Taurine's role in clinical practice

zyx Taurine’s role in clinical practice INTRODUCTION zyxwvut zyxwvutsrqp P.D. Pion* and M. D. Kittlesont Taurine (2-aminoethane sulphonic acid) is a sulphur containing amino acid first isolated from ox bile (Tiedemann and Gmelin 1827). Taurine has been frequently studied in animals, and is seldom encountered in plants. It is not a constituent of proteins. It is present in relatively high (mmol) concentrations dissolved in the cytosolic fluid of cells (Jacobsen and Smith zyxwvutsrq zyxwvutsrqpo School of Veterinary Medicine, Departments of Physiological Sciences* and Medicine,t University of California, Davis, California 95616,USA Journal of Small Animal Practice (1990)31,510-518 ABSTRACT Dilated cardiomyopathy has been recognised as a significant heart disease and cause of death in pet cats in the United States. The cause of dilated cardiomyopathy which was unknown and the prognosis grave. An association between low plasma taurine concentrations and dilated cardiomyopathy was established. Daily administration of taurine (250-1000 mg) orally increased plasma taurine concentrations and reversed the clinical signs. It was previously thought that cats became taurine deficient when fed commercial dog food or unbalanced home-cooked diets. We found a high association between the type of diet fed, plasma taurine concentrations and the incidence of myocardial failure and feline central retinal regeneration. Many commercial cat foods were found to cause taurine depletion associated with myocardial failure or central retinal degeneration. It is now established that taurine deficiency is a major cause of myocardial failure in cats and that modification of commercial cat food formulations with regard to taurine content has resulted in a dramatic decrease in the incidence of dilated cardiomyopathy in cats in the United States. 1968). Taurine is generally associated with excitable tissues. Tissues with the highest taurine concentration include the heart, retina, central nervous system and skeletal muscle (Sturman and others 1986, Huxtable and others 1979). Taurine is also present in high concentrations in leucocytes and platelets (Hino 1956, Nour-Eldin and Wilkinson 1955, Laidlaw and others 1987). The presence of taurine in numerous cell types in most animal species has been accepted as circumstantial evidence that taurine serves a vital role in animal biology (Jacobsen and Smith 1968). However, despite its ubiquitous nature, taurine’s biological function is not well understood. Areas of investigation which have received significant attention from researchers interested in taurine’s biological function include osmoregulation (Thurston and others 1981, Trachtman and others 1989), neuromodulation (Kuriyama 1980), modulation of transmembrane ion fluxes (Lombardini 1985) and intracellular calcium concentration (Lombardini 1985, Huxtable 1987, Franconi and others 1982), interactions with insulin (Maturo and Kulakowski 1987) and inactivation of free radicals (Wright and others 1986). Central to these investigations is a relationship between taurine and biological membranes. There are several excellent reviews of taurine’s biological role (Jacobsen and Smith 1968, Chesney 1985, Wright and others 1986, Huxtable 1989). In this paper we emphasise areas which are or may be significant to clinical veterinary practice. Particular emphasis is placed on what we know about the relationship between taurine and dilated cardiomyopathy in the cat. (See the paper by Morris and others, also in this issue, for coverage of taurine’s role in nutrition and biology function.) TAURINE IN CLINICAL PRACTICE This paper was presented at the Waltham symposium number 13,1989 510 Ophthalmology, theriogenology, neurology, cardiology and possibly immunology are clinical fields in which taurine is relevant to veterinary practice. Taurine may also find a role in the management of feline diabetes. zy zyxwv Taurine's role in clinical practice TAURINE AND THE EYE 0 II I - Taurine is the predominant amino acid in the retina. It is highly concentrated in the photoreceptor cells of the outer nuclear layer. It is not surprising that the first and best defined clinical role for taurine in practice was its relationship to the development of feline central retinal degeneration (FCRD). Many papers describe the lesion in practice (Bellhorn and others 1974, Ricketts 1983), but it was Hayes and others (1975a) who first made the association between FCRD and taurine deficiency. Feline central retinal degeneration appears as bilateral symmetric hyper-reflective lesions of the fundus, dorsotemporal to the optic disc (Fig 1).Lesions vary in size and shape