Mechanisms of gastrointestinal smooth muscle contraction have been a longstanding area of research interest. Our laboratory
has been particularly interested in the role of myosin light chain phosphorylation in the regulation of contraction. Those
studies have revealed two important findings: 1) Myosin phosphorylation is a key regulatory pathway in gastrointestinal smooth
muscle contraction, but steady-state crossbridge cycling rates cannot be predicted by myosin light chain phosphorylation alone.
This finding challenged the prevailing four-state kinetic model of smooth muscle contraction, and suggested that there must
be additional regulatory mechanisms involved in smooth muscle. 2) Length-dependent activation of gastrointestinal smooth muscle
is explained, at least in part, by length-dependent calcium activation and myosin light chain phosphorylation.
Gastrointestinal Motility Disorders
Canine Idiopathic Megaesophagus
Etiology - Most cases of adult-onset megaesophagus have no known etiology and are referred to as acquired idiopathic megaesophagus.
The syndrome occurs spontaneously in adult dogs between 7 to 15 years of age without sex or breed predilection. The disorder
has been compared erroneously to esophageal achalasia in humans. Achalasia is a failure of relaxation of the lower esophageal
sphincter and ineffective peristalsis of the esophageal body. A similar disorder has never been rigorously documented in the
dog. Several important differences between idiopathic megaesophagus in the dog and achalasia in humans have been documented.
Although the etiology(ies) has not been identified, some studies have suggested a defect in the afferent neural response to
esophageal distension similar to what has been reported in congenital megaesophagus.
Clinical Examination - Routine hematology, serum biochemistry, and urinalysis should be performed in all cases to investigate
possible secondary causes of megaesophagus (e.g. hypoadrenocorticism). Survey radiographs will be diagnostic for most cases
of megaesophagus. Contrast radiographs may be necessary in some cases to confirm the diagnosis, evaluate motility, and exclude
foreign bodies or obstruction as the cause of the megaesophagus. Endoscopy will confirm the diagnosis and may further reveal
esophagitis, a frequent finding in canine idiopathic megaesophagus. If acquired secondary megaesophagus is suspected, additional
diagnostic tests should be considered, for example: serology for nicotinic acetylcholine receptor antibody, ACTH stimulation,
serology for antinuclear antibody, serum creatine phosphokinase activity, electromyography and nerve conduction velocity,
and muscle and nerve biopsy. Additional medical investigation will be dependent upon the individual case presentation. Hypothyroidism
has been cited as an important cause of idiopathic megaesophagus in the dog, although risk factor analysis has not revealed
a clear association. Thyroid function testing (e.g., TSH assay, TSH stimulation, free and total thyroid hormones) should be
performed in individual suspicious cases.
Treatment - Animals with secondary acquired megaesophagus should be appropriately differentiated from other esophageal disorders
and treated. Dogs affected with myasthenia gravis should be treated with pyridostigmine (1.0-3.0 mg/kg PO BID) and/or corticosteroids
(prednisone 1.0-2.0 mg/kg PO or SQ BID), dogs affected with hypothyroidism should be treated with levothyroxine (22 µg/kg
PO BID), and dogs affected with polymyositis should be treated with prednisone (1.0-2.0 mg/kg PO BID). If secondary disease
can be excluded, therapy for the congenital or acquired idiopathic megaesophagus patient should be directed at nutritional
management and treatment of aspiration pneumonia. Affected animals should be fed a high-calorie diet, in small frequent feedings,
from an elevated or upright position to take advantage of gravity drainage through a non-peristaltic esophagus. Dietary consistency
should be formulated to produce the fewest clinical signs. Some animals handle liquid diets quite well, while others do better
with solid meals. Animals that cannot maintain adequate nutritional balance with oral intake should be fed by temporary or
permanent tube gastrostomy. Gastrostomy tubes can be placed surgically or percutaneously with endoscopic guidance. Smooth
muscle prokinetic (e.g., metoclopramide or cisapride) therapy has been advocated for stimulating esophageal peristalsis in
affected animals, however metoclopramide and cisapride will not likely have much of an effect on the striated muscle of the
canine esophageal body. Bethanechol has been shown to stimulate esophageal propagating contractions in some affected dogs
and is therefore a more appropriate prokinetic agent for the therapy of this disorder. Because of the high incidence of esophagitis
in canine idiopathic megaesophagus, affected animals should also be medicated with oral sucralfate suspensions (1 g q8h for
large dogs 0.5 g q 8h for smaller dogs 0.25 to 0.5 g q8h to q12h for cats).