Serum Creatine Phosphokinase Activity Research Articles

Creatine Phosphokinase Activity in Blacks vs Whites

To the Editor.— Olerud and associates reported that black marine recruits who developed acute exertional rhabdomyolysis (AER) had significantly higher peak serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), SGOT, and myoglobin levels than non-blacks who developed AER. The overall incidence of AER in blacks was not significantly different from that of non-blacks. Olerud et al stated there was no clear explanation for the differences between black and non-black recruits. 1 However, several studies from this laboratory are relevant to their findings. We have reported that baseline serum CPK activity is significantly higher in black men and women than in white men and women, respectively. 2,3 Olerud et al did not report the preexercise serum CPK levels of their recruits, but it would be surprising if they failed to observe this black-white difference that we have also found in analysis of unpublished data from over 1,000 pre-employment physical examination subjects. We

Study on the effect of megavitamin E supplementation in man

A study was conducted to examine the effect of megavitamin E supplementation in healthy college student volunteers. Two hundred two subjects were randomly assigned to either of two treatment groups, one control and the other experimental. Each subject in the experimental group orally received 600 IU dl-α-tocopheryl acetate daily, while each subject in the control group received identical placebo tablets. The experiment was “double blind” and proceeded for a period of 4 weeks. On day 0 and on day 28 each subject had a fasting blood sample taken for laboratory analysis and completed a questionnaire. Results showed that megavitamin E supplementation did not have an effect on work performance, sexuality, and general well-being and did not cause muscular weakness or gastrointestinal disturbances based on subjective evaluations. Megavitamin E supplementation did not have an effect on prothrombin time, total blood leukocyte count, or serum creatine Phosphokinase activity. Serum cholesterol levels were slightly elevated in both males and females by vitamin E supplementation, but the elevations were not statistically significant. Serum triglyceride levels were significantly elevated in vitamin E-supplemented females, but only slightly increased in the supplemented males. High intake of vitamin E significantly elevated the level of this vitamin in serum and the elevation was greater in females than in males. Megavitamin E supplementation significantly decreased serum T-3 and T-4 levels in males and in females not using steroid oral contraceptive agents. This effect was not seen in females using oral contraceptive agents. The study indicated that under our experimental conditions, megavitamin E supplementation does not have a significant effect, beneficial or undesirable, on general health conditions, but it can cause a significant reduction of serum thyroid hormone levels and also an elevation of serum triglyceride levels in females.

Subacute toxicity of pyridoxine hydrochloride in the beagle dog

Supplemental doses of 0, 50, or 200 mg of pyridoxine HCl/kg/day were administered po to three groups of dogs for an average of 107 days. Ataxia, muscle weakness, and loss of balance developed between 40 and 75 days of treatment in the group that received 200 mg/kg/day. Clinical signs of toxicity were not observed in the 50-mg/kg/day dose group. Histologic examination of the tissues in the animals receiving the highest dose revealed bilateral loss of myelin and axons in the dorsal funiculi (f. cuneatus and f. gracilis) and loss of myelin in individual fibers of the dorsal nerve roots. In the group receiving 50 mg/kg/day pathological damage was limited to a bilateral loss of myelin in the dorsal nerve roots. Serum glutamic oxaloacetic transaminase and creatine phosphokinase activities were greater and cholesterol concentrations were decreased in the serum of animals receiving 200 mg/kg/day at the termination of the study. Analyses of tissues for pyridoxine concentrations revealed elevated values in the blood, cerebral cortex, spinal cord, spleen, kidney, and muscle in the group receiving 200 mg/kg/day. The group receiving 50 mg/kg/day had elevated pyridoxine values only in blood and cerebral cortex.

