The formation of intracellular nitrogen-based oxidants has important physiological and pathological consequences. CK (creatine kinase), which plays a key role in intracellular energy metabolism, is a main target of low concentrations of oxidative and nitrative stresses. In the present study, the interaction between cytosolic CKs [MM-CK (muscle-type CK) and BB-CK (brain-type CK)] and MTs [metallothioneins; hMT2A (human MT-IIA) and hMT3 (human MT-III)] were characterized by both in vitro and intact-cell assays. MTs could successfully protect the cytosolic CKs against inactivation induced by low concentrations of PN (peroxynitrite) and NO both in vitro and in hMT2A-overexpressing H9c2 cells and hMT3-knockdown U-87 MG cells. Under high PN concentrations, CK formed granule-like structures, and MTs were well co-localized in these aggregated granules. Further analysis indicated that the number of cells containing the CK aggregates negatively correlated with the expression levels of MTs. In vitro experiments indicated that MTs could effectively protect CKs against aggregation during refolding, suggesting that MT might function as a chaperone to assist CK re-activation. The findings of the present study provide direct evidence of the connection between the two well-characterized intracellular systems: the precisely balanced energy homoeostasis by CKs and the oxidative-stress response system using MTs.

The effects of increased expression of creatine kinase (CK) in skeletal muscle were studied in control and transgenic animals homozygous for expression of the B subunit of CK. CK activity was 47% higher in transgenic gastrocnemius muscle. The CK activity was distributed as follows: 45 +/- 1% MM dinner, 31 +/- 4% MB dimer, and 22 +/- 5% BB dimer. No significant differences in metabolic or contractile proteins were detected except for a 22% decrease in lactate dehydrogenase activity and a 9% decrease in adenylate kinase activity. The only significant effect in contractile activity was that the rise time of a 5-s isometric contraction was 28% faster in the transgenic muscle. 31P nuclear magnetic resonance (NMR) spectra were obtained from control and transgenic muscles during mechanical activation, and there were no NMR measurable differences detected. These results indicate that a 50% increase in CK activity due to expression of the B subunit does not have large effects on skeletal muscle metabolism or contractile function. Therefore, control muscle has sufficient CK activity to keep up with changes in cellular high-energy phosphates except during the early phase of intense contractile activity.

The levels of carcinoembryonic antigen (CEA) and the activities of creatine kinase isoenzyme BB (CK-BB) were assessed in 84 patients with primary lung carcinoma and in 20 patients with nonmalignant lung diseases. The level of CEA was measured by the immunoenzymatic method using monoclonal antibodies (Abbott). The activity of CK-BB was assayed using a commercial kit (Boehringer Manheim, Monotest CK-NAC aktiviert). Increased levels of CEA were observed in 62% of patients, mostly in patients with nonsmall cell lung carcinoma (NSCLC), while enhanced activities of CK-BB were found in 39%, first of all in patients with small cell lung carcinoma (SCLC). A relationship was found between enhanced levels of CEA or CK-BB and the degree of carcinoma advance. The increased values of studied markers seem to indicate the limited possibility of surgical treatment and they are also important in prognosis after the resection of lung tissue.

High concentrations of creatine kinase BB (CK-BB) were found in all blood samples drawn within 6 hours of accident from 45 patients with brain contusion. The highest concentrations of more than 100 microg/l were measured in blood samples taken shortly after the accident from patients with a Glasgow Coma Score (GCS) of 6 or less. The CK-BB concentrations decreased rapidly to normal within 36 hours of accident in the patients given intensive care guided by intracranial pressure (ICP) monitoring. In patients with less severe injuries according to GCS the initial CK-BB concentrations were generally lower and normalized less rapidly. The outcome after 6 months was moderate or good in all 9 patients who had this rapid normalization of blood CK-BB. On the other hand, of 20 patients who had a more slow CK-BB decrease, only 9 had an acceptable outcome. Delayed ICP increase to more than 40 mm Hg and even delayed brain tamponade did not result in CK-BB levels higher than 5 microg/l. Brain tamponade in the acute stage resulted in rapid CK-BB decrease in the blood. In paired simultaneously drawn samples of lumbar cerebrospinal fluid (CSF) and blood, CK-BB levels were generally higher in the CSF.

