Variation in insulin response to oral sugar test in a cohort of horses throughout the year and evaluation of risk factors for insulin dysregulation

Background The oral sugar test (OST) is commonly used to diagnose insulin dysregulation (ID) and equine metabolic syndrome; however, possible seasonal changes in OST results have not been evaluated. Objective To determine the possible variation in insulin response to OST throughout the year and risk factors associated with maximum insulin concentration (InsMax) and ID. Study design Prospective, longitudinal cohort study. Methods The OST was performed on 29 Finnhorses every other month six times. Serum total adiponectin concentration and phenotypic variables related to obesity were also measured. Changes in InsMax, adiponectin, scale weight, body condition score, cresty neck score (CNS), and fasting glucose concentration were assessed. Risk factor analyses were performed on InsMax and ID status, and ID groups were compared with each other. Results Fourteen horses were categorised with non-ID each time and 15 as having ID at least once during the follow-up period. The ID status of 12 horses varied throughout the year, but neither the insulin variables measured during the OST nor adiponectin expressed significant seasonal variation. Increasing age and CNS, and decreasing adiponectin were observed as risk factors for a high InsMax after OST. The risk of ID was higher in horses with no exercise compared to horses with exercise (OR 7.6, 95% CI 1.2-49.3, P = .03). Horses with ID had lower serum adiponectin concentrations, longer neck circumference and larger height than horses in the non-ID group. Main limitations The environmental conditions (feeding, exercise) were not constant for all horses throughout the study and only one breed was used. Conclusions Neither OST results nor adiponectin varies with season; however, there were a substantial number of horses with variable ID status throughout the year, in which repeated OSTs may be beneficial. Lack of exercise was a risk factor for ID.Peer reviewe

Insulin dysregulation in a population of Finnhorses and associated phenotypic markers of obesity

Background Obesity and insulin dysregulation (ID) predispose horses to laminitis. Determination of management practices or phenotypic markers associated with ID may benefit animal welfare. Objectives Determine ID status of a population of Finnhorses using an oral sugar test (OST) and compare phenotypes and management factors between ID and non-ID Finnhorses. Animals One hundred twenty-eight purebred Finnhorses >= 3 years of age. Methods Owners were recruited using an online questionnaire regarding signalment, history, feeding, and exercise of their horses. Selected contributing stables within a predefined area were visited. Phenotypic markers of obesity and the weight of each horse were recorded. After fasting overnight, horses received 0.45 mL/kg corn syrup PO. Serum samples before and at 60 and 90 minutes after syrup administration were analyzed for insulin by chemiluminescent assay. Horses met ID criteria if insulin concentrations were >= 33 mu IU/mL at T0, >= 66 mu IU/mL at T60 or T90 or some combination thereof. Associations between phenotypic markers, feeding and exercise variables, and ID were examined using mixed effects logistic regression modeling. Results Several phenotypic markers of obesity were significant on univariable analysis but in the final multivariable model, only obesity (body condition score >= 8) was associated with ID (P= .04). Over half of the horses (60% [95% confidence interval (CI), 51%-68%]) were considered overweight or obese whereas 16% (95% CI, 10%-23%) were classified as having ID. Conclusions and Clinical Importance Because obesity is associated with ID in cold-blooded type horses, objective monitoring of phenotypic markers by owners may be beneficial for health outcomes.Peer reviewe

The impact of vatinoxan on medetomidine-ketamine-midazolam immobilization in Patagonian maras (Dolichotis patagonum)

Objective To compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine-ketamine-midazolam combination with or without vatinoxan (MK-467), a peripherally acting alpha(2)-adrenoceptor antagonist. Study design Randomized, blinded, crossover study. Animals A group of nine healthy Patagonian maras (Dolichotis patagonum). Methods Maras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg(-1)) + ketamine (5 mg kg(-1)) + midazolam (0.1 mg kg(-1)) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg(-1)), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO2, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p 120 mmHg), whereas with 372 vatinoxan, four animals were hypotensive (MAP <60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols. Conclusions and clinical relevance In Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.Peer reviewe

Combined effects of dexmedetomidine and vatinoxan infusions on minimum alveolar concentration and cardiopulmonary function in sevoflurane-anesthetized dogs

Objective To evaluate the effects of combined infusions of vatinoxan and dexmedetomidine on inhalant anesthetic requirement and cardiopulmonary function in dogs. Study design Prospective experimental study. Methods A total of six Beagle dogs were anesthetized to determine sevoflurane minimum alveolar concentration (MAC) prior to and after an intravenous (IV) dose (loading, then continuous infusion) of dexmedetomidine (4.5 mu g kg(-1) hour(-1)) and after two IV doses of vatinoxan in sequence (90 and 180 mu g kg(-1) hour(-1)). Blood was collected for plasma dexmedetomidine and vatinoxan concentrations. During a separate anesthesia, cardiac output (CO) was measured under equivalent MAC conditions of sevoflurane and dexmedetomidine, and then with each added dose of vatinoxan. For each treatment, cardiovascular variables were measured with spontaneous and controlled ventilation. Repeated measures analyses were performed for each response variable; for all analyses, p 180 mu g kg(-1) hour(-1) might improve cardiovascular function further in combination with this dose of dexmedetomidine, but beneficial effects on anesthesia plane and recovery quality may be lost.Peer reviewe

Cardiovascular effects of intravenous vatinoxan in wild boars (Sus scrofa) anaesthetised with intramuscular medetomidine-tiletamine-zolazepam

