SURGICAL RELOCATION OF THE CAROTID ARTERIES

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In veterinary practice, anaesthetics and anaesthetic adjuncts are used in order to perform both surgically invasive and non-invasive manipulations of varying degrees of magnitude. This often happens in environments where temperature variations are difficult to control and this is even more so, under field conditions. Seasonal and diurnal changes in temperature create extremes of environmental temperature variations.
Encounters with restless animals in a variety of environmental conditions may require that these animals be sedated for varying periods of time. This calls for an agent which should ideally be easy and safe to administer, one that gives good and excitement free sedation without prolonging the recovery period, one with analgesic action thus making supplementation with local anaesthetics unnecessary, one that is not toxic or irritant to tissues and not toxic to organs even after repeated doses, one that does not com pregnant animals and which can be given in supplemental doses without deleterious effects (Fessl, 1970). It is therefore important for the clinician to understand the effects of environmental temperature variations on the body temperatures of animals and the resultant effects of these changes on the pharmacokinetics of some anaesthetics and anaesthetic adjuncts in order to facilitate prevention and management of any anaesthetic complications that may If an animal has to resort to abnormal behaviour or undergo extreme adjustments in its behaviour or physiology in order to cope with adverse aspects of its environment, then it can be said to be in a state of stress (Fraser et at., 1975; Friend, 1980), and intense heat or cold are recognized as such agents that may cause stress in animals (Guyton, 1992).
In the presence of a stressful situation, physiological and behavioural adjustments are made to in attempt to eliminate that event from being a stressor (Moberg, 1976; Friend, 1980). It is not how pleasant or unpleasant the stressor is that counts but, its intensity During anaesthesia and surgery, several factors including, abolition of behavioural responses, attenuated hypothalamic function, reduced metabolic rate, reduced effector responses and abnormally large thermal stresses combine to interfere with normal thermoregulation (Imrie and Hall, 1990). Thus, deviations of internal temperatures from normothermia that elicit vigorous regulatory responses in unanaesthetized animals, may elicit diminished or no responses in animals anaesthetized for surgery. General anaesthetic agents, with the exception of ketamine, impair thermoregulation, presumably by attenuation of hypothalamic function. General anaesthetics increase warm response thresholds (active vasodilation and sweating) and decrease cold response thresholds (vasoconstriction, shivering and non-shivering thermogenesis). They increase the threshold range from approximately 0.20 C to 40 C. The effect of this is a widened range of core temperatures over which no thermoregulatory responses occur (Imrie and Hall, 1990). Other agents used during general anaesthesia also have a major effect on the general heat balance. Neuromuscular blocking drugs abolish shivering thus making paralysed anaesthetized patients cool more rapidly than unparalysed ones during surgery.
However, this may relate more to the type of surgery being performed than to the neuromuscular blocking (Goldberg and Roe, 1966; Imrie and Hall, 1990), as patients undergoing open body cavity surgeries will incur greater heat losses when compared to those undergoing operations which do not involve open body cavities (Morris and Wilkey, 1970). Agents which produce vasodilation redistribute heat to the periphery thus increasing heat loss to the environment while opioids, barbiturates, phenothiazines and butyrophenones have both central and peripheral actions which tend to decrease body temperature (Imrie and Hall, 1990). The duration of action of anaesthetics and other drugs used during anaesthesia at different body temperatures is not well understood. In man, reported studies indicate that perioperative hypothermia markedly decreases drug metabolism. The duration of action of the muscle relaxant vecuronium is more than doubled by a 2° C reduction in body core temperature (Heier et al., 1991). This prolongation of the duration of action is the result of altered pharmacokinetics (Sessler, 1994). Studies on other drugs indicate that the effect of the muscle relaxant atracurium is less dependent on body core temperature. A 3° C decrease in body core temperature increases its duration of action by only 60%. Under the same conditions of body core hypothermia (30 C), plasma concentrations of propofol, which was being infused constantly, were 30% higher than normal. However, the effect of mild hypothermia on the metabolism and pharmacodynamics of most other drugs have yet to be reported. The results for muscle relaxants and propofol indicate that the effects of body temperature on the duration of drug action are likely to be substantial (Sessler, 1994). Xylazine (Rompun®) was first synthesized in 1962 and given the code name Bay Va 1470.
