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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacodynamics and plasma concentrations of dexmedetomidin...
Journal of veterinary pharmacology and therapeutics2021; 44(5); 754-765; doi: 10.1111/jvp.12992

Pharmacodynamics and plasma concentrations of dexmedetomidine with or without vatinoxan as a constant-rate infusion in horses anaesthetized with isoflurane-A pilot study.

Abstract: The aim was to determine the effects of vatinoxan on dexmedetomidine plasma concentrations and effects on cardiovascular and intestinal tissue pharmacodynamics. In a prospective randomized study, six horses were premedicated intravenously with dexmedetomidine 3.5 µg kg followed by a constant-rate infusion of 7 µg kg  h (group DEX) and six horses with dexmedetomidine of the same dose (bolus and constant-rate infusion) combined with vatinoxan 130 µg kg followed by 40 µg kg  h (group VAT). Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane. Venous blood samples were withdrawn before and at predefined points in time after drug application. During sedation and anaesthesia, cardiopulmonary variables, gastrointestinal tissue perfusion and oxygenation were recorded. Data were analysed using two-way-ANOVA, unpaired-t-test and Dunnett's-t-test (p < 0.05). Group VAT had significantly higher oxygen delivery and lower oxygen extraction ratio, venous admixture, alveolar dead space and alveolar-arterial-oxygen difference. Tissue perfusion of buccal mucosa was reduced during anaesthesia in group DEX. Plasma concentrations of dexmedetomidine in group VAT (n = 6) and group DEX (n = 5) were comparable between groups. In the present pilot study, co-administration of vatinoxan with dexmedetomidine did not alter plasma concentrations of dexmedetomidine but ameliorated tissue perfusion and global oxygenation variables.
© 2021 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
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Publication Date: 2021-06-23 PubMed ID: 34159620DOI: 10.1111/jvp.12992Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research study aims to explore the impact of vatinoxan on the plasma concentrations of dexmedetomidine and its effects on cardiovascular and intestinal tissue pharmacodynamics in anaesthetized horses.

Objective of the Study

  • The study was designed to understand the influence of vatinoxan on dexmedetomidine plasma concentrations. The effect of this interaction on cardiovascular and intestinal tissue pharmacodynamics was also examined. Dexmedetomidine is an anesthetic often used in veterinary medicine, while vatinoxan is a medicine used to counteract some unwanted side effects of dexmedetomidine.

Research Methodology

  • In a randomized study, six horses were induced with dexmedetomidine alone and another six horses were induced with a combination of dexmedetomidine and vatinoxan.
  • Anaesthesia was induced with ketamine and diazepam, and sustained with isoflurane.
  • Blood samples were taken before and at various points after the drugs were administered.
  • The variables recorded included cardiopulmonary health, gastrointestinal tissue perfusion, and the amount of oxygen in the blood.
  • Data from the study were then analyzed using statistical methods including two-way Analysis of Variance (ANOVA), unpaired t-test and Dunnett’s t-test.

Key Findings

  • The group of horses that were administered vatinoxan along with dexmedetomidine showed better global oxygenation figures and tissue perfusion, indicating an improvement in blood flow and oxygen uptake in vital tissues.
  • Plasma concentrations of dexmedetomidine were similar in both groups, suggesting that the administration of vatinoxan did not influence dexmedetomidine’s concentration in the plasma.
  • The buccal mucosa tissue perfusion was reduced in the dexmedetomidine group during anaesthesia, implying that vatinoxan protects the tissues from low perfusion states.

Conclusion of the Study

  • The co-administration of vatinoxan with dexmedetomidine did not alter the plasma concentrations of dexmedetomidine.
  • The addition of vatinoxan improved tissue perfusion and oxygenation, suggesting a beneficial interaction that can ameliorate some effects of dexmedetomidine anaesthesia in horses.

Cite This Article

APA
Neudeck S, Twele L, Kopp V, Kästner S. (2021). Pharmacodynamics and plasma concentrations of dexmedetomidine with or without vatinoxan as a constant-rate infusion in horses anaesthetized with isoflurane-A pilot study. J Vet Pharmacol Ther, 44(5), 754-765. https://doi.org/10.1111/jvp.12992

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 5
Pages: 754-765

Researcher Affiliations

Neudeck, Stephan
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Twele, Lara
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Kopp, Veronika
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Kästner, Sabine
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
  • Clinic for Small Animals, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

MeSH Terms

  • Anesthetics, Inhalation
  • Animals
  • Dexmedetomidine / pharmacology
  • Horses
  • Isoflurane
  • Pilot Projects
  • Prospective Studies
  • Quinolizines