Background The potent sedative medetomidine is a commonly used adjunct for the immobilisation of non-domestic mammals. However, its use is associated with pronounced cardiovascular side effects, such as bradycardia, vasoconstriction and decreased cardiac output. We investigated the effects of the peripherally-acting alpha-2-adrenoceptor antagonist vatinoxan on cardiovascular properties in medetomidine-tiletamine-zolazepam anaesthetised wild boar (Sus scrofa). Methods Twelve wild boars, anaesthetised twice with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (2.5 mg/kg) IM in a randomised, crossover study, were administered (0.1 mg/kg) vatinoxan or an equivalent volume of saline IV (control). Cardiovascular variables, including heart rate (HR), mean arterial blood pressure (MAP), pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP) and cardiac output (CO), were assessed 5 min prior to vatinoxan/saline administration until the end of anaesthesia 30 min later. Results MAP (p < 0.0001), MPAP (p < 0.001) and MPAOP (p < 0.0001) significantly decreased from baseline after vatinoxan until the end of anaesthesia. HR increased significantly (p < 0.0001) from baseline after vatinoxan administration. However, the effect on HR subsided 3 min after vatinoxan. All variables remained constant after saline injection. There was no significant effect of vatinoxan or saline on CO. Conclusion Vatinoxan significantly reduced systemic and pulmonary artery hypertension, induced by medetomidine in wild boar.Peer reviewe

Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs

Peer reviewe

Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs

Objective: We determined the possible effects of a peripherally acting alpha2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) co-administered medetomidine, butorphanol and midazolam. Study design: Randomized, experimental, blinded cross-over study. Animals: Six healthy Beagle dogs. Methods: Two IM treatments were administered: 1) medetomidine hydrochloride (20 μg kg-1) + butorphanol (100 μg kg-1) + midazolam (200 μg kg-1) (MBM), and; 2) MBM + MK-467 hydrochloride (500 μg kg-1) (MBM-MK), mixed in a syringe. Heart rate was recorded at regular intervals. Sedation was assessed with visual analog scales (0 – 100 mm). Drug concentrations in plasma were analyzed with liquid chromatography - tandem mass spectrometry, with chiral separation of dex- and levomedetomidine. Maximum drug concentrations in plasma (Cmax) and time to Cmax (Tmax) were determined. Paired t-tests, with Bonferroni correction when appropriate, were used for comparisons between the treatments. Results: Data from five dogs were analyzed. Heart rate was significantly higher from 20 until 90 minutes after MBM-MK. The Tmax for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with co-administration of MK-467, from 23 ± 9 to 11 ± 6 minutes (p = 0.049) for midazolam and from 32 ± 15 to 18 ± 6 minutes for levomedetomidine (p = 0.036), respectively. Conclusions and clinical relevance: MK-467 accelerated the absorption of IM co-administered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects.Peer reviewe

Owner-Reported Clinical Signs and Management-Related Factors in Horses Radiographed for Intestinal Sand Accumulation

Clinical problems related to intestinal sand accumulation in horses are common in certain geographic areas, but the clinical signs appear nonspecific and the course of the accumulation remains somewhat obscure. This study examined the association between the presence and size of intestinal sand accumulations and owner-reported clinical signs, management, and feeding practices, as well as behavioral patterns in horses with radiographic diagnosis of sand accumulation. Owners of the horses filled in an online questionnaire. A total of 447 responses met the inclusion criteria. The size of the sand accumulation detected in the radiographs was not significantly associated with the age, body condition score, sex, or use of the horses. Horses reported to have expressed colic had significantly larger sand accumulations than those without this sign, and a similar association was detected in horses with poor performance. The highest odds ratio for sand accumulation was for the combination of colic and poor performance, followed by colic combined with diarrhea/loose feces or hyperesthesia to touch of the abdominal wall. Larger sand accumulations were detected in greedy horses that eat all their roughage, whereas dominant position in group hierarchy was associated with less sand. The possibility of abdominal sand accumulation should be considered as one of the differentials in horses with multiple owner-reported clinical signs such as colic, poor performance, diarrhea, and hyperesthesia to touch of the abdomen. (C) 2019 The Authors. Published by Elsevier Inc.Peer reviewe

Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs

Objective To quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levo-medetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine. Study design Experimental, observational study. Animals A group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 +/- 0.1 years (mean +/- standard deviation). Methods All dogs were administered a combination of medetomidine (40 mu g kg(-1)) and vatinoxan (800 mu g kg(-1)) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg(-1)) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography-tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate. Results All dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma. Conclusions and clinical relevance With the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes alpha(2)-adrenoceptors outside the CNS.Peer reviewe

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

Objective: To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously administered detomidine. Study design: Randomised, prospective clinical study. Animals: Twenty dairy calves aged 12.4 ± 4.4 days (mean ± SD), weight 50.5 ± 9.0 kg. Methods: Detomidine at 80 μg kg-1 was administered to ten calves sublingually (GEL) and at 30 μg kg-1 to ten control calves intravenously (IV). Meloxicam (0.5 mg kg-1) and  local anaesthetic (lidocaine 3 mg kg-1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over  240 minutes. Blood was collected during the same period for drug concentration  analysis. Pharmacokinetic variables were calculated from the plasma detomidine  concentration-time data using non-compartmental methods.  Results: The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng  mL-1 (mean ± SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation  scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Conclusions and clinical relevance: Oromucosally administered detomidine is an  effective sedative agent for calves prior to disbudding.Peer reviewe