Effects of dry period energy intake on insulin resistance, metabolic adaptation, and production responses in transition dairy cows on grass silage-based diets.

High energy intake in the dry period has reportedly had adverse effects on mobilization of body reserves, dry matter intake, and productivity of dairy cows. We investigated whether grass silage (GS) fed ad libitum (high energy intake, HEI; 141% of daily metabolizable energy requirements) in an 8-wk dry period affects metabolic adaptation-specifically, peripheral insulin resistance-compared with a total mixed ration consisting of GS, wheat straw, and rapeseed meal (55/40/5%; controlled energy intake, CEI; 108% of metabolizable energy/d) fed ad libitum. Multiparous Ayrshire dairy cows (n = 16) were used in a randomized complete block design until 8 wk after parturition. Commercial concentrates were fed 1 and 2 kg/d during the last 10 to 6 and 5 to 0 d before the expected calving date, respectively. Postpartum, a similar lactation diet with ad libitum access to GS and increasing concentrate allowance (maximum of 16 kg/d) was offered to all. The HEI group gained more body weight and had higher plasma insulin, glucose, and ß-hydroxybutyrate concentrations than the CEI group prepartum. Postpartal plasma glucose tended to be higher and milk yield was greater from wk 5 onward for HEI compared with CEI cows. An intravenous glucose tolerance test (IVGTT) was performed at -13 ± 5 d and 9 ± 1 d relative to calving. The HEI cows had greater insulin response to glucose load and smaller area under the response curve for glucose than CEI cows in prepartal IVGTT. Thus, compensatory insulin secretion adapted to changes in insulin sensitivity of the peripheral tissues, preserving glucose tolerance of HEI cows. Higher insulin levels were needed in HEI cows than in CEI cows to elicit a similar decrement of nonesterified fatty acid concentration in prepartal IVGTT, suggesting reduced inhibition of lipolysis by insulin in HEI cows before parturition. In conclusion, high energy intake of moderately digestible GS with low concentrate feeding in the close-up dry period did not have adverse effects on metabolic adaptation, insulin sensitivity, and body mobilization after parturition. Instead, this feeding regimen was more beneficial to early-lactation performance than GS-based total mixed ration diluted with wheat straw.

Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide (DMSO) in the horse following topical, oral, and intravenous administration.

Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t1/2α ) and beta (t1/2ß ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median absorption (t1/2ab ) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2) hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 µg/ml, occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma concentrations were 1.2-8.2 µg/ml occurring at 2-4 hr. Fractional absorption following TOP administration was 0.48 (0.315-4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr-1  kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were 2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr-1  kg-1 .

Effects of dietary energy allowance and decline in dry matter intake during the dry period on responses to glucose and insulin in transition dairy cows.

We assessed whether high energy intake during the early dry period [144% of metabolizable energy (ME) requirements/d] followed by a gradual restriction of energy intake in the close-up dry period (119% of ME/d; HEI) impaired whole-body insulin sensitivity compared with a controlled energy intake (100% of ME/d; CEI) throughout the 6-wk dry period. Multiparous Ayrshire dairy cows (n = 16) were blocked by body weight, body condition score, and expected date of parturition and were used in a randomized complete block design until 10 d after parturition. Cows were fed either HEI or CEI diets based on grass silage during the first 3 wk of the dry period and grass silage supplemented with a commercial concentrate (30% of ME intake) during the final 3 wk of gestation. After calving, all cows were fed grass silage ad libitum and an increasing amount of commercial concentrate (maximum 9 kg at d 10 postpartum). Intravenous glucose tolerance tests (IVGTT) and intravenous insulin challenges were performed -10 ± 5 d (n = 15) and +10 ± 1 d (n = 14) relative to parturition. Following glucose injection, we did not find any treatment effects on glucose and insulin responses. The prepartal nonesterified fatty acid (NEFA) response of the HEI group was blunted, basal NEFA and the decrement of NEFA were smaller, and the area under the response curve (AUC) of NEFA was less negative in HEI cows than in CEI cows. The NEFA response reversed after parturition; the NEFA AUC of the HEI group was more negative than that of the CEI group. We did not find similar responses after insulin injection. Across the treatments, NEFA AUC correlated strongly with the basal NEFA concentration during the IVGTT pre- and postpartum. Calculated and model-based indices characterizing the overall glucose tolerance and ß-cell function and the insulin sensitivity were higher after parturition than during the dry period. Consistent with the lower basal insulin, the acute insulin release after the glucose infusion was smaller in postpartal IVGTT than in prepartal IVGTT. The results suggest that whole-body insulin sensitivity of the cows increased after parturition. However, the role of peripheral insulin sensitivity in the regulation of glucose partitioning seems to be minor relative to the major change in insulin secretion and clearance during the periparturient period.

