key: cord-0010083-yefp0zph
authors: Navarre, Christine B.; Roussel, Allen J.
title: Gastrointestinal Motility and Disease in Large Animals
date: 2008-06-28
journal: J Vet Intern Med
DOI: 10.1111/j.1939-1676.1996.tb02027.x
sha: 788e747fe0ca5600c85007427751135a914b3f31
doc_id: 10083
cord_uid: yefp0zph

An understanding of the relationship between gastrointestinal (GI) motility and disease is imperative for the proper treatment of large animal patients, especially as new therapeutic agents become available. However, the abundance of information that has become available in the last 2 decades makes gaining this understanding a formidable task. This article summarizes the changes in GI motility caused by some common diseases and conditions encountered in large animal practice, such as GI obstruction, postoperative ileus, resection and anastomosis, diarrhea, endotoxemia, GI parasitism, hypocalcemia, and pregnancy. J Vet Intern Med 1996;10:51–59. Copyright © 1996 by the American College of Veterinary Internal Medicine.

Manuscripts will be considered for publication with the clear understanding that their contents have not been previously published (abstracts presented at scientific meetings are excepted), and have not been (and will not be) submitted or published elsewhere while acceptance by the Journal is under consideration. A cover letter with the name of a corresponding author and the following statement should accompany the manuscript: "The author represents and warrants that hidher part of the work as submitted will in no way violate any copyright, or any other right."

The Journal strongly discourages authors from fragmented reporting of aspects of a single investigation or clinical study. Authors submitting a manuscript that is but one of a number of existing or planned manuscripts related to a single study must, therefore, include a statement in the cover letter that (1) so identifies the paper, and (2) justifies the use of the fragmented approach. Related manuscripts, published or unpublished, should also be included with the submitted manuscript. The submitted manuscript itself must clearly explain and justify the fragmented approach and reveal the full extent of the investigation.

A copyright form will be sent to the corresponding author upon manuscript acceptance and must be signed by all authors prior to final processing of the manuscript.

All manuscripts will be reviewed by two experts in the field, usually, but not restricted to, diplomates of the American College of Veterinary Internal Medicine. Manuscripts will receive a priority score from the reviewers and the Editorial Board: those with a low priority score may be returned to the authors.

At the Editor's discretion, particularly meritorious manuscripts that are of unusually high priority and significance and that represent definitive and original studies will be considered as rapid publications. Authors will be notified by the Editorial Office upon scheduling of their manuscript as a rapid publication.

Manuscripts must be double spaced, typed on one side of standard typewriter or printer paper, leaving at least I-inch margins. Page numbers should be included in the upper right-hand corner of each page. Each manuscript component should begin on a new page and should comprise the following:

Titlepage: The first page should include the title of the manuscript, the names of the authors, their highest degrees, institutions or affiliations, and a short title for use as a running head. Separate paragraphs should specify where the work was done; whether the study was supported by a grant or otherwise; the meeting, if any, at which the paper was presented; acknowledgments; and the name and address of the author to whom reprint requests should be sent.

The abstract should not exceed 250 words. It should provide a concise, factual condensation of the manuscript, including the purpose(s) of the study, basic procedures, main findings, and principal conclusions.

The introduction is untitled. Please provide a clear statement of the objective and rationale of the study, and provide only pertinent references. A brief overview of the topic is appropriate. An extensive review of the subject will not be accepted.

Include a clear description of the observations or experimental subjects. Provide a concise description of the experimental and statistical methods and of the procedures in sufficient detail to allow other workers to reproduce the results. A statement of animal care must be made, ie, animals were cared for according to the principles outlined in the NIH Guide for the Care and Use of Laboratory Animals. Statistical methods used must be outlined and referenced. When the methods have been extensively detailed elsewhere, there is no need to duplicate this material. Instead, list the appropriate reference.

Only high-quality illustrations will be considered for publication. Submit four copies of illustrations, measuring one column or 85 mm in maximum width. Large photographs measuring two columns ( I 75 mm) will be occasionally considered. Smaller photographs are permissible, but they must be grouped to make maximum use of space. To depict magnification in photomicrographs, include in the photograph a line or rule of appropriate length and explain it in the legend. The author may wish to provide a montage of suggested photograph grouping, but the editor reserves the right to regroup them. Blackand-white illustrations, in the form of glossy prints, will be reproduced free of charge, but the editor reserves the right to establish a reasonable limit. Color illustrations may be published; the cost to the author for the publication of color illustrations will be determined for each article.

Line drawings should be done professionally, and photographed and reproduced to conform to the column widths noted above.

To avoid imprints on the face of photographs, do not write directly on the back of the photograph. Instead, affix a label on which the author's name, illustration number in Arabic numerals, indication of top, and brief title of the article have been previously written. The illustrations should be submitted unmounted and should be adequately protected from shipping damage.

The guidelines for letters to the editor, brief communications, and review articles as they relate to illustrations, references, etc, are the same as those for the standard paper.

