The objective is to define the electrical, neural and hormonal controls of gastrointestinal motility in health and disease, and to develop new treatments for gastrointestinal motor disorders based on knowledge of these controls.
The specific aims are: 1) To determine whether retrograde pacing of the duodenum transposed to the distal ileum would slow gastrointestinal transit and improve absorption in dogs with ileostomy. 2) To determine whether pacing a loop of canine jejunum absorption. 3) To determine the frequency, direction of propagation, and velocity of propagation of the human duodenal pacesetter potentials, and whether the potentials can be entrined by electrical pacing. 4) To determine whether the human anorectum participates in the gastrointestinal interdigestive myoelectric complex in health and after ileal pouch-anal anastomosis, both during waking hours and during sleep, and to correlate the participation with the electroencephalographic sleep cycles, the need to defecate, and the degree of fecal continence. 5) To investigate the frequency, amplitude and rhythm of the small fluctuations in pressure that are superimposed on the resting tone of the human anal sphincter in health and after ileoanal anastomosis, and to determine whether changes after operation are secondary to injury of the internal anal sphincter, the external anal sphincter, or both. 6) To determine the mechanism of voluntary onset, pattern and direction of fecal flow, rate of flow, and efficiency of human fecal evacuation in health and after ileal puch anal anastomosis, and to correlate changes in defecatory patterns with intraluminal pressure and clinical result. 7) To assess whether distention of a canine ileal puch will release neurotensin and enteroglucagon, slow the rate of gastric emptying and intestinal transit and enhance intestinal absorption of liquids and solids after ileal pouch-anal anastomosis. Electrical activity will be measured using implanted wire electrodes, motility measured with open-tip catheters and strain gauges, and transit documented using radiolabelled foods and scintigraphy. The gastrointestinal tract will be paced using electrical stimuli. Operations will be performed and their motor effects assessed. This project could lead to new treatments or operations for gastrointestinal motor disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK018278-18
Application #
3483251
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-05-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
18
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Tu, B L; Kelly, K A (1999) Surgical treatment of Roux stasis syndrome. J Gastrointest Surg 3:613-7
Miedema, B W; Kohler, L; Smith, C D et al. (1998) Preoperative perfusion of bypassed ileum does not improve postoperative function. Dig Dis Sci 43:429-35
Morimoto, H; Kelly, K A (1997) Mechanisms of insulin-induced relaxation of the canine proximal stomach after proximal gastric vagotomy. J Gastrointest Surg 1:386-94
Cullen, J J; Kelly, K A (1996) Functional characteristics of canine pylorus in health, with pyloroplasty, and after pyloric reconstruction. Dig Dis Sci 41:711-9
Tu, B N; Kelly, K A (1995) Elimination of the Roux stasis syndrome using a new type of ""uncut Roux"" limb. Am J Surg 170:381-6
Cullen, J J; Eagon, J C; Hould, F S et al. (1995) Ectopic jejunal pacemakers after jejunal transection and their relationship to transit. Am J Physiol 268:G959-67
Cullen, J J; Eagon, J C; Kelly, K A (1994) Gastrointestinal peptide hormones during postoperative ileus. Effect of octreotide. Dig Dis Sci 39:1179-84
Cullen, J J; Kelly, K A (1994) Prospectively evaluating anal sphincter function after ileal pouch-anal canal anastomosis. Am J Surg 167:558-61
Hould, F S; Cullen, J J; Kelly, K A (1994) Influence of proximal gastric vagotomy on canine gastric motility and emptying. Surgery 116:83-9
Cullen, J J; Kelly, K A; Moir, C R et al. (1994) Surgical management of Meckel's diverticulum. An epidemiologic, population-based study. Ann Surg 220:564-8;discussion 568-9

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