Osteopathology in the Equine Distal Phalanx Associated With the Development and Progression of Laminitis.

Although the equine distal phalanx and hoof lamellae are biomechanically and physiologically integrated, bony changes in the distal phalanx are poorly described in laminitis. The aims of this study were (1) to establish a laminitis grading scheme that can be applied to the wide spectrum of lesions seen in naturally occurring cases and (2) to measure and describe changes in the distal phalanx associated with laminitis using micro-computed tomography (micro-CT) and histology. Thirty-six laminitic and normal feet from 15 performance and nonperformance horses were evaluated. A laminitis grading scheme based on radiographic, gross, histopathologic, and temporal parameters was developed. Laminitis severity grades generated by this scheme correlated well with clinical severity and coincided with decreased distal phalanx bone volume and density as measured by micro-CT. Laminitic hoof wall changes included progressive ventral rotation and distal displacement of the distal phalanx with increased thickness of the stratum internum-corium tissues with lamellar wedge formation. Histologically, there was epidermal lamellar necrosis with basement membrane separation and dysplastic regeneration, including acanthosis and hyperkeratosis, corresponding to the lamellar wedge. The changes detected by micro-CT corresponded to microscopic findings in the bone, including osteoclastic osteolysis of trabecular and osteonal bone with medullary inflammation and fibrosis. Bone changes were identified in horses with mild/early stages of laminitis as well as severe/chronic stages. The authors conclude that distal phalangeal pathology is a quantifiable and significant component of laminitis pathology and may have important implications for early detection or therapeutic intervention of equine laminitis.

Diurnal patterns of grazing behavior and humoral factors in supplemented dairy cows.

Offering feed supplements to grazing dairy cows results in a reduction in grazing time. However, the effect differs depending on the time of day that feeds are offered. To understand the physiological basis for this, associations among circulating factors known to be associated with intake regulation in monogastric species and grazing behavior in the dairy cow were investigated. Seventeen multiparous cows at 28 ± 5 d in milk grazed together and consumed 4.4 kg of dry matter/d of a pelleted concentrate feed supplement, equally split, at the a.m. and p.m. milking. Grazing behavior was recorded over 4 consecutive days in all 17 cows. Blood was sampled from 10 of the 17 cows every 4h over a 48-h period following the grazing behavior measurements; sampling times were staggered by 2h to provide a diurnal profile of humoral factors. Grazing profiles illustrated major grazing bouts after the a.m. and p.m. milking; however, the p.m. grazing bout was characterized as the most intensive and time spent grazing was unaffected by supplementation. Associations among proportion of cows grazing and circulating hormones and metabolites differed throughout the day. During the a.m., relationships were consistent with those reported in monogastric species, with ghrelin and nonesterified fatty acids decreasing and insulin increasing with feeding. In comparison, during the major grazing bout predusk, ghrelin concentrations increased until sunset, despite the large proportion of cows grazing, before declining; this is consistent with ghrelin stimulating the predusk grazing bout. Results indicate that humoral factors known to affect hunger and satiety in monogastric animals may also have a potential role in the physiological regulation of diurnal and feeding behavior in ruminants.

Pharmacokinetics of dexamethasone following intra-articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone.

This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.

A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite.

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2-(1-hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. ACP (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A bayesian hierarchical model was fitted to describe concentration-time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half-life of the parent was considerably less than that of the metabolite. The clearance (Cl/F(PM)) and volume of distribution (V/F(PM)), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.

Investigating the Potential of Electroless Nickel Plating for Fabricating Ultra-Porous Metal-Based Lattice Structures Using PolyHIPE Templates.

