Evaluation of EIC
Dogs with EIC are normal at rest. They usually are extremely fit and well-muscled. Cardiovascular and respiratory examinations
are unremarkable, with normal auscultation, electro-cardiograms, thoracic radiographs and cardiac ultrasound before exercise.
After exercise, during collapse, dogs are tachycardic and hyperthermic (often >42°C), but not different from unaffected dogs
exercised in the same manner.
The time it takes for dogs with EIC to return to their resting temperature after exercise is not different from normal dogs.
These dogs are not lame, and they do not have sore joints, muscles or bones before or after exercise. Nervous system examination
is normal at rest, but patellar reflexes are diminished or absent in collapsing dogs with EIC.
Routine blood analysis (CBC, biochemical profile) is normal at rest, and there are only minor changes following exercise when
compared with normal exercising Labradors. Arterial blood gas analysis in the EIC and the normal Labrador Retrievers revealed
significant respiratory alkalosis and metabolic acidemia post-exercise, reflecting hyperventilation and strenuous anaerobic
Similar results have been reported in Labrador Retrievers participating in field training and competition. Lactate and pyruvate
concentrations after exercise are similar in EIC dogs and normal dogs, and muscle biop-sies are normal, making an abnormality
of oxidative metabolism unlikely.
Dogs with EIC do not appear to have progressive disease. They do not develop systemic or neurologic disorders and, except
for their EIC, seem normal. Most affected dogs cannot continue to participate in trigger activities, but as long as intense
exercise, excitement, and training stress are avoided they can live normal lives as pets.
There are numerous anecdotal reports of dogs being able to resume trigger activities if they are managed with phenobarbital
(2 mg/kg PO BID). Treatment with phenobarbital and other sedative drugs simply may decrease the level of excitement or anxiety
associated with inducing an episode of collapse.
Many affected dogs will seem to improve, having fewer episodes of collapse as they age or when they are neutered.
Some affected dogs have died during an episode of collapse; these have not always been considered to be the most severely
Heredity of EIC
Littermates and other related dogs often are affected, making it apparent that EIC is hereditary. Pedigree analysis has established
the mode of inheritance to be autosomal recessive. This was confirmed once the probable causative mutation was identified
and a DNA test was used to verify EIC status.
Most dogs homozygous for the mutation are symptomatic, but a few are not. Collapse may not occur in dogs with EIC unless they
have the opportunity to participate in strenuous exercise with the necessary mix of enthusiasm and excitement.
EIC or heat stroke?
With heat stroke-induced collapse in dogs, recovery is very slow or prolonged, taking hours to days, or else there is progression
Laboratory evaluation reveals a dramatic increase in serum CK (usually seven to 11 times normal). Mentation changes that are
severe, progressive and persistent (lasting hours to days) occur in 80 percent of affected dogs, and significant endothelial
injury leads to microvascular thrombosis, DIC, thrombocytopenia and bleeding as well as acute renal failure in most dogs.
In contrast, dogs with EIC collapse without showing laboratory abnormalities, and they recover completely within five to 25
EIC or malignant hyperthermia?
Malignant hyperthermia (MH) in dogs as in other species is caused by a mutation in the calcium release channel of the sarcoplasmic
reticulum in skeletal muscle — the ryanodine receptor.
All of the affected EIC dogs evaluated were genotyped and tested for the known ryanodine receptor mutation and for linkage
to other sites on chromosome 1, eliminating this mutated gene as the cause of EIC.
Dogs with collapse due to MH typically look very different from those with EIC. Their muscles are rigid (not flaccid like
EIC), and they have increased serum CK.
Histopathologically, their muscles show rhabdomyolysis (EIC muscles are normal). Dogs with MH often hypo-ventilate from persistent
muscular contraction and are hypercarbic, while dogs with EIC hyperventilate.
EIC or mitochondrial myopathy?
Most dogs with mitochondrial myopathies have severe exercise intolerance that can be consistently demonstrated with even mild
They develop extreme lactic aci-demia with even mild exercise and an elevated lactate to pyruvate ratio.
Many have "ragged red fibers" demonstrated on histopathology, which really are just subsarcolemmal mitochondria as well as
ultrastructural changes to the mitochondria.
None of this is evident in dogs with EIC, and it has become apparent that dogs with EIC suffer more from neurologic dysfunction
than from muscular weakness.
Dr. Hoskins is owner of Docu-Tech Services. He is a diplomate of the American College of Veterinary Internal Medicine with
specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: firstname.lastname@example.org