The initial slope of the serum curve (obtained on the average 4.3 h after onset of symptoms) also correlated well to infarct size (r = 0.80; n = 53). In conclusion, estimation of infarct size appears to be as good with the serum peak value of myoglobin as with model-based parameters. The most useful measure for early prediction of infarct size could be the initial slope of the serum curve.     

Predictive value of serum enzyme determinations in acute myocardial infarction

The prognostic significance of serum enzyme measurements in acute myocardial infarction was studied in 146 patients hospitalized shortly after the attack. Creatine kinase (CK), CK-MB, aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH) were serially determined every four hours during the first three days following admission.Peak enzyme levels correlated well with the cumulated CK release (r = 0.95, 0.74, 0.70 for CK, ASAT and LDH respectively). Among all enzyme measurements, LDH levels determined when CK reached its peak value provided the best discrimination between acute phase survivors (15 days) and non-survivors. LDH was also the best measurement for identifying patients with ventricular impairment. LDH and ASAT peak levels were more powerful predictors of the patient's risk than CK peak levels. CK levels determined later in the course of myocardial infarction were more discriminant, indicating prolonged CK elevation in non-survivors. There was no significant difference in CK-MB levels, nor in cumulated CK-MB amounts for survivors and non-survivors.It is concluded that serum LDH activity is a better predictor of the short term evolution of myocardial infarction than CK levels or infarct size estimations from serial CK determinations.     

国产尿激酶经静脉溶栓治疗急性心肌梗死血管再通的评价

观察了51例急性心肌梗死病人静脉应用尿激酶治疗后，冠状动脉再通组及未通组心电图ST段以及血清肌酸激酶（CK）和肌酸激酶同功酶（CK－MB）的变化规律，并对血管再通组及未通组的临床疗效进行了分析。结果表明：急性心肌梗死病人经静脉溶栓治疗后，冠脉再通组的心电图ST段在用药后30min开始下降，90min下降达53．1％，与未通组心电图ST段具有显著差异；冠脉再通组血清CK及CK－MB在胸痛后14h达到高峰，而未通组在胸病后20h达到高峰；冠脉再通率为67％，再通组心力衰竭、心律失常及病死率明显低于未通组。AMI病人早期经静脉应用溶栓剂治疗，可改善急性期预后，应积极推广。     

Diagnostic use of CK-MM and CK-MB isoforms for detecting myocardial infarction

Following acute myocardial infarction, total CK and CK-MB levels begin to rise 5 to 6 hours after the onset of chest pain. The serial profile of the rise and fall of both activities is nearly always indicative of AMI. The recent increase in the use of thrombolytic agents in an attempt to attain reperfusion of occluded coronary arteries alters the enzyme profiles observed in blood after AMI. After successful reperfusion a washout phenomenon occurs in which early restoration of blood flow to damaged myocardium causes an early rise in total CK and MB levels above the normal range 2 to 4 hours after AMI, with earlier and higher peak enzyme values. Recently reports have appeared describing numerous serum and plasma CK-MM and CK-MB isoform patterns after AMI. Following release from injured myocardium CK-MM3 and CK-MB2 (designated the tissue isoforms) are converted in the circulation to post-translation products (MM2, MM1, MB1, respectively). Studies have now shown that CK-MM isoform patterns provide a unique means of assessing the time of onset of necrosis and a monitor of the duration of enzyme release from the site of injury. Following AMI, MM3, the MM3/MM1 ratio, or both rises and peaks earlier than either total CK or CK-MB levels. During successful reperfusion, the rate of rise of CK-MM3 is more rapid and the MM3/MM1 ratio peaks earlier than without reperfusion. However, any concomitant release of CK-MM3 from skeletal muscle would decrease the clinical utility of MM isoforms in detecting myocardial damage. Recent advances in technology have shown that CK-MB2 rise parallels the CK-MM increase and also rises earlier than total CK and total MB levels and provides increased specificity for the myocardium. The full potential of the diagnostic utility of MM and MB isoforms will not be realized until a reliable, sensitive, simple, and rapid quantitative assay becomes available.     