The use of polymerized high internal phase emulsions (polyHIPEs) as templates for electroless nickel plating is a promising method for producing ultra-porous metallic lattice structures with consistent wall thickness. These structures have desirable properties such as low density, high specific strength, resilience, and absorbency, making them suitable for various applications including battery electrodes, catalyst supports, and acoustic or vibration damping. This study aimed to optimize and investigate the electroless nickel plating process on polyHIPEs. Initially, a surfactant (Hypermer)-stabilized water-in-oil emulsion based on 2-ethylhexyl-acrylate and isobornyl-acrylate was used as a 3D printing resin to create polyHIPE structures. Then, the electroless nickel plating process was optimized using polyHIPE discs. The study also examined the effects of air, argon, and reducing atmospheres during the heating process to remove the polyHIPE template using metallized 3D-printed polyHIPE lattice structures. The findings indicated that different atmospheres led to the formation of distinct compounds. While nickel-coated polyHIPEs were fully oxidized in an air atmosphere, nickel phosphide (Ni3P) structures occurred in argon and reducing atmospheres along Ni metal. Moreover, in argon and reducing atmospheres, the porous structure of the polyHIPEs was retained as the internal structure was completely carbonized. Overall, the study demonstrated that intricate polyHIPE structures can be used as templates to create ultra-porous metal-based lattices for a wide range of applications.

Effects of abomasal infusion of tallow or camelina oil on responses to glucose and insulin in dairy cows during late pregnancy.

Late pregnancy is associated with moderate insulin resistance in ruminants. Reduced suppression of lipolysis by insulin facilitates mobilization of nonesterified fatty acids (NEFA) from adipose tissue, resulting in elevated plasma NEFA concentrations. Decrease in dry matter intake (DMI) before parturition leads to accelerated lipomobilization and increases plasma NEFA, which may further impair insulin sensitivity. The aim of the study was to evaluate the effects of elevation of plasma NEFA concentration by abomasal infusions tallow (TAL) or camelina oil (CAM) on whole-body responses to exogenous glucose and insulin. We further assessed whether CAM, rich in C18:3n-3, enhances whole-body insulin sensitivity compared with TAL. Six late-pregnant, second-parity, rumen-cannulated dry Ayrshire dairy cows fed grass silage to meet 95% of metabolizable energy requirements were used in a replicated 3 × 3 Latin square with 5-d periods and 5 recovery days between each period. Treatments consisted of abomasal infusion of 500 mL/d (430 g of lipids/d) of water (control), TAL, or CAM administered in 10 equal doses daily. Intravenous glucose tolerance test (IVGTT) and i.v. insulin challenge (IC) were performed on d 5 after 98 and 108 h of treatment infusions, respectively. Infusion of lipids increased basal plasma NEFA concentrations on d 5 (CAM: 0.25; TAL: 0.28; control: 0.17 mmol/L). Following glucose injection, the rate of glucose clearance (CR) was lower in lipid-treated cows (CAM: 1.34; TAL: 1.48; control: 1.74%/min) and time to reach half-maximal glucose concentration (T(1/2)) was longer (CAM: 54; TAL: 47; control: 42 min). Similar responses were observed after insulin injection. Increased plasma NEFA concentration tended to decrease insulin secretion in IVGTT. Infusion of CAM increased plasma C18:3n-3 content (CAM: 26.4; TAL: 16.1; control: 20.9 g/100g of fatty acids). Data suggest that CAM had an insulin-sensitizing effect, because the disposition index and insulin sensitivity index, derived from minimal model analysis, were higher in CAM than in TAL during IVGTT, and lower insulin concentrations during IC led to similar glucose clearance in CAM as in TAL. These results indicate that elevated plasma NEFA concentration per se induces whole-body insulin resistance in late-pregnant dry cows.

Pharmacokinetic profile and pharmacodynamic effects of romifidine hydrochloride in the horse.

