Acute myocardial infarction (MI) results in activation of neurohormonal systems and increased plasma concentrations of myocardial enzymes and structural proteins. We hypothesized that plasma levels of N-terminal pro-brain natriuretic peptide (NT-BNP) would respond more vigorously after MI than those of other natriuretic peptides. We also sought to compare this response with that of the established myocardial injury markers troponin T (TnT), myoglobin and creatine kinase MB (CK-MB). We obtained multiple blood samples for measurement of atrial natriuretic peptide (ANP), N-terminal pro-ANP, brain natriuretic peptide (BNP) and NT-BNP along with CK-MB, TnT and myoglobin in 24 patients presenting to the Coronary Care Unit within 6 h of onset of MI. Multiple samples were obtained in the first 24 h, then at 72 h, 1 week, 6 weeks and 12 weeks. NT-BNP increased rapidly to peak at 24 h and exhibited greater ( P <0.001) absolute increments from baseline compared with BNP and ANP, whereas NT-ANP did not change from baseline. Proportional increments in NT-BNP were also greater than those for the other natriuretic peptides ( P <0.05). Natriuretic peptide levels reached their peak around 24 h, later than peak TnT, CK-MB and myoglobin (peak between 1–10 h), and NT-BNP and ANP remained elevated on average for 12 weeks. Our present results, with detailed sampling of a cohort of acute MI patients, demonstrate greater absolute and proportional increments in NT-BNP than ANP or BNP with sustained elevation of these peptides at 12 weeks.

1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (< 3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2. This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3. Serum T 4 and T 3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4. The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome- c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects. 2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 ± 3.8 i.u./l) than in normal control subjects (0.4 ± 0.8 i.u./l; P < 0.01). 3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 ± 4.1%, 26.7 ± 2.5% and 33.5 ± 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 ± 3.0%, 21.5 ± 4.4% and 40.7 ± 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 ± 0.25) than in normal control subjects (0.30 ± 0.10; P < 0.01). 4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.

1. Isolated extensor digitorum longus muscles from control C57BL/10 and mutant dystrophin-deficient C57BL/10 mdx mice have been studied in vitro to determine whether dystrophin deficiency influences the susceptibility of muscle to contractile activity-induced damage. 2. mdx muscles were found to release reduced amounts of intracellular creatine kinase compared with control tissue in response to excessive contractile activity with or without simultaneous stretching of the muscle to 130% of its resting length. 3. In contrast, prostaglandin E 2 release from mdx muscle was elevated compared with control tissue in response to either form of contractile activity or to treatment with the calcium ionophore A23187. 4. These results do not support the hypothesis that dystrophin-deficient muscle is more susceptible to damage induced by contractile activity, but suggest that dystrophin deficiency influences the activity of muscle membrane phospholipase enzymes.

1. The present study examined if the presence of creatine kinase (CK) inhibitors might explain the large variability in blood levels of CK among subjects after exercise-induced muscle damage. 2. Twenty-four women performed an eccentric exercise with the forearm flexors and were then classified as no CK responders, low CK responders and high CK responders. High CK responders repeated the exercise two weeks later (bout two). 3. Sera from high CK responders were mixed with sera from no CK responders or low CK responders. Also, serum from high CK responders obtained after bout one was mixed with the same subject's serum from after bout two. 4. In all cases, the differences between the expected and observed CK activity for the mixes were within the expected variability for the assay. 5. Although CK inhibitors have been previously observed in sera from patients with muscle injury or disease, we were unable to demonstrate the presence of CK inhibitors in the sera from subjects who showed evidence of exercise-induced muscle damage.

1. Serum creatine kinase and oral temperature were measured in 20 patients with primary hypothyroidism before and after 48 h bed rest. Fifteen of these patients were heated during the 48 h period. The remaining five acted as control subjects. In addition, creatine kinase and oral temperature were measured in five control subjects after a 30 min period of exercise and again after a 30 min period of resting. 2. The oral temperature rose and the serum creatine kinase levels fell only in those patients who were actively warmed. In the control subjects the period of exercise followed by resting caused no significant change in creatine kinase levels. 3. A subnormal body temperature appears to be an important determinant of the raised serum creatine kinase levels seen in patients with primary hypothyroidism.

1. The stability of enzyme activity of the creatine kinase-l-immunoglobulin-G complex has been determined at 37°C, 4°C and −20°C in heat-inactivated serum and buffer. 2. The complex was formed by incubating creatine kinase-1 and immunoglobulin G at 37°C for 30 min. It was isolated by Sephadex G-100 column chromatography. 3. At all temperatures the complex suspended in buffer was about twice as stable as it was in heat-inactivated serum. Stability decreased in the sequence of 4°C, 37°C and −20°C. Therefore all isolations of the complex were carried out at 4°C. 4. At 37°C the decay of enzyme activity of the complex was found to be biphasic first order. In serum the K d values were −0·045 min −1 and −0·0028 min −1 , and in buffer −0·023 min −1 and −0·0016 min −1 . 5. From column-chromatography experiments it was found that between 10 and 20% of the total creatine kinase-1 was involved in the complexing reaction after a 30-min incubation. 6. With this 10·20% proportion it can be calculated that the overall t 0·5 for the decay of total creatine kinase-1 activity must be in the range 95–201 min. This finding suggests, by comparison with other published data, that the enzyme—immunoglobulin complex is the main route of creatine kinase-1 catabolism in serum. 7. The difference between serum and buffer decay values for the complex is possibly due to the presence of cystine, urate and other substances in serum, which are additional potent creatine kinase inhibitors.

1. Serial venous blood samples were obtained from 45 patients with acute myocardial infarction. Ten of these patients were receiving β-adrenoreceptor-blocking drugs at the time of onset of chest pain and continued on these drugs during their stay in the coronary care unit. The activities of creatine kinase and its MB-isoenzyme (CK-MB) were assayed in the plasma. A lysosomal enzyme, β- N -acetylglucosaminidase, was also assayed. 2. In the 35 untreated patients it was found that creatine kinase activity was maximal at a mean time of 21.3 ± 1.3 h after the onset of chest pain, whereas in the patients receiving β-adrenoreceptor-blocking drugs peak activity of the enzyme occurred at 24.4 ± 0.7 h. 3. Peak CK-MB activity was also delayed from 18.1 ± 1.6 h in the control group to 22.4 ± 1.2 h in the treated patients. 4. The lysosomal enzyme showed a similar pattern of changes to that of CK-MB. Maximum activity in plasma occurred at 18.0 ± 1.0 h after the onset of chest pain in the control group of patients. In the treated patients peak lysosomal enzyme activity was not found until 24.2 ± 1.2 h. 5. These alterations in the time-course of plasma enzyme changes after acute myocardial infarction are consistent with the suggestion that β-receptor antagonists may delay tissue damage during myocardial ischaemia.

1. The dose of pentobarbitone required for anaesthesia was significantly greater for dystrophic hamsters than for normal animals. 2. Serum creatine kinase activity was significantly higher in dystrophic than in normal hamsters. 3. Brain, heart and tibialis anterior muscle from dystrophic animals contained significantly less creatine kinase than the normal tissues. 4. Creatine kinase in normal and dystrophic sera, as in skeletal muscles, consisted of MM isoenzyme. Heart creatine kinase consisted of both MM and MB types and brain contained only the BB isoenzyme. 5. Pentobarbitone raised serum creatine kinase activity of normal and dystrophic hamsters to the same extent, elevation of enzyme activity being dependent on the amount of pentobarbitone injected. 6. The sera of pentobarbitone-treated normal and dystrophic hamsters contained only the MM isoenzyme.