In the dog, creatine kinase (CK) is mostly present in the skeletal muscles, myocardium, brain and intestine. The MM isoenzyme predominates in muscles and myocardium. In plasma, reference values depend on the technique used and CK-MB accounts for about 30-45% of total CK activity. Sex has no influence on plasma CK activity, which is higher in young dogs than in adults. Plasma CK is elevated after physical exercise. After its release from the cells, CK reaches the plasma mostly via the lymphatic route and then remains in the plasma compartment. It is rapidly cleared with a half-life of about 2 hours. Muscle diseases are the main source of plasma CK elevations: inherited myopathies, malignant hyperthermia, hypothyroidism, vitamin E-selenium deficiency, prolonged decubitus, intramuscular injections, surgery, etc. Plasma CK is also increased in experimental myocardial infarction, for which the dog is an interesting model, allowing quantification of the damage by measuring the total CK activity released.
To quantify the extent of muscle alteration during prolonged exercise, the release rate of creatine kinase (CK) from striated muscle was measured in six horses during a rest period (6 h) and during three exercise tests (15, 30, and 60 km) at a constant speed of 200 m/min. CK clearance was measured after intravenous bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1 x min-1. After an intramuscular CK administration, the CK systemic availability was 74.1 +/- 21.2% and the half time of absorption was 9.4 +/- 5.7 h, indicating a slow process for CK transit through the lymphatic system. The CK release rate was only significantly increased during the 60-km exercise test. The increase of CK plasma activity was observed after a delay of approximately 5 h and peaked after the end of the race; the estimated CK release rate was 9.92 +/- 2.62 U.kg-1 x h-1 over a mean duration period of 65.8 +/- 15.8 h. With the CK activity of horse striated muscle taken into account, a 60-km race released a quantity of CK corresponding to an equivalent of 18.8 +/- 4.3 g striated muscle. It is concluded that the equivalent amount of damaged muscle may be considered as negligible for a 60-km test and that only very high plasma CK activity levels (at least higher than 10,000 U/l) may provide some evidence of a myolysis.
Specific reference intervals for biochemical analytes in the Dogue de Bordeaux were determined under controlled pre-analytical and analytical conditions, and according to international recommendations. The use of these breed-specific reference intervals is recommended when using the specified analytic instruments, especially for the 6 analytes for which the reference intervals differed considerably from those provided by manufacturers.
The fate of skeletal muscle-derived creatine kinase (CK) was investigated in six dogs. After i.m. and i.v. injections of 3000 g and 105,000 g supernatants of dog muscle homogenates, plasma CK activity was measured up to 48 h. There was no significant difference in pharmacokinetic parameters dependent on the type of supernatant injected. After i.v. injection, the volume of distribution of CK was equal to the plasma volume, CK clearance was relatively low (about 0.5 mL/kg/min) and its terminal half-life of elimination was about 2.5 h. After i.m. injection, the CK terminal half-life was about 6.5 h, demonstrating a flip-flop mechanism, i.e. a limiting absorption process from the site of injection. Bioavailability after i.m. injection was about 65%, and the rate of absorption from muscle injection site was relatively slow: peak activity occurred at the second hour post administration, and most CK activity had been absorbed by 24 h. These pharmacokinetic parameters can be used as a basis for a minimally invasive means of quantitating muscle damage either after intramuscular drug administration or in canine sports medicine.
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