Cardiovascular changes in horses with atrial fibrillation and high thyroid hormone concentration: a case-control study.

INTRODUCTION: Hyperthyroidism is a predisposing factor for atrial fibrillation (AF) in humans. The relationship between high thyroid hormone (TH) and AF in horses has not been evaluated. OBJECTIVES: The aim of this study is to identify whether (1) high TH concentrations were present in horses with AF, (2) other cardiovascular effects were observed in horses with high TH and AF, and (3) TH status affected recurrence rate. ANIMALS: Twenty-three horses presented with naturally occurring AF. METHODS: Prospective case-control clinical study. Thyroid hormone concentration was measured in horses presenting with AF. Heart rate, electrocardiogram, blood pressure, and an echocardiogram were recorded as part of their clinical workup. Recurrence rate was determined by owner/veterinarian follow-up. RESULTS: High TH concentration was found in 60% of horses with AF. Horses in the high TH group had a higher heart rate (P=0.001), systolic blood pressure (P=0.019), left ventricular free wall thickness (P=0.026), relative wall thickness (P=0.041) and were more likely to have periods of AF with a rapid ventricular response rate (P=0.022). All horses were successfully converted to normal sinus rhythm. The likelihood of recurrence was not different between groups. CONCLUSION: Elevated TH concentration can be found in horses with AF. Other cardiovascular effects of high TH concentrations in other species were also present in horses with AF and elevated TH concentrations. This study recommends measuring TH concentrations in horses presenting for AF with a history of thyroid or iodine supplementation. This study also cautions against TH or iodine supplementation in healthy performance horses.

Nocardioform placentitis in a sample population of mares foaling in southeastern Pennsylvania and northeastern Maryland in 2020.

Nocardioform placentitis (NP) has been associated with mid to late pregnancy loss in mares. To date, disease outbreaks have been described only in central Kentucky, although sporadic, isolated cases have been reported globally. This study describes a series of cases of NP that occurred in a sample population of 299 mares foaling in southeastern Pennsylvania and northeastern Maryland in 2020. These cases coincided with an outbreak of NP that occurred in Kentucky that same year. On farms that reported information on both normal and abnormal foalings, nocardioform organisms/DNA were isolated from 6.3% of placental samples based on aerobic culture and/or PCR. In cases with characteristic gross lesions of the chorion, 41% of cases were positive on aerobic culture and/or PCR. NP was confirmed in 16 mares that had not resided in Kentucky for breeding or any part of gestation. Characteristics of mares confirmed positive for NP, including age, gestation length, and problems during gestation are described. Standardbred mares bred by artificial insemination were less likely to be affected than Thoroughbred mares bred by natural cover. Affected mares had prolonged Stage III labor compared with normal mares. These findings suggest that regional increases in NP may occur outside of Kentucky, potentially in parallel with Kentucky outbreaks.

Cardiac arrhythmias in poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters undergoing high-speed treadmill testing.

The significance of cardiac arrhythmias and their possible association with upper airway obstruction are frequently considered in the clinical investigation of poor performance. The specific aims of this retrospective study of a group of poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters were to: (1) describe the overall frequency and frequency distributions of arrhythmias; (2) describe arrhythmia characteristics including percent prematurity, relative recovery cycle lengths and QRS morphology; (3) describe variability of normal RR intervals; and (4) explore possible associations between upper airway abnormalities and arrhythmia categories during peak exercise and recovery. The records of 103 trotters presented to the Norwegian University of Life Sciences for high-speed treadmill testing were reviewed. The occurrence of at least one arrhythmic event was high (77-78%) when considering all exercise periods and 6-10% prematurity criteria. Triplets, salvos, and/or paroxysmal tachyarrhythmias occurred in 8% of horses during peak exercise. Complex ventricular arrhythmias occurred in 15% of horses in the first 2 min of recovery. Evaluation of QRS morphology and return cycle lengths demonstrated areas of overlap in characteristics typically attributed to either supraventricular or ventricular arrhythmias. There was no association between airway diagnosis and arrhythmias during any exercise period. The maximum average HR during peak exercise was an excellent predicter for complex ventricular arrhythmias during recovery. Because perfect categorization of arrhythmias is not possible, future studies should report descriptive arrhythmia information. Prospective studies that evaluate various degrees of upper airway obstruction and the effect on known initiators of arrhythmogenesis are needed.

