Plasma CPK Activity Research Articles

Mialgias: Approaches to differential diagnosis, treatment

Differential diagnosis in muscle pains often presents great difficulties so all existing signs of the disease should be carefully considered to make its diagnosis and to prescribe adequate therapy. The paper considers the causes of muscle pains, laboratory and instrumental studies (immunological tests, determination of the level of specific muscular enzymes, primarily creatine phosphokinase – CPK, etc.), and the main reasons for enhanced plasma CPK activity. It also describes acute and chronic mialgias associated with enhanced plasma CPK activity, as well as diseases in which mialgias are related to the normal level of CPK, myofascial syndrome (MFS) and fibromyalgia (FM) in particular. The characteristic features of MFS are given in its diagnostic criteria. It is stated that a differential diagnosis should be made between MFS and major muscle pain-associated abnormalities, such as polymyalgia rheumatica, FM, etc. Diagnostic criteria for polymyalgia rheumatica are given. A MFS treatment algorithm is presented. Local exposure methods applied to altered musculoligamentous structures in combination with myorelaxants and non-steroidal anti-inflammatory drugs assume paramount importance in MFS.

Eicosapentaenoic acid attenuates statin-induced ER stress and toxicity in myoblast

We previously reported that eicosapentaenoic acid (EPA) improved statin-induced rhabdomyolysis in rats (Naba et al. [6]). In this study, we report for the first time direct improvement by EPA of statin-induced toxicity in cultured myoblasts and the mechanistic involvement of endoplasmic reticulum (ER) stress. Differentiated rhabdomyosarcoma cells (RD cells) were treated with statins and EPA for 1–4days. Statins induced various toxic changes in RD cells, and EPA attenuated all of these changes. Interestingly, statins increased mRNA expression of ER stress markers (XBP-1 and CHOP) and EPA attenuated both. Further, in a statin-induced rat model of rhabdomyolysis, these markers in skeletal muscle were significantly correlated with plasma CPK activity. In RD cells, statins also increased p-c-Jun protein content and caspase-3/7 activity, while 4-PBA, an ER stress attenuator, PPAR-δ agonist, and EPA attenuated them. These findings suggest that EPA attenuates statin-induced ER stress, JNK activation and toxicity in cultured myoblast cells, and that PPAR-δ may mechanically involved in the effects of EPA.

Catechins attenuate eccentric exercise-induced inflammation and loss of force production in muscle in senescence-accelerated mice

Catechins have a great variety of biological actions. We evaluated the potential benefits of catechin ingestion on muscle contractile properties, oxidative stress, and inflammation following downhill running, which is a typical eccentric exercise, in senescence-accelerated prone mice (SAMP). Downhill running (13 m/min for 60 min; 16° decline) induced a greater decrease in the contractile force of soleus muscle and in Ca(2+)-ATPase activity in SAMP1 compared with the senescence-resistant mice (SAMR1). Moreover, compared with SAMR1, SAMP1 showed greater downhill running-induced increases in plasma CPK and LDH activity, malondialdehyde, and carbonylated protein as markers of oxidative stress; and in protein and mRNA expression levels of the inflammatory mediators such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in muscle. SAMP1 exhibited aging-associated vulnerability to oxidative stress and inflammation in muscle induced by downhill running. Long-term (8 wk) catechin ingestion significantly attenuated the downhill running-induced decrease in muscle force and the increased inflammatory mediators in both plasma and gastrocnemius muscle. Furthermore, catechins significantly inhibited the increase in oxidative stress markers immediately after downhill running, accompanied by an increase in glutathione reductase activity. These findings suggest that long-term catechin ingestion attenuates the aging-associated loss of force production, oxidative stress, and inflammation in muscle after exercise.

Oligotide, a new single-stranded oligodeoxyribonucleotide, preserves postsynaptic β-adrenergic and cholinergic receptor functions in rabbit hearts after acute infarction

Acute myocardial infarction was induced in New Zealand male albino rabbits. 3 days after surgery, the mortality rate and plasma CPK activity were reduced by 64% and 66% respectively by intravenous infusion of Oligotide (32 mg/kg/h for 6h), a single-stranded oligodeoxyribonucleotide of mammalian origin. Perfused hearts, obtained from Oligotide-treated rabbits 3 days after surgery, showed a strength of contraction in the range of that of hearts of sham-operated animals and an ameliorated postsynaptic β-adrenergic and cholinergic receptor function. In addition, in these hearts, “ex vivo” treatment with Oligotide resulted in almost complete preservation of both adrenergic and cholinergic responses to their specific agonists. These data suggest that Oligotide by protecting the hearts from the ischemic damage and possibly by restricting left ventricular tissue necrosis may have normalized the biological responses of this organ to isoproterenol and preserved the integrity of coronary endothelial-dependent relaxant function.