from pin-point to an ellipsoid extending in a band from the temporal fundus across the top of the disc to the nasal fundus. Electroretinographic studies demonstrate diffuse cone dysfunction progressing to a generalised disorder affecting the rods and cones. Histologically, there is degeneration of the retinal layers or full thickness atrophy of the area centralis (Hayes and others 1975a, 1975b). In most clinical cases, the diagnosis of FCRD has probably been an incidental finding during a fundic examination. FCRD usually causes insignificant vision loss but can result in blindness. Although cats with FCRD should be tested for concurrent taurine deficiency, the presence of this lesion is not proof that a cat is presently taurine deficient: it may only be an indication that the cat has been at some time in the past. Contrary to what most veterinarians have been taught, FCRD and taurine deficiency are not zy zyx - Taur ine FIG 2. The structure of taurine (after Huxtable and Sebring 1986) primarily the result of negligent owners feeding their cats dog food or home formulated diets. Many cats with this lesion have developed taurine deficiency while eating commercial cat foods. REPRODUCTION The number of reproductive problems experienced in catteries, or seen in clinical practice, related to taurine deficiency is unknown. However, there is experimental evidence suggesting that taurine deficient queens have low fecundity (Sturman and others 1986, Rogers and Morris unpublished). These observations should be directly applicable to clinical reproductive problems. The nature of the low fecundity, whether it is associated with fertilisation, implantation, or early or late abortion, is being investigated. NEUROLOGY In mammals, taurine is present in high concentration in the central nervous system. It is actively transported into cells in the brain (Lombardini 1978) and it may be necessary for brain development (Sturman 1986). Taurine has been thought of more as a neuromodulator than a classical neurotransmitter because specific post synaptic receptors for taurine have not been identified. As demonstrated in animal models of epilepsy (Mutani and others 1978, van Gelder 1983), taurine may be an effective anticonvulsant agent in some human (Takahashi and Nakane 1978) and feline (van Gelder and others 1977, Tanizawa and others 1986) seizure patients. Taurine is a small (MW 125.1), zwitterionic (Fig 2), poorly diffusible compound and is thus a potent osmotic agent. Its osmoregulatory role is well defined in marine animals. Some invertebrates and fish utilise it for balancing the osmotic pressure of their cells with the extracellular environment, as the concentration of salts change in the surrounding water (Jacobsen and Smith 1968). That this function may be important in mammals is illustrated by the finding that the taurine concentration in the heart of iatrogenically hypernatraemic mice is elevated to a degree consistent with the additional extracellular z zyxwvut FIG 1 . Fundic photograph taken from a patient with dilated cardiomyopathy. The characteristic hyper-reflective lesion of feline central retinal degeneration is easily visualised 511 zyxwvutsrqp zyxwvutsrqpo P. D.PION AND M. D.KITTLESON osmotic load induced by the hypernatraemia (Thurston and others 1981). A recent study has strengthened arguments that cerebral taurine concentration in cats may be a significant factor in maintaining normal cerebral hydration and volume during periods of osmotic stress (Trachtman and others 1988). Taurine may be one of the idiosmolar compounds which protect the brain of diabetic patients against the hyperosmolar effects of hyperglycemia [Chesney 1985). IMMUNOLOGY Lymphocyte and neutrophil function may be suboptimal in taurine deficient animals (Schuller-Levis and Sturman 1989). In addition, interactions between taurine [or its precursor, hypotaurine) with free radicals may be important in the modulation of immunological defense mechanisms, Oxidative processes involving free radicals are utilised by neutrophils to defend against microbial invasion and may play an equally self-destructive role in immune mediated diseases, such as systemic lupus erythematosis. Taurine is found in high concentration in neutrophils (Laidlow and others 1987). Taurine (Wright and others 1985) and hypotaurine (Fellman and Roth 1985) react with, and inactivate free radicals similar to those synthesised by neutrophils. It is not unreasonable to hypothesise that taurine may protect the cell and organism from these potentially self-destructive reactions [Wright and others 1986). TAURINE AND DIABETES Taurine has metabolic effects and may interact with, or be synergistic