Effects of dexmedetomidine, with or without vatinoxan (MK-467), on minimum alveolar concentration of isoflurane in cats

Bruno H Pypendop, Hanna Ahokoivu, Juhana Honkavaara

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To characterize the effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MAC ISO ) in cats. Study design: Randomized crossover experimental study. Animals: A group of six adult healthy male neutered cats. Methods: Cats were anesthetized with isoflurane in oxygen and instrumented. Dexmedetomidine was administered using a target-controlled infusion system to achieve 10 target plasma concentrations ranging from 0 to 40 ng mL –1 . Additionally, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve a target plasma concentration of 4 μg mL –1 . Pulse rate (PR), respiratory rate, systolic arterial pressure (SAP), hemoglobin oxygen saturation, body temperature, end-tidal partial pressure of carbon dioxide and drug concentrations were measured. MAC ISO was determined at each target plasma dexmedetomidine concentration using the bracketing method and the tail clamp technique. Pharmacodynamic models were fitted to the plasma dexmedetomidine concentration-MAC ISO . Pharmacodynamic parameters were tested for equivalence, and if rejected, for difference. Results: Dexmedetomidine alone decreased MAC ISO in a plasma concentration-dependent manner. Maximum reduction was 77 ± 4%; the dexmedetomidine concentration producing 50% of the maximum decrease (IC 50 ) was 0.77 ng mL –1 . Vatinoxan increased MAC ISO in the absence of dexmedetomidine, decreased the potency of dexmedetomidine for its MAC ISO -reducing effect (IC 50 = 12 ng mL –1 ) and lessened the maximum MAC ISO reduction (60 ± 14%). PR decreased less and SAP increased less when dexmedetomidine was administered with vatinoxan compared with saline. Conclusion and clinical relevance: Vatinoxan altered the effect of dexmedetomidine on MAC ISO . A high plasma dexmedetomidine concentration in the presence of vatinoxan resulted in a large decrease in MAC ISO , with attenuation of dexmedetomidine-induced cardiovascular effects. The vatinoxan–dexmedetomidine combination may provide clinical benefits in isoflurane-anesthetized cats.

Original languageEnglish (US)
JournalVeterinary Anaesthesia and Analgesia
DOIs
StatePublished - Jan 1 2019

Fingerprint

L 659066
dexmedetomidine
Dexmedetomidine
Isoflurane
isoflurane
Cats
cats
pharmacology
inhibitory concentration 50
heart rate
Arterial Pressure
Heart Rate
Oxygen
Blood Pressure
oxygen

Keywords

  • cats
  • minimum alveolar concentration
  • α -agonist
  • α -antagonist

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{677680b6b32f4c6c97cf7bce6cae8a97,
title = "Effects of dexmedetomidine, with or without vatinoxan (MK-467), on minimum alveolar concentration of isoflurane in cats",
abstract = "Objective: To characterize the effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MAC ISO ) in cats. Study design: Randomized crossover experimental study. Animals: A group of six adult healthy male neutered cats. Methods: Cats were anesthetized with isoflurane in oxygen and instrumented. Dexmedetomidine was administered using a target-controlled infusion system to achieve 10 target plasma concentrations ranging from 0 to 40 ng mL –1 . Additionally, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve a target plasma concentration of 4 μg mL –1 . Pulse rate (PR), respiratory rate, systolic arterial pressure (SAP), hemoglobin oxygen saturation, body temperature, end-tidal partial pressure of carbon dioxide and drug concentrations were measured. MAC ISO was determined at each target plasma dexmedetomidine concentration using the bracketing method and the tail clamp technique. Pharmacodynamic models were fitted to the plasma dexmedetomidine concentration-MAC ISO . Pharmacodynamic parameters were tested for equivalence, and if rejected, for difference. Results: Dexmedetomidine alone decreased MAC ISO in a plasma concentration-dependent manner. Maximum reduction was 77 ± 4{\%}; the dexmedetomidine concentration producing 50{\%} of the maximum decrease (IC 50 ) was 0.77 ng mL –1 . Vatinoxan increased MAC ISO in the absence of dexmedetomidine, decreased the potency of dexmedetomidine for its MAC ISO -reducing effect (IC 50 = 12 ng mL –1 ) and lessened the maximum MAC ISO reduction (60 ± 14{\%}). PR decreased less and SAP increased less when dexmedetomidine was administered with vatinoxan compared with saline. Conclusion and clinical relevance: Vatinoxan altered the effect of dexmedetomidine on MAC ISO . A high plasma dexmedetomidine concentration in the presence of vatinoxan resulted in a large decrease in MAC ISO , with attenuation of dexmedetomidine-induced cardiovascular effects. The vatinoxan–dexmedetomidine combination may provide clinical benefits in isoflurane-anesthetized cats.",
keywords = "cats, minimum alveolar concentration, α -agonist, α -antagonist",
author = "Pypendop, {Bruno H} and Hanna Ahokoivu and Juhana Honkavaara",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.vaa.2019.02.004",
language = "English (US)",
journal = "Veterinary Anaesthesia and Analgesia",
issn = "1467-2987",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Effects of dexmedetomidine, with or without vatinoxan (MK-467), on minimum alveolar concentration of isoflurane in cats