Romifidine HCl (romifidine) is an α(2)-agonist commonly used in horses. This study was undertaken to investigate the pharmacokinetics (PK) of romifidine following intravenous (i.v.) administration and describe the relationship between PK parameters and simultaneously recorded pharmacodynamic (PD) parameters. Romifidine (80 µg/kg) was administered by i.v. infusion over 2 min to six adult Thoroughbred horses, and plasma samples were collected and analyzed using liquid chromatography-mass spectrometry. Limit of quantification was <0.1 ng/mL. PD parameters and arterial blood gases were measured for 300 min following romifidine administration. Statistical PD data analysis included mixed-effect modeling. After i.v. administration of romifidine, the plasma concentration-vs.-time curve was best described by a two-compartmental model. Terminal elimination half-life (t(1/2ß) ) was 138.2 (104.6-171.0) min and volumes for central (V(c)) and peripheral (V(2)) compartments were 1.89 (0.93-2.39) and 2.57 (1.71-4.19) L/kg, respectively. Maximum plasma concentration (C(max)) was 51.9 ± 13.1 ng/mL measured at 4 min following commencement of drug administration. Systemic clearance (Cl) was 32.4 (25.5-38.4) mL · min/kg. Romifidine caused a significant reduction in heart rate and cardiac index and an increase in mean arterial pressure (P < 0.05). Sedation score and head height values were significantly different from the baseline values for 120 min (P < 0.05). The decline in cardiovascular and sedative effects correlated with the decline in plasma romifidine concentration (P < 0.05). In conclusion, a highly sensitive analytical technique for the detection of romifidine in equine plasma allowed detailed description of its PK profile. The drug produces long-lasting sedation in horses that corresponds with the long terminal elimination half-life of the drug.

Analysis of conformational variations of the cricoid cartilages in Thoroughbred horses using computed tomography.

REASONS FOR PERFORMING STUDY: Loss of arytenoid abduction is a common post operative complication of laryngoplasty without a definitive cause. It has been a clinical impression during laryngoplasty surgery that there is great conformational variability along the caudal edge of the Thoroughbred cricoid cartilage that could impact post operative retention of suture position. A change in suture position would probably lead to some loss of abduction. Defining any structural variability of the cricoid would be an initial step in determining whether this variability could impact on the retention of suture position. HYPOTHESIS: Anatomical variations in the larynx of Thoroughbred horses may be detected and measured using objective analysis and computed tomography. METHODS: Larynges were harvested from 15 mature Thoroughbred horses. Helical CT scans were performed on each specimen. Three independent observers performed a series of measurements on 2D and 3D reconstruction images using digital software. Measurements included the lateral cricoid angle, the caudal cricoid prominences, the distance to the cricoid slope, the angle of the cricoarytenoid joints (CAJ), the cricoid thickness and the suture angle. Mean, standard deviation, coefficient of variation and linear regression analysis were performed among all observers and all measurements. RESULTS: Notable conformational differences were evident on the 3D reconstructions. The highest degree of variability was found in 3 measurements: the distance to the lateral cricoid slope, the lateral cricoid angle and the cricoid thickness. A larger left CAJ angle directly and significantly correlated with a larger suture angle. CONCLUSIONS: There are notable conformational differences among cricoid specimens in the Thoroughbred larynx. POTENTIAL RELEVANCE: The morphometric differences identified may impact on optimal prosthesis placement and long-term retention. Since a larger lateral cricoid angle may facilitate abduction loss secondary to a displaced and loosened suture, alternative techniques for suture placement may be of value to prevent arytenoid abduction loss.

Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance.

REASONS FOR PERFORMING STUDY: Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. OBJECTIVE: To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. METHODS: Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airway endoscopy. Relationships between horse demographics, resting endoscopic findings, treadmill intensity and implementation of head and neck flexion during exercise with exercising endoscopic findings were examined. RESULTS: Dynamic upper airway obstructions were observed in 72% of examinations. Head and neck flexion was necessary to obtain a diagnosis in 21 horses. Pharyngeal wall collapse was the most prevalent upper airway abnormality, observed in 31% of the examinations. Complex abnormalities were noted in 27% of the examinations. Resting laryngeal dysfunction was significantly associated with dynamic arytenoid collapse and the odds of detecting intermittent dorsal displacement of the soft palate (DDSP) during exercise in horses with resting DDSP was only 7.7%. Exercising endoscopic observations were different from the resting observations in 54% of examinations. CONCLUSIONS: Dynamic upper airway obstructions were common in nonracing performance horses with respiratory noise and/or poor performance. Resting endoscopy was only helpful in determining exercising abnormalities with recurrent laryngeal neuropathy. POTENTIAL RELEVANCE: This study emphasises the importance of exercising endoscopic evaluation in nonracing performance horses with abnormal respiratory noise and/or poor performance for accurate assessment of dynamic upper airway function.