Hypercapnia and hyperlactatemia were positively associated with higher-grade arrhythmias during peak exercise in horses during poor performance evaluation on a high-speed treadmill.

Cardiac arrhythmias are common in horses during exercise, especially immediately post-exercise. The objectives of this study were to: (1) describe the frequency and type of cardiac arrhythmias detected in horses during incremental high-speed treadmill exercise testing (ITET); (2) determine if arterial blood gas (ABG) changes at peak and immediately post-exercise were associated with arrhythmias; and (3) determine whether upper or lower airway disease was associated with exercising cardiac arrhythmias. Horses (n = 368) presenting for an ITET underwent resting and exercising upper airway endoscopy, resting, exercising and post-exercise electrocardiography, resting and post-exercise echocardiography and exercising ABG. Arrhythmias were graded by the most severe arrhythmia present. Grade 1 arrhythmias were defined as one or two atrial (APCs) or ventricular premature complexes (VPCs), or one APC and one VPC, detected in 6.9% at peak and 16% at 0-2 min post exercise.. Grade 2 arrhythmias were >2 APCs or VPCs, or both, detected in 5.8% at peak and 16.6% at 0-2 min post exercise. Grade 3 included complex arrhythmias (couplets, triplets, R on T, multiform complexes or paroxysmal atrial or ventricular tachycardia), detected in 4.4% at peak and 7.3% at 0-2 min post exercise. Both partial pressure of arterial CO2 (PaCO2; P = 0.008) and lactate (P = 0.031) were significantly associated with arrhythmias occurring at peak exercise, but not immediately post-exercise. As PaCO2 and lactate increased, arrhythmia severity increased. Blood pH was significantly associated with grades 2 and 3 arrhythmias at 0-2 min post ITET (OR = 0.0002; P < 0.001). There was no significant association between grades 2 and 3 cardiac arrhythmias, inflammatory airway disease (IAD), or exercise-induced pulmonary hemorrhage (EIPH). When adjusted for lactate concentration (P = 0.06), higher PaCO2 concentrations in horses with and without exercising upper respiratory tract (URT) obstruction were associated with higher likelihood of grades 2 and 3 arrhythmias (P < 0.01). This study demonstrated that at peak exercise, with severe hypercapnia and hyperlactatemia, there was increased risk for grades 2 or 3 cardiac arrhythmias and, as the PaCO2 and lactate values increased further, the severity of those arrhythmias increased.

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.

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.

Prevalence of adverse events and their effect on completion of high speed treadmill exercise tests at a single institution (2000-2015).

