Use of multiple admission variables better predicts intestinal strangulation in horses with colic than peritoneal or the ratio of peritoneal:blood l-lactate concentration.

BACKGROUND: Early identification of strangulating obstruction (SO) in horses with colic improves outcomes, yet early diagnosis of horses requiring surgery for SO often remains challenging. OBJECTIVES: To compare blood and peritoneal fluid l-lactate concentrations, peritoneal:blood l-lactate ratio, peritoneal minus blood (peritoneal-blood) l-lactate concentration and other clinical variables for predicting SO and SO in horses with small intestinal lesions (SO-SI) and then to develop a multivariable model to predict SO and SO-SI. STUDY DESIGN: Retrospective cohort. METHODS: A total of 197 equids admitted to a referral institution for colic between 2016 and 2019 that had peritoneal fluid analysis performed at admission were included. Twenty-three admission variables were evaluated individually for the prediction of a SO or SO-SI and then using multivariable logistic regression. Odds ratios (ORs) with 95% confidence intervals (CI) and area under the curve of the receiver operator characteristic (AUC ROC) were calculated. RESULTS: All variables performed better in the model than individually. The final multivariable model for predicting SO included marked abdominal pain (OR 5.31, CI 1.40-20.18), rectal temperature (OR 0.30, CI 0.14-0.64), serosanguineous peritoneal fluid (OR 35.34, CI 10.10-122.94), peritoneal-blood l-lactate (OR 1.77, CI 1.25-2.51), and peritoneal:blood l-lactate ratio (OR 0.36, CI 0.18-0.72). The AUC ROC was 0.91. The final multivariable model for predicting SO-SI included reflux volume (OR 0.69, CI 0.56-0.86), blood l-lactate concentration (OR 0.43, CI 0.22-0.87), serosanguineous peritoneal fluid (OR 4.99, CI 1.26-19.74), and peritoneal l-lactate concentration (OR 3.77, CI 1.82-7.81). MAIN LIMITATIONS: Retrospective, single-hospital study design. CONCLUSIONS: Blood and peritoneal fluid l-lactate concentrations should be interpreted in conjunction with other clinical variables. The relationship between peritoneal and blood l-lactate concentration for predicting SO or SO-SI was complex when included in a multivariable model. Models to predict SO probably vary based on lesion location.

Early Identification of Intestinal Strangulation: Why It Is Important and How to Make an Early Diagnosis.

Horses with colic caused by intestinal strangulation can have an excellent outcome with early surgical correction of the obstruction. The expense associated with surgery is typically less with early lesion correction. The challenge is making an early diagnosis of intestinal strangulation. Although for some horses with a strangulating obstruction, the need for surgery is made based on severe colic signs or lack of response to analgesia, in other horses, it is less obvious. Signalment, history, and meticulous physical examination, combined with some targeted diagnostic procedures can help with early diagnosis of intestinal strangulation. Improving the outcome of these horses requires diligence and a team-based approach from the owner or caregiver, primary care veterinarian, and specialists.

Outcomes of pregnant broodmares treated for colic at a tertiary care facility.

OBJECTIVE: To evaluate, following colic admission during pregnancy, (1) broodmare survival; (2) the frequency of recurrent colic in broodmares and its associated variables, and (3) pregnancy outcome and the variables associated with a negative pregnancy outcome. STUDY DESIGN: Ambidirectional observational cohort study. ANIMALS: One hundred and four client-owned broodmare admissions. METHODS: Admissions of pregnant mares from June 2010 until October 2016 were included. Data were collected until November 2017. Cox proportional hazards regression analysis was performed to evaluate variables associated with broodmare survival. Logistic regression analysis was used to examine the variables associated with recurrent colic and pregnancy outcome. RESULTS: Broodmares from 73/104 (70.2%) admissions were discharged alive. Lesion category, admission hyperlactatemia (hazard ratio (HR) 3.24, 95%, CI 1.28-8.22, P = .013), and admission high packed cell volume (HR 2.89, 95% CI 1.29-6.47, P = .010) were associated with reduced survival. Recurrent colic was observed in broodmares from 33/70 admissions (47.1%). The final multivariable model for recurrent colic included Thoroughbred breed (OR 5.09, 95% CI 1.58-16.4, P = .006) and age (OR .876, 95% CI .747-1.03, P = .105). Overall, negative pregnancy outcome was 14/65 (21.5%). Lesion category, evidence of systemic inflammatory response syndrome (SIRS) in hospital (OR 31.2, 95% CI 2.09-466.5, P = .013), and diarrhea in hospital (OR 379.3, 95% CI 97.1-1482.0, P < .001) were associated with increased negative pregnancy outcome. Altrenogest administration was inversely associated with negative pregnancy outcome (OR 0.029, 95% CI .004-.222, P = .001). CONCLUSION: Pregnant broodmares admitted for colic had lower survival than anticipated and were at risk of recurrent colic. Markers of broodmare disease severity were associated with pregnancy outcome. CLINICAL SIGNIFICANCE: Lesion category, hematologic variables (packed cell volume and l-lactate concentration), evidence of SIRS, and diarrhea were useful for predicting broodmare and pregnancy outcomes.