Putative intestinal hyperammonaemia in horses: 36 cases.

REASONS FOR PERFORMING THE STUDY: Intestinal hyperammonaemia (HA) has been infrequently reported in individual horses; however, there have been no studies describing clinical and laboratory data as well as short- and long-term outcome in a larger number of cases. OBJECTIVES: To describe clinical and laboratory data and short- and long-term outcome in a large group of horses with intestinal HA. METHODS: Multi-centred, retrospective study; case records of horses with HA were reviewed and any horse with a clinical or post mortem diagnosis of intestinal HA was included. Hyperammonaemia was defined as a blood ammonium (NH(4) (+)) concentration ≥60 µmol/l and horses with a diagnosis of primary hepatic disease were excluded. Relevant data were recorded and, if appropriate, data from survivors were compared to nonsurvivors to identify potential prognostic indicators. RESULTS: Thirty-six cases, 26 mature horses and 10 foals with intestinal HA were identified. Case histories included diarrhoea, colic and neurological signs and the most common clinical diagnosis was colitis and/or enteritis. The most common clinical and laboratory abnormalities included tachycardia, increased packed cell volume, hyperlactataemia and hyperglycaemia. Fourteen horses (39%) survived to discharge; NH(4) (+) concentration on admission was the only parameter significantly associated with survival. All surviving horses and foals for which follow-up information was available recovered completely and returned to their intended use without further complications. CONCLUSIONS AND POTENTIAL RELEVANCE: Intestinal HA occurs in mature horses and foals and can be associated with severe clinical and laboratory abnormalities; further studies are required to investigate predisposing factors and delineate possible differences in aetiologies.

Measurement of C-peptide concentrations and responses to somatostatin, glucose infusion, and insulin resistance in horses.

REASONS FOR PERFORMING STUDY: Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C-peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. HYPOTHESIS: A human double antibody radioimmunoassay (RIA) detects C-peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. METHODS: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatostatin administered i.v. as a primed continuous rate infusion, followed by 50 nmol human C-peptide i.v. Insulin and C-peptide concentrations were measured in horses (n = 6) undergoing an insulin-modified frequently sampled i.v. glucose tolerance test, and in horses with insulin resistance (n = 10) or normal insulin sensitivity (n = 20). RESULTS: A human RIA was validated for use with equine sera. Endogenous C-peptide secretion was suppressed by somatostatin and median (range) clearance rate was 0.83 (0.15-1.61) ml/min/kg bwt. Mean + or - s.d. C-peptide-to-insulin ratio significantly (P = 0.004) decreased during the glucose tolerance test from 3.60 + or - 1.95 prior to infusion to 1.03 + or - 0.18 during the first 20 min following dextrose administration. Median C-peptide and insulin concentrations were 1.5- and 9.5-fold higher, respectively in horses with IR, compared with healthy horses. CONCLUSIONS: Endogenous C-peptide secretion decreases in response to somatostatin and increases after dextrose infusion. Results suggest that relative insulin clearance decreases as pancreatic secretion increases in response to dextrose infusion. Hyperinsulinaemia in insulin resistant horses may be associated with both increased insulin secretion and decreased insulin clearance. POTENTIAL RELEVANCE: Both C-peptide and insulin concentrations should be measured to assess pancreatic secretion and insulin clearance in horses.

Association between hypercoagulability and decreased survival in horses with ischemic or inflammatory gastrointestinal disease.