BACKGROUND: Decline in high speed treadmill (HSTM) exercise testing may be attributed to the rise of over-ground endoscopy and telemetric electrocardiography, in addition to concerns of adverse events during treadmill exercise resulting in injury or inadequate testing. OBJECTIVES: To describe adverse events occurring during HSTM exercise tests at a single institution and determine their effect on likelihood of completing diagnostic HSTM exercise testing. STUDY DESIGN: Retrospective cohort study. METHODS: Pearson's chi-square test was used to determine if a significant difference in frequencies of adverse events existed between complete and incomplete HSTM exercise tests. Two Firth logistic regression models were used to determine likelihood of exercise test completion given the presence of any adverse event, and the likelihood of exercise test completion for each type of adverse event. RESULTS: The majority of horses presenting for HSTM evaluation underwent exercise testing (900/1003; 90%). Eight-hundred and seven (90%) exercise tests were completed. Adverse events occurred in 136 (15%) HSTM exercise tests of which 97 (71%) did not impact ability to complete HSTM testing. Adverse events significantly but variably decreased the likelihood of HSTM exercise test completion. Sixty-six percent of incomplete exercise tests were prematurely terminated due to poor performance abnormalities during which diagnosis of poor performance cause(s) was still achieved. MAIN LIMITATIONS: Variable personnel recorded data over the study period. Per-test rather than per-horse evaluation does not account for the effect of multiple training and testing episodes performed in the same horse. CONCLUSIONS: This study supports the continued usage of HSTM exercise testing for examination of horses with poor performance, with adverse events occurring infrequently. Adverse events reduced the likelihood of completing HSTM exercise testing although not all adverse events affected likelihood of completion similarly. In many cases, a performance limiting problem was identified for horses in which an exercise test was considered incomplete. The Summary is available in Spanish - see Supporting information.

A multifaceted analytical approach for detecting effects on semen quality when using small sample sizes.

Driven by technical, logistical and economic limitations, detection of treatment effects on semen quality typically include the design and collection of small sample datasets. A consequence of these small sample studies is that they suffer low statistical power. Historically, researchers faced with small sample size studies have relied upon non-parametric analysis; however, this approach is still unlikely to tease out a true statistical significance based upon limited sample size. Here we propose a novel methodology that can be applied in small samples study situations that combines repeated measures ANOVA and Mixed-Effects linear regression models with Bayesian Linear regression modeling when evaluating for treatment effects on quantitative semen quality parameters. Using this methodology, we show that investigating the data with this multifaceted analytical technique results in improved reproducibility and sensitivity of the findings while minimizing the likelihood of Type 1 errors when combining the inference statistics from multiple models/methodologies using Bayes Factor analysis.

Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis.

BACKGROUND: Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown. OBJECTIVES: To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model. STUDY DESIGN: Randomised, controlled (within subject), blinded, experiment. METHODS: Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (ICE), with the other maintained at ambient temperature (AMB). Dorsal lamellar sections (proximal, middle, distal) were harvested 48 h after initiation of the EHC and were analysed using histological scoring (0-3) and histomorphometry. Cellular proliferation was quantified by counting epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2). RESULTS: Severe elongation and disruption of SEL with dermo-epidermal separation (score of 3) was observed in all AMB feet at one or more section locations, but was not observed in any ICE sections. Overall 92% of the AMB sections received the most severe histological score (grade 3) and 8% were grade 2, whereas ICE sections were classified as either grade 1 (50%) or grade 2 (50%). Relative to AMB feet, ICE sections were 98% less likely to exhibit grades 2 or 3 (OR: 0.02, 95% CI 0.001, 0.365; P<0.01). Histomorphometry measurements of total and nonkeratinised primary epidermal lamellar length were significantly increased (P<0.01) in AMB limbs compared with ICE. TPX2 positive cell counts were significantly increased (P<0.01) in AMB limbs compared with ICE. MAIN LIMITATIONS: Continuous digital hypothermia was initiated before recognition of laminitis and therefore the clinical applicability requires further investigation. CONCLUSIONS: Continuous digital hypothermia reduced the severity of laminitis in the EHC model and prevented histological lesions compatible with lamellar structural failure.

Assessing gastrointestinal motility in healthy horses comparing auscultation, ultrasonography and an acoustic gastrointestinal surveillance biosensor: a randomised, blinded, controlled crossover proof of principle study.

