Total Creatine Kinase Activity Research Articles

Biochemical evidence of myocardial injury after severe head trauma

Serum levels of creatine kinase (CK) and its myocardial isoenzyme (CK-MB) were measured and serial ECG recorded in 24 male and 6 female patients with severe head trauma. All patients were comatose, but no patient sustained a spinal or chest injury. Total CK activity was elevated in at least one sample in each patient. Elevated CK-MB activity was found in 28 patients. The serial CK-MB data did not follow the same pattern as that of patients suffering from myocardial infarctions. The mean CK-MB remained elevated for at least 3 days after injury, although individual patterns were variable. ECG abnormalities included prolonged corrected QT interval (QTc) in 90% and a variety of nonspecific ST segment and T wave changes in 53%. These ECG findings are consistent with other clinical studies of severe neurological disorders, particularly cerebrovascular accidents. The elevated CK-MB activity indicates that ongoing myocardial damage occurs in patients with severe head injury. Although the underlying mechanism is not entirely clear, an excessive release of catecholamines is the most likely mechanism accounting for diffuse myocardial damage, prolonged elevated CK-MB values and the observed ECG abnormalities.

Five creatine kinase isoenzymes in serum of a patient with severe heart disease.

Abnormal creatine kinase (CK) isoenzyme patterns were observed in the serum of a 64-year-old woman with severe heart disease. Agarose electrophoresis revealed the presence of all the usual CK isoenzymes (MM, MB, and BB) plus an extra band between MM and MB. Total serum CK activity was within the normal range. Within 2 h after the patient suffered cardiorespiratory arrest, a fifth CK isoenzyme appeared, cathodal to MM. After cardiac valve replacement, the patient's serum showed a high activity of CK, but the isoenzyme pattern showed only MM and, transiently, an MB band. With return of the serum CK activity to normal, the CK isoenzymes pattern also became normal, virtually ruling out genetic variant(s). The abnormal CK isoenzyme patterns might have been the consequence of severe hypoxemia in the patient, thus such patients may represent an ominous prognostic sign. The association of the abnormal pattern upon admission with rapid deterioration of the condition of the patient suggests prompt attention for the prevention of complications.

Observations on the isoenzymes of creatine kinase in equine serum and tissues.

The isoenzymes of creatine kinase have been measured in serum and selected tissues from horses. The distribution followed that reported in other species in that the MM dimer of the isoenzyme was present in voluntary and non-voluntary muscle, thyroid, liver, spleen, lung and intestine. The BB dimer of the isoenzyme was predominant in brain, pancreas, kidney, intestine, lung, spleen, liver and thyroid. In contrast, in 4 hearts examined less than 1.5 per cent of the total creatine kinase activity was attributable to the MB form of the isoenzyme. The MB isoenzyme was, however, present in intestine and spleen. In this series the isoenzymes were separated by ion exchange chromatography and their presence confirmed by cellulose acetate electrophoresis. It was concluded that as insignificant quantities of MB isoenzyme are present in equine heart, measurement of this isoenzyme in serum cannot be used to detect myocardial or cardiac damage in the horse. Further detailed studies need to be undertaken to assess the clinical relevance of the isoenzyme pattern in serum or other body fluids, if the measurement of creatine kinase isoenzymes in serum is to be used as a diagnostic aid.

Creatine Kinase Levels

To the Editor. —I read with interest the article by Dillon et al entitled Diagnostic Problem in Acute Myocardial Infarction: CK-MB in the Absence of Abnormally Elevated Total Creatine Kinase Levels published in the JanuaryArchives(1982;142:33-38). I agree with the basic premise of the article; however, I would like to address their reliance on Technicon's reference values (calculated from 100 subjects) for total creatine kinase (CK) activity. If Dillon et al had used a reference range established by them for their institution rather than by someone else, I believe they would have found substantially fewer patients with increased CK and MB (its myocardial isozyme) levels with normal total CK levels than reported. They probably would have found that their reference range would have been substantially lower than the Technicon values. At the Methodist Medical Center of Illinois, Peoria, where I work, we have a Technicon automated multiple analysis system

Comparison of the effectiveness of four clinical chemical assays in classifying patients with chest pain.

