{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:44:34Z","timestamp":1792813474559,"version":"4.5.0"},"reference-count":39,"publisher":"American Veterinary Medical Association (AVMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"s001\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s002\">\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>8 purpose-bred, 2-year-old Beagles.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s003\">\n<jats:title>PROCEDURES<\/jats:title>\n<jats:p>A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a \u2265 2-week interval as follows: injection of MED (20 \u03bcg\/kg) or MED mixed with 400 \u03bcg of vatinoxan\/kg (MEDVAT) 30 minutes before AA (100 \u03bcg\/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s004\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at \u2265 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole\u2013treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"s005\">\n<jats:title>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.80.10.912","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T18:08:49Z","timestamp":1569521329000},"page":"912-922","source":"Crossref","is-referenced-by-count":12,"title":["Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral \u03b12-adrenoceptor antagonist vatinoxan hydrochloride"],"prefix":"10.2460","volume":"80","author":[{"given":"Heta","family":"Turunen","sequence":"first","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja R.","family":"Raekallio","sequence":"additional","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhana M.","family":"Honkavaara","sequence":"additional","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Restitutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira J.","family":"Kallio-Kujala","sequence":"additional","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdy","family":"Adam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Nevanper\u00e4","sequence":"additional","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Scheinin","sequence":"additional","affiliation":[{"name":"4Institute of Biomedicine, University of Turku and Unit of Clinical Pharmacology, Turku University Hospital, 20520 Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia K.","family":"M\u00e4nnikk\u00f6","sequence":"additional","affiliation":[{"name":"5Department of Statistics, 4Pharma Ltd, Tykist\u00f6katu 4, 20520 Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi J.","family":"Hautaj\u00e4rvi","sequence":"additional","affiliation":[{"name":"6Admescope Ltd, Typpitie 1, 90620 Oulu, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Larenza Menzies","sequence":"additional","affiliation":[{"name":"2Clinical Unit of Anaesthesiology and Perioperative Intensive Care Medicine, University of Veterinary Medicine Vienna, 1210 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi M.","family":"Vainio","sequence":"additional","affiliation":[{"name":"1Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00100 Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1748-5827.1989.tb01575.x","article-title":"Medetomidine, a new sedative-analgesic for use in the dog and its reversal with atipamezole","volume":"30","author":"Clarke","year":"1989"},{"key":"ref2","series-title":"Acta Vet Scand Suppl","first-page":"29","article-title":"Pharmacological profiles of medetomidine and its antagonist, atipamezole","volume":"85","author":"Virtanen","year":"1989"},{"key":"ref3","series-title":"J Small Anim Pract","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1748-5827.1990.tb00770.x","article-title":"Clinical effectiveness of atipamezole as a medetomidine antagonist in cats","volume":"31","author":"V\u00e4h\u00e4-Vahe","year":"1990"},{"key":"ref4","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/j.1365-2885.1990.tb00769.x","article-title":"The clinical effectiveness of atipamezole as a medetomidine antagonist in the dog","volume":"13","author":"V\u00e4h\u00e4-Vahe","year":"1990"},{"key":"ref5","series-title":"Am J Vet Res","first-page":"724","article-title":"Hemodynamic effects of medetomidine-midazolam-butorphanol and medetomidine-midazolam-buprenorphine combinations and reversibility by atipamezole in dogs","volume":"57","author":"Pypendop","year":"1996"},{"key":"ref6","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.2460\/ajvr.2001.62.1745","article-title":"Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats","volume":"62","author":"Lamont","year":"2001"},{"key":"ref7","series-title":"Vet Rec","first-page":"447","article-title":"Reversal of medetomidine-induced cardiovascular and respiratory changes with atipamezole in dogs","volume":"127","author":"Vainio","year":"1990"},{"key":"ref8","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/vr.160.26.891","article-title":"Evaluation of the clinical efficacy and safety of intramuscular and intravenous doses of dexmedetomidine and medetomidine in dogs and their reversal with atipamezole","volume":"160","author":"Granholm","year":"2007"},{"key":"ref9","series-title":"J Feline Med Surg","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1177\/1098612X17722265","article-title":"Hemodynamic effects of low-dose atipamezole in isoflurane-anesthetized cats receiving an infusion of dexmedetomidine","volume":"20","author":"Martin-Flores","year":"2018"},{"key":"ref10","series-title":"J Pharmacol Exp Ther","first-page":"32","article-title":"A peripherally acting alpha-2 adrenoceptor antagonist: L-659,066","volume":"245","author":"Clineschmidt","year":"1988"},{"key":"ref11","series-title":"J Cardiothorac Vasc Anesth","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S1053-0770(98)90197-5","article-title":"A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs","volume":"12","author":"Pagel","year":"1998"},{"key":"ref12","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"728","DOI":"10.2460\/ajvr.69.6.728","article-title":"Effects of a peripheral \u03b12 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs","volume":"69","author":"Enouri","year":"2008"},{"key":"ref13","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/j.1365-2885.2010.01242.x","article-title":"The effects of increasing doses of MK-467, a peripheral alpha2-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs","volume":"34","author":"Honkavaara","year":"2011"},{"key":"ref14","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/j.1467-2995.2008.00403.x","article-title":"The effects of L-659,066, a peripheral \u03b12-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs","volume":"35","author":"Honkavaara","year":"2008"},{"key":"ref15","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1111\/j.1467-2995.2011.00630.x","article-title":"Effects of different doses of