BACKGROUND: Auscultation and ultrasonography are noninvasive techniques used to assess gastrointestinal motility in horses. Recently, noninvasive acoustic gastrointestinal surveillance (AGIS) biosensors evaluating intestinal motility have been validated in humans. OBJECTIVES: To compare AGIS to auscultation and ultrasonography for detecting decreased motility after xylazine administration. STUDY DESIGN: Randomised, blinded, controlled cross-over proof of principle study. METHODS: Six healthy horses were evaluated under fasted and nonfasted conditions and randomly assigned to receive treatment with 0.4 mg/kg xylazine or an equivalent volume of 0.9% NaCl intravenously. After a 48-h washout period, the process was repeated with the alternate treatment. Motility was assessed pre and posttreatment. Borborygmi were assessed in each abdominal quadrant and graded on a scale of 0-3, with 3 being continuous borborygmi. Duodenal, jejunal and caecal contractions were assessed ultrasonographically in consistent locations. Four AGIS biosensors were applied in standardised locations (duodenum, caecum, ventral midline, right dorsal colon). The biosensors measure acoustic signals and data were recorded in transport metric. Data were analysed using cross-classified multilevel random effects logistic regression including area under the receiver operator characteristic curve (AUC ROC). Sensitivity, specificity and accuracy were calculated for each modality. RESULTS: All three modalities detected a reduction in gastrointestinal motility following xylazine administration with AUC ROC being 0.85, 0.84 and 0.86 for auscultation, ultrasonography and AGIS respectively. The sensitivity, specificity and accuracy for auscultation was 88, 71 and 75%; for ultrasonography was 67, 63 and 64%; and for AGIS was 69, 70 and 70%, respectively. MAIN LIMITATIONS: The study was performed in normal healthy horses and application of this device to clinical patients warrants further investigation. CONCLUSIONS: In this proof of principle study, AGIS was able to discriminate between horses given xylazine from those given 0.9% NaCl with comparable accuracy as auscultation and ultrasonography. The Summary is available in Spanish - see Supporting Information.

Prediction of Packed Cell Volume after Whole Blood Transfusion in Small Ruminants and South American Camelids: 80 Cases (2006-2016).

BACKGROUND: Calculation of desired whole blood transfusion volume relies on an estimate of an animal's circulating blood volume, generally accepted to be 0.08 L/kg or 8% of the animal's body weight in kilograms. OBJECTIVE: To use packed cell volume before and after whole blood transfusion to evaluate the accuracy of a commonly used equation to predict packed cell volume after transfusion in small ruminants and South American camelids; to determine the nature and frequency of adverse transfusion reactions in small ruminants and camelids after whole blood transfusion. ANIMALS: Fifty-eight small ruminants and 22 alpacas that received whole blood transfusions for anemia. METHODS: Retrospective case series; medical record review for small ruminants and camelids that received whole blood transfusions during hospitalization. RESULTS: Mean volume of distribution of blood as a fraction of body weight in sheep (0.075 L/kg, 7.5% BW) and goats (0.076 L/kg, 7.6% BW) differed significantly (P < 0.01) from alpacas (0.103 L/kg, 10.3% BW). Mild transfusion reactions were noted in 16% of transfusions. CONCLUSIONS AND CLINICAL RELEVANCE: The generally accepted value of 8% for circulating blood volume (volume of distribution of blood) is adequate for calculation of transfusion volumes; however, use of the species-specific circulating blood volume can improve calculation of transfusion volume to predict and achieve desired packed cell volume. The incidence of transfusion reactions in small ruminants and camelids is low.

Xenografting of isolated equine (Equus caballus) testis cells results in de novo morphogenesis of seminiferous tubules but not spermatogenesis.