The letters to the editor section provides a forum for issues in veterinary internal medicine. Letters can relate to any aspect of internal medicine, as well as provide an opportunity for the reader to respond to the contents of The Journal of Veterinary Internal Medicine. Preliminary findings of new investigations will also be considered. Letters must not exceed two double-spaced typewritten pages.

Letters should be sent to: C. Guillerrno Couto, DVM, Editor, 4694 Cemetery Road, Suite 395, Hilliard, OH 43026; 614-870-5328 (telephone and fax).

The Journal will contain a separate section of brief communications. This section does not necessarily contain conventional subdivisions but must be accompanied by a brief abstract and essential references not to exceed ten. This section is meant to accommodate reports of small completed investigations, new techniques, or case descriptions where the findings are new or unique. Brief communications must not exceed three printed pages (approximately 7 double-spaced typewritten pages), including tables, illustrations, and references, and should he clearly marked "Brief Communication," Brief communications usually have the same pnority for publication as regular manuscripts.

Clinical Vignettes: The Journal will also consider for publication short items for the "Clinical Vignettes" feature. This feature will be based on good quality photographs of cytological or gross clinical specimens, recordings of electrophysiologic measurements, ultrasound images, radiographs, or other diagnostic data. For each feature, the author will provide concise background clinical data and pertinent description of the illustrations submitted. The material should be presented as an unknown clinical entity to allow the reader to study the data and amve at a clinical diagnosis or list of differential diagnoses. A brief discussion of the diagnostic work-up and definitive diagnosis will follow, and key references will be included. Material for considerations will include interesting diagnostic problems, new clinical entities, or new diagnostic methods that can be portrayed pictorially. The maximum page length for this feature will be two printed pages (approximately five double-spaced typewritten pages). Submissions to this feature will be subjected to peer review. The guidelines for photographs are listed elsewhere.

Review Articles: Review articles, which may be solicited by the editorial board or submitted unsolicited by the authors, are meant to provide the reader with an overview of the state of the art in a specialized area of veterinary internal medicine. They should be submitted by individuals who are actively working in the area and not by individuals who have reviewed the literature as a prelude to beginning a project in the area. The review should be informative and appreciated by the generalists as well as the specialists. Outlines of the unsolicited review articles should be submitted to the editors for approval before extensive writing is done.

Permissions of author and publisher must be obtained for the use of previously published material (text, photographs, drawings) and must accompany the manuscript when it is submitted for publication.

Reprints may be ordered on the reprint order form sent to the authors with page proofs.

If you wish to pay the $50.00 manuscript submission fee by credit card, please complete this fohn and send it attached to your cover letter.

Christine B. Navarre and Allen J. Roussel An understanding of the relationship between gastrointestinal (GI) motility and disease is imperative for the proper treatment of large animal patients, especially as new therapeutic agents become available. However, the abundance of information that has become available in the last 2 decades makes gaining this understanding a formidable task. This article summarizes the changes in he effects of disease on gastrointestinal (GI) motility T have been investigated since the 19th century. However, there has been an explosion of information in the last 20 years, and it is no longer acceptable to describe changes in GI motility as simply increases or decreases in motility. GI motility can be evaluated by quantifying several different parameters. A better understanding of the relationship between GI motility and disease is imperative to proper patient care, especially as new therapeutic agents become available. This article focuses on the specific changes in GI motility caused by some common diseases and conditions encountered in large animal practice.

Until more studies specifically involving large animals are available, we must extrapolate from other species. However, in doing this, we must remember the extreme variation in the structure and function of the GI tract among species, particularly in the large intestine, and make extrapolations with caution. Data from human patients, small animals, and laboratory animals are included in this review; however, only those diseases and conditions affecting large animals are discussed. Also, only results of in vivo studies are included. More extensive reviews, including data from research in vitro, are available for most of these subjects. A brief discussion of normal motility patterns is included to familiarize the reader with terminology. For a more detailed description of normal motility, terminology, and recording methods, the reader is referred e1~ewhere.I.~ Therapeutic options will not be discussed in this article, but several reviews on this subject are also a~a i l a b l e .~.~

Three basic parameters of GI motility can be measured: myoelectric activity, mechanical activity, and transit of intraluminal contents.' Myoelectric and mechanical activities are closely coupled: as one increases, so does the other."' However, transit of gut contents does not always increase as myoelectric and mechanical activities increase.* Two types of myoelectric activity, slow waves and spikes, are produced by the GI tract. Slow waves are subthreshold fluctuations in membrane potential that are not accompanied by muscle contraction (Fig 1) : and are continually propagated from the esophagus to the rectum. Spikes are membrane fluctuations that exceed the threshold, causing depolarization and muscle contraction (Fig 2) .' They are usually superimposed on slow waves, and groups of spikes assume several different patterns depending on the species, the area of the GI tract, and the digestive state studied. The migrating myoelectric complex (MMC) is the myoelectric pattern in the stomach and small intestine of fasted nonruminants, fed and fasted ruminants, and pigs and horses fed ad libitum.23339-" There are 3 phases of the MMC: the quiescent phase, in which very little spike activity occurs; the irregular phase, characterized by intermittent spike activity; and the activity front, characterized by intense, continuous spike activity (Fig 3) .'-3.9.10 There is very little muscle contraction or transit of gut contents during the quiescent phase.',8 During the irregular phase, contractions mix the gut contents and propel them in an aboral direction.'**.'' The activity front is accompanied by intense muscular contraction that obliterates the lumen, preventing backflow of contents as it propagates, or "migrates" down the gut.','" In nonruminants, and pigs and horses fed periodically, feeding abolishes the MMC pattern for several hours. The MMC pattern is replaced by the fed pattern, which is characterized by intermittent spike activity resembling the irregular Normal cecal and colonic myoelectric activities, like those of the small intestine, are Characterized by slow waves and spikes. However, unlike the small intestine, the patterns of spikes vary greatly with the species and the area of the large intestine studied. The two major spike patterns are the short spike burst (SSB) and the long spike burst (LSB).',2.'2SSBs cause segmental contractions and do not propagate; LSBs propagate both orally and aborally.'.'.'' There are many interchangeable terms for all of the patterns described. The terminology used here is preferred and will be used in the rest of the article.

