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Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1991 Effects of Chronic Administration of Phenylbutazone on Reproduction in the Mare. Mareth Ellsworth Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Ellsworth, Mareth, "Effects of Chronic Administration of Phenylbutazone on Reproduction in the Mare." (1991). LSU Historical Dissertations and Theses. 5116. https://digitalcommons.lsu.edu/gradschool_disstheses/5116 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Beil & Howell Information Company 300 North Zeeb Road. Ann Arbor, Ml 48106-1346 USA 313/761-4700 800/521-0600 Order Number 9200059 Effects of chronic administration of phenylbutazone on reproduction in the mare Ellsworth, Mareth, Ph.D. The Louisiana State University and Agricultural and Mechanical Col., 1991 UMI 300 N.ZeebRd. Ann Arbor, MI 48106 EFFECTS OF CHRONIC ADMINISTRATION OF PHENYLBUTAZONE ON REPRODUCTION IN THE MARE A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Interdepartmental Program in Veterinary Medical Sciences (Physiology Option) by Mareth Ellsworth B.A., University of California, 1970 May, 1991 ACKNOWLEDGMENTS Many thanks and much appreciation to the members of my committee Drs. Rodney H. Ingraham, Robert A. Godke, Charles R. Short, D. Gene Luther and Leonard C. Kappel. Thank you to the former members of my committee Drs. Louis F. Archbald, Wayne Flory and Lawrence P. Ruhr, who left Louisiana State University School of Veterinary medicine before I finished this degree. Thank you for all the hours of help and guidance you contributed with research projects, acquiring research funding, writing manuscripts and reading and writing this dissertation. Thank you for the research funds provided by the Louisiana Agricultural Experiment Station of the Louisiana State University Agricultural Center, Department of Veterinary Physiology, Pharmacolo­ gy and Toxicology of the Louisiana State University School of Veterinary Medicine, Louisiana Thoroughbred Racing Breakage Funds, Diagnostic Products Corporation in Los Angeles and Dr. D. Gene Luther who contributed his research funds to my research project. Thank you to the Department of Veterinary Clinical Sciences of the Louisana State University School of Veterinary Medicine for the use of their clinical facilities, supplies, pastures, research mares and feed provided for the mares. Thank you to Dr. Robert A. Godke for technical assistance, supplies and use of his laboratory equipment and space to conduct the progesterone assays. Thank you to Drs. Daniel H. Hwang and Prithiva S. Chanmugam for their expertise, guidance, help and the use of their laboratory to ii conduct the prostaglandin assays. Thank you to Dr. Grace Amborski for her technical assistance, cameras, microscopes, incubator and laboratory space utilized to process the embryos. Thank you to Biomedical Communications Unit of the Louisiana State University School of Veterinary Medicine for drawing the figures for this dissertation, for photographing the horses and research procedures and for preparing slides used for research presentations, seminars and teaching purposes. Thank you to my family, friends and business clients for all your patience, understanding and encouraging support to complete this degree when I was discouraged by personal tragedies and the difficul­ ty of owning and managing a horse business plus pursuing a Ph.D. A special heart warming thanks and great appreciation to my mother Barbara and my sister Sarah, who extended emotional and financial support. This dissertation is dedicated to you for encouraging me to fulfill my father's wish that I finish my Ph.D. This degree is dedicated to the memory of my father Thordore Richards Ellsworth, who initially encouraged me to go back to school. TABLE OF CONTENTS Page TITLE................................................................. i ACKNOWLEDGMENTS .................................................. ii TABLE OF CONTENTS................................................... iv LIST OF TABLES.......................................................ix LIST OF FIGURES. .................................................. xi ABSTRACT...........................................................xiii INTRODUCTION..........................................................1 LITERATURE REVIEW.................................................... 3 Non-steriodal Anti-inflammatory Drugs.......................... 3 Chemical Properties........................................ 3 Mechanism of Action........................................ 7 Pharmacokinetics.......................................... 10 Toxicity.................................................. 12 Clinical Use and Efficacy.................................14 Use of Non-steroidal Anti-inflammatory Drugs in Competing Horses....................................... 19 Phenylbutazone in Horses....................................... 22 Introduction.............................................. 22 Chemistry................................................. 22 Safety.............................................=...... 23 Recommended Dose andRoute of Administration.............. 23 Half-life................................................. 24 Absorption................................................ 28 Distribution.............................................. 32 Plasma Concentration with Intravenous Administration 33 Metabolism................................................ 33 Excretion................................................. 38 Toxicity.................................................. 43 Phenylbutazone and Inflammation.......................... 47 Inflammation and Prostaglandins............................... 50 Inflammation Defined......................................50 Inflammation Process..................................... .51 Prostaglandins in Basal Physiological Functions.......... 54 Prostaglandins and Erythema.............................. 56 Prostaglandins and Edema................................. 56 Prostaglandins and Pain.................................. 57 Prostaglandins and Fever ........................... 59 Prostaglandins and Leukotaxis............................ 59 Prostaglandins and Anti-inflammatory Actions.............60 Prostaglandins and Female Reproduction from Cyclicity to Early Embryonic Development...................... 61 Introduction.............................................. 61 Ovulation................................................. 61 Luteolysis................................................ 63 Luteotropic Effects of Prostaglandins.................... 65 Antifertility Effects of Non-steroidal Anti-inflammatory Drugs.................................. 66 Embryo Prostaglandin Synthesis in Farm Animals................68 Introduction.............................................. 68 Ovine Embryo Prostaglandin Synthesis..................... 68 Porcine Embryo Prostaglandin Synthesis................... 71 Bovine Embryo Prostaglandin Synthesis.................... 71 Hare Estrous Cycle............................................. 75 Introduction.............................................. 75 Breeding Season...........................................75 v Estrous Cycle............................................. 76 Ovulation................................................. 77 Endometrial Biopsy in the Mare.......... ......................80 Induced Luteolysis in the Mare........................... 80 Luteolysis in Mares Induced by Endometrial Biopsy........82 Technique for Performing Endometrial Biopsy in the Mare........................................ 82 High

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