The study of spermatogenesis in the horse is challenging because of the absence of an in vitro system that is capable of reproducing efficient spermatogenesis and because of the difficulties and costs associated with performing well-controlled studies in vivo. In an attempt to develop novel methods for the study of equine spermatogenesis, we tested whether cells from enzymatically digested pre-pubertal equine testicular tissue were capable of de novo tissue formation and spermatogenesis following xenografting under the back skin of immunocompromised mice. Testes were obtained from normal pre-pubertal colts and dissociated into cell suspensions using trypsin/collagenase digestion. Resulting cell pellets, consisting of both somatic and germ cells, were injected into fascial pockets under the back skin of immunocompromised, castrated mice and maintained for between 1 and 14 months. Mice were killed and grafts were recovered and analyzed. As has been reported for testis cell suspensions from pigs, mice, cattle, and sheep, de novo formation of equine testicular tissue was observed, as evidenced by the presence of seminiferous tubules and an interstitial compartment. There was an increased likelihood of de novo testicular formation as grafting period increased. Using indirect immunofluorescence, we confirmed the presence of spermatogonia in de novo formed seminiferous tubules. However, we found no evidence of meiotic or haploid cells. These results indicate that dissociated pre-pubertal equine testis cells are capable of reorganizing into the highly specialized endocrine and spermatogenic compartments of the testis following ectopic xenografting. However, in spite of the presence of spermatogonia within the seminiferous tubules, spermatogenesis does not occur. Although this technique does allow access to the cells within the seminiferous tubule and interstitial compartments of the equine testis prior to reaggregation, the absence of spermatogenesis will limit its use as a method for the study of testicular function in the horse.

Are horse age and incision length associated with surgical site infection following equine colic surgery?

It is our clinical impression that age and incision length are more strongly associated with surgical site infection (SSI) following colic surgery than skin closure or wound protection method. Therefore, the objective of this observational clinical cohort study was to identify the risks for SSI in horses undergoing colic surgery. Data collection included pre-, intra-, and postoperative variables. Variables with P < 0.2 following univariable analysis were used in a logistic regression multivariable model. Variables with P <0.05 were included in the final model. Odds ratios (OR; 95% confidence intervals, 95% CI) were determined. The area under the curve (AUC) for the receiver-operator characteristic was calculated. The final multivariable model included breed (P = 0.008), incision length (P = 0.004), surgical procedure classification (P <0.001), and postoperative (PO) colic (P = 0.037; overall model P <0.001, and AUC was 0.81 [excellent discrimination between SSI vs. no SSI]). Warmbloods (OR 12.0; 95% CI 2.7-74.8), American breeds (OR 6.4; 95% CI 1.2-43.0), and Thoroughbreds (4.5; 95% CI 1.1-25.5) more commonly had SSI than other breeds (ponies/miniature horses, Draft breeds, Standardbreds, Arabians, and Crossbreeds [referent]). A higher SSI rate was associated with incision lengths >27 cm (3.7; 95% CI 1.5-9.9), heavily contaminated procedures (12.0; 95% CI 3.3-49.9), and horses with PO colic (2.7; 95% CI 1.1-6.8). SSI appeared to be more common after heavily contaminated procedures and in horses with PO colic, which probably resulted in more incisional contamination and trauma. Some breeds appeared to have higher odds of SSI. Age was not associated with SSI. The risk of developing SSI was higher for horses with an incision >27 cm; therefore, surgeons are encouraged to use the minimum incision length required to accomplish the necessary abdominal exploration and bowel manipulation in the safest manner possible.

Comparison of Tube, Gel, and Immunochromatographic Strip Methods for Evaluation of Blood Transfusion Compatibility in Horses.

