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Cardiac markers in the early hours of acute myocardial infarction: clinical performance of creatine kinase, creatine kinase MB isoenzyme (activity and mass concentration), creatine kinase MM and MB subform ratios, myoglobin and cardiac troponin T.

We compared early markers of acute myocardial infarction (AMI) in the first 6 h from the onset of symptoms in 133 non-traumatized patients arriving at the emergency department with chest pain suggestive of AMI. Clinical performance parameters were calculated on the basis of 45 patients with AMI and 88 patients with a non-AMI diagnosis. At admission and in the first 0-3 h after the onset of chest pain the creatine kinase-MB (CK-MB) subform ratio was the most sensitive test at a comparable specificity level of 0.95. In the time interval of 3-5 h, myoglobin, the CK-MB mass concentration and the CK-MB subform ratio were associated with the greatest areas under receiver operating characteristic (ROC) curves, but differences between these tests were small and non-significant. At 6 h from the onset of pain, differences in clinical performance between the same three tests were even smaller whether or not samples drawn after the start of thrombolytic treatment were included in the test comparison. For confirmation of AMI at 6 h after onset of pain, CK-MB (activity and mass concentration) demonstrated the highest positive likelihood ratio, and for exclusion of AMI at 6 h the CK-MB subform ratio was associated with the highest negative likelihood ratio. However, differences between the CK-MB subform ratio, CK-MB mass concentration and myoglobin were not significant as estimated by the substantial overlap between the confidence intervals of the likelihood ratios and the ROC areas at 6 h. Cardiac troponin T (cTnT) demonstrated an ROC area equal to the CK-MB isoform ratio and myoglobin at 6 h. However, the likelihood ratio for ruling out AMI was lower, mostly due to the elevated cTnT in unstable coronary disease not defined as AMI. We conclude that the CK-MB subform ratio, CK-MB mass concentration and myoglobin do not demonstrate any significant differences in clinical performance for ruling in or ruling out acute myocardial infarction at 6 h after the onset of chest pain.

Adult↗

Time course of serum cardiac enzymes after intracoronary thrombolytic therapy. Creatine kinase, creatine kinase MB isozyme, lactate dehydrogenase, and serum glutamic-oxaloacetic transaminase.

We analyzed the time course of serum creatine kinase (CK), the CK MB isozyme, lactate dehydrogenase (LDH), and serum glutamic-oxaloacetic transaminase (SGOT) activity and calculated rates of increase and decline for CK in 24 consecutive patients with acute myocardial infarction (AMI) who received intracoronary thrombolytic therapy. In 19 patients with successfully reperfused infarcts, peak CK activity occurred at 14.1 +/- 1.1 hours after onset of symptoms, the maximal rate of CK rise was 595 +/- 102 IU/L/hr, and the fractional disappearance rate (Kd) was (86 +/- 6) X 10(-5)/min. The peak CK MB activity occurred at 12.9 +/- 0.8 hours and the MB Kd was (223 +/- 39) X 10(-5)/min. In five patients in the nonreperfused group the peak CK (24.9 +/- 4.5 hours) and CK MB (22.7 +/- 3.3 hours) activity occurred later, the maximal rate of CK rise (281 +/- 37 IU/L/hr) was less, and the CK Kd [(68 +/- 5) X 10(-5)/min] and MB Kd [(116 +/- 28) X 10(-5)/min] were lower. The peak CK, CK MB, cumulative CK release, and area under the curve were not different. Except for a shortened time to peak SGOT in the reperfused (17.1 +/- 1.3 hours) compared with the nonreperfused (29.1 +/- 5.6 hours) groups, the time course of LDH and SGOT were not different. Thus, the initial serum CK kinetics and time to peak SGOT may be useful in assessing the reperfusion status in patients with AMI receiving thrombolytic therapy without coronary angiography or in those who may have spontaneous recanalization.

Adult↗

Comparison of serum cardiac specific troponin-I with creatine kinase, creatine kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon runners: cardiac or skeletal muscle trauma?