Acute abdominal dehiscence following laparotomy: A multicentre, international retrospective study.

BACKGROUND: Incisional complications are a common cause of morbidity following laparotomy. Although uncommon, acute abdominal dehiscence (AAD) is a potentially fatal post-operative complication. However, few AAD cases are described in the literature. OBJECTIVES: To describe common features of cases of AAD following ventral midline laparotomy, management and outcomes. STUDY DESIGN: Retrospective case series. METHODS: Hospital records of horses that underwent a ventral midline laparotomy at nine hospitals in the UK, Ireland and USA over a 10-year period (2009-2019) were reviewed. Data were collected for pre-, intra- and post-operative factors that were considered relevant. Descriptive statistical analysis was performed. RESULTS: A total of 63 cases of AAD were identified. AAD occurred due to tearing of sutures through the linea alba or rupture of the body wall adjacent to the suture line in 46 horses (73%). AAD occurred at a median of 5 days (0.5-70 days) post-operatively and broodmares accounted for 25% of the cases (n = 16). Surgical site infection developed prior to AAD in 28 horses (44%); leakage of peritoneal fluid occurred in 5% of horses prior to AAD being identified. Surgical repair was performed in 27 horses (43%), 10 (16%) were treated conservatively and 26 (41%) were euthanised immediately. Repair was most frequently performed using suture (n = 14), wire (n = 5) or a combination (n = 5). Overall survival to hospital discharge was 39% (24/63). Where surgical repair was performed, 15 horses (56%) survived to hospital discharge; 9 horses (90%) managed conservatively survived to hospital discharge. MAIN LIMITATIONS: Follow-up was not performed for all cases following hospital discharge and some data were incompletely recorded in hospital files. CONCLUSIONS: Previously stated causative factors for AAD were not consistent features in the present study. Surgical site infection following laparotomy and pregnant or early post-partum mares may be important risk factors for AAD and warrant further investigation.

Experimental crossover study on the effects of withholding feed for 24 h on the equine faecal bacterial microbiota in healthy mares.

BACKGROUND: An association between equine gastrointestinal disease causing colic signs and changes in faecal bacterial microbiota has been identified. The reasons for these changes and their clinical relevance has not been investigated. Withholding feed, which is an integral part of managing horses with colic, may contribute to the observed changes in the microbiota and impact interpretation of findings in horses with colic. Study objectives were, therefore, to determine the effect of withholding feed for 24 h on equine faecal bacterial microbiota in healthy mares to differentiate the effects of withholding feed from the changes potentially associated with the disease. RESULTS: Species richness and Shannon diversity (alpha diversity) were significantly lower at the late withheld (10-24 h post withholding feed) and early refed (2-12 h post re-feeding) time points compared to samples from fed horses (P < 0.01). Restoration of species richness and diversity began to occur at the late refed (18-24 h post re-feeding) time points. Horses having feed withheld had a distinct bacterial population compared to fed horses (beta diversity). Bacteroidetes BS11 and Firmicutes Christensenellaceae, Christensenella, and Dehalobacteriaceae were significantly increased in horses withheld from feed primarily during the late withheld and early refed time points. Bacteroidetes Marinilabiaceae and Prevotellaceae, Firmicutes Veillonellaceae, Anaerovibrio, and Bulleidia, and Proteobacteria GMD14H09 were significantly decreased in horses with feed withheld at late withheld, early refed, and late refed time periods (P < 0.01). Changes in commensal gut microbiota were not significant between groups. CONCLUSIONS: Withholding feed has a significant effect on faecal bacterial microbiota diversity and composition particularly following at least 10 h of withholding feed and should be taken into consideration when interpreting data on the equine faecal bacterial microbiota in horses.

