Source: UNIV OF CALIFORNIA (VET-MED) submitted to NRP
INVESTIGATION OF GASTROINTESTINAL DYSFUNCTION IN THE HORSE
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0180055
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jul 1, 1996
Project End Date
Jun 30, 2005
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIV OF CALIFORNIA (VET-MED)
(N/A)
DAVIS,CA 95616
Performing Department
SURGICAL AND RADIOLOGICAL SCIENCES
Non Technical Summary
(N/A)
Animal Health Component
100%
Research Effort Categories
Basic
(N/A)
Applied
100%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113810106025%
3113810101025%
3113810116025%
3113810102025%
Goals / Objectives
Despite significant advances in the medical and surgical management of horses with gastrointestinal disease, colic remains the leading cause of death in horses. The primary focus of this research has been broadly divided into an investigation of the neuromuscular mechanisms that operate at the cellular level to control normal motility patterns, the effect of motility-promoting agents to stimulate contractions in quiescent intestine and to evaluate the effects of transient compromise to the blood supply on normal cellular processes. Another area of intense research in the equine industy involves studying methods to reduce the effects of toxins ont he body following a severe compromise to the tissue.
Project Methods
The Gastrointestinal Laboratory, in the School of Veterinary Medicine, is the site of the gastrointestinal research on equines. It is equipped to investigate isolated intestinal tissue using an in vitro mechanical testing tissue bath system and intracellular recording device. In addition immunostaining for cyclo-oxygenase receptors is used. Current research focuses includes the efects of endotoxemis on the intestinal tract.

Progress 07/01/96 to 06/30/05

Outputs
This study evaluated Tegaserod in normal horses to determine whether it increased intestinal movement in different regions of the bowel. The study consisted of an in vitro and in vivo part. For the in vitro study, segments of bowel from horses that had died were collected and suspended in special tissue baths under physiological conditions. Increasing concentrations of Tegaserod was added to the baths and the movement of the intestine before and after drug administration was recorded. For the in vivo study, Tegaserod was administered orally and intraveneously to clinically normal horses fasted overnight. An intravenous cathether was placed in the horse's jugular vein and blood and urine samples were obtained at different time points. The blood was processed to obtain the plasma and the concentration of Tegaserod was measure din serum. The data was then analyzed to determine appropriate doses and frequency of administration in horses.

Impacts
Tegaserod has demonstrated analgesic effects in humans, acting to decrease the perception of pain. This project is useful in the management of impaction colic or postoperative ileus in horses because most of the analgesics currently used in such cases have negative effects on gastrointestinal motility.

Publications

  • No publications reported this period


Progress 01/01/04 to 12/31/04

Outputs
Current research is being conducted in the following areas: 1. Effects of Prokinetic Agents on the Pyloric Antrum and Proximal Dudoenum in vitro, 2. Effects of Prostaglandins on Large Colon Motility, 3. Effects of Nitric Oxide on Ischemia and Reperfusion in Equine Jejunum and 4. Intracellular Recording and Pathophysiology in Equine Jejunum

Impacts
The large number of horses requiring euthanasia due to intestinal rupture further supports the need for continued study into the causes and prevention of gastrointestinal disorders.

Publications

  • No publications reported this period


Progress 01/01/03 to 12/31/03

Outputs
Current areas of investigation are: 1. Effects of Prokinetic Agents on the Pyloric Antrum and Proximal Dudoenum in vitro 2. Effects of Prostaglandins on Large Colon Motility 3. Effects of Nitric Oxide on Ischemia and Reperfusion in Equine Jejunum 4. Intracellular Recording and Pathophysiology in Equine Jejunum

Impacts
The large number of horses requiring euthanasia due to intestinal rupture further supports the need for continued study into the causes and prevention of gastrointestinal disorders.

Publications

  • No publications reported this period


Progress 01/01/02 to 12/31/02

Outputs
Description of the Problem: Enterolithiasis (the development of intestinal stones) is a significant cause of death and disease in horses. Study Objectives: Determine the effects of two diets and two different water supplies on intestinal pH and concentrations of magnesium, phosphorus, sulfur, sodium, calcium and potassium in the large intestine of horses. Experimental Approach: A group of 6 horses underwent surgical fistulation of the large intestine to provide daily access to colonic contents. Three had a history of enterolithiasis with subsequent surgical removal of enteroliths and three had no history of colic and no radiographic evidence of enterolith formation at the onset of the study. Each horse underwent four feeding trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered/softened water, and alfalfa hay with filtered/softened water. After a two-week accommodation period, researchers obtained samples of intestinal contents twice daily every five days for the remaining 15-day feed trial period. Researchers analyzed intestinal material for pH, dry matter, and concentrations of magnesium, phosphorus, sulfur, sodium, calcium, and potassium. Drinking water samples from untreated and filtered water were also analyzed for pH and mineral content. Accomplishments/Results: Identified that feeding alfalfa hay resulted in increased calcium, magnesium, and sulfur concentrations in the large intestine. Determined that horses with a history of enterolithiasis had significantly higher concentrations of calcium, magnesium and phosphorus and significantly higher pH in colonic contents than normal horses. Determined that sodium levels were significantly higher in colonic contents of horses drinking softened/filtered water. Identified that alfalfa was associated with a lower sodium and potassium content than grass hay. Alfalfa was also associated with higher dry matter concentrations, and horses with enterolithiasis tended to have lower dry matter concentrations. Determined that feeding alfalfa resulted in more alkaline (higher) pH values when compared with grass hay, and morning (one hour post-feeding) pH values were significantly higher than evening (five hours post-feeding) pH values. Determined that water filtration resulted in the elimination of calcium, magnesium, potassium, sulfate, and nitrates; a reduction in pH; a 90 percent reduction in bicarbonate; and an increased sodium and chloride content in drinking water

