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

IV. Specific Enzymes
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Serum CK-MB, presumably from myocardial injury,
has also been shown to increase in foals with sepsis, but
there is no difference between survivors and nonsurvivors,
thereby suggesting no prognostic value to CK isoenzyme
analysis ( Slack et al. , 2005 ). The mitochondrial form of
CK (MtCK) exists in two isoenzymes encoded by separate
genes ( Payne and Strauss, 1994 ). These have no apparent
diagnostic value at this time.
The half-life of CK activity in blood is relatively short
in all species. The half-life of CK from myocardial extracts
is 2 to 3 h in dogs ( Cairns and Klassen, 1977 ; Sobel et al. ,
1977 ). The mean half-lives for administered CK solution
made from skeletal muscle from dogs, sheep, horses, and
cattle are 2.61, 2.07, 2.05, and 8.67 h, respectively ( Aktas
et al. , 1995 ; Houpert et al. , 1995 ; Lefebvre et al. , 1994 ;
Volfinger et al. , 1994 ; see also Lefebvre et al. [1996] for
review). The half-life following intramuscular injection of
muscle homogenate in dogs was approximately 6.5 h with
the rate-limiting step being the absorption from the site of
injection into blood via lymphatics ( Aktas et al. , 1995 ).
This half-life may be more clinically relevant as it better
reflects the source of CK in blood following muscle injury.
The mechanism by which CK is cleared from blood is not
known, but it may involve inactivation of enzyme thiol
groups. CK activity is not lost via the kidneys, and creation
of a portocaval shunt with arrest of hepatic blood flow
had no effect on the clearance rate of CK activity in dogs
( Oostenbroek et al. , 1985 ).
Reference values for serum CK activity are highest in
dogs under 1 month of age and decline until 1 year of age
( Aktas et al. , 1994 ). The reference value is nearly two-fold
higher in small dogs compared to large dogs. However,
these differences are not likely to have significant impact
on the diagnostic value of CK activity.
In domestic species, CK activity is mainly used as a
marker of skeletal muscle injury associated with trauma,
nutritional myopathies, exercise-induced muscle injury, or
congenital myopathies. Increased CK activity in dog serum
is seen secondary to myocardial diseases such as dirofilariasis
and parvovirus infection, but it is unchanged in myocardial
hypertrophy ( Jacobs et al. , 1980 ; Kitagawa et al. , 1991 ).
Markedly increased serum CK activity has been reported in
congenital myopathies such as myotonia and X-linked myopathy
of golden retrievers ( Cooper et al. , 1988 ; Jones et al. ,
1977 ; Valentine et al. , 1988 ). Only modest to moderate
increases in serum CK activity were observed in acquired
myopathies of dogs such as malignant hyperthermia, hyperadrenocorticism,
hypothyroidism, and vitamin E-selenium
deficiency ( Green et al. , 1979 ; Kaelin et al. , 1986 ; O’Brien
et al. , 1990 ; Van Vleet, 1975). Serum CK can be expected
to increase following surgery. Serum CK activity is often
increased with neurological disorders but is usually due to
increased CK-MM rather than CK-BB ( Hoffmann, 1994 ).
Therefore, the increased serum CK activity is most likely a
result of involuntary skeletal muscle contractions. However,
an increase in CK-BB was observed in a Yorkshire terrier
with necrotizing encephalitis ( Sawashima et al. , 1996 ). The
sensitivity and specificity of serum CK activity for diagnosis
of skeletal muscle, myocardial, and neurological disease
has been assessed in dogs ( Aktas et al. , 1994 ). False-positive
results, causing a decrease in test specificity, were attributed
to the high concentration of CK in muscle, the large muscle
mass, and the release of enzyme for nonspecific reasons.
There were also several false negatives, thereby lowering the
sensitivity, which were attributed to the short half-life of the
CK activity in blood.
In cats, increased serum CK activity can be associated
with trauma, surgery, and intramuscular injections. There
has also been a reported increase (median CK activity of
2529 U/l) observed in anorectic cats ( Fascetti et al. , 1997 ),
suggesting that serum CK activity could serve as a marker
of nutritional status in cats. The increased CK activity with
anorexia in cats is thought to result from muscle catabolism
secondary to decreased caloric intake. Serum CK
activity decreases significantly within 48 h of nutritional
supplementation.
Serum CK activity is increased in horses in a variety of
conditions causing muscle injury. As early as 1967, and in
numerous reports since, increased serum CK activity has
been associated with paralytic myoglobinuria ( Cardinet et al. ,
1967 ). A markedly increased serum CK activity has been
observed in four horses with severe rhabdomyolysis associated
with Streptococcus equi infection (Sponseller et al. ,
2005 ). Increased serum CK activity has also been described
in horses with exertional rhabdomyolysis associated with
heritable polysaccharide storage myopathy ( Ribeiro et al. ,
2004 ). Cattle also have increases in serum CK activity with a
variety of muscle injuries and diseases. Increased serum CK
activity is common with selenium and vitamin E deficiency
( Arthur, 1988 ; Zust et al. , 1996 ). Large animal species also
frequently have increased serum CK activity because of prolonged
recumbency or pressure necrosis of muscle.
There are numerous reports of increases in serum CK
activity associated with intramuscular injection of drugs. A
noninvasive technique using area under the curve and total
plasma clearance of CK activity has been proposed for
determining postinjection muscle damage in dogs, horses,
sheep, and cattle ( Aktas et al. , 1995 ; Houpert et al. , 1995 ;
Lefebvre et al. , 1994 ; Toutain et al. , 1995 ; see Lefebvre
et al. [1996] for review). For example, the amount of
muscle tissue damaged following an IM injection of imidocarb
in a 10-kg beagle is 2.5g ( Aktas et al. , 1995 ). This
quantitative technique has potential use in evaluating local
tolerance of intramuscular administration of new drugs to
satisfy regulatory requirements.
There has been some interest in exercise-induced
increases of CK activity in horses and dogs. Increases have
been observed in sled dogs following long-distance races
and in horses in various training programs ( Harris et al. ,
1998 ; Hinchcliff et al. , 1993, 1998 ; Vnolfinger et al. , 1994).