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Creatine kinase and creatine kinase B-subunit in stable and unstable angina pectoris.

Repetitive ischaemic episodes may have a cumulative effect leading to irreversible myocardial cell damage with enzyme release. Using plasma creatine kinase (CK) and creatine kinase B-subunit (CK-B) concentrations this theory has been tested in forty-eight patients admitted with acute chest pain, but without ECG signs of acute myocardial infarction (AMI). The patients were classified into four groups: Fourteen patients with non-ischaemic heart disease (non-IHD), seventeen with stable angina pectoris (SAP), ten with unstable angina pectoris (UAP), and seven patients who developed AMI during the study period. The enzyme variation in non-IHD delineates the background noise, and the increased variability in AMI indicates the full scale of the enzyme signals in cases of irreversible cell damage. Patients with SAP have the same enzyme signal as the background noise in respect of both CK and CK-B. However, in UAP the signal of CK-B equals the background noise, whereas the CK signal is separated from the latter. The reason may be that the signal to noise ratio of CK-B is poor and the analytical sensitivity low. Therefore, the behaviour of CK-B in this study does not support the above theory although our findings for CK indicate that the consequence of repeated ischaemic attacks is slight enzyme release.

Angina Pectoris↗

Serum creatine kinase and creatine kinase MB isoenzyme responses of post-infarction patients after a graded exercise test.

The response of total creatine kinase (CK) and the creatine kinase isoenzyme (CK MB) was studied in 22 male post-infarction patients (three to six months after myocardial infarction) after a functional graded exercise test, before entering a rehabilitation programme. Eleven subjects (group A) completed the test without developing significant electrocardiographic abnormalities. Eleven subjects (group B) showed changes that necessitated premature termination of the test. No significant differences were observed before the functional graded exercise test between the groups in serum concentration of CK, CK MB, and the percentage of CK MB to CK (MB/ CK%). The two groups were significantly different (p less than 0.01) 24 hours after the graded exercise test in CK MB and MB/CK%, but not in CK. In group B, CK and CK MB rose significantly after the graded exercise test (p less than 0.05) as did MB/CK% (p less than 0.01). In group A only CK showed a significant rise (p less than 0.05). It is probable that increases in CK MB after exercise arise from myocardial tissue efflux, reflecting reversible ischaemia. It is concluded from this study that CK MB appears to be a specific indicator of myocardial ischaemia and could, therefore, be of significant assistance in the clinical and functional assessment of the post-infarction patient.

Clinical Enzyme Tests↗

Beta-blockers, plasma total creatine kinase and creatine kinase myocardial isoenzyme, and the prognosis of subarachnoid hemorrhage.

Under double-blind randomized conditions the effects of early intervention with oral propranolol or a placebo were studied in 51 cases of subarachnoid hemorrhage. Eleven out of 23 patients randomly assigned to placebo had a poor outcome at 6 months, while 2 of the 28 patients randomly assigned to propranolol had a poor outcome (p less than 0.001). Patients with a poor outcome on the placebo had significantly higher mean plasma total creatine kinase levels (742 IU, standard error of the mean +/- 233 IU) on the fifth day after subarachnoid hemorrhage than patients with a good outcome on the placebo (108 +/- 20 IU; p less than 0.05). A raised plasma creatine kinase myocardial isoenzyme was associated with a particularly poor outlook in patients receiving the placebo, in contrast to those taking a beta-blocker. Clinical outcome and plasma creatine kinase levels in patients taking atenolol (hydrophilic) were similar to those observed in patients receiving propranolol.

Adrenergic beta-Antagonists↗

Testing for creatine kinase and creatine kinase-2 in Ontario: reference ranges and assay types.

In 1991, 246 and 136 Ontario laboratories performed total creatine kinase (CK; EC 2.7.3.2) and creatine kinase-2 (CK-2) assays, respectively. A questionnaire mailed to these laboratories requested information about the types of assay used, the origin of their reference ranges, and the source of their instruments and reagents. All laboratories used current test formulations for CK, although seven laboratories did not assay at 37 degrees C. For CK, 69% of all laboratories reported different upper reference limits for men and women (5th-95th percentiles: 160-250 and 115-215 U/L, respectively); 31% reported similar ranges for both sexes. Fifty-six percent derived their own ranges; the remainder used either kit inserts or literature references, and nearly 60% of this latter group claimed to have validated these suggested ranges before use. For 6% of all laboratories, their pediatric ranges were similar to their adult ranges. For CK-2, only 32% used their own reference range; the remainder used kit inserts or literature references, but only 49% of this group validated these ranges before use. Reference limits (5th-95th percentiles) for CK-2 were as follows: activity 6-24 U/L; fraction of CK, 0.022-0.06; and, for mass assays, 5-10 micrograms/L and relative index 0.015-0.04.