Obstruction of the small and large intestines may be intraluminal (eg, intussusceptions, impactions, enteroliths, foreign bodies) or extraluminal (eg, displacements and entrapments).I3 Both types are characterized by bowel distension phase.2.3.9.10 52 NAVARRE AND ROUSSEL and increased intraluminal pressure orally, and absence of intraluminal contents and decreased intraluminal pressure aborally. Most of the information on changes of motility after obstruction was derived from models of acute obstruction of the small intestine in horses and p~n i e s , '~. '~ COWS,'* sheep,'' and rats." Human patients with spontaneous obstruction have also been ~tudied.'~ Despite differences in experimental design and species studied, the pattern of myoelectric activity of the segment oral to small intestinal obstruction was similar in most studies. Myoelectric and mechanical activity of the intestine after a complete obstruction consisted of alternating periods of contraction and quiescence.2",23 The period of contraction was characterized by clusters of discrete spikes on consecutive slow waves, or prolonged, constant spike activity that lasted for several seconds (Fig 4) .14.'5.'8,20*22 The clusters of spikes were approximately 10 to 45 seconds in duration and occurred every 1 to 2 m i n u t e~. l~. *~ The mechanical correlate of the clustered spikes were small groups of contractions of medium amplitude and duration, interrupted by short periods of inactivity.I6 When prolonged, constant spike complexes occurred, the mechanical activity consisted of single, high amplitude, contractions of long duration or spasms. 15 Changes in small intestinal motility aboral to an obstruction were less consistent among studies. Total spike activity was significantly decreased aboral to small intestinal obstruction in dogs.'",'' Long periods of quiescence, infrequent activity fronts, and periods of no irregular activity of the small intestine were described in a pony, in contrast to continuous irregular activity after an initial quiescent period in rats. '6,22 In sheep, total occlusion produced strong and prolonged bursts of activity aborally, whereas partial occlusion caused general inactivity." These inconsistencies may be explained in part by species differences, experimental conditions, relationship of the recording period to feeding, and duration of the obstruction.

After relief of a small intestinal obstruction, the MMC was recognizable within 10 to 20 minutes, although duration of activity fronts is decreased and the quiescent phase was prolonged. Normalization of the MMC continued over time and was complete in 12 to 24 hours.18,1', 22 The pathogenesis of the changes associated with small intestinal obstruction are not clearly understood. It is postulated that distention oral to an obstruction activates local myenteric receptors; activity is then stimulated orad to the obstruction via cholinergic pathways, and activity aborad is inhibited via noncholinergic, nonadrenergic pathways."

The response of the large intestine to obstruction has not been studied extensively. Lowe et all7 placed fistulas in the pelvic flexure of ponies and induced impactions by manipulating diet or creating intraluminal obstructions. Episodes of colic were accompanied by multiple high-amplitude, longduration pressure peaks interpreted as contractions, oral and aboral to the pelvic flexure. Further research is needed before conclusions can be made about the effects of obstruction on large intestinal motility.

Veterinarians and physicians alike have long recognized postoperative ileus (POI) as a relevant clinical p r~b l e m .~~.~~ It is characterized by dilation and lack of propulsive contractions of the gut leading to accumulation of fluid and gas.26 Its importance as a clinical disease is unmistakable. In a retrospective study of postoperative complications of horses with colic, POI was the cause of death in 36 of 84 patients (42.9%). 25 In human patients, POI causes serious discomfort and prolongs hospitalization after surgery. 26 Normal gastric and small intestinal motilities were altered in the postoperative period in several ways. In dogs and horses, an experimental model of POI was produced by rubbing a segment of small bowel with a dry sponge for 5 or 10 minutes, respectively, then leaving the same segment exposed to air for 30 minute^.^^.'^.^^ In dogs, this procedure abolished or greatly decreased the number and duration of activity fronts, and increased the duration of the irregular phase in the stomach and small intestine during the postoperative p e r i~d . *~, '~ The motility index (derived from the magnitude of contractile forces and the duration of myoelectric complexes) was also de~reased.~' In horses, the number of activity fronts was decreased arid the normal synchrony of gastric and oral duodenal MMCs was disrupted." As would be expected with a decrease in myoelectric activity, transit of plastic spheres and nonabsorbable markers was also delayed during the immediate postoperative period in dogs, horses, and rat^.^^,^'.'^ POI also occurs in the colon. In human patients undergoing various abdominal surgical procedures, only random, single, spike bursts were present initially.26~'"~" Within 3 to 4 days, long, propagated, spike bursts resembling a normal pattern

