Pet Trust Funded Projects – Fall 2009

Dr. Shauna Blois

Comparison of a point-of-care blood typing kit with laboratory gel-based blood typing in dogs

This project aims to validate a canine blood typing test kit. Blood transfusions are an increasingly important part of veterinary medical care, and are available at many primary care and referral veterinary practices. Similar to people, animals have unique blood types. Giving a mismatched blood type to a dog may lead to transfusion reactions.

To help ensure that blood transfusion is as safe as possible, it is recommended that both the blood donor and the patient receiving the blood transfusion are blood typed prior to the transfusion. Currently, the best method of blood typing available is through a specialty laboratory. The results of blood typing are therefore not immediately available, and can it take a day or more for these results to reach a private practice.

Therefore, it is desirable to have a quick, in-clinic method of blood typing available to veterinarians. A new blood typing cartridge for dogs is available to veterinarians. However, it is not known how accurate the results of this cartridge are when compared to laboratory blood type testing. The goal of this study is to compare the results of blood typing cartridges to the results obtained from laboratory testing.

If successful, this study will identify a relatively inexpensive, quick, and easy-to-use method of blood typing that is available to perform in any clinic and gives results within minutes. This will help ensure that the critically ill patients receiving blood transfusions have a decreased risk of transfusion reactions.

Dr. Shauna Blois

Establishment of a canine reference range for thromboelastrography

Thromboelastography and platelet mapping are novel, point-of-care tests of blood clotting that show the interaction of platelets and coagulation factors in the formation of a blood clot. Platelet mapping is a modification of thromboelastography that isolates platelet function. Conventional laboratory clotting tests measure an isolated part of the clotting system and are insensitive for detecting increased tendency for blood clotting (hypercoagulability).

Hypercoagulability can occur in conjunction with various diseases in veterinary patients and can lead to abnormal blood clots forming in places in the body such as the lungs and aorta. These clots are difficult to treat and are often fatal. Recent studies have shown that thromboelastography can be used to detect hypercoagulability in dogs with various underlying conditions. However, there is little information in the veterinary literature about the use of platelet mapping. In human medicine platelet mapping is used extensively to measure platelet function, monitor the efficacy of antiplatelet drug therapy and plan surgery and other interventions. In theory, platelet mapping in animals could be used for the same purposes.

Currently a thromboelastography machine is in use in the OVC Hemostasis Laboratory; however the platelet mapping function of the machine has not been utilized. To use platelet mapping for further research it will be necessary to establish values for normal dogs on this machine. At this time, there are no trials describing platelet mapping in a group of normal dogs, and this study will offer unique information to the veterinary community.

Dr. Sarah Boston

Transcatheter arterial chemoembolization for the treatment of canine appendicular osteosarcoma

Transcatheter arterial chemoembolization is a novel technique for the treatment of tumors in people. The technique involves the mapping and visualization of the blood supply to a tumor using X-ray. Once the blood supply is visualized and selected, chemotherapy and a material that will destroy the blood supply is selectively administered to the tumour.

This technique is relatively new, but has been reported for liver tumours in people that are not surgically removable and for osteosarcoma. This technique has been used successfully in people with minimal to no side effects.

Anecdotally, this technique has also been used in dogs with boney tumors of the skull. The purpose of this study is to develop this technique so it may be used to treat clinical cases of bone cancer in canine patients.

Dr. Luis Gaitero

Comparison of hemilaminectomy and pediculectomy in dogs with thoracolumbar IVDD using MRI and CT

Intervertebral disc disease, also called disc herniation or IVDD, is the most common cause of back pain and hind limb weakness in dogs. Small breeds are more commonly affected due to a specific degeneration of their intervertebral discs. Those degenerated discs are not able to resist forces on the spine properly, so they can suddenly blow up expulsing their inner material. That expulsed material usually hits and compresses the spinal cord, causing back pain and/or weakness in the hind limbs.

Surgery is the treatment of choice for many affected dogs. The two most common surgical techniques performed, pediculectomy and hemilaminectomy, have different advantages and disadvantages. Some patients do not improve properly after the surgery and one factor that may contribute is the amount of disc material left at the time of surgery.

