Cambridge University

Cambridge University

Equine research in anesthesia

32

Equine anesthesia still carries a greater risk of serious morbidity or mortality than in other species. The Department's research in equine anesthesia focuses on this problem in two ways: first to elucidate why the horse should be more susceptible to the effects of anesthesia, and second, to develop ways to reduce this risk using alternative anesthetic techniques. This involves both fundamental research into the mechanisms and physiological effects of anesthesia as well as practical development of new anesthetic techniques in the light of the fundamental investigations. Clinical and experimental research in equine anesthesia includes: 1. The Confidential Enquiry into Perioperative Equine Fatalities (CEPEF) provides the basic information which indicates where specific laboratory investigation should be directed. CEPEF is a full epidemiological study investigating all aspects of equine anesthesia in order to reveal techniques, drugs or any other factor that may increase the risk of anesthetic mortality or morbidity. This project collects data from clinics throughout the UK, Europe, Australia and from North America. Data from 40,000 equine anesthetics (310 deaths) have been collected and are now being processed. A number of risk factors have already been revealed along with some protective factors. A randomized controlled trial comparing two maintenance anesthetics is now at the planning stage and will be the first step in using epidemiology itself to show what action can be taken to reduce the risks of equine anesthesia. 2. Research into the endocrine and metabolic effects of anesthesia continues. This work was initiated about ten years ago and a number of features of the effect of anesthesia on horses have been elucidated. Most notable is the marked pituitary-adrenocortical response to routine volatile agent anesthesia and hypotension. The work has led to interest in intravenous anesthesia, thus avoiding use of volatile agents (see below). The role of endogenous opioids in equine anesthesia is under further investigation following a recent visit from Dr. S.P.L. Luna who originally completed his PhD thesis when working with Dr. P. Taylor in this field. 3. Nitric oxide (NO) and the ecoisanoids are known to play a major role in cardiovascular control, particularly in endotoxemia. The objective of this study is to establish the importance of endotoxin/ cytokine inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in equine endotoxemia. In macrophages and chondrocytes from the horse, using PCR, we have demonstrated iNOS and COX-2 induction in response to lipolysaccharide. We aim to collect peritoneal macrophages from normal and LPS treated ponies. We will compare the iNOS/NO and COX-2/prostaglandin levels to those seen in peritoneal cells from clinical colic cases (in collaboration with the RVC). We will try to correlate the NO levels with clinical outcome. We also aim to identify the signal transduction mechanisms that regulate the NOS/COX induction in macrophages to generate novel therapeutic approaches to the treatment of endotoxemia. 4. In view of some of the hazards of volatile agent anesthesia revealed in CEPEF and experimental studies, total intravenous anesthetic (TIVA) regimes are being developed and tested for JOURNAL OF EQUINE VETERINARY SCIENCE

potential use in clinical anesthesia. Pharmacokinetic study of one popular technique using detomidine, ketamine and guaiphenesin has been used to perfect an infusion regimen for longer term, controlled anesthesia. 5. Opioids are commonly used in TIVA in man but are generally considered unsuitable for such a role in horses as they cause excitement. The mechanism of this excitement is to be investigated this year so that methods to reduce the effect may be devised, to allow opioids to be used in clinical anesthesia in horses. 6. Spectral analysis of the EEG and the evoked auditory potential have been used to study the effects on central nervous system (CNS) activity of individual anesthetic and sedative agents. These data are providing the underlying information needed for developing satisfactory TIVA techniques. Although CB Johnson's project is now complete and he has left the department, collaboration with him continues in this field. 7. Clinical studies investigating improved post operative analgesia, use of opioids and muscle relaxants and alternative induction and maintenance agents are undertaken according to the case load of suitable horses in the clinic. 8. In conjunction with Dr. A. Fowden of the Physiological Laboratory, effects of anesthesia on the pregnant mare and fetus are also investigated.

Taylor PM, Johnston GM, Bryant CE, Farnfield B, Harris HJ, Brodbelt DC Collaborators: Hammond R, Evans RJ, Heath MF, Pascoe PJ, Luna SPL, Johnson CB From: University of Cambridge, Equine Research 1996, Dept. of C~inical Veterinary Medicine

Chorioretinal lesions Chorioretinal lesions are common in the UK horse population (occurring in around 15% of otherwise normal horses) and are frequently detected during routine examination of the fundus during pre-purchase examinations. The lesions are a source of clinical concern since their etiology and significance are unknown, although a variety of infectious and non infectious causes have been proposed. It is not known whether lesions are static or progressive and whether they may result in impaired vision or blindness. Consequently, animals in which lesions are detected usually suffer a marked fall in value, even if there is no apparent visual impairment at the time of examination. The aims of this project are to characterize the histopathological appearance of naturally occurring and experimentally induced chorioretinal lesions: to investigate the pathological mechanisms by which the lesions are produced; and to test the hypothesis that EHV-1 infection is an etiology for equine chorioretinopathies. Normal eyes and eyes containing naturally occurring lesions from adult Thoroughbreds are being collected from an abattoir. Lesions have been induced experimentally following intranasal inoculation of adult ponies. Flourescein angiography is being employed to investigate the pathogenesis of the lesions, specifically to address the question of a neural or vascular route of production. Naturally occurring and experimentally induced lesions are being characterized and compared histologically. DNA prepared from normal and affected eyes is being examined for the presence of EHV- 1 DNA by PCR. Eyes in which EHV- 1 can be detected will be examined further by in situ PCR to identify the cellular location of viral DNA. This work is being extended to include the presence of histopathology and EHV- 1 DNA in the CNS of affected horses.

Volume 17, Number 1, 1997

Collaborations have been established with the Royal Postgraduate Medical School, Hammersmith (fluorescein angiography); the Department of Histology, Addenbrokes Hospital, Cambridge (retinal histopathology); and the Free University of Berlin (molecular biology). This project will benefit the industry by clarifying a currently confusing clinical problem which leads, possibly unnecessarily, to substantial loss of sale value for affected horses. Slater JD, Baxi S Collaborators: Arnold J, Cardiac Surgery Unit, Royal Postgraduate Medical School Hammersmith; Anderson J, Department of Histology, Addenbroke's Hospital Cambridge; Borchers K, Free University of Berlin 33