Mechanical activity and intraluminal pressures were decreased, and transit was delayed in the colon after various operative procedures.""' Cecal impaction and rupture have been reported in the horse after various surgical procedures, includitlg elective orthopedic surgery.3"' In those reports, the terms "ileus" and "intestinal hypomotility" were used but not defined.i3~'' It is not known if the authors were referring to gastric reflux, absence of borborygmi, or something else. Unfortunately, like equine duodenitis-proximal jejunitis, an experimental model mimicking the natural disease is not yet available so that more detailed studies can be performed.

Most researchers agree that normal motility returns first to the stomach, then to the small intestine, and finally to the large intestine.26.28.3",36 Gastric and small intestinal motility returns within hours and colonic motility returns within a few days.26,3",lh Surprisingly, neither the length nor the type of operative procedure affected the duration of postoperative changes of motility in monkeys and human patients."','2~'6~,"7

The pathophysiology of POI is incompletely understood at present. Depending on the anesthetic(s) used, general anesthesia alone has immediate variable effects on myoelectric activity, but there is no evidence to suggest that it significantly alters myoelectric activity of the GI tract in the postoperative p e r i~d .~~-~" Disruption of gastroduodenal coordination is thought to be the principal lesion in equine postoperative ileus by some investigators." Sympathetic and dopaminergic hyperactivity activity are proposed to play a role, but many other factors, such as other hormonal influences and the enteric nervous system, are probably also involved."

Resection of devitalized small intestine and subsequent anastomosis is a common surgical procedure in large animal practice. particularly in horses. The effects of simply opening the abdomen and handling the bowel during surgery were discussed in the previous section. Now the effects of interruption of the continuity of the bowel wall on motility will be discussed.

Most of the information in this area was derived from studies of myoelectric activity of animals after a simple small intestinal resection and anastomosis or the creation of Thiry-Vella I~o p s .~' -~~ A Thiry-Vella loop is a section of small intestine that has been transected at both ends from the bowel, but its mesenteric attachments have been preserved." The free ends of the isolated loop are passed through openings in the abdominal wall and sutured to the skin, forming 2 stomas, and the remaining bowel is anastomosed. Early studies of dogs and sheep suggested that propagation of MMCs was not interrupted by resection and anastomosis or Thiry-Vella loop preparation.4',4z The complexes were said to start in the bowel orad to the anastomosis, migrate in sequence to the Thiry-Vella loop, and then to the aboral segment. Even though only a percentage of the complexes (60% in dogs, 30% in sheep) behaved in this manner, the authors suggested that continuity of the bowel was not needed for propagation of the MMC. However, in a similar study of dogs, Bueno et a14' showed that approximately twothirds of the MMCs appear to migrate directly across one anastomotic site, and only about one-third across a second anastomotic site. They also noted that the appearance and properties of these complexes were changed. This led them to the theory that MMCs do not propagate through anastomosis sites, but instead, new complexes are formed beyond the anastomosis. Thus, continuity of the bowel (ie, continuity of the enteric nerves and/or the musculature) is essential for normal propagation of the MMC.43 This theory has since been supported by other ~t u d i e s .~~.~' The new MMCs arising aborad to an anastomosis occur with higher frequency, and the activity fronts of these complexes are increased in dura-Coordination of propagation starts to return as the ti on .43.45.46 normal healing process begins. A closer association between the coordination of the oral and aboral segments was first noticed 8 weeks postoperatively, and normal coordination was completely restored by 10 to 12 The physiological relevance of interruption of the MMC after resection and anastomosis is unknown, but it does not appear to be clinically important. Without complications from strictures, animals can resume normal eating and defecating habits within 1 week, suggesting that aborad movement of ingesta is not considerably altered.

The role of GI motility in the pathogenesis of diarrhea has been extensively researched. One might intuitively assume that diarrhea and an increase in propulsive motility go hand in hand. However, this is not necessarily the case. Thus, the changes that occur in the small and large intestines during diarrhea, and the effects of etiology on the pattern of motility will be discussed.

Three major myoelectric patterns of motility have been recognized in the small intestine in association with diarrhea; the migrating action potential complex (MAPC), the repeti- The MAPC is characterized by action potential discharges (spikes) of 2.5 seconds or longer, that migrate aborally over at least 2 consecutive electrodes, and propel fluid (Fig 5) . 48 The RBAP is an action potential discharge (spike) greater than 1.5 seconds in duration that is repeated on 3 or more successive slow waves on the same recording site (Fig 6) : 9 RBAPs may or may not be propagated, and are less propulsive than MAPCS.'~~'~ MAPCs are associated with noninvasive bacterial agents and their heat-labile toxins, such as Vibrio cholerae, Escherichia coli heat-labile enterotoxin, enteropathogenic E coli, and Salmonella typhimurium.4R~5'~s3~60 RBAPs are associated with invasive and cytotoxic organisms and their heat-stable toxins, such as enteroinvasive E coli, E coli heat-stable enterotoxin, Shigella dysenteriae, and Campylobatter jejuni, 48- S0.S4,611,62 It must be noted that these experiments were performed during anesthesia, and that the rabbit is not a natural host to all of the organisms studied.