Additional ST-segment elevation during thrombolytic therapy in patients with acute ST-elevation myocardial infarction: impact on myocardial salvage and final infarct size

The aim of the study was to investigate the clinical significance of additional ST-segment elevation that occurs during thrombolytic therapy. Therefore, we classified 153 patients with a first acute myocardial infarction (MI) into two groups: Group A, 55 patients with additional ST-segment elevation > or = 1 mm above the initial ST elevation during thrombolytic therapy and Group B, 98 patients without this electrocardiographic pattern. Among the patients with anterior MI, Group A (n = 33) had no reduction from ST-predicted to final QRS-estimated infarct size (+12% versus -27%; p = 0.0005) and a larger final infarct size (QRS-score: 18% versus 12%; p = 0.0002) than Group B (n = 41). Among the patients with inferior MI, Group A (n = 22) had a smaller reduction from ST-predicted to final QRS-estimated infarct size (-30% versus -53%; p = 0.03) and a larger final infarct size (QRS-score: 15% versus 9%; p = 0.03) than Group B (n = 57). The area under the curve (AUC) of CK and CK-MB was higher in patients from Group A compared with those from Group B (anterior MI: AUC-CK: 22,048 versus 19,490 U.h.l-1; p = 0.07; AUC-MB: 2227 versus 2016 U.h.l-1; p = 0.11; inferior MI: AUC-CK: 17,206 versus 11,004 U.h.l-1; p = 0.01; AUC-MB: 2193 versus 1046 U.h.l-1; p = 0.007). Both global left ventricular function and ST-segment elevation resolution were significantly better in Group B. Two and three vessel disease was observed more frequently in Group A. Additional ST-segment elevation during thrombolytic therapy suggests reduced myocardial salvage by thrombolytic therapy and thus may result in larger final infarct size.     

Comparison of ASAT, CK, CK-MB, and LD for the estimation of acute myocardial infarct size in man

The purpose of this study was to set up a simple and reliable procedure for estimating acute myocardial infarct (AMI) size by measuring serum enzymes in a few daily blood samples. Peak enzyme values and estimated infarct size from one, two, or three daily samples of aspartate aminotransferase (ASAT), creatine kinase (CK), CK-MB, and lactate dehydrogenase (LD) were compared with the extent of myocardial necrosis measured at autopsy in 22 patients who died from AMI. The correlation between the extent of the necrosis measured and peak serum enzymes from one daily blood sample was highest for CK-MB (r = 0.78) and LD (r = 0.73) compared to CK (r = 0.68) and ASAT (r = 0.67). To obtain a significant correlation, however, two patients had to be excluded from the ASAT and LD analyses. No significant improvement was obtained by more frequent blood sampling. Estimation of infarct size did not improve the correlation significantly for any enzyme, although the coefficient of correlation for CK-MB increased slightly (r = 0.83). Serum CK-MB determination provides a semiquantitative estimate of infarct size, but the other enzymes may give erroneous estimates owing to lesser cardiospecificity.     

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.     

Diagnosis of perioperative myocardial infarction by considering relationship of postoperative electrocardiogram changes and enzyme increases after coronary bypass operation

We report the results of enzyme determinations in sera from 88 patients, 65 of whom showed inconspicuous reconvalescence, 14 who had myocardial infarction within 24 h (MI 1) after bypass surgery, and nine with myocardial infarction between 24 and 48 h postoperatively (MI 2). We wanted to determine whether the consequent measurement of activities of total creatine kinase (CK), CK isoenzyme MB (CK-MB), lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, and aspartate aminotransferase, conducted as a part of routine laboratory diagnostics, provided meaningful information for diagnosing infarcts besides that obtained from the electrocardiogram. The postoperative mean values of the enzyme activities in blood were significantly different among the three groups; however, only a combined evaluation of CK and CK-MB by means of a discriminant analysis allowed the prediction of MI (sensitivity: MI 1 = 98.5%, MI 2 = 95.4%; specificity: MI 1 = 71.4%, MI 2 = 81.8%). CK greater than 600 U/L or CK-MB greater than 45 U/L supports the diagnosis of acute MI.     

Isoforms of creatine kinase MM and MB in acute myocardial infarction: a clinical evaluation

Serum creatine kinase (CK, EC 2.7.3.2) isoenzymes MM and MB were resolved, respectively, into three (MM1, MM2, MM3) and two (MB1, MB2) isoforms (subforms derived from the same isoenzyme) by electrophoresis and the isoform patterns were determined in multiple sequential serum samples, timed from the onset of chest pain, from 58 patients with acute myocardial infarction (AMI). During the first 3 h after the onset of chest pain, the serum isoform activity resembled the pattern seen in normal volunteers. Specimens obtained 6 h after AMI showed predominantly MM3 and MB2 (45% and 11% of the total CK activity, respectively). Between 10 and 72 h, there was a gradual shift in which MM3, MM2 and MB2 decreased, while MM1 and MB1 increased. MB2 and MB1 disappeared from the pattern for samples collected after 24-48 h, while MM1 was always the most prominent band at the end of the observation period (66%, range 41-77%, at 48 h). These data suggest that a single determination of CK isoform pattern, drawn between 6 and 48 h after AMI, may provide an effective means of predicting the time of onset of necrosis. There were no significant differences in the CK isoform patterns according to infarct location and functional status of patients.     