We compared the usefulness of four serum assays for classifying patients originally suspected of having an acute myocardial infarction. One of these is the long-used measurement of total creatine kinase (CK) activity. The other three are relatively new immunoassays: myoglobin by RIA, CK-BB by RIA, and CK-MB by immunoinhibition. When we evaluated test effectiveness with use of conventionally derived reference ranges, the results were misleading. However, by using receiver operating characteristic curves, we were able to effectively compare the four tests at all possible decision levels, rather than at only one. Multiple closely sequential serum specimens were obtained during the first four days after the onset of chest pain. Total CK, CK-MB, and CK-BB all behaved similarly, reaching peak diagnostic effectiveness at 18-20 h, when all three correctly classified 95% of the infarct patients, with a zero false-positive rate. However, total CK was more useful in identifying infarcts later in their courses than were the two CK isoenzyme tests. Myoglobin assay was most effective earlier in the course, at about 7 to 8 h. Our results indicate (a) that the tests for myoglobin and for CK or its isoenzymes are complementary and (b) that of the three CK tests, measurement of total CK activity provides the most information over the broadest segment of a patient's course.

Immunochemical CK-MB assay for myocardial infarction.

The diagnostic efficiency of an immunochemical assay for CK-MB (I-MB) was compared with that of an electrophoretic procedure for this isoenzyme (E-MB) in 215 consecutive patients in whom acute myocardial infarction (MI) was clinically suspected. All patients were investigated with a standard protocol consisting of serial assays of total creatine kinase (CK) and lactic dehydrogenase (LD) activities, CK-MB and LD1 isoenzymes, and electrocardiograms. Technetium pyrophosphate cardiac scans were obtained for eleven patients; autopsy was performed in six cases. The diagnosis of acute MI was established in 45 patients. The coefficients of variation for the intra-assay and interassay precision of I-MB assay ranged from 2.05%-7.2%. Concordance between the I-MB and E-MB results at the decision values for acute MI was observed in 203 of 215 patients (94.4%). At the cut-off point of 10 U/L, the I-MB assay was 95.5% sensitive and 95.3% specific for acute MI; the corresponding rates for the E-MB test were 93.3% and 94.7% respectively. The test efficiency rate for I-MB assay was 95.3% and that of E-MB procedure 94.4%. A complete time-based isoenzyme protocol for the diagnosis of acute myocardial infarction has several variables; the need for interpretation of individual profiles and for the preparation of a formal report is discussed.

Variant creatine kinase isoenzymes: frequency and clinical significance (author's transl)

To estimate the incidence of variant creatine kinase (CK)isoenzymes, 1,191 unselected patients were screened by means of CK:CK - MB ratio. When CK - MB was higher than 20% of the total CK in the immunoinhibition test, and a myocardial infarction could be excluded, a CK-isoenzyme electrophoresis was performed. We found macro-CK-BB-emia in 13 patients, but only three of them had elevated total CK activity. All patients but two were at the typical age of over 60 years; two males were 2 and 9 years old. The clinical diagnosis in macro-CK-BB-emia was predominantly cardiocerebrovascular insufficiency due to arteriosclerosis. In 16 other patients, the presence of an isoenzyme migrating cathodically to CK-MM was found. In this group, a malignant metastatic tumor was found in eight cases, the rest predominantly suffered from severe liver disease. Presence of both variant CK isoenzymes may lead to diagnostic or therapeutic errors due to the altered CK:CK-MB ratio. According to our studies, a variant CK isoenzyme occurs in 2.6% of hospitalized patients, but this will lead to problems diagnosing acute myocardial infarction only in the group with elevated total CK (0.42% of our patients).

Total CK activity and isoenzyme patterns in normal and neoplastic tissue of gastrointestinal tract.

Total creatine kinase (CK) activity and isoenzyme distribution were determined in normal and tumour of gastrointestinal (GI) tract. Total CK activity per gram wet tissue appeared to be markedly reduced in malignant tumour tissue, yet it was raised in benign tumour tissue. CK-BB was the predominant isoenzyme in both normal and tumour tissue of GI tract. Alteration of isoenzyme pattern was noted between the normal and tumour tissue. In one patient, macro-CK was found in tissue homogenate.

Circulating CK-MB and CK-BB isoenzyme after gastrointestinal surgery.

