Study of the effect of drugs on gastrointestinal motility
The motility function gastrointestinal tract (GIT) is associated with
- Forward propulsion of ingested food
- absorption of nutrients and
- expulsion of unabsorbed food material.
These functions are adequate, supported by cyclic motor activity occurring in almost all parts of the GIT which is due to migrating my electrical complex (MMC) through the electrical activity of the GIT. Any discrepancy in motility pattern can affect, the functionality of the GIT. A decrease in motility can lead to the stasis of food/chime in the intestine which favors the increases in the quantum of bacterial growth and cause constipation. Sometimes such a situation may cause a medical emergency when the barrier is breached, leading to bacterial translocation to other organs of the body. On the other hand, increased motility interferes with the digestion and absorption process and can lead to diarrhea and malabsorption syndrome. The clinically known conditions of motility disorders such as achalasia, gastric stasis, outlet obstruction, acute intestinal ileum, chronic intestinal pseudo-obstruction, megacolon, and, generalized disorders of motility deserve treatment with safer drugs. The evaluation of gastrointestinal (GI) motility is helpful in
- determining the therapeutic potential of new drugs in motility disorders,
- determining alteration in motility secondary to physiological or pharmacological 42 stimuli
- Evaluating the effect of pathological condition on GI transit.
In vivo methods in animals exhibit true effects of investigational drugs in biological milieu. Studies of motility of GI are associated with observation of marker in immediately excised sections of GIT or observation of motility in conscious animals using electrical gadgets. The following are the most popular in vivo methods to study GI motility in experimental animals.
- Assessment of intestinal transit
- Assessment of gastric motility
- Measurement of gastrointestinal transit
- Measurement of colon motility
- Long-term recording of intestinal mechanical and electrical activity.
- Assessment of GIT motility in dogs.
Assessment of gastric motility
The function of the stomach includes the initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. Various techniques have been developed to assess gastric motility causing gastric emptying (GE). The influence of drugs on gastric mechanical action on the bioavailability of novel compounds is of critical importance in drug development. Disturbed gastric my electric activity leading to gastro paresis can cause delayed GE, often found in patients with diabetes mellitus. Electro astrograph (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition 8 and aid in determining effective therapy
Animals: Medium sized rabbit drugs: Adrenaline/ Acetylcholine – 10ug/ml, Atropine Sulphate – 10ug/ ml, isoproterenol/ isopernaline 10ug/ml, Propranolol – 10mg/ml, Solutions: Tyrone solution
Apparatus used: Kymograph, Dissecting board, Dissecting instruments, scissors, petriplates, syringe, Frontal writing lever, water bath with temperature controlling unit, organ bath with aeration tube.
- The procedure adopted for the study is the modified fink leman method developed by walker and scott. Select a medium sized rabbit for the study.
- Fast the animal for 24 hours prior to experiment asfood in gut results in messy dissection and flushing or gut contents may damage the intestine.
- Before sacrificing the rabbit, prepare Thyroids Ringer solution and place about 250ml of this solution in an ice cold flask.
- Sacrifice the animal by cervical decapitation without use of anesthetic as it may affect the gut motility.
- Shave the abdomen of the animal and vacuum the surface to remove adhered fur.
- Make a midline incision through the skin and abdominal muscles.
- Locate ileum and a part of ileum was taken 10cm away from ileocaecal value.
- An optimal length of tissue (5-6cms) is cut carefully and tie the thread to ant mesenteric border on both sides and place them in Thyroid solution (extra pieces of ileum can be stored in ice cold Thyroid solution so that they are viable for hours.
- In ice cold solution the motility will ceases but after placing them in warm solution the tissue gets relaxed and shows motility within 5-10 minutes).
- Record the rhythmic activity of the ileum by using frontal writing lever and kymograph.
- Suspend the tissue in organ bath of Thyroid solution (100ml) at 37c with adequate oxygen supply (mixture of 95% O and 5% of Co).
- Tie one end of the thread of tissue of fixed point inside the organ bath and the other end to the lever for recording constructions on the kymograph.
- Stabilize the tissue in the solution to the conditions for about 30 minutes. Ensure the lever should be placed horizonontally and record the normal constructions followed by effects of drugs on muscles.
- After recording normal constructions inject the drugs one by one and observe for force of contraction and tone (normal, increased or decreased), frequency of constructions (per minute) before and after drug administration.
- Inject 0.1ml of drugs in the succession order in the organ bath and the responses are recorded. After nothing the effect of every drug, drain the muscle bath and refill with fresh warm thyroid solution (100ml). Take the control (without drug) reading before and after each drug response.
- Maintain washout period for 15-20 minutes for change of every drug and check the next drug response only the when the tone and amplitude returned to original value approximately.
- The drug and dose name should be mentioned in the recording after taking response of each drug.
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