Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 15 Skeletal Muscle Function
the properties of the injected solution and on such muscle
factors as species differences in muscle CK activity, local
blood flow, susceptibility of the muscles, and local muscle
binding of the drug ( Steiness et al. , 1978 ). Therefore, an
accurate history is important in evaluating CK activities. A
three- to five-fold increase in serum CK from normal values
is believed to represent necrosis of approximately 20 g of
muscle tissue ( Volfinger et al. , 1994 ).
There are three principal isoenzymic forms of CK.
Creatine kinase has a dimeric structure consisting of
M (muscle) subunits and B (brain) subunits, which combine
to form the three heterogeneous MM (or CK3), MB (or
CK2), and BB (or CK1) isoenzymes ( Dawson et al. , 1968 ;
Dawson and Fine, 1967 ). A fourth variant form, CK-Mt,
is found in mitochondrial membranes and may account for
up to 15% of the total cardiac CK activity. The isoenzymes
can be separated by three methods: (1) electrophoresis, (2)
immunological techniques, and (3) ion-exchange chromatography
( Fiolet et al. , 1977 ). The pattern of isoenzyme
distribution varies among the organs of different species.
Thus, identification of the isoenzymes present can be used
to help determine the tissue source of elevations in CK
( Bulcke and Sherwin, 1969 ). Ontogenic studies in the rat
revealed that all organs investigated contained only BB-CK
in early stages of fetal development. In skeletal muscle,
BB-CK forms slowly disappear and are initially replaced
by MB-CK forms followed by CK-MM forms. Mixtures of
isoenzymes occur during the transition. In the adult pattern,
MB-CK forms have been variously reported to be present
or absent in skeletal muscle. The inconsistency in noting
the presence of MB-CK forms in skeletal muscle of animals
may be due to the source of skeletal muscle sampled,
because all skeletal muscles may not contain the MB-CK
isoenzyme ( Bulcke and Sherwin, 1969 ; Thorstensson et al. ,
1976 ). However, other studies indicate that, although there
is more MM-CK in white muscle of the rat than in red, there
is no MB-CK fraction in either ( Dawson and Fine, 1967 ).
Reasons for the discrepancies in the detection of MB-CK
forms in mammalian skeletal muscles are not evident. The
adult isoenzyme pattern in muscles of the rat appears at
90 days after birth, whereas in cardiac muscle, the shift
occurs earlier and the adult pattern has both MB-CK
and MM-CK forms. In the brain, BB-CK is the major
isoenzyme throughout life ( Eppenberger et al. , 1964 ).
Determinations of serum isoenzyme patterns have found
clinical application in human medicine. The determination
of MB forms has been used as a biochemical diagnostic
tool for acute myocardial infarction ( Hamdan et al. , 2006 ).
However, studies of the isoenzyme composition in cardiac
muscle of the horse reveal that less than 1.5% to 3.9% of
the total CK activity is attributable to the MB-CK form.
Hence, its determination cannot be used for detection of
myocardial disorders in the horse ( Argiroudis et al. , 1982 ).
Elevations in total CK activities have been reported in
a wide variety of species with muscle disorders typified
FIGURE 15-8 The difference in the time course of elevations in AST
and CK activities as a result of muscle necrosis (equine exertional rhabdomyolysis).
The AST activity remained elevated for much longer periods
than CK activity. Adapted from Cardinet et al. 1967 ).
by myofibers necrosis. Pre- and 4 h postexercise CK determinations
have been useful when combined with exercise
testing to identify patients with exertional rhabdomyolysis
( Valberg et al. , 1999 ). Peak serum CK activity occurs
about 4 to 6 h after muscle damage and declines fairly rapidly
with a half-life in serum of approximately 108 min in
horses ( Fig. 15-8 ) ( Cardinet et al. , 1967 ; Valberg et al. ,
1993a ). CK activity in itself, however, does not provide
information relative to the etiology of the disease process.
More precise information regarding the etiology of muscle
diseases can be obtained by the use of histological and histochemical
examination of muscle biopsies.
2 . Aspartate Transaminase
Another enzyme that has been used as a diagnostic aid in
neuromuscular disorders of domestic animals is serum
aspartate transaminase (AST), formerly called serum glutamic
oxaloacetic transaminase (SGOT). Normal values
do not appear to differ greatly between sexes, although
reported values for cows are somewhat higher than values
for bulls ( Cornelius et al. , 1959 ; Roussel and Stallcup,
1966 ). Differences associated with age have been reported
in sheep ( Lagace et al. , 1961 ), and there are seasonal differences
in bulls ( Lagace et al. , 1961 ; Roussel and Stallcup,
1966 ). Also, physical activity is associated with higher values
in horses ( Blackmore and Elton, 1975 ; Cardinet et al. ,
1963, 1967 ; Cornelius et al. , 1963 ).
Elevations of AST activities have been reported in
numerous muscle disorders characterized by myofiber
necrosis. Although the use of AST determinations has
proven valuable as a diagnostic aid, the enzyme lacks organ
specificity because in addition to high concentrations in
skeletal and cardiac muscle, AST activities are also high in
the liver as well as other organs and tissues, including the
red blood cells (RBCs) ( Cardinet et al. , 1967 ; Cornelius
et al. , 1959 ; Loeb et al. , 1966 ).