with, insulin. Like insulin, taurine induces hypoglycaemia and stimulates glycolysis and glycogen synthesis (Maturo and Kulakowski 1987). The clinical implication of these findings with respect to the diabetic cat are presently under investigation. TAURINE AND THE HEART In 1987 we reported that taurine deficiency is the underlying cause of most cases of feline dilated (congestive) cardiomyopathy (Pion and others 1987). The mechanism[s) underlying the effects of taurine on the heart are unknown. All of the possible mechanisms outlined above deserve consideration. There is a large body of literature that preceded OUT findings which make the association between taurine deficiency and myocardial failure in cats more a result of past predictions than a novel finding [Huxtable and Sebring 1983). Taurine is 512 present in high concentration in the heart. This high concentration (100-250 times that found in plasma) is maintained by active transport processes which consume energy and are stimulated by D-adrenergic stimulation (Azari and Huxtable 1980). Teleologically it makes little sense that mechanisms for concentrating and maintaining a high intracellular myocardial taurine concentration would have evolved had it not been advantageous, If the cat with dilated cardiomyopathy secondary to taurine deficiency illustrates what would happen to any mammal with inadequate myocardial taurine concentration, then the advantages of these concentrating mechanisms is obvious. Prior clinically applicable findings include the effects of taurine on arrhythmias induced by high doses of cardiac glycosides and epinephrine. (Read and Welty 1963, Hinton and others 1975, Huxtable and Sebring 1983). Humans exhibiting congestive heart failure (Huxtable and Bressler 1974) and animals with induced heart failure (Newman and others 1977) have increased myocardial taurine concentration. Administration of taurine to humans with valvular heart disease is reported to result in clinical improvement (Azuma and others 1982). Rabbits with induced aortic regurgitation survived longer when taurine was added to their water, compared to animals with similar valvular lesions which did not receive taurine (Takihara and others 1986). These findings among others have led investigators to hypothesise that taurine has an essential function in the heart. However, previous attempts to demonstrate significant decreases in mechanical myocardial function in taurine depleted animals have not succeeded (Mozaffari and others 1986). This may be explained by the fact that previous trials have utilised species which do not have dietary requirements for taurine. Thus, the results of previous attempts are probably not unexpected or incongruous with our findings. A recent report proposes a similar finding in silver foxes (Moise and others 1989). TAURINE DEFICIENCY MYOCARDIAL FAILURE zyxwv The first cat identified as having taurine deficiency in conjunction with dilated cardiomyopathy was presented with posterior paresis associated with an aortic thromboernbolus. It was an eight-year-old male castrated domestic shorthaired cat. The owner chose to actively pursue therapy for the cat even though it had dilated cardiomyopathy, a condition in the majority of cases incurable and fatal within days to months. Blood flow to the legs was restored after one day of thrombolytic therapy (Pion 1988) but zyxw zy Tourine3 role in clinical practice vided this history and asked whether the dilated cardiomyopathy or clot might be related to the taurine deficiency? This question, previously published data relating to taurine's effects on the heart and the lack of any effective therapy for this devastating disease, stimulated our interest enough to begin examining the eyes and blood of all cats with dilated cardiomyopathy. Three more cases of dilated cardiomyopathy were presented. All three had FCRD, low plasma taurine concentration, and were eating similar commercial diets. We therefore designed a set of studies to answer three questions: (1) is plasma taurine concentration decreased in all or most cats with dilated cardiomyopathy; (2) would supplementing affected cats with oral taurine be beneficial and (3) would depleting cats of taurine cause dilated cardiomyopathy? The first and second questions were answered with the cooperation of many veterinarians who referred cats with dilated cardiomyopathy to our clinic and cat owners who agreed to allow us to attempt treatment with taurine. As we reported (Pion and others 1987), all cases of feline dilated cardiomyopathy diagnosed in our hospital since December 1986 have had low plasma taurine concentration and most cases that we treated with taurine recovered. Not