Creatine phosphokinase MB isoenzyme in hypothermia: Case reports and experimental studies

Six patients with severe medical disorders and profound hypothermia are presented who had elevated total serum creatine phosphokinase (CPK) and CPK-MB isoenzyme activity without clinical 3 or postmortem 3 evidence of acute myocardial infarction. Experiments in dogs indicate that hypothermia reduces total CPK activity in both striated and myocardial muscle resulting in increased serum enzyme activity. These data suggest that profound hypothermia may result in diffuse striated and cardiac muscle cellular injury without evidence of discrete infarction with consequent release of CPK-MB isoenzyme into serum.

The use of serum creatine phosphokinase in genetic counseling for Duchenne muscular dystrophy: I. Analysis of results from 29 studies

Several studies reported by various investigators using diverse methods of assay have been carried out to compare the serum creatine phosphokinase (CPK) activity in normal females and carriers of Duchenne muscular dystrophy (DMD), in an attempt to differentiate them biochemically. Results from different centers, even those using the same method of assay at the same temperature, are so divergent as to make simple pooling pointless, and collectively do not provide a satisfactory baseline for use by other clinics in genetic counseling. Examination of the method of moments estimates of the parameters suggests that the logarithm of the serum CPK activity in controls may be distributed normally and with stable variance. The degree of dispersion of CPK values, in controls, about the geometrical mean for each center has been estimated. The distribution in carriers is not so clear and no such maneuver seems appropriate.

An investigation of factors influencing the measurement of creatine phosphokinase activity in serum using coupled enzymatic methods

1. The factors influencing the measurement of creatine phosphokinase (CPK) activity in serum by coupled enzymatic methods were investigated to establish optimum conditions for this type of assay. Such a study was indicated following observations by the authors of poor performance of commerically produced reagent kits together with the failure of most of the established an well accepted methods to operate under true optimum zero order kinetics in the reaction phase state. 2. The factors invested were the effects of pH, substrate concentrations (creatine phosphate, glucose and NADP+), added auxiliary (hexokinase) and indicator (glucose-6-phosphate dehydrogenase) enzymes, dithiothreitol (DTT) as an activator and conditions of storage of substrate stability. DTT was found to be a suitable activator but not a reactivator of the reaction. The optimum concentrations of creatine phosphate, glucose and NADP+ were found to be 20.0, 20.0 and 2.0 mmol/litre, respectively. Optimum activieies of the enzymes, glucose-6-phosphate dehydrosenase and hexokinase were 1000 and 2000 units/litre, respectively. 3. The between-day precision of the method for measuring serum at pH 6.8 and 30 degrees C at three activity levels under the optimum conditions developed was excellent yielding coefficients of variation ranging from 2.0 to 2.7%.

Steroid-CPK test. A new diagnostic aid for muscular dystrophy and its carriers?

The response of serum creatine phosphokinase (SCPK) to intravenous hydrocortisone was studied in different neuromuscular diseases, in Duchenne carriers and relatives of various muscular dystrophy (MD) cases. SCPK activity increased significantly in MD cases, 50% of known and 18.7% of possible Duchenne carriers. No such increase was found in other neuromuscular disease, in other relatives of MD cases and in normal controls. An inverse correlation was observed between the grade of disability and post-steroid percentage increase of SCPK activity in X-linked severe (DMD) cases. Such an inverse correlation was also found between the duration of the disease and post-steroid percentage increase of SCPK activity in DMD cases. A possible explanation is given.

Serum creatine phosphokinase activity in asthma.

Serum creatine phosphokinase activity was measured in 2 groups of asthmatics. The first group consisted of 12 asthmatics followed as outpatients for periods of up to 16 months. Serum creatine phosphokinase activity increased in 8 patients and correlated with the severity of subjective symptoms and objective measurement of airway obstruction, as represented by the forced expiratory volume in 1 second. In the second group, consisting of 5 asthmatic patients studied during hospitalization for acute exacerbations of asthma, serum creatine phosphokinase activity was increased on admission in all the patients and decreased as symptoms and airway obstruction improved and alveolar ventilation decreased. Analysis of creatine phosphokinase isoenzymes showed the increase in every instance to be due entirely to skeletal muscle isoenzyme. The results of additional laboratory tests and further evaluation suggested that the increased serum creatine phosphokinase activity was not derived from the myocardium and was not related to parenteral therapy, specific drugs, hyperthermia, or hyperkalemia. The increase in serum creatine phosphokinase during exacerbations of asthma is probably derived from respiratory muscles, owing to the increased work of breathing.