Creatine Kinase↗

[Effect of temperature of fluid infusion on diamine oxidase, MB isoenzyme of creatine kinase, creatine-kinase and lactate dehydrogenase in hemorrhagic shock rabbits].

OBJECTIVE: To investigate the effects of different temperatures of fluid infusion on diamine oxidase(DAO), MB isoenzyme of creatine kinase (CK-MB), creatine kinase (CK) and lactate dehydrogenase (LDH) in rabbit with hemorrhagic shock so as to provide a clue to improve the nursing care in patients with hemorrhagic shock. METHODS: An animal model of controlled hemorrhagic shock in rabbits as previously reported was used in this randomized experiment. Twenty-three rabbits were randomized to a warm fluid infusion group (n=8), a ambient-temperature fluid infusion group (n=7), and a cold fluid infusion group (n=8). The rabbits were then resuscitated with Ringer's lactate solution three times of that of blood loss. DAO and values of myocardial enzyme were measured before shock, during shock and 1 hour, 2 hours and 4 hours after fluid infusion, respectively. RESULTS: There was no significant difference in DAO and values of myocardial enzymes among groups, though there was a lower value in DAO and values of myocardial enzymes at 1 hour to 4 hours after warm fluid infusion. CONCLUSION: Our data indicate that warm fluid infusion in rabbit model of controlled hemorrhagic shock has some beneficial effect on some biochemical values. In view of this result, temperature of fluid infusion in nursing care for patients with hemorrhagic shock should pay more attention to.

Amine Oxidase (Copper-Containing)↗

Early 'rule-in' diagnosis of acute myocardial infarction 4 h post admission for rapid risk stratification by creatine kinase increment (creatine kinase change).

The use of creatine kinase (CK) measurement on admission, CK at 4 h, percentage CK change and electrocardiography (ECG) were compared for early risk stratification in the diagnosis of acute myocardial infarction (AMI). A total of 248 patients (median age 62 years, range 26-84) were studied (187 men, 61 women) of whom 118 had a final diagnosis of AMI. Median time to presentation was 3.92 h (range 0-11.17 h). Overall, the admission ECG had a sensitivity of 72.6% [95% confidence interval (CI) 64.6-80.7] with specificity of 88.9% (CI 83.4-94.4); 4 h CK change had a sensitivity of 100% (CI 96.1-100) with a specificity of 90.4% (CI 83.5-95.1). After excluding those with contraindication to anti-thrombotic therapy there were 109 patients with an uncertain initial diagnosis. In this group, admission CK had a sensitivity of 37.5% (CI 18.8-59.4) with a specificity of 94% (CI 86.8-98.1); 4 h ECG had a sensitivity of 43.8% (CI 19.8-70.1) with specificity of 97.4% (CI 86.5-99.9%); 4 h CK had a sensitivity of 79.2% (CI 57.8-92.9) with a specificity of 96.5% (CI 90-99.3); 4 h CK increment had a sensitivity of 100% (CI 85.8-100) with a specificity of 94% (CI 86.8-98.1). The admission ECG remains the investigation of choice for early 'rule-in' diagnosis of AMI for thrombolysis. Admission measurement of CK offers a small advantage in the patient with an uncertain diagnosis but the overall benefit is low. A strategy of admission ECG plus serial testing allows diagnosis to be complete by 4 h for accurate risk stratification. Whether this can be used for selection for therapeutic options (thrombolytic, anti-coagulation, anti-platelet or anti-anginal agents) requires further clinical trials.

Adult↗

Influence of indicating enzyme reaction on apparent creatine kinase activity creatine kinase in serum, VII.