Impacts
This study demonstrated the beneficial effects of dietary modifications on the colonic environment, which supports the current recommendations of eliminating alfalfa-based feeds in high risk individuals. This study also helped researchers improve their understanding of the physiology behind why enteroliths form in some individuals and not in others. Horses with enterolithiasis have a unique intestinal environment characterized by increased alkalinity (higher pH) and elevated concentrations of select minerals. These findings will provide the framework for ongoing studies evaluating the molecular and genetic basis of this disease in horses. With information from this study, researchers will now be able to target the specific genes involved in pH regulation and ion transport in the equine intestinal tract to help determine the specific mechanisms contributing to enterolith formation.

Publications

  • No publications reported this period


Progress 01/01/01 to 12/31/01

Outputs
A group of 6 horses underwent surgical fistulation of the large intestine to provide daily access to colonic contents. Three had a history of enterolithiasis with subsequent surgical removal of enteroliths and three had no history of colic and no radiographic evidence of enterolith formation at the onset of the study. Each horse underwent four feeding trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered/softened water, and alfalfa hay with filtered/softened water. After a two-week accommodation period, researchers obtained samples of intestinal contents twice daily every five days for the remaining 15-day feed trial period. Researchers analyzed intestinal material for pH, dry matter, and concentrations of magnesium, phosphorus, sulfur, sodium, calcium, and potassium. Drinking water samples from untreated and filtered water were also analyzed for pH and mineral content.

Impacts
This study demonstrated the beneficial effects of dietary modifications on the colonic environment, which supports the current recommendations of eliminating alfalfa-based feeds in high risk individuals. This study also helped researchers improve their understanding of the physiology behind why enteroliths form in some individuals and not in others. Horses with enterolithiasis have a unique intestinal environment characterized by increased alkalinity (higher pH) and elevated concentrations of select minerals. These findings will provide the framework for ongoing studies evaluating the molecular and genetic basis of this disease in horses. With information from this study, researchers will now be able to target the specific genes involved in pH regulation and ion transport in the equine intestinal tract to help determine the specific mechanisms contributing to enterolith formation.

Publications

  • No publications reported this period


Progress 01/01/00 to 12/31/00

Outputs
Luminal distention is one of the most important factors associated with postoperative ileus after colic surgery in horses. Although distention is always observed after small intestinal obstructions, no experimental studies have described the changes in motility caused by luminal distention in the horse. Several drugs increase intestinal motility in humans, but there is little evidence to support their use in the horse. Current studies assessed if cisapride, erythromycin, lidocaine and metoclopramide alter the contractile activity of the normal jejunum smooth muscle. Researchers looked at the response of smooth muscle to different doses of their drugs; compared the response of the stomach and proximal small intestine to the middle portion of the small intestine and determined which drug has a better effect on tissue subjected to experimental distention and decompression.

Impacts
Information from this study will help decrease postoperative complications and, in some cases, avoid the need for a second surgery that adds financial and emotional distress to the owner. Ultimately, this information will be used to improve the survival of horses after colic surgery.

Publications

  • No publications reported this period


Progress 01/01/99 to 12/31/99

Outputs
The project studied the effects of two diets and two different water supplies on intestinal pH and concentrations of magnesium, phosphorus, sulfur sodium, calcium and potassium in the large intestine of horses. A group of horses each underwent a four-week duration of feed trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered water and alfalfa hay with filtered water. After a two-week accommodation period, samples of intestinal contents will be obtained three times daily every fifth day for the remaining 15-day feed trial period. Intestinal material will be analyzed for pH and concentrations of magnesium, phosphorus, sulfur, sodium, calcium and potassium. Water samples will be analyzed weekly for pH and mineral content.

Impacts
This study will allow researchers to understand the effects of diet on intestinal pH and mineral balance in relation to the development of enteroliths. With this information, researchers can develop more effective preventive measures.

Publications

  • No publications reported this period