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Background Cobalt chloride (CoCl2 ) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2 . Objectives To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. Animals Five, healthy Standardbred mares. Methods Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. Results All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60-126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291-300/163-213, 218-279). Hemodynamics normalized by 1-2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. Conclusions and clinical importance The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns.

BACKGROUND: Despite the paucity of data available, orally administered angiotensin‐converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. OBJECTIVE: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left‐sided valvular regurgitation. STUDY DESIGN: Prospective, randomised double‐blind, placebo‐controlled trial. METHODS: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. RESULTS: Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = −0.97 cm; 95% CI = −1.5 to −0.43 cm), aortic sinus diameter (−0.31 cm; −0.54 to −0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (−17.05%; −31.17 to −2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17–22.73 L/min) and fractional shortening (7.59%; 3.3–11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. MAIN LIMITATIONS: Very small sample size and short treatment period. CONCLUSIONS: Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left‐sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is beneficial in horses with valvular regurgitation. The Summary is available in Spanish – see Supporting Information

Background Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking. Objectives To measure FGF-23 concentration in dogs with different stages of CKD and determine its association with factors involved in CKD-MBD, including serum phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to validate an ELISA for measurement of plasma FGF-23 concentration in dogs. Animals Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy control dogs. Methods Prospective cross-sectional study. An FGF-23 ELISA was used to measure plasma FGF-23 concentration in dogs and their association with serum creatinine, phosphorus, calcium, and PTH concentrations. Results Plasma FGF-23 concentrations increased with severity of CKD and were significantly different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001). Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations were the strongest independent predictors of FGF-23 concentration. Conclusions and clinical importance Plasma FGF-23 concentrations increase in dogs with CKD as disease progresses. Plasma FGF-23 concentrations appear to be useful for further study of the pathophysiology of CKD-MBD in dogs.

SummaryReasons for performing study Serum immunoglobulin (IgG) assessment in neonatal foals is considered standard care in equine hospitals to determine immunity and overall health. However, cut-off values of IgG to predict complete or partial failure of transfer of passive immunity (FTPI) were developed 30 years ago and are largely empirical with little prospective or statistical data to support their use or association with outcome. Objectives To critically evaluate the traditional cut-off values of IgG in the assessment of FTPI (IgG 8 g/l as adequate transfer of passive immunity (ATPI). Odds of nonsurvival increased in proportion to lower IgG concentrations. Higher TP concentrations were associated with lower likelihood of FTPI; however, higher albumin concentrations were associated with a greater likelihood of FTPI. A regression equation was created to predict IgG in foals using serum proteins. Conclusions Serum IgG values of

Objective To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. Case Summary An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. New or Unique Information Provided Atrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.

Summary Reasons for performing study Resistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals. Objectives To investigate components of the somatotropic axis (ghrelin, growth hormone and insulin-like growth factor-1 [IGF-1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase and IGF-1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals. Study design Prospective multicentre cross-sectional study. Methods Blood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged

BACKGROUND Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF-23/klotho axis in healthy and hospitalised foals is lacking. OBJECTIVES The aims of this study were to measure serum FGF-23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals. STUDY DESIGN Prospective, multicentre, cross-sectional study. METHODS A total of 91 foals ≤72 h old were classified as hospitalised (n = 81; 58 septic; 23 sick non-septic [SNS]) and healthy (n = 10). Blood samples were collected on admission. Hormone concentrations were determined by immunoassays. RESULTS Serum FGF-23, PTH, phosphorus, and aldosterone concentrations were higher while klotho, 25(OH)D, 1,25(OH)2 D, and TCa concentrations were lower in septic and SNS compared to healthy foals (P

Background The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. Objectives/Hypothesis To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. Animals A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. Methods Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. Results ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P

Background Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease-mineral bone disorder (CKD-MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD. Objectives The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD-MBD, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), calcium, and phosphorus concentrations. Methods Thirty-seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and 24,25-dihydroxyvitamin D [24,25(OH)2D], and PTH and FGF-23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined. Results Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD (r [creatinine]: −0.49 to −0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF-23, and phosphorus concentrations (r: −0.39 to −0.64; P < .01). Conclusions and Clinical Importance CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.