BACKGROUND: Coagulopathies are common in horses with ischemic or inflammatory gastrointestinal (GI) disturbances. There is indirect evidence suggesting that early stages of these diseases are characterized by hypercoagulability (HC). HYPOTHESIS/OBJECTIVES: HC, assessed via thromboelastography (TEG), is common in horses with ischemic or inflammatory GI diseases. The degree of HC is correlated with nonsurvival and thrombotic complications. ANIMALS: Thirty client-owned horses with ischemic or inflammatory GI disease, 30 client-owned horses with nonischemic or inflammatory GI disease, and 30 healthy horses (control group). METHODS: Prospective, observational clinical study. TEG profiles of 30 horses with ischemic or inflammatory GI disease were obtained on admission and 48 hours after admission, and these were compared with profiles from 30 horses with nonischemic or inflammatory GI disease and 30 healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin activity (AT), and D-Dimer concentrations were also determined in horses with GI disease. RESULTS: Horses with ischemic or inflammatory GI disease had shorter R times compared with healthy horses (14.8±8.3 versus 22.8±12 minute; P=.011). However, changes were subtle and TEG profiles did not resembled those obtained from animals or humans presumed to be hypercoagulable. Although conventional coagulation testing supported the presence of HC (decreased AT and increased D-Dimer concentrations), TEG and coagulation abnormalities were rarely found in the same horses and the methods were not statistically related. CONCLUSIONS AND CLINICAL IMPORTANCE: There is evidence of HC in horses with GI disease but techniques for diagnoses require refinement.

Sequential plasma lactate concentrations as prognostic indicators in adult equine emergencies.

BACKGROUND: Sequential lactate concentration ([LAC]) measurements have prognostic value in that hospitalized humans and neonatal foals that have a delayed return to normolactatemia have greater morbidity and case fatality rate. HYPOTHESIS: Prognosis for survival is decreased in horses with a delayed return to normal [LAC]. ANIMALS: Two hundred and fifty adult horses presented for emergency evaluation excepting horses evaluated because of only ophthalmologic conditions, superficial wounds, and septic synovitis without systemic involvement. METHODS: Prospective observational study. [LAC] was measured at admission and then at 6, 12, 24, 48, and 72 hours after admission. The change in [LAC] over time ([LAC]deltaT) was calculated from changes in [LAC] between sampling points. RESULTS: Median [LAC] was significantly (P < .001) higher at admission in nonsurvivors (4.10 mmol/L [range, 0.60-18.20 mmol/L]) when compared with survivors (1.30 mmol/L [range, 0.30-13.90 mmol/L]) and this difference remained at all subsequent time points. The odds ratio for nonsurvival increased from 1.29 (95% confidence interval 1.17-1.43) at admission to 49.90 (6.47-384) at 72 hours after admission for every 1 mmol/L increase in [LAC]. [LAC]deltaT was initially positive in all horses but became negative and significantly lower in nonsurvivors for the time periods between 24-72 hours (- 0.47, P = .001) and 48-72 hours (- 0.07, P = .032) when compared with survivors (0.00 at both time periods) consistent with lactate accumulation in nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that lactate metabolism is impaired in critically ill horses and [LAC]deltaT can be a useful prognostic indicator in horses.

Comparison of hematologic and biochemical results on blood obtained by jugular venipuncture as compared with intravenous catheter in adult horses.

BACKGROUND: During hospitalization, horses typically undergo frequent blood sampling for diagnostic testing and monitoring. The need for numerous samples in hospitalized horses makes acquisition from an intravenous catheter (IVC) both convenient and less stressful to the patient. HYPOTHESIS: We hypothesized that there would be no significant difference in the plasma chemistry and CBC variables from blood samples obtained from a jugular catheter as compared with direct jugular venipuncture. ANIMALS: Fifty adult hospitalized horses; 25 receiving constant rate crystalloid therapy, and 25 receiving low volume IV medication. METHODS: This study was conducted using a prospective, blinded, cross-over design. Samples were obtained sequentially by direct venipuncture of the jugular vein and aspiration from an IVC in the contralateral vein after an appropriate presample of blood was obtained and discarded. Samples were submitted for blinded analysis including CBC, plasma chemistry analysis, stall side plasma glucose concentration, PCV, and total protein concentration. Data obtained were analyzed using a Student's t-test with compensation for unequal variances between the 2 groups. Analyses were Bonferroni corrected for a 5% 2-tailed hypothesis test. RESULTS: There were no statistically significant or clinically relevant differences associated with sampling method (venipuncture versus catheter) regardless of fluid administration status in any of the 24 analytes measured. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood samples obtained by IVC have clinically equivalent values to those taken by direct venipuncture in commonly performed analyses. Additional investigation is warranted to establish if this technique is associated with increased complications such as phlebitis or bacteremia.