The effect of gastrointestinal surgery on serum creatine kinase activity was studied in 30 patients. The MB isoenzyme was demonstrated in sera of 30% of the patients and BB isoenzyme in 23%. MB content varied from 0.8 to 10.3% of the total creatine kinase activity, and the BB content from 0.6 to 18.4%. The CK-BB was probably of gastrointestinal origin, since gastrointestinal tract contains high CK activity with BB isoenzyme predominating. A cardiac origin for the observed serum CK-MB isoenzyme increase would seem the most likely, although no patients showed evidence of electrocardiographic changes. Increased CK-MB activity has been observed in myocardial ischaemia without infarction.

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.

Creatine kinase activity in normal and Duchenne muscular dystrophy fibroblasts.

Cultured human skin fibroblasts from 9 patients with Duchenne muscular dystrophy (DMD) and 8 normal age- and sex-matched controls were examined for creatine kinase (CK) activity. Both the normal and the DMD fibroblasts were found to have significant levels of CK activity (approximately 10 x 10(-3) IU per milligram of fibroblast protein). The control cells had slightly higher CK activity than the DMD lines, but this difference was not significant (0.2 less than P less than 0.1). The MM (muscle) isozyme, the BB (brain) isozyme, and the MB (hybrid) isozyme, of CK were found to be present in fibroblasts. The isozymes were separated by electrophoresis and the relative amount of each was determined for both normal and DMD cells. In normal fibroblasts, approximately 48% of the total CK activity was of the MM type, 40% was of the BB type, and 12% was of the MB type with no significant differences apparent between normal and DMD groups. The presence in human fibroblasts of significant levels of CK activity with a characteristic isozyme profile is an important consideration for studies of this "marker" enzyme in the pseudohypertrophic muscle of DMD.

Creatine kinase isoenzymes in acute brain injury.

Brain-type creatine kinase (CK) isoenzyme (CK-BB) was detected in the serum in 13 out of 26 patients with acute brain injury (50%). The peak of CK-BB activity ranged from 5 to 188 U/liter, constituting, on average, 10.5% of the total CK activity. The highest activities were seen in patients with gunshot wounds. High CK-BB activity was associated with poor prognosis, but minimal CK-BB elevations did not have prognostic significance. Heart-type creatine kinase isoenzyme (CK-MB) was detected in the serum in 17 out of 26 patients (65%). The peak activity ranged from 5 to 115 U/liter, constituting, on average, 6.6% of total CK activity. Electrocardiogram taken from 20 patients revealed transient T-wave inversions in the precordial leads in four patients; three of them also showed serum CK-MB activity. Subendocardial hemorrhage was detected at autopsy in three of the five CK-MB-positive patients, but in none of the four CK-MB-negative cases. Present findings suggest that acute brain injury may be secondarily cause myocardial damage.

2,4,5-T effects on cardiac and serum lactic dehydrogenase (LDH) and creatine kinase (CK) isozymes. I. Maternal enzyme activities and isozyme profiles.

Pregnant mice were exposed to 100 mg/kg 2,4,5-T, IG, on gestation days 6 through 17, and sacrificed on postpartum day 1 or 21. Toxicologic evaluation showed no changes in body weight, heart weight, heart to body weight ratio, or cardiac supernate protein between corn oil control and 2,4,5-T treated mice on days 1 or 21 postpartum (pp). There were no effects of 2,4,5-T treatment on the total LDH enzyme activity of cardiac supernate on day 1 or 21pp. Serum LDH total activity was depressed on day 1pp and comparable to control values on day 21pp. Cardiac CK total activity was elevated on day 1pp, but not on day 21pp. Serum CK total activity on day 1 was comparable to control values; however, on day 21, a significant decrease in activity was observed. Cardiac LDH and CK isozyme profiles were normal on days 1 and 21pp. The serum LDH isozyme profile was normal at both times. The serum CK isozyme profile on Day 1 was markedly altered by athe appearance of two aberrant isozyme bands while on day 21, there was a profile shift with an increase in the BB band and a compensatory decrease in the MM band. These changes in creatine kinase suggest metabolic or pathologic changes in the cardiac muscle.

Creatine kinase isoenzymes in cultured human muscle cells. I. Comparison of Duchenne muscular dystrophy with other myopathic and neurogenic diseases

The amounts of creatine kinase (CK) and the proportions of isoenzymes have been investigated in human primary cultures. There were increases in total CK activity and the transitions in the isoenzyme profiles showed initial patterns in which only the brain form is present, and later in culture showed patterns in which the muscle or hybrid forms are also present. These changes are similar to those found in muscle cultures grown from other species. These parameters have been compared in cultures derived from boys with Duchenne muscular dystrophy and from patients with various neurological diseases. The dystrophic CK activities were significantly lower and the amounts of brain-type isoenzyme were significantly higher than in the cultures from patients with neurogenic disorders, but the values were similar to the cultures from the myopathic group of diseases. The dystrophic CK isoenzyme profiles resembled those produced by cultures examined at time points, early in their growth period when they were less differentiated.