References

This article includes 41 references
  1. Adam M, Raekallio MR, Keskitalo T, Honkavaara JM, Scheinin M, Kajula M, Mölsä S, Vainio OM. The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal. Journal of Veterinary Pharmacology and Therapeutics 2018, 41(3), 447-456.
    doi: 10.1111/jvp.12486google scholar: lookup
  2. Ambrisko TD, Coppens P, Kabes R, Moens Y. Lithium dilution, pulse power analysis, and continuous thermodilution cardiac output measurements compared with bolus thermodilution in anaesthetized ponies. British Journal of Anaesthesia 2012, 109(6), 864-869.
    doi: 10.1093/bja/aes269google scholar: lookup
  3. Ambrisko TD, Kabes R, Moens Y. Influence of drugs on the response characteristics of the LiDCO sensor: an in vitro study. British Journal of Anaesthesia 2013, 110(2), 305-310.
    doi: 10.1093/bja/aes380google scholar: lookup
  4. Araos J, Kenny J-ES, Rousseau-Blass F, Pang DSJ. Dynamic prediction of fluid responsiveness during positive pressure ventilation: a review of the physiology underlying heart-lung interactions and a critical interpretation. Veterinary Anaesthesia and Analgesia 2020, 47(1), 3-14.
    doi: 10.1016/j.vaa.2019.08.004google scholar: lookup
  5. Bennett RC, Salla KM, Raekallio MR, Hänninen L, Rinne VM, Scheinin M, Vainio OM. Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs. Journal of Veterinary Pharmacology and Therapeutics 2016, 39(4), 336-343.
    doi: 10.1111/jvp.12292google scholar: lookup
  6. Bettschart-Wolfensberger R, Freeman SL, Bowen IM, Aliabadi FS, Weller R, Huhtinen M, Clarke KW. Cardiopulmonary effects and pharmacokinetics of iv dexmedetomidine in ponies. Equine Veterinary Journal 2005, 37(1), 60-64.
    doi: 10.2746/0425164054406801google scholar: lookup
  7. Brady AJ, Poole-Wilson PA, Harding SE, Warren JB. Nitric oxide production within cardiac myocytes reduces their contractility in endotoxemia. American Journal of Physiology-Heart and Circulatory Physiology 1992, 263(6), H1963-H1966.
    doi: 10.1152/ajpheart.1992.263.6.h1963google scholar: lookup
  8. Burrows GE. Hemodynamic alterations in the anesthetized pony produced by slow intravenous administration of Escherichia coli endotoxin. American Journal of Veterinary Research 1970, 31, 1975-1982.
  9. Clark ES, Moore JN. The effects of slow infusion of a low dosage of endotoxin in healthy horses. Equine Veterinary Journal 1989, 21(S7), 33-37.
    doi: 10.1111/j.2042-3306.1989.tb05652.xgoogle scholar: lookup
  10. Clineschmidt BV, Pettibone DJ, Lotti VJ, Hucker HB, Sweeney BM, Reiss DR, Lis EV, Huff JR, Vacca J. A peripherally acting alpha-2 adrenoceptor antagonist: L-659,066. Journal of Pharmacology and Experimental Therapeutics 1988, 245(1), 32-40.
  11. Dancker C, Hopster K, Rohn K, Kästner SBR. Effects of dobutamine, dopamine, phenylephrine and noradrenaline on systemic haemodynamics and intestinal perfusion in isoflurane anaesthetised horses. Equine Veterinary Journal 2018, 50(1), 104-110.
    doi: 10.1111/evj.12721google scholar: lookup
  12. Dutta S, Lal R, Karol MD, Cohen T, Ebert T. Influence of cardiac output on dexmedetomidine pharmacokinetics. Journal of Pharmaceutical Sciences 2000, 89(4), 519-527.
    doi: 10.1002/(sici)1520-6017(200004)89:4<519:aid-jps9>3.0.co;2-ugoogle scholar: lookup
  13. Edner A, Nyman G, Essén-Gustavsson B. The relationship of muscle perfusion and metabolism with cardiovascular variables before and after detomidine injection during propofol-ketamine anaesthesia in horses. Veterinary Anaesthesia and Analgesia 2002, 29(4), 182-199.
    doi: 10.1046/j.1467-2995.2002.00101.xgoogle scholar: lookup
  14. Gozalo-Marcilla M, Gasthuys F, Schauvliege S. Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia. Part 2: opioids and alpha-2 adrenoceptor agonists. Veterinary Anaesthesia and Analgesia 2015, 42(1), 1-16.