only have they recovered to live more comfortably, but surprisingly the function of the heart muscle and the cats' clinical appearance actually returned to normal (Figs 3, 4,5). This was previously thought to be impossible. Most cardiologists believed that in the majority of cases, dilated cardiomyopathy in cats was an irreversible disease process. Previously there had been anecdotal reports of cats with dilated cardiomyopathy resolving spontaneously but these cases were certainly the zyxwvutsrqpon zyxwvutsrq zyxwvutsrqp FIG 3. M-mode echocardiogram from a cat with dilated cardiomyopathy treated with taurine. (A) First examination. fB] Ten weeks after beginning taurine therapy. The ultrasound beam is passing through (top to bottom] the right ventricular wall, right ventricular cavity, interventricular septum, left ventricular cavity (chamber with labels], and left ventricular wall. EDD, end-diastolic diameter; ESD, end-systolic diameter. [Used with permission, P. D. Pion and others (1987). Copyright 1987 AAAS] unfortunately the cat died two days later from the heart disease. One year earlier, the owner had been told that the cat had feline central retinal degeneration (FCRD). The clinician was surprised to learn that it was eating a popular commercial cat food, as it was generally believed that cats only get low taurine and FCRD from eating dog food or home cooked diets. The plasma taurine concentration measured in the plasma was 10 to 20 per cent of normal. The reason for this deficit was unknown and no therapy was prescribed. The owner pro- -- 40 25 I ESC EDD 35 20 30 26 15 15 - zyxwv zyxwvutsrqponmlkjih E E E E 10 L w 10 20 15 I ! 10 5 - 5 6 zyxwvutsrqp 0 0 1 2 3 PERIOD 4 5 0 0 1 2 3 4 5 PERIOD FIG 4. Mean f SEM of (left to right] end-diastolic diameter (EDD], end-systolic diameter (ESD], and shortening fraction (SF, defined as: [EDD-ESDl/EDD) for 15 taurine-supplemented cats with dilated cardiomyopathy. Period 0 (PO), date of presentation; PI, 1-2 weeks after presentation; P2, 3-4 weeks; P3, 5-6weeks: P4, 7-8 weeks: P5,9-12weeks. The horizontal dotted lines represent the upper (EDD and ESD) and lower (SFI limits of clinical normality at the time the studies were performed [used with permission, P. D. Pion and others (1987).Copyright 1987 AAAS] 513 P. D. PION AND M. D. KITTLESON zyxwvutsrq FIG 5a. Thoracic radiographs (lateral projection) of a 4-year-old cat with dilated cardiomyopathy before [top) and six months after (bottom) beginning taurine supplementation. This cat received taurine supplementation (in crystalline form) for a total of four months. Altering the cat’s diet to a taurine-supplemented diet then maintained adequate plasma taurine concentrations and normal myocardial function as assessed by echocardiography (used with permission, P. D. Pion and others 1989b) I zyxwvutsrqpo FIG. 5b. Thoracic radiograph [dorso-ventral projection) of the same cat as in Fig 5a before (left) and six months after [right) taurine repletion (used with permission, P. D. Pion and others 1989b) I exception and not the rule. The answer to the third question (would depleting cats of taurine cause dilated cardiomyopathy?) could have taken months or years to arrive at had it not been for work in progress by Rogers and Morris. They had been studying the effects of feeding marginally low amounts of taurine to 11 cats for four years. Echocardiographic evaluation of these cats, six eating amounts of taurine slightly less (250 mg/kg dry diet) than the minimum amount recommended by the National Research Council (400 mg/kg dry diet) and five eating slightly more (500 mg/kg dry diet), revealed that two had dilated cardiomyopathy. Re-evaluation of these cats 2, 4, 8 and 1 2 weeks after beginning to supplement their diets with taurine demonstrated a remarkable recovery of left ventricular function similar to that we were seeing after taurine supplementation [treatment) of clinical cases of dilated cardiomyopathy. Subsequent to these early findings we have demonstrated that: 11) most cases of dilated cardiomyopathy, a previously lethal and incurable cardiac disease in cats, are associated with low plasma taurine concentration (Pion and others 1988a); (2) feeding cats experimental diets low in taurine causes dilated cardiomyopathy in some animals (Pion and others 1988b); (3) feeding certain commercial diets containing amounts of taurine previously thought to be adequate, resulted in low plasma taurine concentration and eventually results in dilated cardiomyopathy in some cats (Pion and others, 1988b) and (4) administering taurine to cats with dilated cardiomyopathy associated with low plasma taurine results in an apparently permanent recovery of