G. B. Edwards

Molecular characterisation of carbohydrate digestion and absorption in equine small intestine.

Dietary carbohydrates, when digested and absorbed in the small intestine of the horse, provide a substantial fraction of metabolisable energy. However, if levels in diets exceed the capacity of the equine small intestine to digest and absorb them, they reach the hindgut, cause alterations in microbial populations and the metabolite products and predispose the horse to gastrointestinal diseases. We set out to determine, at the molecular level, the mechanisms, properties and the site of expression of carbohydrate digestive and absorptive functions of the equine small intestinal brush-border membrane. We have demonstrated that the disaccharidases sucrase, lactase and maltase are expressed diversely along the length of the intestine and D-glucose is transported across the equine intestinal brush-border membrane by a high affinity, low capacity, Na+/glucose cotransporter type 1 isoform (SGLT1). The highest rate of transport is in duodenum > jejunum > ileum. We have cloned and sequenced the cDNA encoding equine SGLT1 and alignment with SGLT1 of other species indicates 85-89% homology at the nucleotide and 84-87% identity at the amino acid levels. We have shown that there is a good correlation between levels of functional SGLT1 protein and SGLT1 mRNA abundance along the length of the small intestine. This indicates that the major site of glucose absorption in horses maintained on conventional grass-based diets is in the proximal intestine, and the expression of equine intestinal SGLT1 along the proximal to distal axis of the intestine is regulated at the level of mRNA abundance. The data presented in this paper are the first to provide information on the capacity of the equine intestine to digest and absorb soluble carbohydrates and has implications for a better feed management, pharmaceutical intervention and for dietary supplementation in horses following intestinal resection.

Long‐term survival of equine surgical colic cases. Part 1: Patterns of mortality and morbidity

Postoperative complications and mortality can occur many weeks or months after colic surgery. We are interested in the long-term outcome of these cases. This study documents patterns of mortality and morbidity among 341 horses that recovered from colic surgery March 1998-August 2000. The progress of each horse was rigorously followed by periodic telephone and postal questionnaires. Event time data were recorded for each animal and a total of 321 horse years of survival, together with death from all causes, colic-related death and various postoperative complications. Postoperative survival (of all horses excluding grass sickness cases) was triphasic over the first 600 days and there was marked mortality in the first 10 days postoperatively. The probability of survival postoperatively decreased to 0.87 by 10 days, 0.82 by 100 days and declined slowly to 0.75 at 600 days. Horses suffering from epiploic foramen entrapment had a significantly reduced probability of postoperative survival (RR = 2.1, P = 0.033). The causes of death for 104 horses that died postoperatively and the prevalence of postoperative complications are recorded for the study population. Postoperative colic was the most prevalent complication with 100 horses (29%) suffering one or more episodes. However, only 16 horses (4.6%) suffered 3 or more episodes. The incidence of postoperative colic was 0.55 episodes/horse year at risk. This study provides data that will inform the prognosis for postoperative colic cases and identifies epiploic foramen entrapment as carrying a worse prognosis for survival than other strangulating lesions.

Case control study to identify risk factors for simple colonic obstruction and distension colic in horses

A case control study was performed to identify risk factors for colic caused by simple colonic obstruction and distension (SCOD) in the horse. Case horses were recruited from 2 veterinary school clinics. Control horses were population based and matched by time of year. A number of risk factors were considered in the following areas: general carer and premises information; exercise information; husbandry information (housing- and pasture-related); feeding information; breeding information; behavioural information; travel information; preventive medicine information and previous medical information. All variables with a P value of <0.2 in the univariable analysis were considered for possible inclusion in a multivariable model. A final model, produced by a forward stepwise method, identified crib-biting or windsucking, an increasing number of hours spent in a stable, a recent change in a regular exercise programme, the absence of administration of an ivermectin or moxidectin anthelmintic in the previous 12 months and a history of travel in the previous 24 h as associated with a significantly increased risk of SCOD. An alternative final model, produced by a backwards elimination method, identified the same variables as the forward model with, in addition, a history of residing on the current establishment for less than 6 months, a history of a previous colic episode and the fewer times per year the teeth were checked/treated as associated with a significantly increased risk of SCOD. Three of the risk factors in this model were associated with a large increase in risk: stabling for 24 h/day, crib-biting/windsucking and travel in the previous 24 h.

Equine surgical colic: risk factors for postoperative complications.