Augmentation of serum CPK activity by digitalis in patients with acute myocardial infarction.

The effect of acetyl strophanthanin on the rate of creatine phosphokinase (CPK) efflux was evaluated in 59 predominantly class I and II patients randomly allocated between treated and control. Therapy (0.5 mg) was begun 11-15 hours after the onset of symptoms and repeated four hours later (0.25 mg). Accumulated CPK activity (ACA) was determined from serial serum CPK changes sampled every two hours and compared to predicted CPK activity (PCA) determined from the first seven hours of CPK changes. In the control group, ACA was not significantly different from PCA. Digitalis consistently resulted in an augmentation of CPK efflux into serum which was temporally related to drug administration and resulted in a corresponding increase in ACA (P less than 0.001). Thus acetyl strophanthanin appears to increase apparent CPK activity in serum in class I and II patients.

Serum creatine phosphokinase activity in newly admitted chronic alcoholics.

Serum CPK activity was measured for a total of 33 cases of chronic alcoholics who were admitted to the mental hospital from April, 1975 to January, 1976. The result was examined in relation to the manifestation of the psychotic symptoms in the patients: (1) Twenty six (78.8%) out of 33 cases showed increased serum CPK activity within 48 hours of admission. (2) In most cases that showed abnormal CPK activity, CPK value was the highest at the moment of admission, and then began to fall rapidly, and after one or two weeks settled to the normal CPK level. (3) There was a positive correlation between abnormal CPK activity and the manifestation of the psychotic symptoms in the month before and after entering hospital. In this cases of those having more than 101 IU in serum CPK value, the rate of presenting the psychotic symptoms in a month before or after admission was 90.5% and 71.4%, respectively. The author has given here a report on the above-mentioned results and made some considerations as to pathogenesis of abnormal CPK activity in chronic alcoholism.

Growth responses and serum enzyme activities in growing pigs resultant from supplementing diets based on aged barley with synthetic δ-α-tocopherol

SUMMARYIn group and individual feeding experiments of 98 days duration, a total of 96 Large White x Landrace 9-week-old pigs were fed diets (containing 0–09 mg selenium/kg) based on 85% of barley (containing 3 mg δ-α-tocopherol/kg), which had been stored aerobically for 1 year, with 0 (basal), 10, 20, 40, 80 or 160 mg/kg of synthetic δ-α-tocopherol added. In both experiments the tocopherol supplementation significantly improved growth rates over those obtained from the basal diet. Serum creatine phosphokinase and aspartate aminotransferase activities were not significantly affected.

Quantitative assessment of myocardial infarct size from serial determinations of serum creatine phosphokinase activity: significance of previous infarction for the cardiac function and prognosis.