In the rabbit ileum model, MAPCs were also recorded after gradual luminal distension of obstructed loops (but not of patent loops), exposure of the loops to castor oil and ncinoleic acid, and in the intestine orad to the ligated loop.49,s5,63 MAPCs also occurred in human patients after laxative abuse and secretory diarrhea of unknown etiology.h4 In contrast, pigs infected with coronavirus (transmissible gastroenteritis) had decreased numbers of MAPCs, and calves exposed to E coli heat-stable enterotoxin PO had no change in the numbers of MAPCS.~'"~ The definition of the 1 min MAPC (ie, propagated spikes longer than 2.5 seconds in duration) encompasses many patterns, including RBAPs and the long spike complexes described in response to obstruction. Also, although its frequency usually increases in patients with diarrheal diseases, the MAPC (also called a penstaltic rush) is a normal myoelectric pattern during the irregular phase in several species when flow of contents is greatest.""' Therefore, the MAPC is thought to be a nonspecific motor pattern resulting from fluid distension, although it has also been induced by subunits of the enterotoxin molecules that do not induce secretion."

The third and most frequently recorded myoelectric pattern from the small intestine during diarrhea is the minute r h~t h r n ,~~,~~ which is characterized by propagating clusters of 3 to 10 spike bursts lasting 10 to 45 seconds, recurring at approximately 1-minute intervals, and separated by periods of quiescence (Fig 7) .s9.70 Infusion of saline into the jejunum in pigs, and of D-mannitol into the duodenum of sheep resulted in well defined minute rhythms7' Grain overload in sheep, administration of E coli heat-stable enterotoxin to calves PO, and of ricinoleic acid and magnesium sulphate in dogs, all produced minute rhythm^.",'^,^^ Minute rhythms are reported to be the most common myoelectric pattern recorded in humans with diarrhea, especially after laxative abuse.69 Minute rhythms were also recorded in several species during normal fasting and fed states.70 By definition, the minute rhythm also includes the clusters of discrete spikes described orad to an obstruction. Because the minute rhythm was recorded from normal animals during the irregular phase (when flow of digesta is greatest), during diarrheal states, and orad to obstructions, it is possible that this myoelectric pattern is a response to fluid distension.

The exact mechanisms leading to MAPCs, RBAPs, and minute rhythms are unclear. They may be a result of bacterial invasion or toxin production, or a reflex response to fluid distension. Prostaglandins are proposed to be involved in the pathophysiology of MAPCs, and tissue destruction is proposed to be important in the pathophysiology of In vitro data suggest that nitric oxide is involved in the physiology and pathophysiology of intestinal m~t i l i t y .~' -~'

Inhibitors of nitric oxide synthesis decreased the severity of castor oil-induced diarrhea in rats,74 so nitric oxide may also be involved in the pathophysiology of these motility patterns. Research into the cellular mechanisms of these changes is already underway, and will be one of the major focuses of future studies.

The effects of diarrhea on small intestinal mechanical activity and transit are less well studied compared to the myoelectric activity. Ring-like contractions occurred simultaneously with RBAPs, and similar contractions that propagated rapidly were observed simultaneously with MAPCS.~*,'' Prolonged, propagated contractions and giant migrating contractions recorded in normal dogs and after exposure to cholera toxin may be the motor correlates of the MAPC.75-77 Also, discrete clustered contractions and migrating clustered contractions recorded from the same dogs may be the motor correlates of the minute rhythm.

Lack of uniformity in the terminology used to describe colonic patterns of motility during diarrhea makes correlation of information from different studies difficult. Colonic motility was altered in human patients with irritable bowel syndrome (IBS),78 human patients and dogs with laxativeinduced (castor oil, senna extract, magnesium citrate, oleic acid) diarrhea:*-8o and human patients and dogs with ulcerative ~o l i t i s . * '~~~ Gross and histopathologic lesions are absent in IBS and laxative-induced diarrhea, but occur in those with ulcerative Despite this difference, the changes in motility are similar for both. Myoelectric activity was altered by a decrease in the frequency of SSBs and LSBs, and a decrease in the duration of total spiking Mechanical activity was altered by an increase in the duration of colonic migrating motor complexes, and the occurrence of giant migrating contractions ( G M C S ) .~~,~" ,~~ GMCs are distinct, high-amplitude contractions that rapidly migrate aborally, and are frequently followed by expulsion of feces or gas. As would be expected with the occurrence of GMCs, colonic transit is increased.*0. 82 The pathophysiology of changes in colonic motility during diarrhea are unclear. Because the changes are similar regardless of whether morphological changes in the colon occur, it is difficult to attribute these changes to a structural change in the gut wall. As is suspected in the small intestine, prostaglandins are also proposed by some to play a role in these changes. R4.85

Endotoxemia is a contributing factor in the pathogenesis of many diseases, including diseases of the GI tract." Changes in GI motility induced by endotoxin may contribute to the pathogenesis of GI diseases. In addition, the magnitude and duration of effects of endotoxin on motility, like those on clinical signs are dose-dependent.*"*' It should be noted that in the studies subsequently cited in this section, diarrhea was not induced by any of the doses of endotoxin administered.