Creatine kinase isoenzymes in cultured human muscle cells. II. A study of carrier females for Duchenne muscular dystrophy by needle and open biopsy

Creatine kinase (CK) isoenzymes, total and specific CK activities and protein concentrations were measured in the cultured cells from muscle biopsies of 18 carriers of Duchenne muscular dystrophy (DMD) and the results compared with those in the cultures of patients with DMD and other neuromuscular disorders. The proportion of MB and BB isoenzyme in the carriers was similar to that in boys with DMD and in patients with other myogenic disorders, and significantly different from neurogenic patients. CK isoenzyme analysis appears to be a more sensitive index of in vitro differentiation than estimation of CK activities. Cell differentiation is reduced and the incidence of cell death increased in cultures derived from needle rather than open biopsies.

Plasma creatine kinase isoenzymes in the Bar Harbor dystrophic mouse

Increased activity of the MM isoenzyme of creatine kinase (CK) was found in plasma from Bar Harbor dystrophic mice of the 129/ReJ dy/dy strain when compared to the findings in non-dystrophic controls. Total plasma CK activity was only slightly increased in dystrophic animals but plasma from both normal and dystrophic mice showed large amounts of the BB isoenzyme of creatine kinase. This isoenzyme was also found to be present in mouse platelets. It is concluded that BB isoenzyme from platelets could have obscured the contribution of muscle CK to the total plasma CK activity and that CK isoenzyme quantitation is needed to evaluate muscle disorders in rodents.

MB Fraction of Creatine Kinase

To the Editor.— In a recent BRIEF REPORT (1980;244:580) Siegel and Dawson correctly point out that small levels of the MB fraction of creatine kinase (CK) can be detected in the undiluted sera of patients without myocardial involvement if the total CK levels are substantially elevated. Since numerous studies, including those they cite, demonstrate that the MB fraction in noncardiac patients is typically 0% to 2% of the total CK activity and if we accept the authors' assessment that about 5 IU/L is the minimum detectable level of CK by the fluorescent method, then it is clear that many noncardiac patients with total CK activity of about 500 IU/L will possess detectable levels of CK-MB in their undiluted sera. This underscores the need for a percentage quantitation of the CK-MB as a fraction of the total CK level, although the absolute level of CK-MB is also generally regarded as important

Myocardial Oxygenation and Recovery after Topical Cooling of the Ischaemic Heart and after Hypothermic Coronary Perfusion:A Clinical Study of Aortic Valve Replacement Patients

Myocardial oxygenation and recovery during aortic valve replacement were studied at different stages of operations, in which either topical cooling of the ischaemic heart (TCI) or hypothermic coronary perfusion (HCP) was used for myocardial protection. During HCP the utilization of available oxygen by the myocardium decreased by 65%. During rewarming significant lactate washout and production by the myocardium was found in the TCI-group with no significant signs of defective oxygen utilization. Already 10 min after initiation of reperfusion a greater oxygen extraction by the heart was seen in the TCI-group than in the HCP-group. This tendency persisted until the end of operation. There was some lactate production in the HCP-group during rewarming. The CI relative to PCWP showed a marked increase over prebypass values after bypass during lonotropic load in both patient groups, but the increase was more marked in the HCP-group, probably indicating a greater reserve of mechanical performance capacity. The increase in CI was associated with an increase in heart rate, but because of simultaneous decrease of systemic arterial pressure the pulse-pressure product, an indicator of myocardial oxygen consumption, did not increase. There were no intergroup differences in the cardiac performance after the immediate post-bypass period. The total activity of creatine kinase (CK) in blood increased nearly twice as much in the HCP-group as in the TCI-group. On the basis of the metabolic findings, it is concluded that there is no significant postischaemic reperfusion injury after TCI, that there is probably a transitory diminution in the reserve of mechanical performance capacity of the heart after TCI and that the greater increase in the total CK-activity after HCP is related either to a greater degree of skeletal muscle injury because of longer bypass time or to a greater degree of myocardial injury.