AU - Pypendop, Bruno H

AU - Ahokoivu, Hanna

AU - Honkavaara, Juhana

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: To characterize the effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MAC ISO ) in cats. Study design: Randomized crossover experimental study. Animals: A group of six adult healthy male neutered cats. Methods: Cats were anesthetized with isoflurane in oxygen and instrumented. Dexmedetomidine was administered using a target-controlled infusion system to achieve 10 target plasma concentrations ranging from 0 to 40 ng mL –1 . Additionally, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve a target plasma concentration of 4 μg mL –1 . Pulse rate (PR), respiratory rate, systolic arterial pressure (SAP), hemoglobin oxygen saturation, body temperature, end-tidal partial pressure of carbon dioxide and drug concentrations were measured. MAC ISO was determined at each target plasma dexmedetomidine concentration using the bracketing method and the tail clamp technique. Pharmacodynamic models were fitted to the plasma dexmedetomidine concentration-MAC ISO . Pharmacodynamic parameters were tested for equivalence, and if rejected, for difference. Results: Dexmedetomidine alone decreased MAC ISO in a plasma concentration-dependent manner. Maximum reduction was 77 ± 4%; the dexmedetomidine concentration producing 50% of the maximum decrease (IC 50 ) was 0.77 ng mL –1 . Vatinoxan increased MAC ISO in the absence of dexmedetomidine, decreased the potency of dexmedetomidine for its MAC ISO -reducing effect (IC 50 = 12 ng mL –1 ) and lessened the maximum MAC ISO reduction (60 ± 14%). PR decreased less and SAP increased less when dexmedetomidine was administered with vatinoxan compared with saline. Conclusion and clinical relevance: Vatinoxan altered the effect of dexmedetomidine on MAC ISO . A high plasma dexmedetomidine concentration in the presence of vatinoxan resulted in a large decrease in MAC ISO , with attenuation of dexmedetomidine-induced cardiovascular effects. The vatinoxan–dexmedetomidine combination may provide clinical benefits in isoflurane-anesthetized cats.

AB - Objective: To characterize the effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MAC ISO ) in cats. Study design: Randomized crossover experimental study. Animals: A group of six adult healthy male neutered cats. Methods: Cats were anesthetized with isoflurane in oxygen and instrumented. Dexmedetomidine was administered using a target-controlled infusion system to achieve 10 target plasma concentrations ranging from 0 to 40 ng mL –1 . Additionally, vatinoxan or an equivalent volume of saline was administered using a target-controlled infusion system to achieve a target plasma concentration of 4 μg mL –1 . Pulse rate (PR), respiratory rate, systolic arterial pressure (SAP), hemoglobin oxygen saturation, body temperature, end-tidal partial pressure of carbon dioxide and drug concentrations were measured. MAC ISO was determined at each target plasma dexmedetomidine concentration using the bracketing method and the tail clamp technique. Pharmacodynamic models were fitted to the plasma dexmedetomidine concentration-MAC ISO . Pharmacodynamic parameters were tested for equivalence, and if rejected, for difference. Results: Dexmedetomidine alone decreased MAC ISO in a plasma concentration-dependent manner. Maximum reduction was 77 ± 4%; the dexmedetomidine concentration producing 50% of the maximum decrease (IC 50 ) was 0.77 ng mL –1 . Vatinoxan increased MAC ISO in the absence of dexmedetomidine, decreased the potency of dexmedetomidine for its MAC ISO -reducing effect (IC 50 = 12 ng mL –1 ) and lessened the maximum MAC ISO reduction (60 ± 14%). PR decreased less and SAP increased less when dexmedetomidine was administered with vatinoxan compared with saline. Conclusion and clinical relevance: Vatinoxan altered the effect of dexmedetomidine on MAC ISO . A high plasma dexmedetomidine concentration in the presence of vatinoxan resulted in a large decrease in MAC ISO , with attenuation of dexmedetomidine-induced cardiovascular effects. The vatinoxan–dexmedetomidine combination may provide clinical benefits in isoflurane-anesthetized cats.

KW - cats

KW - minimum alveolar concentration

KW - α -agonist

KW - α -antagonist

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SN - 1467-2987

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