The myoelectric and mechanical activities of the ruminant forestomach and abomasum, and of the monogastric stomach were decreased in response to IV administered endo-toXin.x6,x7'.9n-9z D ecreased frequency and amplitude of ruminal contractions at low doses, and complete inhibition of reticular and abomasal spikes at higher doses were recorded in sheep and

In the stomach of ponies and pigs, total spike activity, and the amplitude and rate of contractions were also de~reased."~~~~'*

The effects of endotoxin on small intestinal activity were not as consistent. During myoelectric and mechanical recordings in sheep, rats, pigs, and horses, the MMC was disrupted and replaced by short periods of intense activity that resembled activity fronts, but were shorter in duration and more This occurred with low doses of endotoxin in horses and pigs, and relatively high doses in sheep and rats. In these studies, the authors compared these complexes with MAPCs, RBAPs, and minute rhythms, but evaluation of these comparisons cannot be made without more detailed descriptions of the complexes than those published in the texts.

The myoelectric and mechanical activities of the large intestine were evaluated in

The number of contractions of the cecum and right ventral colon, the contractile product of the left dorsal colon, and the spike rate of the small colon were d e~r e a s e d .~' ,~~

The IV administration of endotoxin induced alterations in GI motility very rapidly. The inhibition of reticular contractions and MMCs in sheep, and the decrease in the amplitude and rate of gastric contractions in ponies occurred within minutes of endotoxin a d m i n i s t r a t i~n~~,~~; normal motility was reestablished within h o~r s .~~,~* The pathophysiology of these changes is still being investigated. Some of the proposed mechanisms include increases in concentrations of platelet-activating factor, free radicals, and inflammatory mediators (in particular prostaglandins); interference with blood flow to the bowel; increased sympa- 

The pathogenic mechanisms of parasites, like bacteria, vary with the species. Despite these variations, changes in motility in different animal species with different parasites are somewhat consistent.

The myoelectric activity of the nematode-infested small intestine was studied in dogs and rats infested with Trichinella spirulis, dogs with hookworm infestations, horses with mixed small and large strongyle infestations, and sheep infested with Huemonchus c o n t o r t u .~.~~-'~~ Similar changes were found in all cases. The cycle length of the MMC was increased, and therefore the number of MMCs per unit time was decreased in all cases, except sheep with H contortus, in which the opposite Various rapidly propagating, intense, spike complexes were also re-One author described these as MAPCs, but without more detailed descriptions of these complexes, it is not possible to know if these complexes are synonymous with the MAPCs described previously in this article.99 In another study, both live and dead strongyle larvae disrupted the MMC pattern in ponies.07

The mechanical activity of the small intestine was recorded from dogs infested with T spirulis. The frequency and amplitude of contractions, and the distance of propagation of contractions were all An increased number of GMCs, like those described in the colon during diarrhea, were recorded in these dog^."^'"^ It is possible that GMCs are the motor correlate of the rapidly propagating spike com-Corded.97,99, 100,103 plexes described previously. Diarrhea was a consistent finding in these animals and the decrease in numbers of GMCs to normal coincided with cessation of diarrhea.

In rats infested with T spiralis, however, the transit time was decreased.'"' In the case of the dogs with T spiralis, this discrepancy may be due to the fact that transit time was measured only during periods when no GMCs were present.

Cecal motility was not changed in fasted ponies with mixed strongyle infestations, but cecal spike bursts were more frequent in foals infested with Strongylus vulgaris and in rabbits with E magna. i02,i03~i"h Opposing results were also found in the colon. The cranial colon showed a decrease in spike frequency in ponies, but no change in rabbits, whereas the spike frequency of the colonic pelvic flexure in foals was increased.'"*~'"'~'n~ These discrepancies could be due to species differences or differences in experimental design.

Calcium is of vital importance to the proper functioning of smooth muscle and nervous tissue, both of which are abundant in the GI tract. Hypocalcemia, a clinical problem in postparturient dairy cattle, would therefore be expected to cause changes in GI motility. Indeed, decreased ruminal contractions and ruminal tympany often accompany clinical signs of postparturient paresis."" Hypocalceniia is also believed to be a predisposing factor in abomasal displacement in postparturient dairy cattle.'"'."'' These facts prompted the investigations' '"-I I* of the effects of hypocalcemia on ruminal and abomasal motility.

