EFFECT OF CHAGAS-DISEASE ON NITRIC OXIDE-CONTAINING NEURONS IN SEVERELY AFFECTED AND UNAFFECTED INTESTINE

PURPOSE: The pathophysiology of Chagas' disease is incompletely unders tood. Neuronal nitric oxide has been cited as a candidate neurotransmi tter responsible for relaxation of the internal anal sphincter. Neuron al nicotinamide adenine dinucleotide phosphate diaphorase can be used as a marker for neuronal nitric oxide synthase. This study was designe d to examine the alterations of the nitric oxide-containing neurons in the enteric nervous system of the colon of patients who underwent res ections for advanced megacolon and to compare these specimens with sma ll-bowel el specimens from the same patients and with specimens from c ontrol subjects. METHODS: Specimens from resected rectum and extramuco sal small-bowel biopsy specimens from 11 patients with Chagas megacolo n but no apparent small-bowel clinical involvement were compared with the uninvolved colon and jejunum of 10 control patients with colon can cer. Tissues were fixed in Zamboni solution and evaluated by histochem istry for nicotinamide adenine dinucleotide phosphate diaphorase-conta ining neurons. Reactivity was evaluated on a 0 to 4 scale in the longi tudinal muscle, myenteric plexus, circular muscle, submucosal plexus, and mucosa. RESULTS: Specimens from control patients showed well-stain ed myenteric and submucosal neurons and an abundant network of termina l nerve fibers in the muscle layers. Chagasic specimens had decreased staining in all layers of the gut. Overall there was a statistically s ignificant decrease in nicotinamide adenine dinucleotide phosphate dia phorase-containing neurons. Biopsy specimens from clinically uninvolve d small bowel of patients with Chagas' disease also showed decreased r eactivity, but to a lesser degree. CONCLUSIONS: Nicotinamide adenine d inucleotide phosphate diaphorase activity is decreased in patients wit h advanced megacolon. The alterations are more relevant in the myenter ic plexus and the circular muscle. Reactivity is also diminished in th e clinically uninvolved small bowel, but to a lesser extent.