We would like to compare the ability of hemilaminectomy and pediculectomy to remove disc material in 20 patients, to identify if remaining disc material can cause a lack of improvement, and under what circumstances either surgical procedure is better suited. Additional data obtained using MRI and CT scans would provide vital information that would guide us to decide between any of both techniques in every particular case.

Dr. Carolyn Kerr

Effects of acepromazine or medetomidine on cardiopulmonary preference and fentanyl pharmacokinetics during recovery from isoflurane/fentanyl anesthesia in the dog and cat

Anesthesia in dogs and cats is associated with a risk of anesthesia related mortality of approximately 0.17 to 0.24% respectively, values unfortunately considerably higher than the approximately 0.0001 to 0.002% reported in humans. Failure of the cardiovascular or respiratory systems was identified as the primary cause of anesthetic-related mortality in the most recent large study in dogs and cats. The time of the greatest risk for morbidity or mortality to occur was end of the anesthesia period when the animal was recovering.

To date, there is little information regarding the cardiovascular and respiratory effects of the sedative and analgesic drugs we routinely administer to dogs and cats during the recovery of anesthesia. The goals of this study are to evaluate the effect of different drug regimes on cardiovascular and respiratory function during recovery from anesthesia in dogs and cats. The information obtained from this study will help improve the way veterinarians manage the recovery phase of anesthesia in dogs and cats.

Dr. Gordon Kirby

Validation of serum collage XXVII A-1 as a screening assay for canine hemangiosarcoma

Hemangiosarcoma is a highly aggressive cancer of dogs, developing as a cancerous growth of abnormal blood vessels and occurring most commonly in the spleen of large breed dogs over the age of six years. These cancers are often not obvious to their owners until late in the development of the disease when the cancerous vessels rupture and the dog bleeds into the body cavities. By this time, the cancer is very advanced and often has spread to other parts of the body.

It would be useful to detect hemangiosarcoma early on, before the tumor has grown large and has spread as it would then be possible to remove the spleen including the small tumors and begin chemotherapy earlier, when it is most effective. Unfortunately, the only available method for early detection is ultrasound imaging, which is expensive, requires special training to perform and is usually only available through veterinary referral clinics. A blood test that could rapidly screen for early evidence of hemangiosarcomas would be clinically very useful, inexpensive and readily available to most veterinary practitioners.

This proposal describes two studies in which veterinary researchers from the Ontario Veterinary College and three veterinary referral hospitals in Toronto and Ottawa plan to confirm whether a recently identified blood protein found at high levels in dogs with hemangiosarcoma is useful in screening for the presence of this cancer. The studies will compare levels of the blood protein with ultrasound evidence of the cancer both at early stages of development and when the cancer reappears after surgical removal and chemotherapy. This so-called “validation” study is a necessary step before the blood test is made available commercially.

Dr. Michael O'Grady

Utility of speckle tracking strain in the assessment of global systolic and diastolic cardiac function in the dog

Heart disease continues to be a common cause of death and sickness in dogs. In almost all cases after a relatively short course of illness (weeks to 1.5 years), it is inevitably fatal. Additionally, response to our best therapies is highly variable. Therefore it is important to find tests that identify heart disease earlier, assist with selection of the best therapies, and that predict outcome all to enable us to better empower owners with accurate expectations.

Speckle tracking strain analysis provides new echocardiographically parameters that evaluate the function of the heart. It is easy to perform and in people offers outstanding promise as the best non-invasive test to identify early disease and accurately predict the severity of heart disease. We expect it will be similarly helpful to assess heart disease in the dog.

Prior to adopting and using any test it is imperative to establish the accuracy and reliability of the test. The present study will establish the accuracy and reliability of the non-invasive speckle strain in dogs when compared with the invasive gold standard parameters. The research dogs used in this study will be provided the care and respect afforded client dogs and will be adopted to families at the completion of the study.