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.     

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.     

急性心肌梗死患者血浆N-末端脑钠肽前体水平检测及其临床意义

目的探讨急性心肌梗死(AMI)患者住院早期血浆N-末端脑钠肽前体(NT-proBNP)水平与梗死面积、心功能及住院期心脏事件的关系。方法采用ELISA法测定41例AMI患者住院后48小时内血浆NT-proBNP水平,并与患者肌酸激酶(CK)和肌酸激酶同功酶(CK-MB)峰值浓度、左室射血分数(LVEF)、住院期主要不良心脏事件(MACE)对比分析。结果AMI患者血浆NT-proBNP水平明显高于正常对照组(699.44±386.28pg/ml vs 41.75±24.26pg/ml,P<0.001)。血浆NT-proBNP水平与CK、CK-MB峰值浓度呈正相关(r=0.817,P=0.001;r=0.772,P=0.001),与LVEF呈负相关(r=-0.661,P<0.01)。住院期发生MACE患者的血浆NT-proBNP水平明显高于未发生MACE者(971.50±367.01pg/ml vs 393.60±261.16pg/ml,P<0.001)。结论AMI患者血浆NT-proBNP水平与CK、CK-MB峰值呈正相关,与LVEF呈负相关。检测血浆NT-proBNP水平可预测AMI患者梗塞面积、心功能及住院期心血管事件。     

Creatine kinase isoenzyme MB assay by electrophoresis

A method for determination of the creatine kinase isoenzyme MB (CK-MB) is reported: separation of the isoenzymes was done by electrophoresis and the activity of the isoenzyme bands quantitated by scanning fluorometry. Total CK activity was used for calculation of CK-MB level. The precision of the method was satisfactory: coefficient of variation 5-10%. Its accuracy good: CK-MB was consistently found in high concentrations in tissue extracts of myocardium, but was virtually absent in skeletal muscle and could not be demonstrated in serum from patients with skeletal muscle damage. The sensitivity of the method fitted its clinical use: CK-MB was undetectable (less than 5 U/l) in normal sera, below 30 U/l in seventy-six out of seventy-seven patients in whom the diagnosis of acute myocardial infarction (AMI) was disproved, and above 30 U/l in all seventy-two patients with AMI according to WHO criteria. The CK-MB concentration in serum rises to a maximum about 20 h after onset of clinical symptoms of AMI and reaches baseline levels 20-30 h later. The electrophoretic CK-MB method is easy, fast and reliable and is considered as an important diagnostic test for AMI.     

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.     

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.     

Measurement of troponin I 48 h after admission as a tool to rule out impaired left ventricular function in patients with a first myocardial infarction.

Few studies have evaluated cardiac troponin I (cTnI) as a marker for infarct size and left ventricular (LV) dysfunction. Here we investigated the ability of a single-point cTnI, measured with a second-generation assay (Access AccuTnI), to estimate infarct size and assess LV function in patients with a first myocardial infarction (AMI). cTnI measurements were performed 12 and 48 h after admission in 63 consecutive AMI patients. LV function was evaluated by gated single-photon emission computed tomography (SPECT) and infarct size was estimated by CK-MB peak and SPECT myocardial perfusion. LV function and infarct size were evaluated by SPECT before hospital discharge. SPECT was also repeated 3 months later. Significant correlations (p<0.001) were found between cTnI at 12 and 48 h and both the peak CK-MB (r=0.61 and r=0.82, respectively) and the perfusion defect size at SPECT (r=0.55 and r=0.61, respectively). cTnI at 12 and 48 h were inversely related (p<0.001) to LV ejection fraction (LVEF) assessed both early (r=-0.45 and r=-0.57, respectively) and 3 months after AMI (r=-0.51 and r=-0.69, respectively). cTnI >14.8 microg/L at 48 h predicted an LVEF <40% at 3 months with a sensitivity of 100% [95% confidence interval (CI) 73.5-100%], specificity of 65% (CI 49-79%), and a negative predictive value of 100%. Our findings demonstrate that a single cTnI measurement 48 h after admission is useful for ruling out impaired LV function in a routine clinical setting.