the function of the heart in most cases (Pion and others 1988a). Due to the poor prognosis, in cats, associated with dilated cardiomyopathy it has always been a frustrating condition to treat. It should now be considered a disease which is associated with a guarded prognosis in the critically ill patient, but which can be reversed with appropriate therapy. The prognosis is good to excellent in cats that survive longer than four weeks after starting therapy [see clinical management below). There is no known relationship between taurine and other forms of heart disease in cats. zyxwvut 514 zyx zyx zy zyxwv Taurine’s role in clinical practice COMMERCIAL CAT FOODS, PLASMA TAURINE CONCENTRATION ’ Why did cats eating certain commercial cat foods have measurably low plasma taurine concentration? It is presumably not because of intentional negligence on the part of pet food companies. Most pet food companies strive to provide the proper nutrients needed for cats and dogs. They claim to meet or exceed government recommendations regarding the minimum amount of each nutrient the foods should contain. Many of these companies fund nutritional and veterinary research in an attempt to (among other reasons) improve the science upon which their formulations are based. During 1987, most cat food manufacturers began to increase the amount of taurine in their diets. Prior to that time, most of the diets we analysed contained 1 to 15 times the published National Research Council (NRC) recommendation for dietary taurine concentration (ie, 5007500 mg/kg of dry diet). To explain why many of these cat foods were associated with plasma taurine depletion we hypothesised that either the recommendation was too low, or the taurine present in the diets was not adequately absorbed or retained. Both hypotheses may be true. Many dry foods produced before this time contained 500-750 mg of taurine/kg of dry diet. Most cats fed commercial diets containing 500 mg/kg of dry diet maintain a plasma taurine concentration lower than our research indicates is safe. At the time the NRC recommendation for adequate dietary taurine content was made, the evidence indicated that these plasma concentrations were safe. Most canned (wet) foods that we evaluated contained 2 to 10 times the recommended amount of taurine. Despite this apparently adequate dietary level, many were associated with low plasma taurine concentrations in client-owned cats (Pion and others 1987) and some were shown to cause low plasma concentrations when fed to cats. Adding more taurine to these foods appears to provide enough taurine to maintain adequate plasma concentrations (see paper by Morris, Rogers and Pacioretty in this publication for details). In our original report (Pion 1987), certain cat foods were implicated as possibly causing low plasma taurine concentration associated with myocardial failure (dilated cardiomyopathy). The foods mentioned in that paper are not the only foods that were capable of inducing this syndrome. We do not believe that any manufacturer’s implicated food was more or less able to deplete plasma taurine concentration than diets produced by other manufacturers. The incidence of dilated cardiomyopathy associated with individual diets in our clinic appears to have been related to the popularity and marketing practices of certain manufacturers. A survey of the pet cat population in three clinics in the United States, around the time that manufacturers began supplementing their formulations with additional taurine, indicated that 1020 per cent of cats eating commercial cat foods had low plasma taurine concentration (Pion unpublished). Had this deficiency not been corrected, some of these cats might have developed eye problems (FCRD), heart problems (dilated cardiomyopathy), both or neither. Adding more taurine to the diets appears to prevent the associated clinical problems. However, to prevent the possibility of this problem recurring it is important that the factors responsible for this phenomenon are identified. Most manufacturers, that we have communicated with in the USA, have supplemented their foods with taurine. Since that time, the subjective impression of our group and those at other institutions in the USA is that the incidence of dilated cardiomyopathy in cats has decreased markedly. Studies to validate these impressions are in progress. ~ ~ MANAGING CATS WITH SUSPECTED TAURINE DEFICIENCY The most efficient way to determine if a cat is at risk is to submit a plasma sample to a laboratory for taurine analysis. Interpretation of plasma taurine values is dependent upon several variables. There is not a ‘normal’ plasma concentration. Plasma taurine concentration is