Experimentally induced hypocalcemia in sheep and cows was accompanied by changes in intestinal mechanical activity; more specifically, there was a decrease in the rate and amplitude of ruminal and abomasal contractions.""-"' Two studies showed that as blood calcium concentrations decreased, ruminal and abomasal mechanical activity decreased in a positive linear relationship.""^'" In some instances, the mechanical activity decreased until stasis occurred (rumen of sheep, abomasum in some COWS).""^"^ However, a third study showed no linear relationship for the abomasum, but an "all or none" response, where mechanical activity remained unchanged despite decreasing calcium concentrations, until a threshold was reached and stasis occurred.' Different conclusions were reached with these experiments. In the first, Huber et al"" concluded that rumen stasis occurred because of a failure of neuromuscular transmission. Daniel'" concluded that the changes in motility were caused by the generalized effects of calcium on smooth muscle contractility. Both agreed that subclinical hypocalcemia may play a role in the pathogenesis of abomasal displacement because abomasal motility is decreased before clinical signs of postparturient paresis occur. Because Madison and Troutt"' found that decreased abomasal motility occurred in an "all or none" response, and only at serum calcium concentrations corresponding to clinical stage 3 postparturient paresis, they disagreed and concluded that subclinical hypocalcemia is not a predisposing factor in abo-masal displacement. Differences in experimental design, species differences, low numbers of animals, and inferences drawn from data that are not statistically significant make it difficult to draw a conclusion regarding the importance of blood calcium concentrations in motility.

GI disturbances such as constipation, heartburn and nausea, are frequent complaints of pregnant women."' In animals, the only clinically recognized GI disturbance associated with pregnancy is vagal indigestion in cattle.'I4 Studies of GI motility have not been performed in pregnant cattle, but have been performed in pregnant women and laboratory animals.' 14-i1'

Gastric emptying is delayed, and small intestinal and colonic transit times are increased in humans, guinea pigs, and rats, especially in late gestation.'i5~''x There is also more variation in MMC cycle length due to prolongation of some, but not all MMC cycles in rats in late gestation."' Gastric emptying increased and the MMC cycle length returned to normal within a few days after parturition in guinea pigs and

These changes are thought to be caused by hormonal changes, particularly increases in progesterone concentrations."' Although vagal indigestion in late pregnancy is presumed by some to be caused by the large gravid uterus compressing the abomasum and/or the cranial small intestine. hormonal influences should not be di~counted."~

As investigations continue and information accumulates, we will gradually learn more about the diseases just discussed and their effects on GI motility. However, there are other diseases, such as equine duodenitis-proximal jejunitis, postoperative cecal impaction, and enteric neuropathy (grass sickness), about which very little information is known in regard to their relationship to GI motility. As large animal practitioners, we must continue to seek knowledge about these diseases, and we must support and encourage clinical and experimental investigations into these diseases.

Intestinal Motility: A Review

Motor functions of the intestine

Backwards and forwards with the migrating complex

Prokinetic agents

Effects of pharmacological agents on gastrointestinal motility

Gastrointestinal electrical activity: Terminology

Gastrointestinal motility: Some basic concepts

Milk feeding and xylazine treatment induce increased antroduodenal motility in young cattle with opposite effects on duodenal digesta flow rate

The migrating myoelectric complex

Migrating myoelectrical complexes: disruption, enhancement and disorganization

Rate of How of digesta and electrical activity of the small intestine in dogs and sheep

Colonic myoelectrical spiking activity: Major patterns and significance in six different species

Electromyoenterography during normal gastrointestinal activity, or painful or non-painful colic and morphine analgesia, in the horse

Electromyographic, myomechanical, and intraluminal pressure changes associated with acute extraluminal obstruction of the jejunum in conscious ponies

Observations on the colic motor complex in a pony with a small intestinal obstruction

Effects of experimental duodenal occlusion on electrical activity of the proximal duodenum in cattle

Summers RW, Anuras S, Green J. Jejunal manometry patterns in health, partial intestinal obstruction, and pseudoobstruction

Incidence, diagnosis and treatment of postoperative complications in colic cases

Postoperative ileus: A colonic problem?

Pathophysiology of postoperative ileus

Metoclopramide reversal of decreased gastrointestinal myoelectric and contractile activity in a model of canine postoperative ileus

Pathophysiology of equine postoperative ileus: Effect of adrenergic blockade, parasympathetic stimulation and metoclopramide in an experimental model

testinal myoelectric and clinical patterns of recovery after laparotomy

Resolution of postoperative ileus in humans

Postoperative motility of the large intestine in man

Effects of selected drugs on intestinal motility in the horse

Cecocolic anastomosis for the surgical management of cecal impaction in horses

Duration of postoperative ileus related to extent and site of operative dissection

Gastrointestinal Motility in Health and Disease

Effects of general anesthesia on myoelectric activity of the intestine in horses

Large Animal Internal Medicine

Grivel ML, Ruckebusch Y. The propagation of segmental contractions along the small intestine

Propagation of electrical spiking activity along the small intestine: Intrinsic versus extrinsic neural influences

Myoelectric and absorptive activity in the transected canine small bowel

Adaptation to surgical perturbations

A study in the dog and cat of the electrical activity of the small intestine some months after transection and transplantation of the gut

Intestinal myoelectric activity in response live Vihriu cholerae and cholera enterotoxin