No CK MM was found in human brain tissue. Both human and rat brain tissue, however, contain a non MM, non BB CK isozyme. The protein is membrane bound. Evidence is presented that it is a mitochondrial variant of the enzyme. This mitochondrial brain CK occurs in two forms. Both a low molecular mass form (Mr = 65,000) and a high molecular mass form are detectable. The isoelectric point of the low molecular mass form, Br-CKm1, is similar to the isoelectric point of CK MM. Complications may arise when techniques are used that try to separate the mitochondrial CK forms from CK MM on basis of differences in net change. The two mitochondrial brain CK forms are called Br-CKm1 and Br-CKm2. Whether these two enzymes are identical to the mitochondrial heart CK forms remains unclear.

The novel natural product DT56a (Tofupill/Femarelle), derived from soybean, has been shown to relieve menopausal vasomotor symptoms and to increase bone mineral density with no effect on sex steroid hormone levels or endometrial thickness. In the present study, we compared the effects of DT56a and estradiol-17beta (E2) on bone and cartilage (Ep) of immature or ovariectomized female rats, by measuring the changes in the specific activity of the BB isozyme of creatine kinase (CK). Single short-term injection of high doses of DT56a induced estrogenic activity in bones and uterus similar to that of E2. When administered in multiple oral doses, DT56a stimulated skeletal tissues similarly to E2, but whereas E2 increased CK specific activity in the uterus, DT56a did not. The selective estrogen receptor modulator (SERM) raloxifene (Ral) blocked the stimulation of CK by either DT56a or by E2 in all tissues tested. Our findings suggest that DT56a acts as a selective estrogen receptor modulator stimulating skeletal tissues without affecting the uterus. The effect of DT56a on other systems, such as the vascular and the central nervous system, are currently under investigation.

The individual creatinine kinase (CK) isoenzymes CK-BB and CK-Macro II have previously been investigated as potential tumour markers. We believe there is a need for a system to measure those CK forms not usually present in serum. We have studied a CK-MB immunoinhibition kit which measures all residual CK activity following inactivation of M-subunit activity. In 162 patients with cancer we found no difference in grading (+ or -) between detailed isoenzyme studies and the simple non-M assay. In 33 samples with elevated non-M CK, detailed analysis showed BB alone (45%), Macro II alone (9%), or both (36%). Raised activities were mainly found in patients with small cell lung cancer (SCLC) (17/40; 43%) and GI Tumours (6/11; 55%). In patients with SCLC, elevated activities were associated with disseminated disease. Preliminary evidence indicates that Non-M CK may also be a simple means of monitoring initial treatment response.

The normal values of serum-CK-activity in healthy newborns varied greatly (95% range: 4--165 U/l; 257 probands) and the borderline to pathological values was not sharp. Brain-typical CK-isoenzyme (CK-BB) could be detected in serum of 6 of 8 infants with perinatal brain damage by means of agar gel electrophoresis. The combination of neuropathological symptoms, increased total-serum-CK-activity, and significant amount of CK-BB in serum seemed to be a sure sign of severe CNS-damage in newborns.

Cardiac hypertrophy is associated with modifications in Ca2+ transport processes, enzymes of energy metabolism and antioxidant capacity. It is unknown whether these changes occur in infarct-induced hypertrophy with regard to an altered susceptibility to ischemia/reperfusion injury. We examined changes in sarcoplasmic reticulum (SR) Ca2+ transport, creatine kinase (CK) system, and the antioxidant enzymes glutathionperoxidase (GSH-Px) and superoxide dismutase (SOD) in rats 6 weeks after infarction due to coronary ligation (MI). Phenotypic modifications v sham operation (SHAM) were related to the contractile response of hypertrophied papillary muscle to hypoxia/reoxygenation for 30 min each. Under aerobic conditions we observed in MI v SHAM: decreases in isometric contraction and relaxation rate, a reduced Vmax-equivalent of sarcomeric shortening, a faster twitch-to-twitch decay of post-rest potentiation (PRC) which correlated closely to the decrease in SR Ca2+ uptake (-25%), a decrease in CK activity (-20%), reduced CK-MI and CK-MM, increased CK-MB and CK-BB, and enhanced activities of SOD (40%) and GSH-Px (50%). During hypoxia, an initial increase in peak force (PF) was followed by a slower PF decline in MI v SHAM. Reoxygenation caused a recovery of PF to approximately 30% in both groups; rates of contraction and relaxation recovered better in MI. In SHAM but not MI, twitch-to-twitch decay of PRC was accelerated after reoxygenation v aerobic control. The results suggest that adaptive changes in SR Ca2+ handling, CK isoenzymes and antioxidant enzymes may contribute to higher resistance against reduced oxygen supply and reoxygenation in hypertrophy due to MI.