BACKGROUND: Assessment of blood compatibility, typically by tube agglutination (TUBE) and hemolysis crossmatch or, less commonly, by blood typing and alloantibody screening, often is performed before blood transfusion in horses. In contrast, gel column (GEL) and immunochromatographic strip (STRIP) techniques are preferred for compatibility testing in dogs and cats. OBJECTIVE: To determine the accuracy of novel and standard crossmatch and typing methods. ANIMALS: Thirty-eight healthy horses, previously blood typed and alloantibody screened. METHODS: TUBE and GEL crossmatches were performed on 146 different recipient-donor pairs with 56 incompatible TUBE crossmatches. Crossmatches were compared by nonparametric area under the curve of receiver operating characteristic (AUC-ROC) analyses. Horses also were blood typed by the novel immunochromatographic Ca typing STRIP. RESULTS: Compared to TUBE crossmatch, GEL had excellent accuracy for agglutination (AUC-ROC = 0.903), but marginal accuracy for hemolysis (AUC-ROC = 0.639). Compared to macroscopic TUBE, microscopic TUBE had excellent accuracy for agglutination (AUC-ROC = 0.912). The predicted crossmatch compatibility based on blood type and alloantibody assay showed excellent accuracy compared to TUBE and GEL (AUC-ROC = 0.843 and 0.897, respectively). However, there were more recipient-donor pairs identified as incompatible by both TUBE and GEL than predicted by blood type and antibody screen, suggesting the presence of unidentified alloantibodies. A Ca typing STRIP exhibited 100% sensitivity and specificity for the 35 Ca+ and 3 Ca- horses tested. CONCLUSIONS AND CLINICAL RELEVANCE: Gel column crossmatch and Ca typing immunochromatographic strip are simple and accurate methods to evaluate clinical blood compatibility.

Components of metabolic syndrome and 5-year change in insulin clearance - the Insulin Resistance Atherosclerosis Study.

AIMS: Cross-sectional evidence indicates that abdominal adiposity, hypertension, dyslipidaemia and glycaemia are associated with reduced metabolic clearance rate of insulin (MCRI). Little is known about the progression of MCRI and whether components of metabolic syndrome are associated with the change in MCRI. In this study, we examined the association between components of metabolic syndrome and the 5-year change of MCRI. METHODS: At baseline and 5-year follow-up, we measured fasting plasma triglycerides (TG), high-density lipoprotein (HDL) cholesterol, blood pressure (BP), waist circumference (WC) and fasting blood glucose (FBG) in 784 non-diabetic participants in the Insulin Resistance Atherosclerosis Study. MCRI, insulin sensitivity (SI ) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. RESULTS: We observed a 29% decline of MCRI at follow-up. TG, systolic BP and WC at baseline were inversely associated with a decline of MCRI regression models adjusted for age, sex, ethnicity, smoking, alcohol consumption, energy expenditure, family history of diabetes, BMI, SI and AIR [ß = -0.057 (95% confidence interval, CI: -0.11, -0.0084) for TG, ß = -0.0019 (95% CI: -0.0035, -0.00023) for systolic BP and ß = -0.0084 (95% CI: -0.013, -0.0039) for WC; all p < 0.05]. Higher HDL cholesterol at baseline was associated with an increase in MCRI [multivariable-adjusted ß = 0.0029 (95% CI: 0.0010, 0.0048), p = 0.002]. FBG at baseline was not associated with MCRI at follow-up [multivariable-adjusted ß = 0.0014 (95% CI: -0.0026, 0.0029)]. CONCLUSIONS: MCRI declined progressively over 5 years in a non-diabetic cohort. Components of metabolic syndrome at baseline were associated with a significant change in MCRI.

The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS).

AIMS/HYPOTHESIS: Insulin clearance may decline as an early mechanism compensating for deteriorating insulin sensitivity. However, no previous studies have investigated the association between subclinical inflammation or impaired fibrinolysis and insulin clearance. We examined the association between plasminogen activator inhibitor (PAI)-1, C-reactive protein (CRP), TNF-α, leptin and fibrinogen and the progression of metabolic clearance rate of insulin (MCRI) over time. METHODS: We studied 784 non-diabetic white, Hispanic and African-American individuals in the Insulin Resistance Atherosclerosis Study (IRAS). Insulin sensitivity, acute insulin response and MCRI were determined from frequently sampled intravenous glucose tolerance tests at baseline and at 5-year follow-up. Inflammatory and fibrinolytic proteins were measured in fasting plasma at baseline. RESULTS: MCRI had declined significantly by 29% at the 5-year follow-up. We observed a significant association between higher plasma PAI-1 levels and the decline in MCRI in multivariable-adjusted regression models (ß = -0.045 [95% CI -0.081, -0.0091]). Higher plasma CRP and leptin levels were associated with a decline in MCRI in unadjusted models, but these associations were non-significant after adjusting for BMI and waist circumference (ß = -0.016 [95% CI -0.041, 0.0083] for CRP; ß = -0.044 [95% CI -0.10, 0.011] for leptin). A higher plasma TNF-α concentration was associated with a decline in MCRI in unadjusted (ß = -0.071 [95% CI -0.14, -0.00087]) but not in multivariable-adjusted (ß = -0.056 [95% CI -0.13, 0.017]) models. Plasma fibrinogen level was not associated with the change in MCRI. CONCLUSIONS/INTERPRETATION: We identified that higher plasma PAI-1 (but not CRP, TNF-α, leptin or fibrinogen) levels independently predicted the progressive decline of insulin clearance in the multiethnic cohort of the IRAS.

Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study.

AIMS/HYPOTHESIS: Impaired insulin secretion, insulin action, insulin-independent glucose effectiveness, glucose tolerance and the associated abnormalities in insulin and glucose metabolism phenotypes are precursors of type 2 diabetes. Genome-wide multipoint variance component linkage scans were carried out using 654 markers to identify quantitative trait loci for insulin sensitivity, acute insulin response to glucose, disposition index and glucose effectiveness training responses in whites and blacks in the HERITAGE Family Study. METHODS: These phenotypes were obtained from an IVGTT with the minimal model. The distributions of insulin sensitivity, acute insulin response to glucose and disposition index training responses (post-training minus baseline) were approximately normalised using a square-root transformation. All phenotypes were adjusted for the effects of age, BMI and their respective baseline values within sex and generation by race prior to linkage scans. RESULTS: In blacks, a promising linkage with a maximum lod score of 3.1 on 19q (54-62 Mb) for glucose effectiveness training response was found. Six interesting linkages with lod scores of at least 1.0 were found for disposition index training response in whites. They included 1p (30 Mb), 3q (152 Mb), 6p (23-42 Mb), 7q (95-96 Mb), 10p (15 Mb) and 12q (119-126 Mb). CONCLUSIONS/INTERPRETATION: Quantitative trait loci for 20 weeks of endurance exercise training responses in insulin action and glucose metabolism phenotypes were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but consistent (6p) linkages across the races.

Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings.

Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptation. Modified frequent-sampling i.v. glucose tolerance tests were applied after adaptation to forage, SS, and FF. For the tolerance tests, horses were kept in stalls overnight and provided hay, and venous catheters were placed the next morning. Baseline samples were collected, 0.3 g of glucose/kg of BW was given i.v., and blood was sampled at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At 20 min, 30 mU of insulin/kg of BW was given, followed by sampling at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Plasma was analyzed for glucose and insulin, and Si, Sg, acute insulin response to glucose, and the disposition index were calculated. Normality was tested using the Shapiro-Wilk statistic. Body condition effects were analyzed using a mixed model with repeated measures. Diet effects were analyzed using a Wilcoxon signed rank test. The Sg was higher in obese than nonobese (P = 0.003) and moderately obese (P = 0.007) horses; Si was lower in obese than nonobese (P = 0.008) horses, and acute insulin response to glucose was higher in obese than nonobese (P = 0.039) horses. Effects of diet were likely confounded by body condition, but horses had lower Si (P = 0.066) when fed SS compared with FF, especially when nonobese. In conclusion, the minimal model effectively estimated Sg, Si, acute insulin response to glucose, and disposition index in horses. Obese geldings were insulin-resistant and seemed to rely primarily on Sg for glucose disposal. Feeding a diet rich in sugar and starch decreased insulin sensitivity of horses. Maintenance of body condition and avoidance of grain-based meals rich in sugar and starch would be beneficial to decrease the risk of developing insulin resistance and associated metabolic syndromes in horses, especially for horses at risk for these syndromes.