The effects of an alpha-2-adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses

Box, Justin R.; Karikoski, Ninja; Tanskanen, Heidi; Raekallio, Marja

doi:10.1016/j.tvjl.2021.105610

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…In the rats receiving vatinoxan, blood glucose concentration also tended to be slightly higher than the physiological values. In horses, a similar effect has been reported with the detomidine/vatinoxan combination, which caused the blood glucose concentration to increase but significantly less and for a shorter period of time than in those receiving detomidine alone [20]. Stability in blood glucose is clinically beneficial in reliably monitoring rats' well-being [31] and differentiating from stress-induced hyperglycaemia or other disease processes.…”

Section: Discussionmentioning

confidence: 63%

“…Mitigation of peripheral cardiovascular effects have been described in many animal species [16][17][18] when administering vatinoxan together with various α 2 -agonists. Vatinoxan also alleviates the adverse metabolic effects of α 2 -agonists [19][20][21]. However, when administered intravenously (IV), it does not markedly affect sedation induced by α 2 -agonists [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl

Lindh,

Meller,

Raekallio

2024

Acta Vet Scand

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Background Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. Results Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1–41.6), range (median) versus 0.9 (0–8.0) mL /kg/min] were significantly higher without vatinoxan. Conclusions Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl

Lindh,

Meller,

Raekallio

2024

Acta Vet Scand

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“…Sample size was determined with an alpha of 0.05, a power of 80%, an expected difference in serum insulin concentrations of 15 μIU/mL between pre and post IA TA injection, a standard deviation of 5, and a moderate effect size (G*Power 3.1.9.2, Kiel Germany). The expected difference and standard deviation were based on a pilot study and previous literature evaluating blood insulin in horses without insulin dysregulation 8 . This predicted the need for 9 horses.…”

Section: Methodsmentioning

confidence: 99%

“…The presence of synovial fluid was confirmed prior to administration of 18 mg of TA (Bristol Myers Squibb) into the middle carpal joint. Sampling times were determined utilising a similar study in the human literature, 12 a horse study measuring insulin and glucose after detomidine hydrochloride intravenous sedation 8 (to ensure that the effects of the sedation needed for safe IA injections would not affect measured insulin and glucose values) and a pilot horse study where multiple timepoints post IA TA injection were evaluated for insulin concentrations. Serial whole blood samples were collected at 4‐, 6‐, 8‐, 24‐ (Day 3), 48‐ (Day 4), and 72‐ (Day 5) hours post‐injection obtained via a catheter using the 3‐step method.…”

Section: Methodsmentioning

confidence: 99%

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Intra‐articular triamcinolone acetonide injection results in increases in systemic insulin and glucose concentrations in horses without insulin dysregulation

Boger,

Manfredi,

Loucks

et al. 2023

Equine Veterinary Journal

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BackgroundCorticosteroids are a commonly used, inexpensive intra‐articular treatment for osteoarthritis which may increase the risk for laminitis in horses due, in part, to hyperinsulinaemia. Humans with metabolic syndrome experience increases in insulin and glucose concentrations post‐injection, but responses in horses are unknown.ObjectivesTo determine the effect of a single intra‐articular (IA) dose of triamcinolone acetate (TA) on blood insulin and glucose concentrations.Study designBefore‐after study.MethodsTen horses with normal insulin regulation as assessed by an oral sugar test received 18 mg of TA into one middle carpal joint. Insulin and glucose concentrations were evaluated at baseline and 4, 6, 8, 24, 48, and 72 h following IA corticosteroid injection. Differences from baseline were evaluated using a repeated measures ANOVA with Dunnett's multiple comparison testing or a Friedman test with Dunn's correction (significant at p < 0.05).ResultsMean ± SD blood insulin concentration post IA TA injection was increased at 6 h (15.8 ± 3.1 μIU/mL, p = 0.01), 24 h (23 ± 5.8 μIU/mL, p ≤ 0.001), and 48 h (29 ± 13 μIU/mL, p ≤ 0.01) compared to baseline (10 ± 12.3 μIU/mL), with the peak at 48 h. Median ± 95% CI blood glucose concentration post IA TA injection was increased at 6 h (112.7 ± 20.3 mg/dL, p = 0.006), 8 h (112.9 ± 21.4 mg/dL, p = 0.004), 24 h (122.6 ± 14.6, p ≤ 0.0001), and 48 h (123.5 ± 15.4 mg/dL, p ≤ 0.0001) compared to baseline (89.2 ± 6.6 mg/dL), with the peak at 48 h.Main limitationsOnly horses with normal insulin regulation were evaluated.ConclusionsBlood insulin and glucose concentrations modestly increased for 48 h following IA TA.

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Endocrine Physiology in the Neonatal Foal

Toribio,

Dembek,

Hostnik

et al. 2024

Equine Neonatal Medicine

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The effects of an alpha-2-adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses

Cited by 7 publications

References 21 publications

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl

Effects of vatinoxan in rats sedated with a combination of medetomidine, midazolam and fentanyl

Intra‐articular triamcinolone acetonide injection results in increases in systemic insulin and glucose concentrations in horses without insulin dysregulation

Endocrine Physiology in the Neonatal Foal

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