Gastrointestinal Motility

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

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).