Equine cheek tooth extraction: Comparison of outcomes for five extraction methods.

BACKGROUND: Post-operative complications are reported for all methods of equine cheek tooth extraction but not all methods carry the same risks. An outcome comparison for commonly used methods is needed so that clinicians can make informed treatment decisions. OBJECTIVES: We conducted a side-by-side comparison of five cheek tooth extraction methods, comparing types and incidence of complications among oral extraction, tooth repulsion (three surgical approaches) and lateral buccotomy techniques. STUDY DESIGN: Retrospective clinical study using hospital medical records. METHODS: Medical records of all horses undergoing cheek tooth extraction between 1997 and 2013 were reviewed. Logistic regression was used to determine the likelihood of various post-operative complications, comparing oral extraction, tooth repulsion by maxillary and mandibular trephination or maxillary sinus bone flap, and lateral buccotomy. RESULTS: The study included 137 horses and 162 cheek teeth extractions. Oral extraction was successful in 71% of patients in which it was attempted. Oral extraction (n = 55) had the lowest incidence of complications (20%) and repulsion by sinus bone flap (n = 20) the highest (80%). Complication rates for repulsion by maxillary (n = 19) and mandibular trephination (n = 28), and extraction by lateral buccotomy (n = 15) were 42, 54 and 53%, respectively. Cheek tooth repulsion by sinus bone flap significantly increased the odds of damage to adjacent teeth, post-operative sinusitis, damage to alveolar bone, delayed alveolar granulation and orosinus fistulation. Repulsion by maxillary trephination significantly increased the odds of superficial incisional surgical site infection; and extraction by lateral buccotomy significantly increased the odds of facial nerve neuropraxia. Post-operative pyrexia was more common in all repulsion methods. MAIN LIMITATIONS: Some clinically relevant differences may have been missed due to small group numbers in several categories. CONCLUSIONS: Oral extraction was associated with fewer post-operative complications than any other methods. Standing oral extraction remains the preferred choice, and recent surgical advances promise to further improve its success rate.

Metabolic modeling using statistical and spreadsheet software: Application to the glucose minimal model.

Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems.

Inflammatory mediators are potential biomarkers for extracorporeal shockwave therapy in horses.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) can potentially mask painful injuries in equine athletes. Tests to detect whether a horse has received ESWT prior to competition are needed. Extracorporeal shockwave therapy is known to affect inflammatory mediators in other species, and if these mediators are altered in the horse, these could serve as biomarkers of ESWT. OBJECTIVES: To test the hypothesis that a single application of ESWT will alter the circulating protein concentrations of 10 inflammatory mediators in horse plasma. STUDY DESIGN: Prospective repeated measures experimental study. METHODS: Eleven healthy horses were administered a single dose of ESWT on the dorsal surface of proximal MCIII. Blood samples were collected at -168, -144, -120, -96, -72, -70, -68, -66, -48, -24, -6, -4, -2, 0 h before and 2, 4, 6, 24, 48, 72, 96, 168, 336 and 504 h after ESWT. Plasma concentrations of interleukin 1 beta (IL-1ß), IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-15, interferon gamma (IFN-γ), soluble toll-like receptor 2 (sTLR2) and tumour necrosis factor alpha (TNF-α) were measured to assess the effects of ESWT on these mediators. RESULTS: Baseline concentrations of inflammatory mediators did not change substantially during the week prior to ESWT. Plasma concentrations of five inflammatory factors changed following ESWT. IL-1ß and IL-6 were significantly down-regulated (P<0.01), while TNF-α, IL-1RA and TLR2 were significantly up-regulated (P<0.01). The remaining cytokines were not significantly affected by ESWT. MAIN LIMITATIONS: This study was performed in a small number of sedentary, healthy pasture-kept horses using a single dose of ESWT applied to a single location. Additional studies are necessary to determine the effect of ESWT on inflammatory mediators in athletic horses undergoing treatment for musculoskeletal injuries. CONCLUSIONS: Plasma concentrations of TNF-α, IL-1ß, IL-1RA, IL-6 and TLR2 were significantly affected by ESWT, and deserve further investigation as possible biomarkers of ESWT.