Background Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. Objectives The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). Animals Twelve healthy, light-breed horses. Methods Randomized, prospective study. Each of the above tests was performed on 12 horses. Results Minimal model analysis of the FSIGTT was considered the reference standard and classified 7 horses as insulin resistant (IR) and 5 as insulin sensitive (IS). In contrast, BIC and OST assessment using conventional cut-off values classified all horses as IS. Kappa coefficients, measuring agreement among BIC, OST, CGIT, and FSIGTT were poor to fair. Sensitivity of the CGIT (positive phase duration of the glucose curve >45 minutes) was 85.7% and specificity was 40%, whereas CGIT ([insulin]45 >100 μIU/mL) sensitivity and specificity were 28.5% and 100%, respectively. Area under the glucose curve (AUCg0-120) was significantly correlated among the OST, CGIT, and FSIGTT, but Bland–Altman method and Lin's concordance coefficient showed a lack of agreement. Conclusions Current criteria for diagnosis of insulin resistance using BIC and the OST are highly specific but lack sensitivity. The CGIT displayed better sensitivity and specificity, but modifications may be necessary to improve agreement with minimal model analysis.

Background Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals. Methods and Results One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone (PTH) 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and μCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and 1) total bioluminescence (r = 0.595; P = 0.019); 2) total fluorescence (r = 0.474; P = 0.074); and 3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

Critically ill foals often present to veterinary hospitals with impaired organ perfusion which can be demonstrated by increased blood L-lactate concentrations. As a compensatory mechanism to low blood pressure and electrolyte abnormalities, aldosterone and arginine vasopressin (AVP) are released to restore organ perfusion and function. Several studies have investigated the ability of blood L-lactate concentrations to predict severity of disease and outcome in critically ill human patients, adult horses and foals. However, information on the aldosterone and AVP response to hypoperfusion and its association with L-lactate concentrations in neonatal foals is limited.To determine the association between clinical hypoperfusion and endocrine markers of reduced tissue perfusion in normo- and hypoperfused foals.Prospective, multicentre, cross-sectional observational study.Blood samples were collected on admission from 72 clinically hypoperfused, 110 normoperfused (73 hospitalised and 37 healthy) foals of ≤4 days of age. Foals were considered clinically hypoperfused if they had L-lactate concentrations ≥2.5 mmol/l and one of the 3 following findings: heart rate120 beats/min, packed cell volume (PCV)0.44 l/l or azotaemia (increased creatinine and blood urea nitrogen [BUN]). Blood concentrations of aldosterone and AVP were determined by radioimmunoassays.Aldosterone, AVP, creatinine and BUN concentrations and heart rate, PCV and blood osmolality were higher in clinically hypoperfused compared with normoperfused foals (P0.05). Risk of hypoperfusion increased with the presence of hypothermic extremities (OR = 5.26) and with each one unit increase in albumin concentrations (OR = 3.5) (P0.05). The proposed admission L-lactate cut-off value above which nonsurvival could be reliably predicted in hospitalised foals was 10.6 mmol/l with 82% of sensitivity and 74% of specificity.Hyperaldosteronaemia and hypervasopressinaemia as well as hypothermic extremities and increased albumin concentrations are potent predictors of hypoperfusion in hospitalised foals.

Background Medical management of critically ill equine neonates (foals) can be expensive and labor intensive. Predicting the odds of foal survival using clinical information could facilitate the decision-making process for owners and clinicians. Numerous prognostic indicators and mathematical models to predict outcome in foals have been published; however, a validated scoring method to predict survival in sick foals has not been reported. The goal of this study was to develop and validate a scoring system that can be used by clinicians to predict likelihood of survival of equine neonates based on clinical data obtained on admission. Methods and Results Data from 339 hospitalized foals of less than four days of age admitted to three equine hospitals were included to develop the model. Thirty seven variables including historical information, physical examination and laboratory findings were analyzed by generalized boosted regression modeling (GBM) to determine which ones would be included in the survival score. Of these, six variables were retained in the final model. The weight for each variable was calculated using a generalized linear model and the probability of survival for each total score was determined. The highest (7) and the lowest (0) scores represented 97% and 3% probability of survival, respectively. Accuracy of this survival score was validated in a prospective study on data from 283 hospitalized foals from the same three hospitals. Sensitivity, specificity, positive and negative predictive values for the survival score in the prospective population were 96%, 71%, 91%, and 85%, respectively. Conclusions The survival score developed in our study was validated in a large number of foals with a wide range of diseases and can be easily implemented using data available in most equine hospitals. GBM was a useful tool to develop the survival score. Further evaluations of this scoring system in field conditions are needed.