Cimetidine and neonatal small bowel adaptation: an experimental study.
Histamine2-blockers are being used more extensively in the pediatric short gut patient as an agent to accelerate small bowel adaptation. Reversal of lipid malabsorption and a direct trophic effect on the intestinal crypt cells have been postulated as the mechanism for the salutary influence of cimetidine. Weanling Sprague-Dawley rats underwent 85% small bowel resection. Controls had repair of a simple ileal transection. Rats received either a fat-defined rat chow only, or chow with high- or low-dose cimetidine, 2% cholestyramine, or cholestyramine/low-dose cimetidine. All animals were killed 2 weeks postresection, and ileal and jejunal sections were examined for changes in villous and crypt morphology. The animals receiving cimetidine showed earlier and more consistent weight gain than resected animals who received no adjunctive treatment. High- and low-dose regimens were equally efficacious. Cimetidine administered alone decreased fecal fat losses, but not when given with cholestyramine. The cimetidine/cholestyramine group showed increased weight gain when referenced to the resection controls despite continuing lipid malabsorption. Villous and crypt lengthening did not correlate with clinical evidence of adaptation. An augmented lymphocytic activity (plasma cell hyperplasia, enlargement Peyer's patches) was present in the hyperplastic ileal segments of the cimetidine-treated rats. Overall immunoreactivity was similar in all study groups. No significant differences in villous morphology or immunologic activity were seen in jejunal segments. The effects of H2-blockers on lipid absorption and intestinal hyperplasia are inadequate to explain the benefits of cimetidine in the short gut patient. Examination of the immunology of the short bowel complex merits further attention in elucidating cimetidine's action in this setting.
D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D007082:Ileum / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology / Q000601:surgery; D007583:Jejunum / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D008286:Malabsorption Syndromes / Q000188:drug therapy*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration; D012778:Short Bowel Syndrome / Q000188:drug therapy*
D002927:Cimetidine