RESEARCH PAPER Effects of methadone on the minimum alveolar concentration of isoflurane in dogs Renato G Credie*, Francisco J Teixeira Neto*, Tatiana H Ferreira*, Anto ˆnio JA Aguiar*, Fabio C Restitutti  & Jose ´ E Correnteà *Departamento de Cirurgia e Anestesiologia Veterina ´ria, Faculdade de Medicina Veterina ´ria e Zootecnia, Universidade Estadual Paulista, Botucatu, SP, Brazil  Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland àDepartmento de Bioestatı ´stica, Instituto de Biocie ˆncias, Universidade Estadual Paulista, Botucatu, SP, Brazil Correspondence: Francisco J Teixeira Neto, Departamento de Cirurgia e Anestesiologia Veterina ´ria, Faculdade de Medicina Veterina ´ria e Zootecnia, Universidade Estadual Paulista, Distrito de Rubia ˜o Jr S/N, CEP 18618-000, Botucatu, SP, Brazil. E-mail: fteixeira@fmvz.unesp.br Abstract Objective To investigate the effects of methadone on the minimum alveolar concentration of isoflurane (ISO MAC ) in dogs. Study design Prospective, randomized cross-over experimental study. Animals Six adult mongrel dogs, four males and two females, weighing 22.8 ± 6.6 kg. Methods Animals were anesthetized with isoflurane and mechanically ventilated on three separate days, at least 1 week apart. Core temperature was main- tained between 37.5 and 38.5 °C during ISO MAC determinations. On each study day, ISO MAC was determined using electrical stimulation of the antebrachium (50 V, 50 Hz, 10 mseconds) at 2.5 and 5 hours after intravenous injection of physio- logical saline (control) or one of two doses of methadone (0.5 or 1.0 mg kg )1 ). Results Mean (±SD) ISO MAC in the control treat- ment was 1.19 ± 0.15% and 1.18 ± 0.15% at 2.5 and 5 hours, respectively. The 1.0 mg kg )1 dose of methadone reduced ISO MAC by 48% (2.5 hours) and by 30% (5 hours), whereas the 0.5 mg kg )1 dose caused smaller reductions in ISO MAC (35% and 15% reductions at 2.5 and 5 hours, respectively). Both doses of methadone decreased heart rate (HR), but the 1.0 mg kg )1 dose was associated with greater negative chronotropic actions (HR 37% lower than control) and mild metabolic acidosis at 2.5 hours. Mean arterial pressure increased in the MET1.0 treatment (13% higher than control) at 2.5 hours. Conclusions and clinical relevance Methadone re- duces ISO MAC in a dose-related fashion and this effect is lessened over time. Although the isoflurane sparing effect of the 0.5 mg kg )1 dose of methadone was smaller in comparison to the 1.0 mg kg )1 dose, the lower dose is recommended for clinical use because it results in less evidence of cardiovascular impairment. Keywords isoflurane, methadone, minimum alveo- lar concentration. Introduction Inhalant anesthetics allow rapid and precise control of anesthetic drug concentration at the effect site (central nervous system, CNS) via monitoring end- tidal inhalant anesthetic concentrations. Modern inhalant agents are also devoid of cumulative effects and this characteristic allows fast recoveries that are not substantially influenced by the duration of anes- 240 Veterinary Anaesthesia and Analgesia, 2010, 37, 240–249 doi:10.1111/j.1467-2995.2010.00528.x