Changes in the faecal bacterial microbiota during hospitalisation of horses with colic and the effect of different causes of colic.

BACKGROUND: Previous studies have identified alterations in the faecal microbiota of horses with colic; however, further work is needed to interpret these findings. OBJECTIVES: To compare the faecal microbiota of horses presenting for colic at hospital admission, day 1 and day 3/discharge and with different colic duration and lesion locations. STUDY DESIGN: Prospective observational clinical study. METHODS: Faecal samples were collected from 17 colic cases at hospital admission, on day 1 and on day 3 post-admission or at the time of hospital discharge if prior to 72 hours. Faecal samples were extracted for genomic DNA, PCR-amplified, sequenced and analysed using QIIME. Species richness and Shannon diversity (alpha diversity) were estimated. The extent of the relationship between bacterial communities (beta diversity) was quantified using pairwise UniFrac distances, visualised using principal coordinate analysis (PCoA) and statistically analysed using permutational multivariate analysis of variance (PERMANOVA). The relative abundance of bacterial populations at the different time points and in different types of colic was compared using ANCOM. RESULTS: There was a decrease in species richness from admission to day 3/hospital discharge (P < .05), and a lower species richness (P = .005) and Shannon diversity (P = .02) in horses with colic ≥60 h compared to <60 h. Based on PCoA and PERMANOVA, there was a significant difference in bacterial community composition for horses with different colic duration (P = .001) and lesion location (P = .006). Several differences in bacterial phyla and genera were observed at different time points and with different types of colic. MAIN LIMITATIONS: Relatively low numbers and a diverse population of horses. CONCLUSIONS: The microbiota change from hospital admission to day 3/discharge in horses with colic and horses with colic ≥60 h and large colon lesions have a distinct bacterial population compared to horses with colic <60 h and small intestinal lesions.

Geographic Disparities in Clinical Characteristics of Duodenitis-Proximal Jejunitis in Horses in the United States.

Duodenitis-proximal jejunitis (DPJ) is an idiopathic and potentially fatal disease of horses characterized by abdominal pain, proximal intestinal inflammation, and subsequent gastric and small intestinal fluid accumulation. Although this disease is known to be costly and life threatening in the equine industry, the severity of clinical signs can vary widely, and an exact etiology has yet to be elucidated. This study looked to identify differences in clinical parameters of horses with DPJ between geographic regions in an effort to corroborate anecdotal reports and support theories of differing etiologies. Case records were compared from veterinary academic referral hospitals in three different geographic locations in the United States to determine if significant differences in clinical, clinicopathologic, and prognostic characteristics exist among horses with DPJ. Clinical measurements on presentation that were significantly different between regions included heart rate, peritoneal total protein, albumin, anion gap, aspartate aminotransferase, gamma-glutamyl transferase, sodium, chloride, potassium, and creatinine. Duration of hospitalization and maximum body temperature while hospitalized were also different between regions. There were no significant differences in peritoneal cell count, total white blood cell count, neutrophil count, band neutrophils, calcium, total plasma protein, temperature on presentation, duration of reflux, total reflux volume, or age between hospitals. The mortality rates between hospitals were not significantly different. Increased severity of clinical signs and biochemical abnormalities were identified in the Southeastern United States hospital compared with the Northeastern and Western hospitals. A prospective, multicenter case-control study could identify risk factors contributing toward regional differences in this disease in the future.

Multicenter Placebo-Controlled Randomized Study of Ethyl Pyruvate in Horses Following Surgical Treatment for ≥ 360° Large Colon Volvulus.