We determined serum CK-BB mass concentration using a specific RIA method, in 267 patients with carcinoma confirmed histologically distributed as follows: 46 prostatic adenocarcinoma, 52 lung neoplasies, 70 colon carcinoma, 52 breast carcinoma and 41 gastric carcinoma; and also in 135 patients with histologically proved non-neoplastic diseases distributed as follows: 28 prostatic hyperplasy, 31 lung tuberculosis, 29 inflammatory bowel disease, 27 fibrocystic mastopathy and 20 gastroduodenal ulcer. Reference values in healthy subjects (n = 360) were 5.46 +/- 2.68 (SD) ng/ml. We found that serum CK-BB mass concentration is not a specific tumor marker but it is a valuable indicator of responsing to therapy and metastatic widespread. However, in prostatic carcinoma--prevalence 0.25, predictive positive value (PPV) 0.51 and predictive negative value (PNV) 0.88--and breast carcinoma--prevalence 0.32, PPV 0.60 and PNV 0.87--serum CK-BB can be used as a tumor marker. Only 12 over 268 patients with different neoplastic disease (4.47%) showed detectable serum CK-BB catalytic concentrations.

Immunogold labelling of creatine kinase B (BB-CK) and gastric H+/K(+)-ATPase in the parietal cells of the stomach revealed colocalization of these two enzymes on the apical membrane and the membranes of the tubulovesicular system. Upon fractionation of hog parietal cells, a specific fraction of the BB-CK proteins remained associated with the purified vesicles, in which gastric H+/K(+)-ATPase is highly enriched. The BB-CK present in this highly purified preparation was able to support pronounced H+/K(+)-ATPase activity in K(+)-loaded vesicles in the presence of phosphocreatine and ADP, although only low levels of ATP were measured. In contrast, when pyruvate kinase, phosphoenolpyruvate and ADP were used as an ATP-generating system to sustain similar levels of H+/K(+)-ATPase activity, ATP levels were more than 10-fold higher. Changing the experimental conditions such that ATP levels were the same for both systems resulted in significantly elevated H+/K(+)-ATPase activities in the BB-CK/phosphocreatine system in comparison with the pyruvate kinase/phosphoenolpyruvate system. These results indicate that gastric H+/K(+)-ATPase has preferential access to ATP generated by creatine kinase co-localized on the membranes of the vesicles.

To characterize the isoenzyme distribution of creatine kinase (CK) in endothelial cells (ECs) and its functional role during substrate depletion, ECs from aorta (AECs) and microvasculature (MVECs) of pig and rat were studied. In addition, high- energy phosphates were continuously monitored by (31)P NMR spectroscopy in pig AECs attached to microcarrier beads. CK activity per milligram of protein in rat AECs and MVECs (0.08 +/- 0.01 and 0.15 +/- 0.08 U/mg, respectively) was <3% of that of cardiomyocytes (6.46 +/- 1.02 U/mg). Rat and pig AECs and MVECs displayed cytosolic BB-CK, but no MM-CK. Gel electrophoresis of mitochondrial fractions of rat and pig ECs indicated the presence of mitochondrial Mi-CK, mostly in dimeric form. The presence of Mi(a)-CK was demonstrated by indirect immunofluorescence staining using Mi(a)-CK antibodies. When perifused with creatine-supplemented medium, phosphocreatine (PCr) continuously increased with time (1.2 +/- 0.6 nmol x h(-1) x mg x protein(-1)), indicating creatine uptake and CK activity. Glucose withdrawal from the medium induced a rapid decrease in PCr, which was fully reversible on glucose addition, demonstrating temporal buffering of an energy deficit. Because both cytosolic and mitochondrial CK isoforms are present in ECs, the CK system may also contribute to energy transduction ("shuttle hypothesis").