The reason for undertaking this study was that postoperative complications of colic surgery lead to patient discomfort, prolonged hospitalisation and increased cost. Potential risk factors for the 6 most common postoperative complications (jugular thrombosis, ileus, re-laparotomy, wound suppuration, incisional herniation and colic) were evaluated using multivariable models. Jugular thrombosis was associated significantly with heart rate greater than 60 beats/min and with increased packed cell volume (PCV) at admission. The risk of postoperative ileus also increased with increasing PCV at admission and was higher in horses recovering from pedunculated lipoma obstruction. Incisional herniation was strongly associated with wound suppuration and with increasing heart rate at admission. The emergence of cardiovascular parameters as risk factors for several postoperative complications is consistent with the hypothesis that endotoxaemia is important in the development of these complications. Early referral of colic cases, prior to the development of severe endotoxaemic shock, may minimise the risk of some postoperative complications. Horses that have suffered epiploic foramen entrapment, are more than 4 times as likely to undergo re-laparotomy than other horses. Horses that have suffered postoperative ileus have a similarly increased risk of undergoing re-laparotomy. The risk of postoperative colic is significantly associated with horses recovering from large colon torsion (>360 degrees) and with having undergone re-laparotomy. Hazard ratios (with 95% confidence intervals) for these last two effects are 3.1 (1.7, 5.7) and 3.4 (1.9, 6.2), respectively. Knowledge of the risk factors for postoperative complications allows more accurate prognostication postoperatively and suggests ways in which the risk of postoperative complications can be minimised.

Factors affecting long-term survival of horses recovering from surgery of the small intestine

REASONS FOR PERFORMING STUDY Epiploic foramen entrapment (EFE) has been associated with a particularly poor post operative prognosis for equine colic cases, but the reasons for this are unknown. OBJECTIVES To identify variables associated with post operative survival following surgery for small intestinal disease; develop a model describing long-term post operative survival; and identify reasons for the poor prognosis associated with EFE. METHODS Data from 382 horses undergoing surgery were used to identify variables associated with survival. A multivariable Cox proportional hazards model for post operative survival was developed and model fit evaluated. RESULTS The final model included the variables total plasma protein (TP) and packed cell volume (PCV) at admission, duration of surgery and the dichotomous variable relaparotomy (yes/no). Risk of death was positively associated with increasing PCV, but negatively associated with increasing TP (which decreased the probability of death). In a univariable model, EFE cases had a significantly higher death rate than other types of small intestinal disease (hazard ratio = 1.7, P = 0.035). Multivariable modelling indicated that some of the increased risk associated with EFE cases was due to lower TP values and longer duration of surgery. CONCLUSIONS Preoperative TP is associated negatively with the risk of post operative death in horses recovering from small intestinal surgery. Other variables associated with the probability of survival are preoperative PCV, duration of surgery and relaparotomy. The increased post operative death rate of EFE cases can be explained in part by lower TP and longer surgery times of these cases. POTENTIAL RELEVANCE Total plasma protein may be not simply a measure of hydration status in small intestinal colic cases, but an important determinant of survival. Further investigation of this relationship is warranted. Our model for post operative survival highlights the importance of preoperative TP, PCV and duration of surgery as prognostic indicators. This information should allow a more accurate post operative prognosis following small intestinal surgery.

Long‐term survival of equine surgical colic cases. Part 2: Modelling postoperative survival

Colic surgery is a frequently performed operation with high postoperative mortality. This study was undertaken to identify variables associated with decreased postoperative survival. We used data from 321 horse years of postoperative survival time to model the probability of survival following recovery from colic surgery. Continuous variables were modelled using a 6 variable, penalised Cox regression model. This demonstrated approximately linear relationships between survival and the following variables: increase in packed cell volume (PCV), intestinal resection length, time to surgery (interval between onset of colic and surgery) and duration of surgery. No significant decrease in survival was demonstrated with increasing age of the patient or with heart rate. The only categorical variable to be significantly associated with decreased survival was epiploic foramen entrapment. The final, fixed effects Cox proportional hazards model of postoperative survival included the variables epiploic foramen entrapment, PCV, resection length and duration of surgery, each variable adjusted for the nonlinear relationship with time to surgery. Residual variation in postoperative survival attributable to professional personnel (referring veterinary surgeon, anaesthetist and surgeon) was explored by fitting each as a random effects term in the model. Little of the residual variation could be attributed to any category of personnel. Model diagnostics indicated little influence by individual outliers on model parameters and little evidence of subjects poorly predicted by the final model. The study highlights factors influencing the long-term survival of horses recovering from colic surgery and proposes a model that can be used to inform prognosis.

Equine grass sickness is associated with low antibody levels to Clostridium botulinum: a matched case-control study

REASONS FOR PERFORMING STUDY Equine grass sickness is a high mortality disease which, despite many years of investigation, is of unknown aetiology. Recent findings indicating that the disease is associated with Clostridium botulinum require support from an epidemiological study that recognises and controls for potential confounders, e.g. age, time of year and premises. HYPOTHESIS EGS is associated with low antibody levels to C. botulinum antigens. METHODS A matched case-control study was conducted. Data were collected from 66 histologically confirmed cases of EGS and 132 premises-matched control horses. The probability of EGS in horses was modelled using conditional logistic regression. RESULTS EGS was significantly associated (age-adjusted P < 0.005) with low antibody levels to each of 3 clostridial antigens; C. botulinum type C and C. novyi type A surface antigens and a C. botulinum type C toxin complex toxoid. These serological risk factors for EGS remained highly significant when entered into multivariable models. This study also identified new horse-level risk factors for EGS; feeding hay or haylage was associated with a decreased risk of disease, change of feed type or quantity during the 14 days prior to disease was associated with increased risk, and the use of an ivermectin anthelmintic at both the ultimate and penultimate treatments was also associated with a significantly increased risk of EGS. CONCLUSIONS This study provides strong support for the role of C. botulinum in the aetiology of EGS and identifies managemental risk factors for the disease. POTENTIAL RELEVANCE Increasing anticlostridial antibody levels by vaccination and appropriate managemental interventions may decrease the risk of EGS occurring.