Identifying therapies that mitigate ischemic colonic injury and improve mucosal healing and intestinal viability are crucial to improving survival in horses with ≥360° large colon volvulus (LCV). Ethyl pyruvate is the ethyl ester of pyruvate with diverse pharmacologic effects that limit ischemic injury and hasten intestinal mucosal repair in preclinical rodents, sheep and swine models. The objective of this study was to determine the effects of ethyl pyruvate on systemic indices of colon viability, expression of inflammatory genes in whole blood, morbidity and survival after surgical correction of LCV compared to controls. Horses received either 150 mg/kg ethyl pyruvate in 1 liter lactated Ringer's solution (LRS) or 1 liter LRS intravenously (IV) every 6 h for 24 h following surgical recovery for correction of LCV. Colic duration, perioperative heart rate (HR), packed cell volume (PCV), total solids (TS), blood L-lactate concentration, surgical time, intraoperative episodes of hypoxemia and hypotension, expression of inflammatory cytokine genes, fecal consistency and survival to hospital discharge were compared between ethyl pyruvate treated horses and controls. Twenty-two horses, 12 receiving ethyl pyruvate and 10 controls, were enrolled in the study. Ethyl pyruvate was safely administered to horses following surgical correction of LCV. No significant effects of ethyl pyruvate on post-operative variables, including survival, were found. Seven of 12 ethyl pyruvate treated horses and 5/10 controls survived to hospital discharge. Higher HR, PCV and blood L-lactate concentration at the time of hospital admission, P = 0.005, 0.01, 0.04, respectively, 24 h after surgery, P = 0.001, 0.03, 0.02, respectively, were associated with death. Heart rate, P = 0.005, 48 h after surgery was associated with death. Ethyl pyruvate was safely administered to horses following correction of LCV with no apparent adverse events but was not associated with improved post-operative outcomes including survival. A larger, randomized control trial is needed to fully evaluate the effectiveness of ethyl pyruvate. A major limitation of this investigation is the small sample size, making the study underpowered and creating a high possibility of type II error.

Use of perioperative variables to determine the requirement for repeat celiotomy in horses with postoperative reflux after small intestinal surgery.

OBJECTIVE: To determine whether perioperative variables can be used to differentiate a medical vs a surgical reason for postoperative reflux (POR) after small intestinal (SI) surgery in horses. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Horses >1 year of age that recovered from SI surgery and had POR. METHODS: Medical records of horses that underwent SI surgery and developed POR from 2009-2015 were reviewed. Surgical reasons for POR were defined as an anastomosis complication, mechanical obstruction, or nonviable intestine identified at repeat celiotomy/necropsy. A medical reason for POR was presumed when the POR improved with medical treatment or when no surgical reasons were identified at repeat celiotomy/necropsy. Perioperative variables were analyzed and used to develop a logistic regression model. RESULTS: Fifty-one horses had POR after SI surgery. After initial SI surgery, 14 horses had surgical reasons for POR diagnosed at repeat celiotomy or necropsy. Thirty-seven horses were considered to have medical reasons for POR because their POR resolved with medical management or functional ileus was diagnosed at repeat celiotomy/necropsy. A greater volume and a greater duration of POR were not associated with a surgical reason for POR. Rather, a postoperative (PO) fever and the timing of colic in the PO period were associated with a surgical reason for POR. CONCLUSION: Horses that developed a fever and colic in the PO period after SI surgery were more likely to have a surgical reason for POR. CLINICAL SIGNIFICANCE: These findings may provide guidance for clinicians when they are making decisions about repeat celiotomy in horses with POR after SI surgery.

In vitro effects of poly(ADP-ribose) polymerase inhibitors on the production of tumor necrosis factor-α by interferon- γ - and lipopolysaccharide-stimulated peripheral blood mononuclear cells of horses.