  15. Grosenbaugh DA, Muir WW. Cardiorespiratory effects of sevoflurane, isoflurane, and halothane anesthesia in horses. American Journal of Veterinary Research 1998, 59(1), 101-106.
  16. Honkavaara J, Raekallio MR, Syrja PM, Pypendop BH, Knych HK, Kallio-Kujala IJ, Vainio OM. Concentrations of medetomidine enantiomers and vatinoxan, an α2-adrenoceptor antagonist, in plasma and central nervous tissue after intravenous coadministration in dogs. Veterinary Anaesthesia and Analgesia 2020, 47(1), 47-52.
    doi: 10.1016/j.vaa.2019.07.004google scholar: lookup
  17. Honkavaara J, Restitutti F, Raekallio MR, Kuusela EK, Vainio OM. The effects of increasing doses of MK-467, a peripheral alpha2-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs. Journal of Veterinary Pharmacology and Therapeutics 2011, 34(4), 332-337.
    doi: 10.1111/j.1365-2885.2010.01242.xgoogle scholar: lookup
  18. Honkavaara J, Restitutti F, Raekallio M, Salla K, Kuusela E, Ranta-Panula V, Rinne V, Vainio O, Scheinin M. Influence of MK-467, a peripherally acting α2-adrenoceptor antagonist on the disposition of intravenous dexmedetomidine in dogs. Drug Metabolism and Disposition 2012, 40(3), 445-449.
  19. Hopster K, Wittenberg-Voges L, Geburek F, Hopster-Iversen C, Kästner SBR. Effects of controlled hypoxemia or hypovolemia on global and intestinal oxygenation and perfusion in isoflurane anesthetized horses receiving an alpha-2-agonist infusion. BMC Veterinary Research 2017, 13(1), 361.
    doi: 10.1186/s12917-017-1265-3google scholar: lookup
  20. Krug A. Mikrozirkulation und Sauerstoffversorgung des Gewebes. Phlebologie 2006, 35(06), 300-312.
    doi: 10.1055/s-0037-1622158google scholar: lookup
  21. Linton RA, Young LE, Marlin DJ, Blissitt KJ, Brearley JC, Jonas MM, O’Brien TK, Linton NW, Band DM, Hollingworth C. Cardiac output measured by lithium dilution, thermodilution, and transesophageal Doppler echocardiography in anesthetized horses. American Journal of Veterinary Research 2000, 61(7), 731-737.
    doi: 10.2460/ajvr.2000.61.731google scholar: lookup
  22. Marshall C, Lindgren L, Marshall BE. Effects of halothane, enflurane, and isoflurane on hypoxic pulmonary vasoconstriction in rat lungs in vitro. Anesthesiology 1984, 60(4), 304-308.
    doi: 10.1097/00000542-198404000-00006google scholar: lookup
  23. McCuskey RS, Urbaschek R, Urbaschek B. The microcirculation during endotoxemia. Cardiovascular Research 1996, 32(4), 752-763.
    doi: 10.1016/s0008-6363(96)00113-7google scholar: lookup
  24. Neudeck S, Kästner SBR, Wittenberg-Voges L, Rohn K, Hopster K. Comparison of desflurane and propofol at equipotent doses in combination with a constant rate infusion of dexmedetomidine on global and peripheral perfusion and oxygenation in horses. American Journal of Veterinary Research 2018, 79(5), 487-495.
    doi: 10.2460/ajvr.79.5.487google scholar: lookup
  25. Pakkanen SAE, Raekallio MR, Mykkänen AK, Salla KM, Vries A, Vuorilehto L, Scheinin M, Vainio OM. Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane. Veterinary Anaesthesia and Analgesia 2015, 42(5), 527-536.
    doi: 10.1111/vaa.12238google scholar: lookup
  26. Pypendop BH, Honkavaara J, Ilkiw JE. Pharmacokinetics of dexmedetomidine, MK-467, and their combination following intravenous administration in male cats. Journal of Veterinary Pharmacology and Therapeutics 2016, 39(5), 460-468.
    doi: 10.1111/jvp.12302google scholar: lookup
  27. Pypendop BH, Honkavaara J, Ilkiw JE. Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats. Veterinary Anaesthesia and Analgesia 2017, 44(4), 823-831.
    doi: 10.1016/j.vaa.2017.02.008google scholar: lookup
  28. Raekallio MR, Honkavaara JM, Vainio OM. The effects of L-659,066, a peripheral α2-adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep. Journal of veterinary pharmacology and therapeutics 2010, 33(5), 434-438.