Modelling long-term survival of horses following surgery for large intestinal disease.

REASONS FOR PERFORMING STUDY Large intestinal diseases are an important cause of equine colic that require surgical management, but there is little published information about long-term survival of such cases. OBJECTIVES To identify variables associated with post operative mortality and to develop a model for post operative survival following surgery for large intestinal disease. METHODS Clinical data and long-term follow-up information from 275 horses undergoing surgery for large intestinal disease were used. A multivariable, Cox proportional hazards model for post operative death was developed and the fit of the model evaluated. RESULTS The continuous variables age, heart rate and packed cell volume (PCV) were associated positively with the risk of post operative death, as were the categorical variables resection (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-5.1) and relaparotomy (OR 3.5, 95% CI 1.4-8.4). CONCLUSIONS In the population studied, the probability of post operative survival following surgery for large intestinal disease was associated with the cardiovascular parameters heart rate and PCV on admission, age of the horse and whether it underwent resection or relaparotomy. POTENTIAL RELEVANCE The prognosis for post operative survival for horses with large intestinal disease may be improved by early surgery, prior to the development of cardiovascular compromise. Surgeons should be aware that increasing age, resection of large colon and relaparotomy are all associated with a worsening prognosis for survival.

Interstitial cells of Cajal (ICC) in equine colic: an immunohistochemical study of horses with obstructive disorders of the small and large intestines

REASONS FOR PERFORMING STUDY The gastrointestinal pacemaker cells, the interstitial cells of Cajal (ICC), have been implicated in several human gastrointestinal dysmotility syndromes. Recently, the involvement of these cells in equine gastrointestinal diseases has been investigated in cases of equine grass sickness where a significant reduction in ICC density was observed. OBJECTIVE To investigate ICC density in equine obstructive gastrointestinal disorders using immunohistochemical labelling methods. METHODS Intestinal samples were analysed from 44 horses undergoing exploratory surgery for colic and from 11 control animals subjected to euthanasia for conditions not related to the gastrointestinal tract. Immunohistochemical labelling of ICC was carried out using an anti-c-Kit antibody. Two independent observers assessed ICC density using a semiquantitative grading system. RESULTS There was a significant reduction in ICC density in horses with large colon disorders compared to the controls (P<0.01). Horses with strangulating lesions of the small intestine showed no difference when compared to the controls. CONCLUSIONS There was a reduction in ICC density in horses with large intestinal disorders. POTENTIAL RELEVANCE The reduction in ICC density may be associated with the clinical findings as well as recurrent colic episodes observed in a number of these cases. This immunohistochemical study provides a basis for future functional electrophysiological investigations to determine the precise effect of ICC reduction on equine intestinal motility.

Differential survival in horses requiring end-to-end jejunojejunal anastomosis compared to those requiring side-to-side jejunocaecal anastomosis.

REASONS FOR PERFORMING STUDY Horses requiring different methods of intestinal anastomosis during equine colic surgery may have differences in mortality and morbidity. HYPOTHESES Horses requiring side-to-side jejunocaecal anastomosis have a higher mortality and morbidity rate than those requiring end-to-end jejunojejunal anastomosis. Morbidity and mortality of handsewn vs. stapled side-to-side jejunocaecal anastomoses are not significantly different. METHODS A prospective, nonrandomised, observational study was conducted. Clinical and surgical details were recorded during hospitalisation and survival data acquired by periodic telephone questionnaire. Differences in mortality and morbidity rate were evaluated by survival analysis. RESULTS A total of 184 horses underwent end-to-end jejunojejunal anastomosis and 178 underwent side-to-side jejunocaecal anastomosis. Horses with a jejunocaecal anastomosis had a significantly higher mortality rate. The incidence of post operative colic in horses requiring side-to-side jejunocaecal anastomoses was greater than those requiring end-to-end jejunojejunal anastomoses. Within the group undergoing side-to-side jejunocaecal anastomosis there was no evidence of differential survival between horses with handsewn vs. stapled anastomoses. CONCLUSIONS Mortality rate is higher in horses that have required side-to-side jejunocaecal anastomosis than in those that needed end-to-end jejunojejunal anastomosis; and post operative colic is more common after side-to-side jejunocaecal anastomosis. No difference in mortality was found between horses with handsewn and stapled side-to-side jejunocaecal anastomoses. POTENTIAL RELEVANCE Surgeons should be aware of the increased mortality and morbidity in horses requiring side-to-side jejunocaecal anastomosis. Our finding of no difference in mortality between handsewn and stapled side-to-side jejunocaecal anastomoses justifies surgeons exercising personal preference in their selection of anastomosis method.