OBJECTIVE: To evaluate effects of poly(ADP-ribose) polymerase-1 (PARP1) inhibitors on the production of tumor necrosis factor-α (TNF-α) by interferon-γ (IFN-γ)- and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of horses as an in vitro model of inflammation in horses. SAMPLE: 1,440 samples of PBMCs from 6 healthy research horses. PROCEDURES: From heparinized whole blood samples, PBMC cultures were obtained. An initial dose-response trial on 48 PBMC samples from 2 horses (24 samples each) was used to determine concentrations of IFN-γ and LPS for use as low- and high-level stimulation concentrations. Seventy-two PBMC samples from 6 horses were assigned equally to 1 of 4 PARP1 inhibition categories: no PARP1 inhibitor (PARP1 inhibition control); 2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carbozamide dihydrochloride (ABT888);4-(3-(1-(cyclopropanecarbonyl)piperazine-4-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one (AZD2281); or N-(6-oxo-5,6-dihydrophenanthridin-2-yl) -N,N-dimethylacetamide hydrochloride (PJ34). Samples of PBMCs from each horse and each PARP1 inhibition category were then assigned to 1 of 3 levels of IFN-γ and LPS stimulation: none (control), low stimulation, or high stimulation. After a 24-hour incubation period, a TNF-α ELISA was used to measure TNF-α concentration in the supernatant. Results were compared across treatments and for each horse. Data were analyzed with repeated-measures ANOVA. RESULTS: Median TNF-α concentration was significantly lower for PJ34-treated, high-level stimulated PBMCs than for PARP1 inhibition control, high-level stimulated PBMCs; however, no other meaningful differences in TNF-α concentration were detected among the inhibition and stimulation combinations. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that PJ34 PARP1 inhibition may reduce TNF-α production in horses, a potential benefit in reducing inflammation and endotoxin-induced damage in horses.

Clinical findings associated with development of postoperative reflux and short-term survival after small intestinal surgery in geriatric and mature nongeriatric horses.

OBJECTIVE: To determine risk factors, especially age, associated with postoperative reflux (POR; >2 L of reflux present upon intubation), high-volume POR (≥20 L in 24 hours), and short-term outcome after small intestinal (SI) surgery. STUDY DESIGN: Retrospective case-control study. SAMPLE POPULATION: Horses aged ≥16 years (geriatric; range, 16-30; n = 44) and <16 years (mature; range, 2-15; n = 39) with an SI surgical lesion that survived general anesthesia and did not have a second exploratory celiotomy during the same visit. METHODS: Medical records (2009-2015) were reviewed; perioperative variables were evaluated for associations with outcomes by using multivariable logistic regression. RESULTS: Postoperative reflux was associated with an increasing packed cell volume at admission (odds ratio [OR], 1.08; 95% CI, 1.00-1.16; P = .042) and presence of nasogastric reflux at admission (OR, 4.61; 95% CI, 1.3-15.69; P = .014). High-volume POR was associated with an increasing glycemia at admission (OR, 1.19; 95% CI, 1.01-1.40; P = .041), presence of nasogastric reflux at admission (OR, 10.05; 95% CI, 2.21-45.74; P = .003), and SI resection (OR, 10.52; 95% CI, 1.81-61.25; P = .009). Increasing surgical time (OR, 2.50; 95% CI, 1.16-5.29; P = .019) and high-volume POR (OR, 6.37; 95% CI, 2.12-19.12; P = .001) were associated with nonsurvival. CONCLUSION: Age, considered as both a continuous variable and a categorical variable, was not associated with the development of POR, high-volume POR, or nonsurvival. CLINICAL SIGNIFICANCE: Age does not influence the occurrence of POR and should not negatively impact an owner's decision to pursue surgery in aged horses.

Serum amyloid A concentration in postoperative colic horses and its association with postoperative complications.