Chemically, it is 2[2,6-dimethylphenylamino]-4H-S,6-dihydro- 1,3-thiazine. Pharmacologically, xylazine is classified as an analgesic as well as a sedative and skeletal muscle relaxant (Booth, 1988). Xylazine has been used extensively in various animal species because of its potent sedative, analgesic and myorelaxant properties (Clarke and Hall, 1969). It may not possess all the attributes of an ideal sedative but it seems to possess certain properties that earned it its place in veterinary practice for may years. The development of a number of xylazine antagonists that can be used to reverse its adverse effects, has improved its safety in veterinary practice (McDonnell et al., 1993). The veterinary anaesthetist is called upon to deal with a number of species of animals that exhibit great variation in size and temperament as well as in anatomical and physiological development. Apart from differing response of each species to the various anaesthetic agents, there is often marked variation in response between breeds within each particular species (Hall and Clarke, 1983). The sedative and anaesthetic effects of xylazine hydrochloride not only show considerable variation from species to species but, the variation is also exhibited among individual animals of the same species (Neophytou, 1982; Raptopoulos and Weaver, 1984). Studies carried out in heifers injected with xylazine hydrochloride and exposed to heat stress and thermoneutral environmental temperature conditions (Fayed et al., 1989) showed that there are significant differences in the response of some physiological variables to different environmental temperature conditions. In these studies in heifers, significant differences were noted in serum insulin and glucose concentrations, body from the sedative effects of xylazine under the different environmental xylazine in cats exposed to different

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CHAPTER ONE: GENERAL INTRODUCTION :

  • CHAPTER TWO: LITERATURE REVIEW
    • 2.1 INTRODUCTION
    • 2.1.1 STRESS
    • 2.1.2 PHYSIOLOGY OF TEMPERATURE REGULATION
    • 2.1.3 HOMEOTHERMY
    • 2.1.4 THERMAL BALANCE
    • 2.1.5 TEMPERATURE RECEPTORS
    • 2.1.6 HEAT BALANCE DURING ANAESTHESIA
    • 2.1. 7 TEMPERATURE MONITORING
    • 2.1.8 TEMPERATURE MONITORING SITES
    • 2.1. 9 THERMOMETERS
    • 2.2 XYLAZINE HyDROCHLORIDE
    • 2.2.1 CLASSIFICATION
    • 2.2.2 PHARMACOLOGIC PROPERTIES
    • 2.2.3 ABSORPTION
    • 2.2.4 METABOLISM AND ELIMINATION
    • 2.2.5 PHARMACOKINETICS
    • 2.2.6 DETERMINATION OF XYLAZINE HYDROCHLORIDE IN BIOLOGICAL MATERIALS
    • 2.3 BEHA VIOURAL AND CLINICAL EFFECTS OF XYLAZINE IN ANIMALS
    • 2.3.1 INTRODUCTION
    • 2.3 .2 SEDATION
    • 2.3 .3 SALIVATION
    • 2.3.4 ANALGESIA
    • 2.3.5 URINATION
    • 2.4 EFFECTS OF XYLAZINE ON HAEMATOLOGY AND CARDIOPULMONARY FUNCTION
    • 2.5 EFFECTS OF XYLAZINE ON ARTERIAL BLOOD GAS TENSIONS AND ACID-BASE BALANCE
    • 2.6 EFFECTS OF XYLAZINE ON PLASMA GLUCOSE AND INSULIN
    • 2.7 XYLAZINE HYDROCHLORIDE AND BODY
    • TEMPERATURE
  • CHAPTER THREE: CLINICAL, CARDIOPULMONARY AND HAEMOCYTOLOGIC EFFECTS OF XYLAZINE HYROCHLORIDE IN GOATS UNDER DIFFERENT ENVIRONMENTAL TEMPERATURE AND HUMIDITY COND ITIONS
