Veterinary Clinical Sciences - Theses
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ItemInvestigations on the pathophysiology of canine idiopathic epilepsy( 2018)The causes of canine epilepsy are poorly understood. The current aetiologic classification scheme for canine epilepsy includes the categories structural epilepsy, idiopathic epilepsy with genetic or suspected genetic cause, or idiopathic epilepsy of unknown cause. It is likely that dogs with idiopathic epilepsy of unknown cause have heterogeneous underlying pathologies, including subtle structural change that cannot be identified on conventional visual inspection of brain magnetic resonance images. This thesis examines the causes of epilepsy in a sample of Australian dogs presented to the University of Melbourne Veterinary Hospital. The general hypotheses explored by the studies described in this work are that some cases of canine idiopathic epilepsy have underlying structural brain pathologies similar to those identified in humans with epilepsy, and that canine idiopathic epilepsy is associated with increased cerebral levels of the excitatory neurotransmitter glutamate. The prevalence of epilepsy in dogs presented to the University of Melbourne Veterinary Hospital was 1.1%, and idiopathic epilepsy of unknown cause represented 75% of epilepsy diagnoses. Of the 25% of dogs with structural epilepsy, brain tumours were the most frequent cause (60%), followed by meningoencephalitis of unknown origin (11%). In dogs with idiopathic epilepsy, odds ratio analysis identified 21 breeds of dog with an increased risk of a diagnosis of epilepsy. The Hungarian viszla had a particularly strong association with this diagnosis, but in none of the dogs diagnosed with idiopathic epilepsy was a familial history of epilepsy reported. Based on retrospective, randomised and blinded, subjective review of brain magnetic resonance imaging scans of dogs with idiopathic epilepsy and controls, there was no convincing evidence of the magnetic resonance imaging findings of hippocampal sclerosis or focal cortical dysplasia. Brain MRIs were also evaluated using atlas-based segmentation and volumetry, based on a novel canine brain atlas developed for this research. Hippocampal atrophy was used as a biomarker for possible hippocampal sclerosis. Unilateral or bilateral hippocampal atrophy was identified in 15% of dogs with idiopathic epilepsy, based on identifying those dogs with a hippocampal formation volume below the lower 95% reference limit for hippocampal volume established in control dogs. Increased volume of the cerebral cortex was used as a biomarker for possible cortical dysplasia, and reduced volume of the cerebral cortex was a biomarker for cerebrocortical atrophy. Dogs with idiopathic epilepsy had statistically significant reductions in cerebrocortical volume in the left and right olfactory, temporal, occipital, and right parietal lobes. The second hypothesis was that dogs with idiopathic epilepsy had elevated cerebral glutamate, the major excitatory neurotransmitter in the brain. This was explored non-invasively in dogs with naturally occurring epilepsy, using proton magnetic resonance spectroscopy to measure in vivo brain glutamate. There was no significant difference in either glutamate or glutamate to creatine ratio between dogs with epilepsy and controls. Further work is required to establish whether hippocampal atrophy in dogs with epilepsy is due to hippocampal sclerosis. This work could use both volumetry, T2 relaxometry, and histopathologic evaluation of brain samples. Future investigation of the mechanisms of cerebrocortical atrophy in epilepsy may involve cortical thickness measures to allow targeted correlation of regions of localised cerebrocortical atrophy with brain histology, and fibre tracking to map epileptogenic networks, exploring the connections between EEG identified seizure focus and regions of cortical atrophy. The role of brain glutamate may be further investigated using multi-voxel magnetic resonance spectroscopy at 3 Tesla, and glutamate transporter proteins and receptors may be investigated through laboratory techniques.
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ItemViscoelastic coagulation changes in dogs with tiger snake envenomation( 2018)Snake venom induced consumption coagulopathy (SVICC) is an important yet poorly described clinical syndrome in the field of veterinary medicine. Publications referencing humans, on the other hand, are numerous in comparison, especially since the establishment of the Australian Snakebite Project. Since the introduction of Australian snake-specific antivenoms, SVICC has become the most common underlying reason for human fatality from snake envenomation in Australia.1 The annual canine snakebite caseload in Australia alone is vast and could be established as a model for the human condition. The overall objective of this study is to extend the scientific literature on SVICC in veterinary medicine, namely the role of thromboelastography (TEG) in tiger snake envenomed dogs. The study assessed the changing clot kinetics of canine whole blood after natural tiger snake envenomation using an established technique called thromboelastography (TEG). Specifically, we will be determining the TEG changes in dogs at several time points: T0 = time of presentation; T1 = 1 hour after antivenom administration; T18 = 18 hours after antivenom administration; and, finally, T24 = 24 hours after antivenom administration. Tiger snake venom caused alterations in TEG parameters, specifically the prolongation of R time (time to initiation of clot formation) during the first 24 hours of envenomation.2 No clinical benefit exists in using TEG over classical coagulation parameters in the identification of SVICC in tiger snake envenomed dogs. Hypercoagulability occurs for 24 hours after envenomation and VetSVICC appears to resolve 18–24 hours after antivenom, which is suggestive of a shorter period to apparent clinical recovery compared to humans, suggesting that VetSVICC may be a unique clinical syndrome. This project is a stepping stone to future research into both SVICC and tiger snake envenomation in veterinary medicine, including establishing an accessible and reliable diagnostic test for SVICC and further delineation of its importance regarding the severity of illness and outcome.
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ItemThe effects of intravenous fluids on thromboelastrographic variables in dogs( 2018)Intravenous fluid resuscitation plays a fundamental role in treating dogs in haemorrhagic shock, as it can rapidly replenish lost intravascular volume and improve tissue perfusion. However, a consequence of intravenous fluid therapy is interference with haemostasis, which has a detrimental effect to trauma patients that are already haemostatically compromised. In people, intravenous fluid therapy can effect haemostasis and subsequently can increase haemorrhage, transfusion needs and mortality. The effects of intravenous fluids on haemostasis in dogs have not been widely established. More recently, viscoelastic devices like thromboelastography have been used to examine haemostasis. Compared to conventional coagulation testing, viscoelastic devices have the advantages to be able to assess the speed and kinetics of clot formation, clot strength and even the breakdown of the clot. The aim of our study was to determine the effects of intravenous fluids on coagulation in dogs with the use of thromboelastography. The objective of our study was to determine the effect of dilution of canine whole blood with clinically relevant doses of common intravenous fluids on thrombelastographic variables. Our hypothesis was that in vitro dilution of canine whole blood from healthy dogs with intravenous fluids will induce dose-dependent changes in thromboelastographic variables consistent with hypocoagulability. Further, we hypothesized that the characteristics of the fluids, such as its ionic strength and osmolality, will effect thromboelastographic variables in addition to those of dilution alone. The results of our study showed that in vitro dilution of canine whole blood with commonly used intravenous fluids lead to thromboelastographic changes consistent with hypocoagulability in a dose dependent manner. Besides dilution percentage, viscoelastic changes were influenced by fluid characteristics, specifically ionic strength, osmolality and colloidal properties. In our study, 7% hypertonic saline had the most severe effects on coagulation, followed by 20% Mannitol then 3.4% hypertonic saline. Hydroxyethyl starch 130/0.4 had minimal effects on coagulation besides a dilutional effect. The differential effect of fluid characteristics should be taken into consideration when resuscitating dogs with large fluid volumes, but clinical studies are still required to further delineate the importance of different resuscitation fluids and volumes on haemostasis in dogs.