In 50 patients with acute myocardial infarction (16 patients with previous infarction and 34 patients without), total creatine phosphokinase (CPK) released which represents infarct size was calculated from the serial change of serum CPK activity by the method of Sobel improved by Norris, and related it to the presence or absence of heart failure, the ejection fraction and one-year-mortality. If the patients with previous myocardial infarction were excluded, mean total CPK released in 10 patients with heart failure (1428 ± 200.4 IU/ml in Group II) was significantly larger (P<0.01) than that in 24 patients without heart failure (735.3 ± 83.6 IU/ml in Group I). However, in patients with previous myocardial infarction there was no significant difference in infarct size between these two groups (Groups I and II) indicating that the complication of heart failure does not directly relate to the size of the recent infarction but in large extent to the presence of prior infarction. The ejection fraction was obtained in 15 patients who had left ventriculography. Both of two patients with prior myocardial infarction in these 15 patients showed smaller ejection fraction than the predicted values myocardial infarction could contribute to impaired cardiac function as well as the recently occured infarction. One-year-mortality in Group II (37.5%) was higher than that of Group I (7.4%). In four patients with prior infarction who died within one year after the onset, mean total CPK released (275.3 IU/ml) was significantly smaller than that in three patients without prior infarction (899.0 IU/ml). These results strongly suggest that the patients with previous myocardial infarction are often complicated with heart failure and have poor prognosis even with comparatively small infarction and also demonstrate the substantially large contribution of the reduced contractility resulting from the previous myocardial infarction to the impaired cardiac function.

Serum myoglobin in myocardial infarction: The “staccato phenomenon”: Is acute myocardial infarction in man an intermittent event?

When serum was sampled frequently and soon after acute myocardial infarction, myoglobinemia was extremely common, occurring in 12 of 13 selected patients. Myoglobin first appeared in the serum within a few hours after infarction, but not consistently earlier than creatine phosphokinase. The peak level of serum myoglobin was reached appreciably earlier than the peak values of serum creatine phosphokinase activity. Time of earliest myoglobin appearance in the serum, peak level of myoglobin measured, and duration of detectable myoglobin release all correlated poorly with clinical and biochemical estimates of severity of myocardial infarction. There was no correlation between myoglobin levels and infarct size as estimated from creatine phosphokinase kinetics. Myoglobin appeared in the serum in multiple short “staccato” bursts, or episodes, often lasting only one to two hours. The hypothesis is suggested that the pattern of myoglobin appearance is a reflection of the episodic nature of acute myocardial infarction. Although isolated myoglobin determination may not be useful at present, for quantification of total myocardial damage, its pattern of release may be a sensitive marker for studying the time course of infarction, and may be useful to evaluate therapeutic interventions designed to interrupt an ongoing syndrome of myocardial necrosis.

Motor endplate alterations in schizophrenic patients.

NEUROMUSCULAR pathology has been described in a variety of mentally ill patients, primarily those suffering from schizophrenia or the affective psychosis. Some psychotic patients have increased electrical activity of skeletal muscle at rest1, abnormal electromyograms2, perform poorly on various tests of neuromuscular coordination3, have elevated serum creatine phosphokinase activity during an acute psychotic episode4 and show an increased incidence of morphological abnormalities of skeletal muscle5,6. Such studies have suggested that there may be an alteration of muscle innervation in such patients. We have previously reported that psychotic patients have an increased incidence of branching and sprouting of intramuscular nerve twigs6. We now report significant alterations in the morphology of the nerve terminals at the motor endplate in psychotic patients. This suggests that there may be an abnormality of transmission at neuromuscular synapses in some psychotic patients.

Isoenzymes of creatine phosphokinase in serum of families with malignant hyperpyrexia.

The activity and isoenzymes of creatine phosphokinase (CPK) in the serum of 2 women vulnerable to malignant hyperpyrexia were studied. Serum CPK activity was markedly elevated but, in contrast to a previous report, only skeletal-muscle type CPK activity was present.

Effects of isometric exercise on serum creatine phosphokinase activity.

The effect of isometric exercise on serum creatinine phosphokinase (CPK) activity in 14 psychotic patients in remission and ten normal controls was studied. The increases in serum CPK activity at 18 and 42 hours after exercise were no significantly different in patients and controls. The postexercise serum CPK activities in the patients were significantly less than the peak serum CPK levels when they were psychotic. There were no significant correlations between postexercise serum CPK activity and preexercise or peak serum CPK activity in the patient group. It is unlikely that increased isometric muscle tension is a major causative factor in the increased serum CPK levels frequently found in psychotic patients.