By studying early postmortem changes in cerebrospinal fluid (CSF) it is possible to draw conclusions as to premortem focal brain cell injury and terminal brain ischemia. Cisternal fluid (CF) from 40 different adult cadavers with no known neurological disorder was analyzed and compared with known in vivo values. They were divided into four groups (n = 10 in each group), CF samples taken 2, 4, 10, and 24 h after death. The enzyme activity of CK and CK-BB (EC 2.7.3.2) increased linearly and statistically significantly 4-24 h postmortem (P < 0.001) the 2 h values being already 10 to 20 times higher than in vivo, LD and its isoenzymes 1 to 3 (EC 1.1.1.27) distinctly 10 to 24 h after death. Glucose and pyruvate concentrations in the CF declined, as did Na+ and Cl-. Lactate and K+ increased over time. The earliest statistically significant changes between different timepoints were seen in lactate, pyruvate and K+ concentrations. The GABA concentration was already more than 170 times at 2 h postmortem, and glutamate more than 20 times higher than in vivo. The concentrations of alanine, glycine, lysine, histidine, isoleucine, phenylalanine, and tyrosine were 2 to 3 times higher at 2 h postmortem than during life. The concentrations of all amino acids and ammonia increased linearly and statistically significantly (P < 0.001) in the CF 4 to 24 h postmortem.

The value of serum creatine kinase B subunit activity (CK B) in the diagnosis of acute myocardial infarction was studied in 238 consecutive cases. All were admitted to a coronary care unit because of suspected acute myocardial infarction. Serum CK B activity was determined by an immunoinhibition procedure, using a CK M subunit inhibiting antibody (anti-M). For the evaluation of serum CK B, patients were classified into acute myocardial infarction and non-acute myocardial infarction groups. This classification was based on electrocardiographic findings, on quantitative determinations of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total serum creatine kinase (CK) activities, and on qualitative electrophoretic determinations of serum CK and serum lactate dehydrogenase (LD) isoenzymes. The prevalence of acute myocardial infarction in the patient material was 0.47. Serum CK B subunit activity was found to be a highly selective indicator of acute myocardial infarction with a predictive value of a positive test result of 0.97 and a predictive value of a negative test result of 0.99. The serum CK B activity increased above the acute myocardial infarction discrimination limit within 12 hours from onset of symptoms. Two non-acute myocardial infarction patients, who were resuscitated after cardiac arrest, had increased serum CK B values caused by the transient presence of CK isoenzyme BB in serum.

Serum creatine kinase (CK) and lactic dehydrogenase (LD) isoenzyme activities were measured in blood serum of pigs having myocardial damage and skeletal muscular lesions. Myocardial and muscular damage was induced by restraint stress provoked by intravenous infusion of a pharmacological restraint (succinylcholine-chloride) during 12 minutes. Pigs of Swedish Landrace and Swedish Landrace X Yorkshire breed, stress-susceptible (halothane-sensitive) and nonreacting pigs were studied. Severe myocardial damage and slight to moderate skeletal muscle necrosis were found 24 hours after restraint stress in the stress-susceptible pigs whereas in nonreacting pigs generally only myocardial lesions of moderate extent were registered. No significant increase was detected in the serum CK-BB (CK-1) or CK-MB (CK-2) activity whereas a pronounced elevation of the CK-MM (CK-3) activity was found, particularly in the stress-sensitive animals. In the myocardial tissue of pigs only a low CK-MD activity was found (about 4-5% CK-MD in addition to CK-MM) and this may explain the low CK-MB activity in serum of pigs subjected to severe myocardial damage. This is further supported by the pronounced increase in the anodal serum fractions LD 1-2 in animals free from skeletal muscular lesions. In the halothane-sensitive pigs skeletal muscle necrosis besides the myocardial lesions contributed to the high levels of CK-MM activity in serum.

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100-200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.

Experimental studies have shown that peripheral serum creatine kinase and lactate dehydrogenase change with bowel infarction. Some clinical reports have suggested that similar changes occur in patients. This prospective study documents the changes in these enzymes associated with acute myocardial infarction, acute bowel necrosis (MES INF), and uncomplicated abdominal aortic reconstruction. Analysis of 15 patients with AMI, 13 patients undergoing major AAS, and eight patients with MES INF has shown that these conditions may be differentiated by analysis of serum CK and LD isoenzymes. The study suggests that in the absence of electrocardiographic changes, a patient with epigastric distress with elevated levels of serum CK and either CK-MB or CK-BB bands present may well have a mesenteric rather than a myocardial infarction. Acute myocardial infarction can be ruled out further through analysis of serum LD1/LD2 ratios.