Comparison of the indicative systems yeast glucose-6-phosphate dehydrogenase/NADP+, leuconostoc glucose-6-phosphate dehydrogenase/NADP+ and leuconostoc glucose-6-phosphate dehydrogenase/NAD+ showed excellent correlation and no differences in apparent creatine kinase activity with the two methods using NADP+. By using NAD+ with the leuconostoc enzyme enzyme relative recovery of apparent creatine kinase activity is lower due to interference of other serum constituents. The mean value of the relative differences versus methods using NADP+ was 5.8% in our experiments.

Creatine Kinase↗

Identification of a 43-kDa polypeptide associated with acetylcholine receptor-enriched membranes as MM creatine kinase.

Creatine kinase isoenzymes from Torpedo californica electric organ, skeletal muscle, and brain were purified and characterized. Torpedo electric organ and skeletal muscle creatine kinase have identical apparent Mr, electrophoretic mobility, and cyanogen bromide fragments. The electrophoretic mobility of the Torpedo creatine kinase was anodal as compared to mammalian MM creatine kinase. No creatine kinase isoenzyme with an electrophoretic mobility similar to mammalian BB creatine kinase was seen in any of the Torpedo tissues examined. Hybridization studies demonstrate the Torpedo electric organ creatine kinase to be composed of identical subunits and capable of producing an enzymatically active heterodimer when combined with canine BB creatine kinase. Creatine kinase from sucrose gradient-purified Torpedo electric organ acetylcholine receptor-rich membranes has an electrophoretic mobility identical with the cytoplasmic isoenzyme and an apparent Mr identical with mammalian MM creatine kinase. Western blot analysis showed Torpedo electric organ skeletal muscle creatine kinase and acetylcholine receptor-enriched membrane creatine kinase reacted with antiserum specific for canine MM creatine kinase. NH2-terminal amino acid sequence determinations show considerable sequence homology between human MM, Torpedo electric organ, chicken MM, and porcine MM creatine kinase. The acetylcholine receptor-associated creatine kinase is, therefore, identical with the cytoplasmic form from the electric organ and is composed of M-subunits.

Amino Acid Sequence↗

Creatine kinase and creatine kinase isoenzymes as a marker of uterine activity.

Creatine kinase (CK) and CK isoenzymes are known to fluctuate in labor. Reliable information about the longitudinal changes of CK and CK isoenzymes during labor is sparse. Nevertheless, they have been used to direct care in women with cardiopulmonary disease and preterm labor requiring tocolysis. This study evaluated fluctuations of CK and its isoenzymes longitudinally across labor in 49 women. Blood samples were obtained at 33 to 34 weeks' estimated gestational age, on admission in labor at 3 cm or less dilation, 8 cm to complete dilation, and postpartum in the recovery room. Specimens were analyzed for total CK, CK-MM, CK-MB, and CK-BB activity. CK levels increased for all peripartum patients (p < 0.001). CK activity at 3 cm was greater than at 34 weeks (p < 0.01). Furthermore, the early rise in CK activity was greater in those in active labor compared with those who required oxytocin stimulation (p < 0.001). CK values at 8 cm and postdelivery (mean IU/liter) were often above nonpregnant norms. The early rise of CK in spontaneously laboring patients versus those requiring oxytocin augmentation may represent a difference in uterine activity. Nonpregnant normative data for CK is not appropriate when assessing cardiovascular side effects of betamimetic therapy.

Biomarkers↗

Results of a nationwide survey of analyses for creatine kinase and creatine kinase isoenzymes.

More than 300 laboratories participated in an interlaboratory survey of creatine kinase (CK, EC 2.7.3.2) determinations in which they analyzed seven lyophilized samples for total CK and CK isoenzymes and furnished information about their methodology. The samples were not necessarily intended to mimic typical patients' specimens but rather to determine the analytical ability of the laboratories to distinguish isoenzyme fraction CK-MB from CK-BB and to detect small but abnormal amounts of CK-BB. For total CK measurement, most laboratories used an NADP+ reduction method monitored at 340 nm (89%), and reported results in units per liter (U/L) (99%) at either 30 degrees C (34%) or 37 degrees C (60%). Despite the variety of analytical conditions, most laboratories (89%) correctly reported results within their normal range for all samples. The 287 laboratories that reported isoenzyme distributions in the samples used either cellulose acetate (37%) or agarose (44%) electrophoresis, ion-exchange chromatography (9%), or immunoinhibition (7%). Results from laboratories that used nonspecific CK-MB immunoinhibition techniques were biased when a significant amount of CK-BB isoenzyme was present.