Histochemistry of creatine phosphokinase

In a preliminary experiment, brief formaldehyde fixation of rat myocardium permitted preservation of creatine phosphokinase (CPK) activity and fine structure. Electrophoresis of the homogenate of the fresh and fixed myocardium demonstrated mitochondrial and three non-mitochondrial CPK isoenzymes. An osmiophilic tetrazolium salt and ferricyanide were used for the electron microscopic demonstration of CPK. With tetrazolium, the reaction products were localized near the inner mitochondrial membrane in the intermembranous space of mitochondria, but the reaction was noted on the matrix side of the membranes with ferricyanide. Reaction was also present in the sarcoplasmic reticulum (SR) of the skeletal muscle. Both heart and skeletal muscle showed diffuse background cytoplasmic reaction. The heat-sensitive brain-type isoenzyme of CPK was present in the extramitochondrial sarcoplasm of the heart muscle. CPK activity was demonstrated in isolated heart mitochondria and skeletal muscle SR. Myocardial degeneration was produced in the rat myocardium by injection of isoproterenol. Two to 4 h after the injection there was an extensive histochemical reduction of CPK activity in the myocardium. Twelve to 24 h after injection, most of the areas with initially reduced CPK reaction recovered the enzyme activity and only the subendocardial layer underwent necrosis without recovery of the CPK activity. The maximal rate of increase in serum CPK activity coincided with the most extensive depletion of the myocardium CPK. Mitochondrial isoenzyme did contribute to elevation of serum CPK and appeared to remain in the injured myocardial cells.

Effect of acute carbon monoxide poisoning on serum lactate dehydrogenase and creatine phosphokinase

Young adult rats were exposed to 1,500 ppm CO in air for 2 hr. Blood carboxyhemoglobin (COHb) concentration immediately postexposure was 55.68 +/- 0.90%. Serum lactate dehydrogenase (LDH) activity peaked at 117% above control 2 hr postexposure, while serum creatine phosphokinase (CPK) activity was maximal at 132% above control immediately following termination of exposure. Serum LDH activity declined to control within 8 hr, while serum CPK undershot controls at 8 hr and returned to the control value by 24 hr.

Serum creatine phosphokinase activity in psychiatrically hospitalized children.

Serum creatine phosphokinase (CPK) activity was determined in a series of 101 sequential admissions to the Pritzker Children's Hospital, an inpatient psychiatric facility. Black children had significantly higher serum CPK levels than whites, and males had significantly higher levels than females, as is the case with adults. There was a higher incidence of CPK elevations in children with organic brain pathology than in children with personality disorders or schizoprenia. Children with chronic symptoms of a psychotic nature did not have increased serum CPK activity, which is similar to the findings in adults. There were no children in the sample with acute psychotic symptoms, so it was not possible to determine whether acute psychosis in children is accompanied by increased serum CPK activity, as it frequently is in psychotics over the age of 17.

Serum creatine phosphokinase (CPK) activity in monozygotic twins discordant for schizophrenia: Heritability of serum CPK activity

Recent studies with normal monozygotic and dizygotic twins have established that serum creatine phosphokinase (CPK) activity in man is under genetic control (Meltzer, Dorus, and Davis, in preparation). This is of interest because of the reports that serum CPK activity is increased in many acutely psychotic patients, provided that they are studied in the first days after the onset of gross psychotic symptoms and throughout hospitalization. 1–12 The increases range from slightly above the 95% upper limits of normal to 50–75 times the limits for each race-sex group. Furthermore, 25%–30% of the first degree relatives of psychotic patients have slight but persistent increases in serum CPK activity. 2,3,7 These increases occur significantly more frequently in relatives of psychotic patients who have themselves had increases in serum CPK activity (Meltzer and Moretti, in preparation). Prior to the studies with normal twins which established that serum CPK activity is under some genetic control, we had the opportunity to study serum CPK activity in twins discordant for schizophrenia. These results will be reported here.