OBJECTIVE: To determine serum amyloid A (SAA) concentrations in the postoperative (PO) colic horse and its association with PO complications and infection. STUDY DESIGN: Prospective case series. ANIMALS: Fifty-one horses after colic surgery. METHODS: Blood samples from horses undergoing exploratory celiotomy were analyzed for quantitative SAA and fibrinogen concentrations and for neutrophil count at days 0, 1, 2, and 4-6 and at hospital discharge. RESULTS: Complications developed in 35 (69%) horses and included PO colic (n = 13, 25%), PO reflux (n = 11, 22%), intravenous catheter (IVC) complications (n = 11, 22%), low-grade fever (n = 11, 22%); surgical site infection (SSI; n = 9, 18%), high-grade fever (n = 7, 14%), and diarrhea (n = 4, 8%). There was an association between day 2 SAA and PO colic (P = .004), diarrhea (P = .042), IVC complications (P = .008), and PO reflux (P = .008) as well as day 4-6 SAA and PO colic (P = .004) and diarrhea (P = .018). Discharge SAA concentration was associated with SSI (P = .001). Fibrinogen concentrations at days 4-6 and at discharge were associated with PO colic (P = .003), diarrhea (P = .004), IVC complications (P = .002), and PO reflux (P = .023). No differences were seen in SAA, fibrinogen, or neutrophils between horses with PO infection vs those with non-infection-associated complications. CONCLUSION: Serum amyloid A was markedly increased in the PO period in all horses but did not differ between PO infection and noninfection complications. The amount of inflammation associated with PO colic and colic surgery was high and may have affected the predictive value of SAA for early PO infection. CLINICAL SIGNIFICANCE: Although increases occurred earlier, measurement of SAA with a point-of-care analyzer may not be a more sensitive indicator of infection in the early PO colic horse than fibrinogen concentration. Serum amyloid A may help detect SSI in the late PO period.

Characterization of the fecal microbiota of healthy horses.

OBJECTIVE To characterize the fecal microbiota of horses and to investigate alterations in that microbiota on the basis of sample collection site (rectum vs stall floor), sample location within the fecal ball (center vs surface), and duration of environmental exposure (collection time). ANIMALS 6 healthy adult mixed-breed mares. PROCEDURES From each horse, feces were collected from the rectum and placed on a straw-bedded stall floor. A fecal ball was selected for analysis immediately after removal from the rectum and at 0 (immediately), 2, 6, 12, and 24 hours after placement on the stall floor. Approximately 250 mg of feces was extracted from the surface and center of each fecal ball, and genomic DNA was extracted, purified, amplified for the V1-V2 hypervariable region of the 16S rDNA gene, and analyzed with a bioinformatics pipeline. RESULTS The fecal microbiota was unique for each horse. Bacterial community composition varied significantly between center and surface fecal samples but was not affected by collection time. Bacterial community composition varied rapidly for surface fecal samples. Individual bacterial taxa were significantly associated with both sample location and collection time but remained fairly stable for up to 6 hours for center fecal samples. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, for horses, fecal samples for microbiota analysis should be extracted from the center of fecal balls collected within 6 hours after defecation. Samples obtained up to 24 hours after defecation can be analyzed with the realization that some bacterial populations may deviate from those immediately after defecation.

Influence of Salmonella status on the long-term outcome of horses after colic surgery.

OBJECTIVE: To compare long-term outcome of Salmonella-positive versus Salmonella-negative horses discharged from hospital after colic surgery. STUDY DESIGN: Retrospective case-control. ANIMALS: Horses discharged from the hospital after colic surgery. For each horse with positive culture for Salmonella enterica (SAL-POS, n = 59), at least 2 horses testing negative for S. enterica (SAL-NEG, n = 119) were enrolled. METHODS: Owners were interviewed via phone at least 12 months after surgery regarding: (1) complications after discharge from the hospital; (2) duration of survival; and (3) return to prior or intended use. Association between immediate postoperative clinical variables such as Salmonella status and long-term measures of outcome was tested via ratios (odds ratio [OR]) and 95% confidence intervals. Data were analyzed for survival using a Cox proportional hazards model and for return to use using multivariable logistic regression. RESULTS: SAL-POS horses had a higher OR of surgical site infection (2.7 [1.1-6.9] P = .027) and weight loss (6.8 [1.8-26.1] P = .002). At the time of follow-up, there were 53/56 (95%) SAL-POS and 99/118 (84%) SAL-NEG horses alive. The final multivariable model for nonsurvival included postoperative colic (hazard ratio 7.6 [2.8-19.2] P = .002) and the interaction between Salmonella status and duration of rectal temperature > 103°F postoperatively (SAL-POS 1.04 [1.01-1.07] and SAL-NEG 1.16 [1.06-1.25], P = .005). The majority of horses returned to their intended use regardless of their SAL-POS (38/50, 76%) or SAL-NEG (77/96, 80%, P = .498) status. CONCLUSION: Salmonella-positive horses that survive to discharge from the hospital after colic surgery have similar risks of long-term complications (colic/diarrhea), survival, and return to function than Salmonella-negative horses.