dependent upon dietary intake. A cat eating a tuna diet (high in taurine) will have a higher plasma taurine concentration than a cat eating a commercial dry diet. Clinically, the critical value of plasma taurine concentration, below which a cat may be at risk for developing dilated cardiomyopathy, is approximately 20 nmol/ml. To ensure a margin of safety, any cat whose plasma taurine concentration is less than 40 nmol/ml should be changed to another diet known to maintain a higher concentration. Submitting a plasma sample requires special handling and can be facilitated by requesting instructions from the laboratory. Recent evidence suggests that taurine concentration measured from whole blood provides more useful information than that obtained from measurement from plasma (Pacioretty and others 1988, Pion 1989a). zyxwv zyxw 515 zyxwvutsrqpon zyxwvutsrqpo P.D. PION AND M. D. KITTLESON Cats with a presumptive diagnosis of dilated cardiomyopathy should be prescribed standard therapy as previously recommended in textbooks and publications. The major points to remember are: (1) minimise stress; (2) if the patient is not severely dyspnoeic, obtain a thoracic radiograph to evaluate the patient’s cardiac size and shape, and determine whether pleural effusions or pulmonary oedema is present; (3) if the patient is severely dyspnoeic radiography may be too stressful. Pleurocentesis to identify and remove any pleural effuision followed by cage rest (with enriched oxygen concentration) and a diuretic (furosemide [Lasix, Hoechst Roussel, Somerville, N.J., USA] 0.5-2.0 mg/kg, intramuscularly) are required; (4) maintenance therapy for congestive heart failure, if present, should include diuretics (furosemide 0-25-2.0 mg/kg orally two or three times daily) and if necessary, the angiotensinconverting enzyme inhibitor, captopril (Capoten 3-6 mg orally two or three times daily). Pleurocentesis and diuretic therapy should be utilised as indicated clinically. Excessively dehydrating these patients should be avoided as it will cause them to become more depressed and anorexic. The use of digoxin is controversial; the majority of patients successfully treated in our study were not given digoxin. To confirm the diagnosis of dilated cardiomyopathy, an echocardiogram is generally required. Non-selective angiograms can be utilised but may prove deleterious to the compromised patient. A plasma sample for taurine analysis should be obtained before commencing therapy with taurine. Once plasma samples have been acquired, it is time to begin treatment with taurine (250 mg orally twice daily). Taurine tablets may be obtained from health food stores and are also available through veterinary supply companies, Cats with dilated cardiomyopathy associated with a low plasma taurine concentration and treated with taurine, that live more than one week, have a high probability of recovering and may be ‘normal’ within four months. In most cases diuretic and vasodilator therapy can be discontinued within 12 weeks of beginning taurine therapy. Beyond the initial treatment period, dietary alteration is usually all that is necessary to maintain the needs for taurine. It is our usual policy to discontinue taurine supplementation when echocardiographic parameters improve significantly, usually within 16 weeks of beginning therapy. After discontinuing taurine supplementation, a plasma or blood taurine concentration should be determined after 1, 2 and 4 months to confirm that the diet fed is maintaining adequate plasma or whole blood taurine concentration (above 50 and 250 nmol/ml, respectively). If not, the diet fed should be changed to one which maintains blood taurine above these concentra- tions. A more detailed discussion on diagnosis and treatment has been published elsewhere (Pion and others 1989b). The four major points to emphasise are as follows. (1)There is no evidence that other cardiac conditions in cats will respond favourably to taurine therapy. The diagnosis of hypertrophic cardiomyopathy has not in any way been correlated with plasma taurine concentration or diet. (2) The clinical signs of pleural effusion, pulmonary oedema and, or, ascites, with or without electrocardiographic changes, do not constitute sufficient evidence to support a diagnosis of dilated cardiomyopathy (or any other specific condition). Nor is a measured low plasma or blood taurine concentration sufficient evidence for a diagnosis of dilated cardiomyopathy. The ultimate cardiac diagnosis should be determined by correlating all of the available physical and radiographic findings with an echocardiogram performed and interpreted by a skilled diagnostician. (3) Most cases of dilated