Postmortem brain tissues of schizophrenic patients were found to contain 5-10 times less water-soluble creatine kinase (BB CK) and 1.5-3 times less mitochondrial creatine kinase as compared to control. The major part of BB CK in schizophrenic brain tissues, contrary to control, was found to be insoluble in water (particulate form of BB CK) and could be extracted from brain tissue with strong denaturating agents. The particulate form of BB CK did not have any enzymatic activity but activity was found after the solubilization of this isoenzyme. The observed BB CK translocation into the particulate inactive form and the decrease of mitochondrial CK content to schizophrenic brains may reflect changes in the synthesis and the utilization of creatine phosphate.

OBJECTIVE

To investigate the prognostic importance in neurologic recovery of the lumbar cerebrospinal fluid (CSF) variables creatine kinase (CK) and brain-type creatine kinase isoenzyme (CK-BB), lactate dehydrogenase (LDH) and its isoenzymes (LDH 1-5), CSF acid phosphatase, beta-D-N-acetylglucosaminidase activity, and CSF lactate, pyruvate, sodium, potassium, and calcium concentrations in patients who experienced cardiac arrest.

METHODS

Prospective clinical study with blood and CSF samples collected 4, 28, 76, and 172 hrs after resuscitation.

METHODS

Medical ICU in a university hospital.

METHODS

Twenty consecutive victims of out-of-hospital cardiac arrest. Eight patients recovered neurologically and 12 patients remained comatose or neurologically disabled until death.

RESULTS

CSF CK, CK-BB, LDH, and LDH isoenzyme 1-3 concentrations in all disabled patients were markedly increased at 76 hrs after the resuscitation. However, these variables were not changed in the recovered subjects. Patients (n = 7) with a mean CSF CK level of 25 +/- 33 (SD) U/L, CK-BB 23 +/- 33 U/L, and CSF lactate 3.8 +/- 0.9 mmol/L at 28 hrs after cardiac arrest remained unconscious and died. In the recovered patients, the mean CSF CK concentration was 2.0 +/- 1.5 U/L (p less than .001) and CSF lactate concentration 2.5 +/- 0.5 mmol/L (p less than .002). The lactate concentration was highest at 4 hrs after resuscitation, declining thereafter. Patients with a mean CSF total LDH level of 609 +/- 515 U/L and acid phosphatase 2.4 +/- 1.2 U/L 76 hrs after resuscitation died without regaining consciousness. In the recovered patients, the mean total CSF LDH activity was 82 +/- 58 U/L (p = .003) and CSF acid phosphatase was 0.8 +/- 0.5 U/L (p = .01) 76 hrs after resuscitation.

CONCLUSIONS

CSF CK, CK-BB, and CSF lactate concentrations reflect a patient's outcome most reliably when measured within 28 to 76 hrs of the cardiac arrest. Similarly, CSF LDH, its isoenzymes 1-3, and CSF acid phosphatase concentrations, when measured at 76 hrs, can be used to monitor the patient's outcome after cardiac arrest. When correlated with Glasgow Coma Scale scores, the closest negative correlation was again seen in CSF CK and CK-BB at 28 and 76 hrs, as well as in LDH, LDH1-3, and acid phosphatase values at 76 hrs. The negative correlation between CSF lactate and Glasgow Coma Scale scores was most distinct at 28 hrs.

This study was carried out on 45 newborns to evaluate the accuracy of 1 minute Apgar score and umbilical arterial pH for prediction of the risk of perinatal brain damage. Using a new and very sensitive method for CK-BB determination, which is considered a good indicator of brain damage, CK-BB was used as reference. Patients with low Apgar score at one minute of life had significantly higher cord blood CK-BB values than the control group (p less than 0.01). No difference was found between the control group and the group with umbilical cord blood acidosis (p less than 0.2).

We investigated the problem of outcome prediction from seven risk factors in 40 severely head injured patients - 13 favorable and 27 unfavorable outcomes. By applying stepwise logistic discriminant analysis to the patients' data, we selected three significant risk variables: cerebrospinal fluid (CSF) CK-BB isoenzyme activity recorded on admission, severely raised intracranial pressure (more than 40 mmHg) and age, respectively. CSF CK-BB activity, which quantifies the initial neurological damage, proved to be the best prognostic factor. The presence of severe intracranial hypertension was always associated with a bad outcome, whereas its absence was not necessarily indicative of good prognosis. Finally, we combined the three selected variables into a single risk index, which allowed correct predictions in 92% of patients with favorable outcome and in 85% of patients with unfavorable outcome (total predictive efficiency 88%).