Selenium and glutathione peroxidase in blood of lambs born to ewes injected with barium selenate

In the previous paper (Zachara et al., 1992), we have shown that Deposel (barium selenate) injected to ewes before the breeding season was effective in raising the selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in blood components of ewes, and in maintaining them at adequate levels during pregnancy and lactation. Lambs born from these ewes were weighed after birth and a month later. After 2 and 6 weeks blood samples from lambs were taken for Se, GSH-Px and creatine kinase (CPK) measurements. A month after lambing, wool was also collected for Se analysis. The birth weight and weight gain during the first month of life were identical in both flocks and equal to 4.4 kg and 221 g/day, respectively. Whole blood and plasma Se concentrations in the lambs of the experimental flock were 164 and 43.8 ng/ml, respectively, 2 weeks after lambing, and 137 and 39 ng/ml, respectively, at 6 weeks. Whole blood and plasma Se concentrations in the lambs of the untreated flock were highly deficient and significantly lower, being 28.0 and 10.0 ng/ml, respectively ( P<0.0001). Significant differences ( P<0.0001) in red cell and plasma GSH-Px activities were also noted between the two flocks studied. They were 375 vs. 59 U/g Hb in red cells and 427 vs. 61 U/l plasma 2 weeks after lambing, and 264 vs. 39 U/g Hb in red cells and 337 vs. 59 U/l plasma in week 6 of life. Plasma CPK activity was significantly higher in the untreated flock compared to Deposel-treated (1000 vs. 163 U/l, respectively, P<0.0001). Significantly higher Se concentration in wool was found in the Deposel-treated group (0.267 vs. 0.108 μg/g; P<0.0001). The results show that barium selenate injected to ewes during breeding season elevates the Se level in milk during lactation and increases the Se concentration and GSH-Px activity in blood components of lambs in the period when they are at the greatest risk from Se-deficiency disorders.

Delayed-onset muscular soreness and plasma CPK and LDH activities after downhill running

We tested the hypothesis that running down an incline, during which muscles primarily perform eccentric contractions, causes greater delayed-onset muscle soreness and greater increases in plasma enzyme activities than does running on the level, during which muscles perform similar amounts of concentric and eccentric contractions. Subjective sensations of muscular soreness and plasma activities of CPK and LDH were assessed in seven subjects at 0, 24, 48, and 72 h after 45 min of running (one time on the level and a second time down a 10% incline). Following downhill running (57% of VO2max), significant delayed-onset soreness was experienced in gluteal, quadricep, anterior leg, and posterior leg muscles, and plasma CPK (but not LDH) activity was significantly increased (351% at 24 h). In contrast, following level running (78% of VO2max), no statistically significant soreness occurred in any muscle group, and plasma CPK and LDH activities were not elevated. Thus, our results generally support the hypothesis. Secondarily, we investigated whether delayed-onset soreness with downhill running is accompanied by increases in peripheral white blood cell counts suggestive of inflammation. No such association was observed. We suggest that both delayed-onset muscular soreness and plasma enzyme activities are affected by structural changes in muscle tissue resulting from eccentric contractions.

Retention of sarcoplasmic calcium inhibits development of the phencyclidine-restraint experimental myopathy

The myopathy induced in the rat by the central nervous system stimulant, phencyclidine (PCP), and restraint is characterized by extensive myofibrillar sarcomere disruption in hind limb muscles and massive increases in plasma creatine kinase (CPK) activity. The effects of dantrolene sodium on this myopathy were studied to determine if modulation of calcium release from the sarcoplasmic reticulum could alter the development of the myopathy. Dantrolene prevented both the sarcomere disruption and the increase in plasma CPK activity produced in the PCP-restraint model. The inhibitory effect was not due to a decrease in the locomotor activity produced by PCP. The findings are consistent with a role for excess sarcoplasmic calcium, originating from the sarcoplasmic reticulum, in the development of this myopathy.

Mechanism of the beneficial effect of dexamethasone on myocardial cell integrity in acure myocardial ischemia.