Dr. Scott Weese

Investigation of cytotoxicity of essential oils, biocides and topical antimicrobials

Skin infections are a very common problem in dogs and a common reason for veterinary visits and antimicrobial therapy. Typically, skin infections or other superficial infections (wound infections, surgical incision infections) are treated with oral antibiotics. However, this approach does not always work. Long-term or repeated treatment may be required, which becomes problematic because of difficulty treating some animals, cost of treatment and the potential for side effects such as diarrhea, vomiting, and anorexia. Further, there has been a tremendous increase in highly drug resistant skin infections, which can be very difficult to treat. Therefore, alternative options are needed to supplement or replace oral antibiotics.

One approach is the use of topical treatments. Various options are available, including topical antibiotics, biocides (antiseptic solutions) and essential oils. These substances can have good efficacy against bacteria and are appealing options but there is inadequate information about safety. Topical treatments must be both effective against the infection and have no negative consequences on the body’s tissues.

Tissue damage is a potential concern with these substances and information about tissue damage is required to determine which of these options should be used and at what concentrations. This study will evaluate the cell-damaging effects of various compounds on canine skin cells, using a range of concentrations that could be achievable during treatment.

Dr. Darren Wood

Development and characterization of recombinant canine activated protein C

Sepsis is common in dogs and often results in morality despite treatment. More effective therapy for canine sepsis is thus needed. In humans, activated protein C (APC) is an effective treatment for severe sepsis. APC is derived from protein C (PC) in plasma and has anti-coagulant, anti-inflammatory, pro-fibrinolytic, and cytoprotective effects.

Reduced PC levels are associated with mortality in humans with sepsis.

Currently, recombinant human activated protein C (rhAPC) is the only US FDA-approved therapy that increases survival in adult patients with high-risk, severe sepsis. Similar to humans, PC activity is significantly decreased in canine sepsis and such decreases predict mortality.

Success in treating sepsis in humans with rhAPC provides a rationale for treating septic dogs with APC. However, rhAPC is highly antigenic in dogs, rending it inappropriate for canine use, and knowledge of PC biology in dogs is limited. Therefore, canine-specific PC needs to be isolated or genetically engineered and better characterized before intervention with the PC pathway in septic canine patients is attempted.

We propose a study that examines the anti-coagulant, anti-inflammatory, pro-fibrinolytic, and cytoprotective effects of PC purified from canine plasma. Canine PC is expected to have similar biological properties as its human counterpart. The results from this study will provide a basis for developing and characterizing recombinant canine protein (rCnAPC).

Dr. Paul Woods

Preclinical evaluation of potential of Nabidiolex to attenuate nausea/vomiting/anorexia in dogs undergoing chemotherapy treatment

Malignant lymphoma is the most common hematopoietic neoplasm in the dog. Without treatment lymphoma is a fatal disease with usually rapid rate of progression and an average survival of about 30 days. With serial sequential chemotherapy complete re-missions rates of 60 to 80% with median survivals of six to 12 months have been reported.

OVC has a busy caseload, treating approximately150 lymphoma cases each year with standard chemotherapy protocol. However, dogs undergoing chemotherapy treatment for lymphoma often experience nausea, vomiting, and anorexia for which current treatments may be ineffective in relieving these signs.

Considerable evidence indicates that the psychoactive compound found in the marijuana plant, Δ9-tetrahydrocannabinol (THC), attenuates nausea and vomiting in animal models. However, the marijuana plant contains over 60 cannabinoid compounds other than THC, including the non-intoxicating compound, cannabidiol (CBD). CBD has no reported intoxicating effects and recently it has been shown to have a number of therapeutic effects in animal models and clinical trials with humans. The Parker laboratory has provided considerable evidence showing that CBD, like THC, attenuates nausea and vomiting in animal models. CBD has been shown to inhibit toxin-induced vomiting in the musk shrew (Suncus murinus) and to suppress toxin-induced nausea in rats. In addition, CBD has also been shown to prevent the expression of anticipatory nausea in the shrew and nausea in rats. CBD may be a potential non-intoxicating alternative to medical marihuana in the treatment of nausea and vomiting.

This project seeks to evaluate the effectiveness of CBD to attenuate nausea and vomiting in dogs undergoing chemotherapy treatment.