Chemistry, Clinical↗

Comparison of serum creatine kinase and creatine kinase MB activities post marathon race versus post myocardial infarction.

Serial total creatine kinase (CK) and CK MB activities were determined in the serum of seven runners following a marathon race and compared to enzyme activities in the sera from five patients following acute myocardial infarction (AMI). In the runner's sera, total CK and CK MB activities were significantly elevated at 1, 24, 48 and 72 hours post marathon race when compared to the 1 hour pre-marathon samples (p less than 0.01). Serum CK MB activities peaked at 24 hours in both groups of subjects. The MB activities 24 hours following the marathon were substantially higher (91 +/- 30 U/l; mean +/- SD) than the MB activities 24 hours following AMI (46 +/- 38 U/l). However, the percentages of CK MB 24 hours following the marathon and AMI were almost identical (7.0 +/- 2.4% and 7.2 +/- 2.3%, respectively). Furthermore, CK and CK MB clearances were significantly prolonged (p less than 0.02 and p less than 0.001, respectively) following the marathon race (T 1/2 CK, 49 hours; T 1/2 CK MB, 29 hours) as compared to following AMI (T 1/2 CK, 27 hours; T 1/2 CK MB, 12 hours). These results suggest release of CK MB from the skeletal muscle of marathon runners. Therefore, we recommend that elevation of CK MB in the range indicative of myocardial damage be interpreted with caution in long-distance runners.

Adult↗

Diagnostic value of creatine kinase and creatine kinase MB isoenzyme in chronic hemodialysis patients: a longitudinal study.

Serial measurements of total creatine kinase (CK) and the MB isoenzyme of CK (CK-MB) were performed on 18 stable hemodialysis patients over a 36 month interval in a longitudinal study designed to examine CK and CK-MB variability. Total CK was measured by the DuPont ACA pack procedure. CK-MB was quantitated by the ACA CK-MB ion exchange pack procedure, and by electrophoresis. The mean CK level was 242 +/- 179 IU/l (+/- SD). The mean CK-MB level was approximately 8% of the total CK. Seventy-two percent of the patients had at least one elevated CK level during the course of this study. Depending upon the method of analysis, 88 to 100% of the patients had at least one elevated CK-MB level. Marked and sporadic variations in both total CK and CK-MB levels were apparent, but were not related to the assay. Patients receiving long-term intramuscular androgens had higher CK, but not CK-MB, than did hemodialysis patients not receiving these agents. Discontinuation of the intramuscular androgens for four weeks led to a fall in CK in only one of four patients. Therefore there appears to be a biological effect of exogenous androgens which may play a role in elevating CK in hemodialysis patients.

Adult↗

Effect of Mg2+ during reactivation and refolding of guanidine hydrochloride-denatured creatine kinase.

Creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2) was completely denatured using 3 M guanidine hydrochloride for 2 h as in previous studies [Yao et al. (1982), Sci. Sin. 25B, 1296-1302; Yao et al. (1984), Biochemistry 23, 2740-2744; Yao et al. (1982), Sci. Sin. 25B, 1186-1193]. Under suitable conditions, about 60-70% of the activity can be recovered in the presence of different Mg2+ concentrations. Both the reactivation and the refolding processes follow two-phase courses after dilution in the proper solutions. A comparison of the rate constants for the refolding of unfolded creatine kinase with those for the recovery of its catalytic activity at various Mg2+ concentrations shows that these are not synchronized. The reactivity of guanidine hydrochloride-denatured creatine kinase can be inhibited by Mg2+; however, the rates of reactivation are independent of the Mg2+ concentration. In addition, Mg2+ affects the fluorescence intensity, but the rate constants of refolding are independent of Mg2+ concentration. Although the reactivation of GdHCl-denatured creatine kinase is complete about 3 h after dilution with reactivation solutions, the conformational changes during refolding occur in a much slower reaction. Mg2+ can induce complex changes in the relative fluorescence intensity during refolding over a broad range of concentrations.

Animals↗

Proficiency testing of creatine kinase and creatine kinase-2: the experience of the Ontario Laboratory Proficiency Testing Program.

