DISSERTATIONES SCHOLAE DOCTORALIS AD SANITATEM INVESTIGANDAM UNIVERSITATIS HELSINKIENSIS 91/2015 FLAVIA RESTITUTTI Central, Cardiovascular and Metabolic Effects of Dexmedetomidine Associated with the Selective Peripheral Alpha2-adrenoceptor Antagonist MK-467 in Dogs DEPARTMENT OF EQUINE AND SMALL MEDICINE FACULTY OF VETERINARY MEDICINE DOCTORAL PROGRAMME IN CLINICAL VETERINARY MEDICINE UNIVERSITY OF HELSINKI
Central, cardiovascular and metabolic effects of dexmedetomidine associated with the selective peripheral alpha 2 -adrenoceptor antagonist MK-467 in dogs ACADEMIC DISSERTATION
Contents
Abstract
List of original publications
Abbreviations
1 Introduction
2 Review of the literature 2.1 α-adrenergic receptors 2.1.1 α 2 -adrenoceptors
2.1.1.1 Subtypes and physiological effects
2.2 α 2 -adrenoceptor agonists used in veterinary medicine 2.2.1 Xylazine 2.2.2 Romifidine
2.2.3 Detomidine
2.2.4 Medetomidine 2.2.5 Dexmedetomidine 2.2.5.1 Central effects
2.2.5.2 Cardiovascular effects
2.2.5.3 Effects on glucose, insulin and free fatty acids
2.2.5.4 Other effects
2.3 Use of anticholinergics with α 2 -adrenoceptor agonists
2.4 α 2 -adrenoceptor antagonists 2.4.1 Atipamezole
2.4.2 MK-467
2.5 Contrast-enhanced ultrasound
3 Aims of the study
4 Materials and methods 4.1 Animals 4.2 Instrumentation
4.3 Study design 4.4 Treatments, drugs and dosages
4.5 Clinical assessment of sedation and hypnosis (I)
4.6 Cardiorespiratory monitoring (II)
4.7 CEUS (III)
4.8 Iohexol test (III) 4.9 Plasma glucose, insulin, NEFA, cortisol (IV) and lactate measurements (II, IV)
4.10 Statistical analysis
5 Results 5.1 Clinical sedation and bispectral index (I)
5.2 Cardiovascular effects (II, III)
5.3 Plasma glucose and insulin 5.4 Plasma lactate (II, IV) 5.5 Plasma NEFA (lv)
5.6 Plasma cortisol (IV)
6 Discussion 6.1 Central effects (I) 6.1.1 Sedation score
6.1.2 Bispectral index
6.2 Cardiovascular effects (II, III) 6.2.1 Haemodynamic parameters
6.2.2 Blood flow in abdominal organs (III)
6.2.3 Lactate (II, IV)
6.3 Glucose and insulin (IV)
6.4 Effects on NEFA (IV)
6.5 Methodological considerations and limitations of the studies
7 Conclusions
Acknowledgements
References
Recent Publications in this Series 71/2015 Johanna Lotsari-Salomaa Epigenetic Characteristics of Lynch Syndrome-Associated and Sporadic Tumorigenesis 72/2015 Tea Pemovska Individualized Chemical Systems Medicine of Acute and Chronic Myeloid Leukemia 73/2015 Simona Bramante Oncolytic Adenovirus Coding for GM-CSF in Treatment of Cancer 74/2015 Alhadi Almangush Histopathological Predictors of Early Stage Oral Tongue Cancer 75/2015 Otto Manninen Imaging Studies in the Mouse Model of Progressive Myoclonus Epilepsy of Unverricht-Lundborg Type, EPM1 76/2015 Mordekhay Medvedovsky Methodological and Clinical Aspects of Ictal and Interictal MEG 77/2015 Marika Melamies Studies on Canine Lower Respiratory Tract with Special Reference to Inhaled Corticosteroids 78/2015 Elina Välimäki Activation of Inflammasome and Protein Secretion by Endogenous Danger and Microbe-Derived Signals in Human Macrophages 79/2015 Terhi Keltanen Postmortem Biochemistry - Analysis of Metabolic Imbalance 80/2015 Mari Savolainen The Effects of Prolyl Oligopeptidase Inhibition in α-synuclein Based Mouse Models of Parkinson s Disease 81/2015 Teemu Luostarinen Studies on Hemodynamics and Coagulation in Neuroanesthesia 82/2015 Olaya Llano Novel Molecular Mechanisms of Dendritic Spine Development 83/2015 Abdirisak Ahmed Haji Omar Oral and Cutaneous Squamous Cell Carcinomas: Differences in Tumor and Tumor Microenvironment 84/2015 Katja Airaksinen Modifications of Cortical Activity by Deep Brain Stimulation in Advanced Parkinson s Disease: an MEG Study 85/2015 And Demir Clinical Use of Urinary Gonadotropin Determinations in Children and Adolescents 86/2015 Raisa Haavikko Synthesis of Betulin Derivatives with New Bioactivities 87/2015 Hongxin Chen Heterobasidion annosum sensu stricto Pathogenesis: Bioinformatic and Functional Study of Cerato-Platanin Family Proteins 88/2015 Kristiina Rajamäki Role of the Inflammasome Pathway in Atherosclerosis 89/2015 Pirkko Kriikku Toxicological Abuse Profile of New Recreational Drugs in Driving-Under- The-Influence and Post-Mortem Cases in Finland 90/2015 Eeva Mustonen Red Clover Isoflavonoids in Feed, Plasma and Milk of Ruminants Helsinki 2015 ISSN 2342-3161 ISBN 978-951-51-1734-2