    • 3.1 INTRODUCTION
    • 3.2 MATERIALS AND METHODS
    • 3.2.1 EXPERIMENTAL ANIMALS
    • 3.2.2 SURGICAL RELOCATION OF THE CAROTID ARTERIES
    • 3.2.3 EXPERIMENTAL PROCEDURE
    • 3.2.3.1 EXPERIMENTAL DESIGN
    • 3.2.3.2 TREATMENT PHASES
    • 3.2.4 STATISTICAL ANALySIS
    • 3.3 RESULTS
    • 3.3.1 CLINICAL AND HEHAVIOURAL EFFECTS
    • 3.3.2 CARDIOPULMONARY AND HAEMOCYTOLOGICAL EFFECTS
    • 3.4 DISCUSSION
    • 3.4.1 CLINICAL AND BEHA VIOURAL EFFECTS
    • 3.4.1.1 SEDATION
    • 3.4.1.2 SALIVATION
    • 3.4.1.3 ANALGESIA
    • 3.4.1.4 URINATION
    • 3.4.2 CARDIOPULMONARY AND HAEMOCYTOLOGICAL EFFECTS TENSIONS IN GOATS UNDER DIFFERENT ENVIRONMENTAL
    • 4.1 INTRODUCTION
    • 4.2 MATERIALS AND METHODS
    • 4.2.1 ANIMALS
    • 4.2.2 SURGICAL RELOCATION OF THE CAROTID ARTERIES
    • 4.2.3 EXPERIMENTAL PROCEDURE
    • 4.2.3.1 EXPERIMENTAL DESIGN
    • 4.2.3.2 TREATMENTS PHASES
    • 4.2.4 STATISTICAL ANAL YSIS
    • 4.3 RESULTS
    • 4.3.1 CLINICAL AND BAHA VIOURAL EFFECTS
    • 4.3.2 ARTERIAL BLOOD GAS TENSIONS AND ACID-BASE BALANCE
    • 4.4 DISCUSSION
    • 4.4.1 ARTERIAL GAS TENSIONS AND ACID-BASE
    • BALANCE
  • CHAPTER FIVE: THE HYPERGL YCAEMIC AND HYPOINSULINAEMIC EFFECTS OF XYLAZINE HYDROCHLORIDE IN GOATS UNDER DIFFERENT ENVIRONMENTAL TEMPERATURE AND HUMIDITY COND ITI0NS :
    • 5.1 INTRODUCTION
    • 5.2 MATERIALS AND METHODS
    • 5.2.1 ANIMALS
    • 5.2.2 EXPERIMENTAL PROCEDURE
    • 5.2.2.1 EXPERIMENTAL DESIGN
    • 5.2.2.2 TREATMENTS PHASES
    • 5.2.2.3 RADIOIMMUNOASSAY PROCEDURE FORTHE DETERMINATION OF PLASMA INSULIN CONCENTRATION
    • 5.2.3 STATISTICAL ANALySIS
    • 5.3 RESULTS
    • 5.3.1 CLINICAL AND BEHAVIOURAL EFFECTS
    • 5.3.2 EFFECTS OF XYLAZINE ON PLASMA GLUCOSE
    • AND INSULIN
    • 5.4 DISCUSSION
  • CHAPTER SIX: THE EFFECT OF DIFFERENT AMBIENT TEMPERATURE AND HUMIDITY CONDITIONS ON THERMAL RESPONSES TO XYLAZINE IN GOATS
    • 6.1 INTRODUCTION
    • 6.2 MATERIALS AND METHODS
    • 6.2.1 ANIMALS
    • 6.2.2 EXPERIMENTAL PROCEDURE
    • 6.2.2.1 EXPERIMENTAL DESIGN
    • 6.2.2.2 TREATMENTS PHASES
    • 6.2.3 STATISTICAL ANALySIS
    • 6.3 RESULTS
    • 6.3.1 CLINICAL AND BEHA VIOURAL EFFECTS
    • 6.3.2 EFFECTS OF XYLAZINE ON BODY TEMPERATURE
    • 6.4 DISCUSSION
    • SOLUTIONS AND REFERENCE SAMPLES
    • EXTRACTION PROCEDURE AND EFFICIENCy
    • CALIBRATION PROCEDURE
    • VALIDATION RESULTS
    • 7.3.1.1 CHARACTERISTICS OF CALIBRATIONCHAPTER SEVEN: THE EFFECTS OF AMBIENT TEMPERATURE
      • XYLAZINE IN GOATS
      • 7.1 INTRODUCTION
      • 7.2 MATERIALS AND METHODS
      • 7.2.1 ANIMALS
      • 7.2.2 EXPERIMENTAL DESIGN
      • 7.2.3 TREATMENT PHASES
      • 7.2.4 MEASUREMENT OF XYLAZINE CONTENT IN PLASMA
      • 7.2.4.1 INTRODUCTION
      • 7.2.4.2 REAGENTS
      • 7.2.4.3 INSTRUMENT ATION
      • 7.2.4.4 HPLC CONDITIONS
      • 7.2.4.5 STOCK SOLUTIONS, SECONDARY XYLAZINE
      • 7.3.1.2 SPECIFICITY AND SENSITIVITy
    • 7.3.1.3 ACCURACY AND PRECISION
    • 7.3 .1.4 REPEATABILITy
    • 7.3.1.5 EXTRACTION EFFICIENCy
    • 7.3.2 INTRAVASCULAR DISPOSITION OF XYLAZINE
    • 7.4 DISCUSSION
    • 7.4.1 HPLC ANALYTICAL METHOD
    • 7.4.2 PHARMACOKINETIC RESULTS

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