The diagnosis of myocardial infarction using cardiac-specific isoenzyme profiles

Creatine kinase (CK) and lactate dehydrogenase (LD) isoenzyme activities were measured in 100 patients with suspected acute myocardial infarction (AMI). The method employed was electrophoresis on thin agarose films using the Corning-ACl apparatus and reagents. The usefulness of this procedure as an aid to diagnosis and management was assessed. Specimens were collected at critical times on the enzyme release curve, the first on admission, then at intervals of 6-13 and 24-37 h. A comparison was made using significant elevations in total CK and α-Hydroxybutyrate dehydrogenase (α-HBDH) activities on specimens collected as part of the daily routine. In 34 patients there was an excellent correlation between both methods of analysis. However, the isoenzyme profile provided confirmation of AMI in a further 7 patients. In these patients total CK remained within the reference range (<80 μ 1) or showed borderline increases (80-160 μ/l), although α-HBDH remained normal. Among the remaining 48 patients in which AMI was ruled out. 4 showed elevations in total CK due to non-cardiac conditions. In a further 2 patients, in which total CK remained normal, trace amounts of CK-MB were detected. Both of these patients suffered episodes of atrial fibrillation. The individual assays for each collection period revealed that 61%, of the specimens were positive for CK-MB on the admission sample, whereas 93% were positive by the second specimen. However elevations in total CK ( > 160 μ/l) occurred in only 24% of patients on the first specimen, whereas 68%, were elevated by the second. The ratio of LD1:LD2> 1 occurred in 20% on admission but 85%, by 24-37 h. This coincided with α-HBDH being elevated in 24%, and 78% of patients respectively. Therefore, the combination of CK and LD isoenzyme profiles provided a more rapid and specific indication of AMI. Creatine kinase (CK) and lactate dehydrogenase (LD) isoenzyme activities were measured in 100 patients with suspected acute myocardial infarction (AMI). The method employed was electrophoresis on thin agarose films using the Corning-ACl apparatus and reagents. The usefulness of this procedure as an aid to diagnosis and management was assessed. Specimens were collected at critical times on the enzyme release curve, the first on admission, then at intervals of 6-13 and 24-37 h. A comparison was made using significant elevations in total CK and α-Hydroxybutyrate dehydrogenase (α-HBDH) activities on specimens collected as part of the daily routine. In 34 patients there was an excellent correlation between both methods of analysis. However, the isoenzyme profile provided confirmation of AMI in a further 7 patients. In these patients total CK remained within the reference range (<80 μ 1) or showed borderline increases (80-160 μ/l), although α-HBDH remained normal. Among the remaining 48 patients in which AMI was ruled out. 4 showed elevations in total CK due to non-cardiac conditions. In a further 2 patients, in which total CK remained normal, trace amounts of CK-MB were detected. Both of these patients suffered episodes of atrial fibrillation. The individual assays for each collection period revealed that 61%, of the specimens were positive for CK-MB on the admission sample, whereas 93% were positive by the second specimen. However elevations in total CK ( > 160 μ/l) occurred in only 24% of patients on the first specimen, whereas 68%, were elevated by the second. The ratio of LD1:LD2> 1 occurred in 20% on admission but 85%, by 24-37 h. This coincided with α-HBDH being elevated in 24%, and 78% of patients respectively. Therefore, the combination of CK and LD isoenzyme profiles provided a more rapid and specific indication of AMI.

Diltiazem pretreatment reduces experimental myocardial infarct size in rat.

Diltiazem (DZ) is a calcium channel blocking drug which has been shown to be a potent coronary artery dilating agent in the rat. Since this agent has been shown to reduce heart rate and contractility as well as to inhibit calcium transport in the ischemic myocardium, the present study was conducted to determine if DZ is effective in reducing myocardial infarct (MI) size in a rat model utilizing experimental left coronary artery ligation. Rats were pretreated (30 min presurgery) with either DZ (20 mg/kg i.p.) or saline (SA). At 48 h postsurgery, left ventricles were removed and assayed for total creatine kinase activity (CK). Percent infarct size was calculated and found to be significantly reduced from 14.8% in control SA to 6.7% of the total left ventricle in the DZ-treated group (p less than 0.01). Thus, pretreatment with DZ significantly preserves total CK activity and reduces % infarct size in the left ventricle of rats 48 h after experimental MI.