Problems arise in distinguishing skeletal from cardiac muscle trauma on the basis of serum enzyme tests following severe muscle exercise. The contributions of cardiac and skeletal sources have been assessed in eleven marathon runners by measuring pre- and post-race serum levels of cardiac-specific myofibrillar troponin-I together with total creatine kinase, creatine kinase-MB isoenzyme, myoglobin, myofibrillar tropomyosin and C-reactive protein. Total creatine kinase, creatine kinase-MB isoenzyme, tropomyosin and myoglobin were significantly elevated above pre-race levels in all runners between 1 h and 128 h post-race. Neither mean cardiac troponin-I nor C-reactive protein was elevated post-race. Nine out of sixty-three samples fulfilled conventional positive criteria for cardiac muscle damage on the basis of combined creatine kinase and creatine kinase-MB isoenzyme levels. Six runners had one or more positive samples. No samples had levels above twice the upper normal limit for either cardiac troponin-I or C-reactive protein. Correlation analysis of levels in each sample indicated skeletal and not cardiac muscle as the source of raised serum protein.

Athletic Injuries↗

Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology.

BACKGROUND: Spurious increases in serum troponins, especially troponin T, have been reported in patients with and without acute myocardial syndromes. METHODS: We studied 78 autopsied patients without clinical myocardial infarction (MI) and correlated histologic cardiac findings with antemortem serum creatine kinase (CK), its MB isoenzyme (CK-MB), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). RESULTS: There was no significant myocardial pathology in 15 patients. Cardiac pathologies were in five groups: scarring from previous MI or patchy ventricular fibrosis (n = 9), recent MI (n = 27), healing MI (n = 7), degenerative myocyte changes consistent with congestive heart failure (CHF; n = 12), and other cardiac pathologies (n = 8). The median concentrations in the five groups were not significantly different for either CK or CK-MB. Compared with the no-pathology group, only the MI group was significantly different for cTnI, and the MI and other pathology groups were significantly different for cTnT. For patients with MI, 22%, 19%, 48%, and 65% had increased CK, CK-MB, cTnI, and cTnT, respectively; for CHF and other cardiac pathologies combined, the percentages were 28%, 17%, 22%, and 50%. For patients with increased cTnI, 72% and 28% had MI and other myocardial pathologies, respectively; patients with increased cTnT had 64% and 36%, respectively. Patients without myocardial pathology had no increases in CK-MB, cTnI, or cTnT. CONCLUSIONS: All patients with increased serum CK-MB, cTnI, and cTnT had significant cardiac histologic changes. The second-generation cTnT assay appears to be a more sensitive indicator of MI and other myocardial pathologies than the cTnI assay used in this study.

Autopsy↗

Stability of macro creatine kinases and creatine kinase isoenzymes compared: heat inactivation test for determination of thermostable creatine kinases.

Creatine kinase isoenzymes showed decreasing thermal stability and increasing lability towards pH changes in the order: MM, MB, and BB. The three isoenzymes exhibited their highest stability between pH 6.5 and 7.0. At 37 degrees C and an almost physiological pH of 7.5 the decay constants were 0.025, 0.164 and 0.580 h-1 (MM, MB, and BB isoenzyme), respectively. In contrast to free creatine kinase BB, immunoglobulin-linked creatine kinase BB (macro creatine kinase BB, type 1 macro creatine kinase) showed a markedly higher stability; this accounts for the persistence of creatine kinase BB activity in macro creatine kinasaemia. In addition we identified a second type of macro creatine kinase in patients' sera, which is also thermostable. A simple heat inactivation test (20 minutes, 45 degrees C, immunoinhibition of the M-subunits) differentiates thermostable macro creatine kinases from thermolabile creatine kinases and thus completes isoenzyme diagnosis.

Creatine Kinase↗

Soluble interleukin-2 receptor and interleukin-8 plasma levels during and after cardiopulmonary bypass: correlations with creatine kinase and creatine kinase MB.