The activity and inhibition of poly(ADP-ribose) polymerase-1 in equine peripheral blood mononuclear cells in vitro.

OBJECTIVES: To evaluate the poly (ADP-ribose) polymerase-1 (PARP1) enzyme and its inhibition in horses and explore its potential as a novel therapeutic target for equine intestinal ischemia-reperfusion injury by (1) identifying poly (ADP-ribose) (PAR) as an indication of PARP1 activation in equine cells using available immunoblot analytical techniques, (2) inducing PARP1 activation in an in vitro oxidative DNA damage model, (3) and demonstrating the inhibition of PARP1 in equine cells using commercially available PARP1 inhibitors. DESIGN: Experimental study. ANIMALS: Blood samples were collected from systemically healthy ponies (n = 3) and horses (n = 3). INTERVENTIONS: (1) Equine peripheral blood mononuclear cells were exposed to 3 different concentrations of hydrogen peroxide (H2 O2 ) and were lysed at specific time points. PARP1 activity was then assessed by using immunoblot analyses to determine PAR levels. (2) Equine peripheral blood mononuclear cells were preincubated with defined concentrations of PARP1 inhibitors prior to H2 O2 -mediated PARP1 stimulation. PAR levels reflecting PARP1 activity were determined using immunoblot analyses. MEASUREMENTS AND MAIN RESULTS: Commercially available anti-PAR antibodies were used successfully to identify equine PAR. There was a significant increase in PAR accumulation following treatment with H2 O2 . All of the tested PARP inhibitors significantly reduced PAR accumulation to or below basal levels following treatment with H2 O2 . CONCLUSIONS: This proof of principle study demonstrated that PAR, an indicator of PARP1 activity, can be identified in the equine species using immunoblot techniques, that equine PARP1 can be activated by H2 O2 -induced DNA damage, and that this activation can be inhibited by PARP1 enzyme inhibitors. The data suggest that the PARP1 pathway plays a role in the equine cellular response to oxidative DNA damage and supports its potential as a novel therapeutic target. Further research documenting an increase in PAR levels in vivo and the efficacy of PARP1 inhibitors in an equine intestinal ischemia-reperfusion model is needed.

End-to-Side Versus Side-to-Side Jejunocecostomy in Horses: A Retrospective Analysis of 150 Cases.

OBJECTIVES: To determine factors associated with postoperative reflux, postoperative colic, repeat celiotomy, and survival in horses after end-to-side (E2S) or side-to-side (S2S) jejunocecostomy. STUDY DESIGN: Retrospective, multicenter study. SAMPLE POPULATION: Horses (n = 150). METHODS: Admissions, intra- and postoperative data were collected from medical records of horses that had E2S or S2S jejunocecostomy. Descriptive statistics were calculated and data were analyzed using parametric and nonparametric tests, linear and multivariate logistic regression with significance set at P < .05. Kaplan-Meier estimate of the survival function was performed. RESULTS: One hundred fifty horses (S2S = 90, E2S = 60) were included. S2S procedures were performed using staples (n = 57) or hand-sewn (33). Method of anastomosis was not significantly associated with development of postoperative reflux or colic, repeat celiotomy, whether the horse was alive at hospital discharge or 12 months after discharge. The number of years that the principal surgeon was boarded by the American College of Veterinary Surgeons significantly affected whether the horse was discharged from the hospital alive (P = .003). Age (P = .006) was significantly associated with 12-month survival. Increased age (P = .013) and administration of prokinetic medication (P = .0006) were significantly associated with development of postoperative reflux. Sixty-eight (76%) horses with S2S and 52 (87%) horses with E2S were discharged alive. CONCLUSION: Age, patient related variables, and surgeon experience may influence morbidity and mortality more than method of jejunocecostomy.

Short-term complications after colic surgery in geriatric versus mature non-geriatric horses.