The Ontario Laboratory Proficiency Testing Program has regularly monitored the analytical performance of total creatine kinase (CK) (approximately 230 participants) and CK isoenzyme-2 (CK-MB) (approximately 160 participants) throughout the entire province. Consistently, a wide dispersion of results has been observed not only between different analyzer systems but also among identical analyzers. Accordingly, the results of the last three proficiency surveys for these analytes were examined statistically to establish both the extent of these variations and the range of values reported for the male upper reference ranges. The results of many of the analyzer systems were significantly different from each other, as were many of the reference ranges. This unsatisfactory situation may only be remedied by the use of reference materials as shown by others. The consequences of these findings also effect the reliability of epidemiological surveys such as the WHO MONICA Project (Circulation 1994;90:583-612), which monitors deaths due to heart disease and includes cardiac enzyme results in its criteria.

Clinical Enzyme Tests↗

Myoglobin, creatine kinase and creatine kinase subunit-beta in serum from patients and relatives with hypokaliaemic familial periodic paralysis.

Increased levels of serum myoglobin (S-myoglobin) were found in 6 investigated patients with hypokaliaemic familial periodic paralysis (hypoKPP) in their habitual condition. Furthermore, in 3 of the 6, increased levels of serum creatine kinase (S-CK) were found. These findings support the hypothesis that hypoKPP is a permanent myopathy, which is aggravated during attacks. It was found that 1 definite carrier had elevated S-myoglobin and among healthy relatives 6/11 had elevated S-myoglobin and 3/11 elevated S-CK. The use of S-myoglobin and S-CK for carrier detection is discussed.

Adolescent↗

[Creatine kinase and creatine kinase isoenzymes in the serum of newborn infants. 1. Effect of the mode of delivery on total CK and CK-B].

The total CK-, CK-B- and CK-M-activity was determined in 48 newborns from the first to the third day of life by use of the "CK-Monotest" (Boehringer Mannheim). Opposite to a very small decrease of the total CK-activity a significant decrease of the CK-B is evident in the same time. At the first day the detection of CK-B was impossible in only 1 of 27 patients, but at the third day a low CK-B level was detectable in only 5 of 11 test persons. The activities of total CK and the CK-B were determined based upon these investigations in 245 newborns at the first day of life by use of the "CK-Monotest NAC activated" (Boehringer Mannheim). There was no significant difference of total CK- and CK-B-activity dependent on the mode of delivery (spontaneous vertex presentation, forceps delivery, caesarean section, breech presentation.) The proportion of the CK-B varied between 8 and 11% of the total creatine kinase in dependence on the mode of delivery.

Breech Presentation↗

Evidence for an associative mechanism in the phosphoryl transfer step catalyzed by rabbit muscle creatine kinase.

Creatine kinase does not catalyze the scrambling of 18O in adenosine 5'-[alpha beta-18O, beta-18O2]triphosphate in the absence of creatine, in the presence of L-arginine or taurocyamine (competitive inhibitors of creatine), or in the presence of poor substrates where single turnover experiments were performed. In order to support this prima facie evidence for an associative mechanism of phosphoryl transfer, an investigation was undertaken of 1-carboxymethyl-2-aminoimidazole, a new substrate analogue of creatine. This analogue has a binding constant for rabbit muscle creatine kinase similar to creatine and 1-carboxymethyl-2-iminoimidazolidine, but the initial rate of phoshorylation by MgATP in the presence of creatine kinase is almost 5 orders of magnitude slower. The phosphorylation product, assigned the structure 1-carboxymethyl-2-imino-3-phospho-4-imidazoline is also a poor substrate for the phosphorylation of MgADP by creatine kinase. These observations can be accounted for by an associative SN2(P) mechanism of phosphoryl transfer and by a microenvironment of the enzyme-bound creatine (or creatine analogue) which lowers the pKa of the guanidino group by several pH units compared with that in aqueous solution.

Animals↗

Correlation of ominous fetal heart rate patterns and brain-specific creatine kinase.

Creatine kinase isoenzyme analysis was performed on the cord blood of 125 infants who had undergone at least 30 minutes of intrapartum electronic fetal monitoring. The tracings were scored blindly according to severity of abnormal patterns, and the infants were grouped into ominous, intermediate, and normal scores. No differences were seen in creatine kinase MM or creatine kinase MB levels among the three groups. However, infants with ominous fetal heart rate patterns had higher creatine kinase BB levels and poorer outcome than infants with normal patterns.

Birth Weight↗