In this study, soluble receptor of interleukin-2, interleukin-8, creatine kinase, and creatine kinase MB isoenzyme levels were determined serially before, during, and after cardiopulmonary bypass in blood samples of 24 patients. Interleukin-2 receptor levels were 683+/-80 U/ml in the preoperative period and 640+/-60 U/ml during hypothermia. Subsequently, these levels increased significantly at the end of the procedure (791+/-70 U/ml, P<0.01), remaining elevated 1 h after (882+/-92 U/ml, P<0.001) and reaching peak values 24 h postoperatively (1,752+/-200 U/ml, P<0.001). Preoperative plasma values of interleukin-8 were 230+/-43 pg/ml. Interleukin-8 concentrations were 185+/-25 pg/ml during hypothermia. The peak interleukin-8 levels were observed at the end of cardiopulmonary bypass (754+/-94 pg/ml, P<0.001) and tended to decrease 1 h after the procedure (643+/-76 pg/ml, P<0.001), declining to preoperative values, 24 h postoperatively (273+/-41 pg/ml). Interleukin-2 receptor levels correlated well with creatine kinase levels during the procedure. Furthermore, creatine kinase MB levels were correlated with interleukin-2 receptor values only at the end and 1 h after completion of cardiopulmonary bypass. We concluded that interleukin-8 and Interleukin-2 receptor levels are elevated after cardiopulmonary bypass and may contribute to myocardial injury as reflected by increased levels of creatine kinase and creatine kinase MB and correlations between interleukin-2 receptor and both creatine kinase and creatine kinase MB levels.

Adult↗

Increased serum total creatine kinase and creatine kinase isoenzyme MB after cryosurgical ablation of the prostate.

PURPOSE: Several reports have documented that the MB isoenzyme of creatine kinase is present in prostatic tissue. However, since it has been shown that lower urinary tract manipulations, including transurethral prostatectomy, do not significantly increase serum creatine kinase isoenzyme MB levels, such elevations, which are found in patients after prostatic surgery, are believed to be specific for myocardial infarction. We examined whether cryosurgical ablation of the prostate altered serum creatine kinase or isoenzyme MB levels. MATERIALS AND METHODS: In 81 consecutive patients undergoing routine cryosurgical ablation of the prostate serum levels of creatine kinase and creatine kinase isoenzyme MB were measured from peripheral blood specimens drawn preoperatively, in the recovery room and at 8 and 24 hours postoperatively. Postoperative electrocardiograms were compared to the preoperative study. RESULTS: In 72 of 81 patients (89%) significant elevations in creatine kinase and creatine kinase isoenzyme MB levels were noted at all time points after cryosurgical ablation of the prostate and appeared to reach a peak at 16 hours postoperatively. The mean increases within the first 8 hours after cryosurgical ablation of the prostate were 1,355 units per 1. for creatine kinase and 46.6 ng./ml. for creatine kinase isoenzyme MB. No patient had any significant changes on the postoperative electrocardiogram. All 9 patients (11%) who did not have significant creatine kinase or creatine kinase isoenzyme MB levels after cryosurgery had undergone prior cryosurgery or combined radiation and hormonal therapy. CONCLUSIONS: Cryosurgical ablation of the prostate appears to produce elevations in serum creatine kinase and creatine kinase isoenzyme MB, which are specific to the procedure. Assays for creatine kinase isoenzyme MB are unreliable to render a diagnosis of myocardial infarction after cryosurgical ablation of the prostate.

Adenocarcinoma↗

[Sensitivity of creatine kinase and creatine kinase MB in myocardial infarction. Evaluation of a new optimized standard method (author's transl)].

In 70 patients with confirmed transmural myocardial infarction the sensitivity of creatine kinase and creatine kinase MB at different times after admission was investigated by 364 measurements. Beside the number of correctly positive results the optimized standard method hitherto used was compared with the new optimized standard method with N-acetylcystein as activator. During the first 12 hours after admission the percentage of correctly positive results was 64,4% for creatine kinase (GSH) and 86,7% for creatine kinase (NAC). The sensitivity of cretine kinase MB, however, was found to be 71,1% (GSH) and 86,7% (NAC). With respect to the poor specifity of creatine kinase the sensitivity of creatine kinase MB, especially when using the new optimized standard method is superior. Similar results were established 24 and 48 hours after admission. Creatine kinase MB only fails in detection of myocardial infarction if the stroke is older than 3 days or if the enzyme activity determination intervals are too long.