We have reported that multiple treatments with so-called 'non-hypercalcemic' analogs of 1 alpha,25(OH)(2) vitamin D(3) (1,25(OH)(2)D(3)) stimulate the specific activity of creatine kinase BB (CK) in ROS 17/2.8 osteoblast-like cells, and that pretreatment with these analogs upregulates responsiveness and sensitivity to 17 beta estradiol (E(2)) for the induction of CK. However, since the analogs showed toxicity in vivo, we have now studied the action of a demonstrably non-calcemic hybrid analog of vitamin D in ROS 17/2.8 cells, and prepubertal rats. The analog JKF was designed to separate its calcemic activity from other biological activities by combining a calcemic-lowering 1-hydroxymethyl group with a potentiating C, D-ring side chain modification including 24 difluoronation. Treatment with 1 pM JKF alone significantly stimulated CK specific activity at 4 h by 30+/-10%. However after three daily pretreatments, JKF upregulated the extent of induction by 30 nM E(2) by 33% at 1 pM and by 97% at 1 nM; the E(2) dose needed for a significant stimulation of CK activity was lowered to 30 pM. The action of the SERMS tamoxifen, tamoxifen methiodide and raloxifene, at 3 microM, was also upregulated by three daily pretreatments with 1 nM JKF; unexpectedly, this pretreatment prevented the inhibition of E(2) stimulation by the SERMS. Upregulation of E(2) action by 1 nM JKF was inhibited by 1 nM ZK159222, an inhibitor of the nuclear action of 1,25(OH)(2)D(3). In vivo, three daily injections of 0.05 ng/g body weight of JKF augmented the response of prepubertal female rat diaphysis and epiphysis to E(2). Therefore, demonstrably non-calcemic analogs of 1,25(OH)(2)D(3) may have potential for use in combination with estrogens or SERMS in the prevention and/or treatment of metabolic bone diseases such as postmenopausal osteoporosis.

Total CK and CK-MB (by the inhibition test, Merck-1-CK-MB) were measured in 33 patients which had to be admitted to the department of psychiatry due to acute withdrawal symptoms (predelirium, delirium) caused by chronic alcohol abuse. The results were evaluated together with the routinely performed laboratory determinations as well as clinical examination and morphologic investigations (ECG, X-ray examination of the thorax, EEG, CT). The results show that the CK-MB/total CK relationship represents also in these patients the most reliable parameter to discriminate elevated total CK values. In no but one case a substantial CK-BB release from the central nervous system could be demonstrated by the inhibition test. In 83% of the patients with elevated total CK activities it was possible to exclude an affection of the heart muscle (CK-MB portion below 6%). The CK-MB/total CK-quotient was clearly superior to the total CK/GOT relationship, by which a myocardial affection could be excluded in less than 40%. In four patients the CK-MB portion was above the critical decision limit of 6%: three obtained between 6% and 7%, one even 17%. The results suggest that the CK-MB/total CK-quotient may represent the most sensitive and reliable parameter of myocardial affection in patients with an alcohol intoxication and/or a delirium tremens.

The purpose of this study was twofold. First, we evaluated the financial impact of a rapid, monoclonal antibody-based CK-MB mass assay (Stratus, Dade Division, Baxter Laboratories, Miami, Fla) for the direct measurement of CK-MB in serum samples from 65 patients admitted to the coronary care unit with the possible diagnosis of acute myocardial infarction. Second, we evaluated retrospectively the Stratus assay and an activity assay (electrophoresis) for CK-MB in the following patient categories: acute myocardial infarction treated with and without thrombolytic therapy, angina, congestive heart failure, skeletal muscle trauma, and the acutely ill without acute myocardial infarction. The advantageous features of the Stratus mass assay were as follows. First, the laboratory was able to perform the assay more frequently because of the short assay time per specimen (less than 10 minutes) without additional personnel. This had a substantial impact on the clinician's ability to diagnose acute myocardial infarction and to move patients out of an intensive care unit at substantial financial savings to the patient, the hospital, or the third-party payer. Second, the Stratus assay was able to detect low levels of CK-MB (1 to 2 micrograms/L) in the presence of low total creatine kinase activity (less than 100 U/L). Third, the Stratus assay showed no interference due to very-high-total creatine kinase activities (greater than 100,000 U/L), CK-BB, macro-creatine kinase, and mitochondrial creatine kinase.