Dexamethasone (6 mg/kg) given intravenously to anesthetized cats exerted no significant hemodynamic effect on control open-chest cats or in cats subjected to acute myocardial ischemia by coronary artery ligature. However, dexamethasone normalized elevated S-T segments toward preischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CK activity within ischemic myocardial tissue five hours after the onset of ischemia. Dexamethasone also reduced the extent of ischemic damage as assessed by a nitro-blue tetrazolium staining technique, providing anatomic verification of the reduced ischemic damage. Moreover, dexamethasone prvented the swelling and vacuolization of myocardial lysosomes in the ischemic region, indicating a stabilization of lysosomal membranes within the heart. These data indicate that lysosomal disruption is an important consequence of myocardial ischemia and that early treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.

Hepatic blood flow in acute myocardial ischemia.

Hepatic blood flow was monitored in cats during myocardial ischemia (MI). Increased plasma CPK activity, the S-T segment of the electrocardiogram, and hepatic flow was reduced by 5 h to 40% of control. The results suggest that MI can influence organs distant from the original ischemic episode.

The Effect of Reducing Plasma Calcium Levels on Some Plasma Enzyme Levels in Cows and Sheep

Elevations of plasma AAT, CPK and LDH occurred in cows in which hypocalcaemia was induced by the infusion of 4.7% Na 2 EDTA. Levels of α HBDH during the same period did not differ significantly from those obtained during a control infusion of 0.9% saline in the same cows over a similar period of time, suggesting that the elevation in LDH levels was due to elevations of the isoenzymes other than LDH-1 and LDH-2. It was concluded that the elevations in AAT, CPK and LDH were due to release from skeletal muscle tissue and that the effects of recumbency may have contributed to them. In six wethers elevation of plasma CPK activity, which was not due to the effects of recumbency, occurred in hypocalcaemia induced by the infusion of 4.7% Na 2 EDTA solution.

The Sequence of Myodegeneration in Nutritional Myopathy of the Older Calf

SUMMARY Calves between 6 and 16 months of age were housed for at least four months and then turned out to pasture. Raised plasma CPK activity suggested acute myodegeneration and this was confirmed by histological examination of a biopsy of the proximal part of the biceps femoris muscle. Two apparently distinct myodegenerative episodes are described.

Increased plasma creatine kinase activity in rabbits: effect of systematically repeated blood sampling.

Various physical, chemical and biological factors are involved in an increased plasma creatine kinase activity. Repeated blood sampling induced in all rabbits studied a reaction of similar pattern but of different intensity, expressed by a maximum of plasma CPK activity. The physiological origins of this variation of CPK activity seems to be, as seen in control animals, the consequence of emotional stress due to handling and possibly an additional stress due to the venepunctures.

Effects of dexamethasone on myocardial cells in the early phase of acute myocardial infarction

Dexamethasone exerted no significant hemodynamic effect in sham-operated cats or in cats subjected to acute myocardial ischemia. However, the glucocorticoid did normalize elevated S-T-segments toward pre-ischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CPK activity and restricted the loss of lysosomal hydrolase within ischemic myocardial tissue. These data indicate that lysosomal disruption is an early consequence of myocardial ischemia and that treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CPK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.

Plasma creatine phosphokinase activity in the cold-exposed and cold-acclimated chicken.

SummaryChickens cold exposed to 2-3° had significantly elevated levels of plasma CPK compared with controls. After an initial increase during the first week, no significant difference was seen in plasma CPK activity of chickens cold acclimated at either 8-11 or 4-7° for 2-4 weeks when compared with controls. It is concluded that muscle activity (shivering thermogenesis) in cold-exposed chickens resulted in elevated plasma CPK, while the absence of muscle involvement (nonshivering thermogenesis) in cold-acclimated chickens resulted in no alterations in plasma CPK activity.

Plasma creatine phosphokinase study in thyroidectomized rabbits and effect of thyroxine and analogues

Thyroidectomy was followed in eleven of fourteen surviving rabbits by an increase in plasma creatine phosphokinase activity, followed after some time by a spontaneous decrease. Normal CPK activity in control rabbits was 0.2–1.7 mU/ml (determination without addition of glutathione) and 2.5–11.2 mU/ml (with addition of glutathione). CPK activity in thyroidectomized rabbits was 0.4–31.6 mU/ml (determination without addition of glutathione) and 3.8–140 mU/ml (with addition of glutathione) but was in at least at one time higher than 20 mU/ml in eleven of fourteen animals. This increased plasma CPK activity can be rapidly normalized by subcutaneously injected 3:5:3′-triiodo- l-thyronine 3:5:3′: 5′-tetraiodo- l-thyronine (= l-thyroxine) and by the thyroxine analogue 3:5:3′:5′-tetraiodothyropropionic acid (= desaminothyroxine) but 3:5:3′-triiodo- d-thyronine is much less effective than its l-form.