L-659\u2032066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine","volume":"38","author":"Restitutti","year":"2011"},{"key":"ref16","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"587","DOI":"10.2460\/ajvr.73.5.587","article-title":"Cardiopulmonary and sedative effects of the peripheral \u03b12-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs","volume":"73","author":"Rolfe","year":"2012"},{"key":"ref17","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1111\/jvp.12292","article-title":"Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs","volume":"39","author":"Bennett","year":"2016"},{"key":"ref18","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.vaa.2016.04.006","article-title":"Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral \u03b12-antagonist MK-467 in dogs","volume":"44","author":"Restitutti","year":"2017"},{"key":"ref19","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.vaa.2017.02.008","article-title":"Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats","volume":"44","author":"Pypendop","year":"2017"},{"key":"ref20","series-title":"Drug Metab Dispos","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1124\/dmd.111.042671","article-title":"Influence of MK-467, a peripherally acting \u03b12-adrenoceptor antagonist on the disposition of intravenous dexmedetomidine in dogs","volume":"40","author":"Honkavaara","year":"2012"},{"key":"ref21","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.vaa.2016.08.011","article-title":"The impact of MK-467 on sedation, heart rate and arterial blood pressure after intramuscular coadministration with dexmedetomidine in conscious cats","volume":"44","author":"Honkavaara","year":"2017"},{"key":"ref22","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/vaa.12397","article-title":"Cardiovascular effects of dexmedetomidine, with or without MK-467, following intravenous administration in cats","volume":"44","author":"Pypendop","year":"2017"},{"key":"ref23","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1111\/j.1365-2885.1995.tb00599.x","article-title":"Atipamezole increases medetomidine clearance in the dog: an agonist-antagonist interaction","volume":"18","author":"Salonen","year":"1995"},{"key":"ref24","series-title":"Am J Vet Res","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.2460\/ajvr.2001.62.1255","article-title":"Assessment of lithium dilution cardiac output as a technique for measurement of cardiac output in dogs","volume":"62","author":"Mason","year":"2001"},{"key":"ref25","series-title":"Comp Med","first-page":"156","article-title":"Reference cardiopulmonary values in normal dogs","volume":"55","author":"Haskins","year":"2005"},{"key":"ref26","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1365-2885.1990.tb00742.x","article-title":"Reversal of medetomidine sedation by atipamezole in dogs","volume":"13","author":"Vainio","year":"1990"},{"key":"ref27","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.1467-2995.2005.00233.x","article-title":"Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog","volume":"32","author":"Murrell","year":"2005"},{"key":"ref28","series-title":"Vet Rec","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1136\/vr.104045","article-title":"Dexmedetomidine oromucosal gel for noise-associated acute anxiety and fear in dogs\u2014a randomised, double-blind, placebo-controlled clinical study","volume":"180","author":"Korpivaara","year":"2017"},{"key":"ref29","series-title":"J Vet Med Sci","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1292\/jvms.56.1009","article-title":"Antagonistic effects of atipamezole on medetomidine-midazolam induced sedation in dogs","volume":"56","author":"Hayashi","year":"1994"},{"key":"ref30","series-title":"J Pharmacol Exp Ther","first-page":"690","article-title":"Hemodynamic and sedative effects of dexmedetomidine in dog","volume":"263","author":"Bloor","year":"1992"},{"key":"ref31","series-title":"J Cardiothorac Vasc Anesth","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/1053-0770(93)90117-4","article-title":"Effects of dexmedetomidine on systemic and coronary hemodynamics in the anesthetized dog","volume":"7","author":"Flacke","year":"1993"},{"key":"ref32","series-title":"Anesthesiology","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1097\/00000542-199109000-00018","article-title":"The effects of the stereoisomers of the \u03b12-adrenergic agonist medetomidine on systemic and coronary hemodynamics in conscious dogs","volume":"75","author":"Schmeling","year":"1991"},{"key":"ref33","series-title":"Can Vet J","first-page":"725","article-title":"Article survey of utilization of medetomidine and atipamezole in private veterinary practice in Quebec in 2002","volume":"48","author":"Kaartinen","year":"2007"},{"key":"ref34","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1046\/j.1365-2885.1997.00080.x","article-title":"Reversal of medetomidine-induced sedation in reindeer (Rangifer tarandus tarandus) with atipamezole increases the medetomidine concentration in plasma","volume":"20","author":"Ranheim","year":"1997"},{"key":"ref35","series-title":"J Vet Pharmacol Ther","first-page":"428","article-title":"Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction","volume":"21","author":"Ranheim","year":"1998"},{"key":"ref36","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1046\/j.1365-2885.1999.00231.x","article-title":"A pharmacokinetic study including some relevant clinical effects of medetomidine and atipamezole in lactating dairy cows","volume":"22","author":"Ranheim","year":"1999"},{"key":"ref37","series-title":"J Vet Pharmacol Ther","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/jvp.12486","article-title":"The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal","volume":"41","author":"Adam","year":"2018"},{"key":"ref38","series-title":"Arch Int Pharmacodyn Ther","first-page":"190","article-title":"Highly selective and specific antagonism of central and peripheral alpha 2-adrenoceptors by atipamezole","volume":"297","author":"Virtanen","year":"1989"},{"key":"ref39","series-title":"Vet Anaesth Analg","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1111\/vaa.12058","article-title":"Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine","volume":"40","author":"Restitutti","year":"2013"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/80\/10\/ajvr.80.10.912.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/80\/10\/ajvr.80.10.912.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/80\/10\/ajvr.80.10.912.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T20:43:08Z","timestamp":1696538588000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/80\/10\/ajvr.80.10.912.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":39,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.80.10.912","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10]]}}}