cardiomyopathy diagnosed at the University of California at Davis have been associated with taurine deficiency. However, not all cases of feline dilated cardiomyopathy are due to deficiency. It is important to measure plasma taurine concentration in all cats with dilated cardiomyopathy to confirm or rule out taurine deficiency. Cases of dilated cardiomyopathy not associated with a low plasma taurine concentration, when identified, must still be thought of as a condition with a grave prognosis. (4) It is important to correlate the diagnosis with diet, so that foods which are not maintaining normal plasma taurine concentrations may be identified and corrected. (5) The attending veterinarian must emphasise to clients that cats with dilated cardiomyopathy associated with low plasma taurine concentrations, have a favourable prognosis if they survive 1-2 weeks (the time necessary to see the initial clinical improvement - note that echocardiographic signs of improvement do not become apparent for three to six weeks after commencing therapy (Fig 4). A cat that is presented dying of cardiomyopathy will probably die despite taurine therapy if diuretics, vasodilators and, or, pleurocentesis do not provide sufficient symptomatic relief. Our clinical impression is that these cats, no matter how ill, have a better chance of survival if sent home to be nursed by the client. The stress of hospitalisation can be fatal to these severely compromised patients, zyxwvutsr 516 CONCLUSIONS Although we emphasise the importance of echocardiography in the diagnosis of dilated Taurine’s role in clinical practice zy zyxwvut cardiomyopathy we are aware that echocardiography may not be readily available in all practice areas. There are no contraindications to beginning taurine therapy in the absence of a definitive diagnosis. However, it is difficult to confirm the diagnosis and response. A satisfactory response in these cases may be related to the diuretic or vasodilator therapy, or reported beneficial effects of taurine in patients with congestive heart failure not associated with myocardial failure (Azuma and others 1982). In the latter situations, withdrawal of therapy for congestive heart failure may be followed by a recurrence of clinical signs. As an obligate carnivore with an absolute dietary requirement for taurine, the cat has provided researchers with a unique model in which to study the role of taurine in mammals. This same dietary requirement has proven to be a significant and recurring clinical problem for veterinarians dealing with cats in daily practice. The extent of this problem is yet to be fully defined and we believe that these problems would have been difficult to predict. 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(1988) Taurine and osmoregulation: taurine is a cerebral osmoprotective molecule in chronic hypernatremic dehydration. Pediatric Research 23,35-39 VAN GELDER, N.M., KOYAMA,I. & JASPER, H. H. (1977)neatment of spontaneous chronic epilepsy in a cat. Epilepsia 18,45-54 GELDER, N. M. (1983)A central mechanism of action for taurine: osmoregulation, bivalent cations and excitation threshold. Neurochemical Research 8,687-699 WRIGHT, C. E., LIN, T. T., LIN, Y. Y.,STURMAN, J, A. & GAULL, G. E. (1985)Taurine scavenges oxidized chlorine in biological system. In Taurine: Biological Actions and Clinical Perspectives, Liss, New York. Ed. S. S. Oja, L. Ahtee, P. Kontro, and M. K. Paasonen, pp 137-147 WRIGHT, C. E., TALLAN, H. H., LIN,Y. Y . , & GAULL, G. E. (1986) Taurine: biological update. Annual Review of Biochemistry VAN 55,427-53 drug, were investigated in 10 laboratory beagles. Medetomidine initially induced hypertension, which was followed by a longer lasting period of hypotension. Bradycardia with second degree atrioventricular blocks and a decrease in respiratory frequency were also observed. Atropine sulphate and glycopyrrolate temporarily abolished the bradycardiac effect of medetomidine. Xylazine induced a similar cardiovascular and respiratory pattern to medetomidine. VAINO,0. & PALMU, L. (1990)Acfa Veterinaria Scandinavica 30,401 Mast cell tumours in three ferrets OPEN, 5 mm diameter, pruritic skin lesions were found on the head, neck or thorax of three ferrets. All had been present for some time (up to 14 months). Mast cell tumour was identified in each case by skin biopsy. Excised tumours did not reoccur, neither were there signs of metastases. All three animals died from unrelated conditions; two from other types of neoplasia. Mast cell tumours do not appear to be as virulent in ferrets as in other mammals. STAUBER, E., ROBINETTE, J. & BASARABA, R. (1990)Journal of the American VeterinaryMedical Association 196,766