Acetylcysteine↗

Creatine kinase and creatine kinase isoenzyme responses to heat stress.

During this investigation the effects of heat acclimation and exercise on creatine kinase and creatine kinase BB isoenzyme responses in various tissues and serum of male Sprague-Dawley rats were ascertained. Forty rats were randomly divided into two groups of 20 rats each. One group was housed at 22+/-1 degrees C and the other at 33+/-1 degrees C. Each of the two groups were subdivided into two subgroups of ten rats each. One subgroup of each group was subjected to a programme of treadmill running of progressive intensity over a period of 6 weeks at the temperature at which it was housed while the other served as a resting control. At the end of the acclimation programme the rats were running at 23 m/min for 80 min. On the day of sacrifice all four subgroups were subjected to a discontinuous exercise protocol (10 min running alternated by a 2-min rest period; repeated three times) at 30+/-1 degrees C on a rodent treadmill at 23 m/min. The tissues investigated were kidney, heart and muscle. The rats were anaesthetized with pentobarbital sodium (6 mg/100 g body mass) injected intraperitoneally. The tissues were freeze-clamped and stored in liquid air until analysed. The body temperature of the four subgroups at the end of the experimental protocol were not significantly different. Acclimation at 33+/-1 degrees C resulted in significantly lower creatine kinase activity levels. Exercise at 30+/-1 degrees C also resulted in decreased creatine kinase activity levels in both acclimated groups. A similar trend was observed regarding creatine kinase BB isoenzyme activity levels, especially in kidney.

Acclimatization↗

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.

Creatine Kinase↗

[Measurements of serum activity of creatine kinase and creatine kinase isoenzyme MB in suspected myocardial infarction. Experiences from a hospital material].

Total creatine kinase and the creatine kinase isoenzyme MB activities were measured simultaneously in 767 serum samples from 592 patients with suspected myocardial infarction. The main and obligate finding was that in the 89 patients with verified infarction the fraction of MB-activity related to the total creatine kinase activity lay between 4 and 25%. In 72 patients diagnosed as not-having an infarction this fraction tended to lie below 4%. However, false positives frequently occurred within the lower total creatine kinase activity range.

Creatine Kinase↗

[Creatine kinase and creatine kinase isoenzyme MB: determination of normal values and values for myocardial infarct, using the new, optimized method with N-acetyl cysteine as the activator (author's transl)].

Preliminary results are reported for the determination of creatine kinase and its isoenzyme MB in healthy individuals and in patients with acute, transmural myocardial infarct, using N-acetyl cysteine as the activator of the enzyme. In healthy individuals, the upper normal limit for creatine kinase activity was 54 U/l; the decision level for the presence of creatine kinase MB activity 9 U/l. The limiting values were only slightly different from those for the GSH-activated creatine kinase, and the results with the old and new methods showed a linear relationship with a slope of 1.0. The differences in the activation of creatine kinase MM by GSH and by N-acetyl cysteine are discussed; the activities obtained for creatine kinase and creatine kinase-MB by the GSH-activation method cannot simply be recalculated to give the appropriate values of the N-acetyl cysteine activation method.

Acetylcysteine↗

Creatine kinase and creatine kinase B-subunit activity in serum in cases of suspected myocardial infarction.