OBJECTIVE: To compare in geriatric and mature horses the occurrence of short-term complications and short-term outcome associated with complications after colic surgery. STUDY DESIGN: Retrospective case-control study. SAMPLE POPULATION: Horses aged ≥20 years (geriatric, n = 78) and 4-15 years (mature non-geriatric, n = 156) that had exploratory celiotomy for colic and survived recovery from general anesthesia. METHODS: Medical records (2000-2010) of horses that recovered from general anesthesia after colic surgery were reviewed. Postoperative complications evaluated included postoperative reflux (POR), diarrhea, inappetence, fever, leukopenia, incisional infection, incisional dehiscence, thrombophlebitis, colic, repeat celiotomy, pneumonia, and laminitis. Short-term outcome (alive vs. dead at hospital discharge) of geriatric and mature horses with these complications were compared. Data were analyzed using a χ(2) or Fisher's exact test or an ANOVA. Level of significance P < .05. RESULTS: Geriatric horses had higher odds of having a small intestinal strangulating lesion than mature horses. A higher proportion of geriatric horses had POR and inappetence; however, there was no difference in the proportion of geriatric and mature horses with small intestinal strangulating lesions having POR. Short-term outcome with and without complications was similar between the 2 age groups. CONCLUSION: Geriatric and mature horses have similar occurrences of short-term complications and short-term outcomes associated with complications after colic surgery.

Current treatment of ascending colon volvulus in horses: a survey of ACVS Diplomates.

OBJECTIVE: To report the results of a survey of opinions on current treatments and estimated outcomes of ascending colon volvulus in horses. STUDY DESIGN: Web-based survey. SAMPLE POPULATION: American College of Veterinary Surgeons (ACVS) Diplomates (n = 151) who perform gastrointestinal surgery in horses. METHODS: ACVS Diplomates with credentials in the large animal specialty obtained by examination in 2010 or earlier (n = 410) were solicited by e-mail to complete a web-based survey designed to determine ascending colon volvulus treatment preferences and outcomes. RESULTS: Responses were obtained from 162 ACVS Diplomates, of which 151 currently performed gastrointestinal surgery in horses. Horses surgically treated with ascending colon volvulus accounted for ≤ 20 cases/year and primary treatment was most often anatomic reduction with or without pelvic flexure enterotomy. Median estimated survival rate was 70% and surgical treatments were not associated with estimated survival (P = .27). Diplomates identified early surgical correction as the single most important factor impacting survival of horses surgically treated for ascending colon volvulus. CONCLUSIONS: Reported survival rates for horses with ascending colon volvulus were good. Respondents indicated this might be due in part to early surgical treatment. Survey investigations can provide preliminary data for future prospective studies and facilitate a consensus among Diplomates in treatment of surgical disease.

Outcome of Surgical and Medical Management of Cecal Impaction in 150 Horses (1991-2011).

OBJECTIVE: To evaluate short- and long-term outcome after medical and surgical management of horses with cecal impaction and to determine reasons for death or euthanasia. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 150). METHODS: Data collected from medical records (1991-2011) of horses with a diagnosis of cecal impaction, included signalment, history of recent disease/surgical procedure, admission data, management (medical, typhlotomy alone, jejunocolostomy), complications, and outcome. Short-term outcome (alive or dead at discharge) and long-term outcome (alive or dead at ≥1 year) were determined by telephone interview. Data were analyzed using a χ(2) or Fisher's exact test. Level of significance was P < .05. RESULTS: Of 150 horses hospitalized with a diagnosis of cecal impaction, 102 (68%) had a history of recent disease or a surgical procedure. Thirty-eight horses (25%) had cecal perforation at admission and 3 horses (2%) were euthanatized without treatment. Of 109 horses treated, 59 (54%) were managed medically and 50 (46%) surgically (typhlotomy [26]; jejunocolostomy [24]). The proportion of horses alive at hospital discharge was significantly lower for horses managed medically (61%) compared with surgically (82%; P = .02) but there was no difference between horses managed with typhlotomy alone (77%) or with jejunocolostomy (88%; P = .47). There were 57% of horses managed medically alive at 1 year. There was a similar proportion of horses alive at 1 year after typhlotomy alone (73%) and jejunocolostomy (70%; P = .86). CONCLUSIONS: Compared to the recent reports, the proportion of horses alive at hospital discharge was lower for both medically and surgically managed horses with cecal impaction. There was decreased survival for horses treated medically than those treated surgically; however, no significant difference was seen in survival between horses managed with typhlotomy alone versus jejunocolostomy.