    doi: 10.1111/j.1365-2885.2009.01156.xgoogle scholar: lookup
  29. Ranheim B, Risberg AI, Spadavecchia C, Landsem R, Haga HA. The pharmacokinetics of dexmedetomidine administered as a constant rate infusion in horses. Journal of Veterinary Pharmacology and Therapeutics 2015, 38(1), 93-96.
    doi: 10.1111/jvp.12157google scholar: lookup
  30. Restitutti F, Kaartinen MJ, Raekallio MR, Wejberg O, Mikkola E, Del Castillo JRE, Scheinin M, Vainio OM. Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs. Veterinary Anaesthesia and Analgesia 2017, 44(3), 417-426.
    doi: 10.1016/j.vaa.2016.04.006google scholar: lookup
  31. Restitutti F, Laitinen MR, Raekallio MR, Vainionpää M, O’Brien RT, Kuusela E, Vainio OM. Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine. Veterinary Anaesthesia and Analgesia 2013, 40(6), e48-e56.
    doi: 10.1111/vaa.12058google scholar: lookup
  32. Severinghaus JW, Stupfel M. Alveolar dead space as an index of distribution of blood flow in pulmonary capillaries. Journal of Applied Physiology 1957, 10(3), 335-348.
  33. Skimming JW, Cassin S, Nichols WW. Calculating vascular resistances. Clinical Cardiology 1997, 20(9), 805.
    doi: 10.1002/clc.4960200918google scholar: lookup
  34. Talke PO, Traber DL, Richardson CA, Harper DD, Traber LD. The effect of α2 agonist-induced sedation and its reversal with an α2 antagonist on organ blood flow in sheep. Anesthesia & Analgesia 2000, 90(5), 1060-1066.
    doi: 10.1097/00000539-200005000-00011google scholar: lookup
  35. Tapio H, Raekallio MR, Mykkänen AK, Al-Ramahi D, Scheinin M, Hautajärvi HJ, Männikkö S, Vainio OM. Effects of vatinoxan on cardiorespiratory function, fecal output and plasma drug concentrations in horses anesthetized with isoflurane and infusion of medetomidine. The Veterinary Journal 2019, 251, 105345.
    doi: 10.1016/j.tvjl.2019.105345google scholar: lookup
  36. Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio OM. Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses. Equine Veterinary Journal 2019, 51(5), 646-652.
    doi: 10.1111/evj.13085google scholar: lookup
  37. Vainionpää MH, Raekallio MR, Pakkanen SAE, Ranta-Panula V, Rinne VM, Scheinin M, Vainio OM. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine. Veterinary Anaesthesia and Analgesia 2013, 40(3), 257-264.
    doi: 10.1111/vaa.12012google scholar: lookup
  38. Virtanen R, Savola J-M, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an α2-adrenoceptor agonist. European Journal of Pharmacology 1988, 150(1-2), 9-14.
    doi: 10.1016/0014-2999(88)90744-3google scholar: lookup
  39. Vries A, Pakkanen SAE, Raekallio MR, Ekiri A, Scheinin M, Taylor PM, Vainio OM. Clinical effects and pharmacokinetic variables of romifidine and the peripheral α2-adrenoceptor antagonist MK-467 in horses. Veterinary Anaesthesia and Analgesia 2016, 43(6), 599-610.
  40. Wittenberg-Voges L, Kästner SBR, Raekallio M, Vainio OM, Rohn K, Hopster K. Effect of dexmedetomidine and xylazine followed by MK-467 on gastrointestinal microperfusion in anaesthetized horses. Veterinary Anaesthesia and Analgesia 2017, 45(2), 165-174.
  41. Yamashita K, Tsubakishita S, Futaok S, Ueda I, Hamaguchi H, Seno T, Katoh S, Izumisawa Y, Kotani T, Muir WW. Cardiovascular effects of medetomidine, detomidine and xylazine in horses. Journal of Veterinary Medical Science 2000, 62(10), 1025-1032.
    doi: 10.1292/jvms.62.1025google scholar: lookup

Citations

This article has been cited 1 times.
  1. Verhaar N, Kopp V, Pfarrer C, Neudeck S, König K, Rohn K, Kästner S. Alpha(2) Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine. Animals (Basel) 2023 Aug 30;13(17).
    doi: 10.3390/ani13172755pubmed: 37685019google scholar: lookup
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