We evaluated a diagnostic strategy by studying 481 patients suspected of having had an acute myocardial infarction; the prevalence of infarction by independent criteria was 0.43. This strategy is based on the sequential application of: (a) clinical criteria; (b) total creatine kinase determinations in two serum samples drawn within 10 to 20 h of the onset of acute symptoms; and (c) creatine kinase B-subunit (S-CK B) determinations after immunoinhibition with antibodies to creatine kinase M-subunit in the reaction medium in all samples found to have increased total creatine kinase activity. Discrimination limits of 150 U/L total creatine kinase for women and 200 U/L for men gave a diagnostic sensitivity of 0.99. Activities less than these limits in samples identified 68% of the 274 non-infarct cases (posterior probability of a negative result of 0.99) within 20 h. Subsequent determination of S-CK B in 292 patients who were positive by the discrimination limits for total creatine kinase verified myocardial infarction in 99% of 207 cases for which S-CK B exceeded the discrimination limit of 12 U/L. The strategy excluded 98% of all non-infarct cases at a posterior probability of 0.99.

Alanine Transaminase↗

Creatine kinase and creatine kinase MB in endurance runners and in patients with myocardial infarction.

Following a 100 km race creatine kinase (CK) creatine kinase MB (CKMB) activities were serially measured in well trained athletes and compared with enzyme activities in patients with acute myocardial infarction (AMI). The half-time of disappearance of CK (CKt1/2) was 1.75 +/- 0.70 days in runners who trained within the 1st week after the race, and was 0.81 +/- 0.18 days in patients with AMI, P less than 0.005. CKt1/2 in runners was shorter (1.17 +/- 0.28 days) when no training was performed in the first postrace week. CKt1/2 was linearly correlated with age (P less than 0.01) in the runners but not in the patients. CKMBt1/2 was 1.30 and 1.11 days in two runners and 0.56 +/- 0.10 days in patients with AMI (P less than 0.05). In line with histologic and enzymatic findings in skeletal muscle of long distance runners as reported by other workers, our kinetic data provide further evidence that CK and CKMB are released from muscular compartments in runners other than those in patients with AMI.

Adult↗

Re-evaluation of the diagnostic utility of serum total creatine kinase and creatine kinase-2 in myocardial infarction.

The diagnostic utility of total creatine kinase activity (I), creatine kinase-2 isoenzyme activity (II), and II as a percentage of I, was examined by receiver-operating characteristic curve and likelihood ratio (LR) analyses in 310 persons admitted to the Coronary Care Unit (151 proven cases of myocardial infarction and 159 non-myocardial infarction controls), from whom blood was sampled at 6-h intervals for 48 h after the onset of chest pain. I was ineffective either as a "rule-in" or as a "rule-out" test within the first 6 h of the onset of chest pain; thereafter, it was an effective test. II was the most effective test during the entire 48-h period. III was more effective than I in the first 24-h period, but was less effective than I during the next 24-h period. The decision threshold for high test sensitivities varies with time over the entire 48-h period, but remains constant for high test specificities. It is essential to tabulate the LR(+) and LR(-) values for both test sensitivity and specificity at constant values to determine the utility of each test at each time interval for respectively ruling out or ruling in a diagnosis of myocardial infarction.

Creatine Kinase↗

Increases of neuron-specific enolase, S-100 protein, creatine kinase and creatine kinase BB isoenzyme in CSF following intraventricular catheter implantation.

In 15 patients without acute brain injury the concentrations of Neuron-specific Enolase (NSE), S-100 Protein (S-100), Creatine Kinase (CK), and Creatine Kinase BB isoenzyme (CK-BB) in ventricular cerebrospinal fluid (CSF) were measured immediately after lateral ventricle cannulation for diagnostic or treatment purposes. From patients who were treated with a shunt another CSF sample was obtained one week after shunt implantation by puncture of the antechamber of the valve. The CSF concentrations of NSE, S-100, CK and CK-BB after cannulation were found to be of the same order as found in patients with severe head injury, stroke or subarachnoid haemorrhage. One week after shunt implantation the concentrations of S-100, CK and CK-BB had returned to normal levels in almost all patients, while the NSE concentrations remained elevated. These findings indicate that the sampling procedure may result in contamination of CSF with NSE, S-100, CK and CK-BB and they should be taken into account in the prognostic evaluation of enzyme concentrations after brain injury.

Brain Damage, Chronic↗