Abstracts
1997 Digestive Disease Week

Loss of nitric oxide neurons in patients with Chagas' disease is greater in the megacolon than the clinically uninvolved small bowel.

U Ribeiro Jr., AV Safatle-Ribeiro, A Habr-Gama, JJ Gama-Rodrigues, LF Mileo, J Sohn, JC Reynolds. Departments of Gastroenterology and Surgery, University of Pittsburgh, PA/University of Sao Paulo, Brazil.

The pathophysiology of Chagas' disease is incompletely understood. Nitric oxide (NO), the leading candidate for non-adrenergic and non-cholinergic inhibition in the bowel, is a likely target for injury. The mechanisms for damage at these sites are not known. Neuronal nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase can be used as a marker for neuronal NO synthase. Aim: To evaluate the relative level of NO depletion in the colon and small bowel of patients with severe megacolon requiring surgery. Methods: Specimens from resected rectum and clinically uninvolved small bowel biopsies of 11 Chagasic patients were compared to 10 controls with colon cancer. Tissues were fixed in Zamboni' solution and evaluated by immunohistochemistry for NADPH diaphorase-containing neurons. Immunoreactivity was evaluated on a 0 to 4 scale in the longitudinal muscle (LM), myenteric plexus (MP), circular muscle (CM), submucosal plexus (SMP), and mucosa (M). Results: Control cases showed intensely stained myenteric and submucosal neurons, and a rich network of terminal nerve fibers in the muscle layers. Chagasic specimens had decreased NADPH diaphorase-containing neurons in all layers of the colon. Clinically uninvolved small bowel biopsies also showed decreased immunoreactivity compared to controls, but to a lesser degree (Table)

                          LM        MP       CM       SMP      M
 MEGACOLON               1.5       1.9      1.5      1.5      1.5
 CONTROLS                3.1       3.9      3.7      3.3      3.7
 p VALUE                 0.04      0.02     0.01     0.03     0.03
 SMALL BOWEL             2.0       2.6      2.1
 CONTROLS                3.7       3.7      3.7
 p VALUE                 0.11      0.16     0.18

Conclusions: 1. Nitric oxide depletion, indicated by decreased NADPH diaphorase activity, appears to play a role in the Chagas' disease. 2. The damage is widespread, but predominates in the clinically involved organ.