Alteration of myoelectric activity of small intestine by invasive Escherichia coli

Myoelectrical effects of Clustridium diflcile: Motility-altering factors distinct from its cytotoxin and enterotoxin in rabbits

Migrating action-potential complex activity in absence of fluid production is produced by B subunit of cholera enterotoxin

Migrating action 1990:668-674

potential complex of cholera: A possible prostaglandin-induced response

Effect of Salmonella typhimurium on myoelectrical activity in the rabbit ileum

Escherichia coli heat-stable toxin: Its effect on motility of the small intestine

Ricinoleic acid effect on the electrical activity of the small intestine in rabbits

The myoelectric activity of the small intestine in response to Clostridium pevfringens A enterotoxin and Clostridium difjicile culture filtrate

Myoelectric activity in the small intestine in response to Clostridium perfringens A enterotoxin: Correlation with histologic findings in an in vivo rabbit model

Shigella dysenteriae I enterotoxin: Proposed role in pathogenesis of shigellosis

Speculations on the role of motility in the pathogenesis and treatment of diarrhea

Altered intestinal motility precedes diarrhea during Escherichia coli enteric infection

Stimulation of action potential complexes by fluid distension of rabbit small intestine-Evidence that migrating action potential complexes are a non-specific myoelectric response

Myoelectric activity of the small intestine in enterotoxin-induced diarrhea of calves

Influence of coronavirus (transmissible gastroenteritis) infection on jejunal myoelectrical activity of the neonatal pig

Evaluation of the myoelectrical activity of the equine ileum infected with Strongylus vulgaris larvae

The interdigestive myoelectrical complex and other migrating electrical phenomena in the human small intestine

Minute rhythm of electrical spike bursts of the small intestine in different species

Role of nitric oxide-related inhibition in intestinal function: Relation to vasoactive intestinal polypeptide

Ng-nitro-L-arginine reduces nonadrenergic, noncholinergic relaxations of human gut

Patients with achalasia lack nitric oxide synthase in the gastroesophageal junction

Nitric oxide and castor oil-induced diarrhea

Distinctive patterns of interdigestive motility at the canine ileocolonic junction

Contractile patterns and transit of fluid in canine terminal ileum

Effect of cholera toxin on small intestinal motor activity in the fed state

Colonic myoelectrical activity in diarrhea and constipation

Effects of oral laxatives on colonic motor complexes in dogs

Decreased fluid tolerance, accelerated transit, and abnormal motility of the human colon induced by oleic acid

Abnormal gastrocolonic response in patients with ulcerative colitis

Gastrointestinal motility in patients with ulcerative colitis

Colonic motor activity in acute colitis in conscious dogs

Physiology and pathophysiology of colonic motor activity: Part two of two

Van Miert ASJPAM, Van Duin CTM. The effect of flurbiprofen upon fever and ruminal stasis induced by Escherichia coli endotoxin, poly I: Poly C and sodium nucleinate from yeast in conscious goats

Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters

Role of free radicals and platelet-activating factor in the genesis of intestinal motor disturbances induced by Escherichia coli endotoxins in rats

Involvement of platelet-activating factor (PAF) in endotoxin-induced intestinal motor disturbances in rats

Central opiate mechanism involved in gastro-intestinal motor disturbance induced by E. coli endotoxin in sheep

Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086

The action of low dose endotoxin on equine bowel motility

Blockade of endotoxin-induced cecal hypoperfusion and ileus with an a2 antagonist in horses

Protective and pathological roles nitric oxide in endotoxin shock

Shock and tissue injury induced by recombinant human cachectin

Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor

Effect of T. spiralis infection on intestinal motor activity in the fasted state

Trichinella spiralis: Intestinal myoelectric activity during enteric infection in the rat

Intestinal myoelectric activity of the dog during hookworm infection

Gastro-duodenal motor and transit disturbances associated with Haernonchus confortus infection in sheep

Disturbances of digestive motility in horses associated with strongyle infection

Intestinal motor and transit disturbances associated with experimental coccidiosis (Eimeria mugna) in the rabbit

Trichinella spiralis infection alters small bowel activity in the fed state

Altered small bowel propulsion associated with parasitism

Strnngylus vulgaris larvae on equine intestinal myoelectrical activity

Disorders of calcium metabolism

Abomasal displacement-2: Hypocalcemia as a contributing causative factor

Hypocalcemia at parturition as a risk factor for left displacement of the abomasum in dairy cows

Effect of hypocalcemia on motility of the ruminant stomach. Am 3 Vet Res 11 1. Daniel RCW. Motility of the rumen and abomasum during hypocalcaemia

Effects of hypocalcaemia on abomasal motility

Treatment of gastrointestinal disorders of pregnancy

Indigestion in ruminants

Gastrointestinal transit time in human pregnancy: Prolongation in the second and third trimesters followed by postpartum normalization

Effect of pregnancy on intestinal transit: Cornparison of results using radioactive and non-radioactive test meals

Colonic transit in rats: Effect of ovariectomy, sex steroid hormones, and pregnancy

Pregnancy-related changes in small intestinal myoelectrical activity in the rat