EHRF Research Grants: 2015-2016

Developing a treatment for acute laminitis
Drs. David Wilson, James Carmalt, Kathryn Carmalt, WCVM

Laminitis is a common, life-threatening condition in horses. The inflammatory disease causes the sensitive laminae, which connect the hoof wall to the coffin bone within the foot, to separate. This process results in rotation of the coffin bone within the hoof due to the pull of the deep digital flexor tendon. Once bone rotation begins, it is debatable whether any therapeutic approach can alter the course of the disease.

Researchers in Australia have recently shown that repair of the laminar tissue occurs quickly without physical disruption. Building on these findings, a team of WCVM researchers including Drs. Kathryn Carmalt, David Wilson and James Carmalt will continue their work studying the impact of using a screw to provide mechanical support to the hoof.

WCVM scientists have already proven that using screws to “anchor” the coffin bone to the hoof wall is enough to withstand the pull of the deep digital flexor tendon. They have also shown that screw placement is well tolerated by live horses without undue discomfort or infection. Wilson and his team believe effective mechanical support could prevent disruption of the hoof wall and rotation of the coffin bone during the early stages of the disease.

During this project, Dr. Kathryn Carmalt will induce laminitis in nine horses and administer screw placements. The study’s results will help them determine whether this treatment can reduce pain associated with laminitis, prevent coffin bone rotation and facilitate repair of laminar tissue.

Could a surgical technique called forage help treat arthritis in horses?
Drs. David Wilson, James Carmalt, Keri Thomas, Joe Bracamonte, WCVM

When veterinarians diagnose osteoarthritis of the pastern joint — or high ringbone — in a highly-trained, middle-aged horse, it often signals the end of the animal’s performance career. Surgeons can surgically fuse the pastern joint to remove the pain, but pastern arthrodesis is a highly invasive treatment with long recovery times. A technique that could facilitate surgical fusion of the affected joint would represent a major advance in managing this condition.

In 2002, WCVM researchers revealed that the injection of ethyl alcohol was effective in promoting fusion of the lowest hock joint in normal horses. Further research found that affected cartilage of the pastern joint can be broken down by intraarticular alcohol, but the process did not lead to fusion.

In human surgery, a technique called forage — drilling holes through the subchondral bone plate — is commonly used to promote joint fusion. Led by Dr. David Wilson, a group of researchers will evaluate whether the forage technique effectively promotes the fusion of pastern joints that are treated with intraarticular alcohol.

The researchers will inject ethyl alcohol into the rear pastern joints of six healthy horses. One limb of each horse will receive the forage therapy and be post-operatively observed for lameness. Researchers will use radiographs to evaluate the horses’ joints at intervals over an eight-month period. If the study’s results show that the treatment is successful, it may provide a less invasive therapy option for pastern osteoarthritis.

Does lactated ringers solution (LRS) affect horses’ blood lactate concentration values?

Drs. Fernando Marqués, Cheryl Waldner, Sara Higgins, WCVM

When critically ill horses suffer from severe diarrhea, colic, pleuropneumonia or dehydration, their bodies are often unable to provide tissues with the necessary oxygen to support life. Tissues need oxygen to produce energy and to function normally. Veterinarians can indirectly assess whether oxygenation is occurring by measuring the blood lactate concentration (BLC) in the horse’s body. They use this measurement to assess the severity of the disease and to provide a prognosis.

Clinicians often treat critically ill horses with intravenous (IV) fluids such as lactated ringers solution (LRS). To minimize stress for their patient, and to prevent thrombus formation in other veins, veterinarians typically collect the blood sample using the same IV catheter that’s used to administer fluids. A previous report done with human IV catheters suggests that residual lactate could influence BLC measurement.

Dr. Fernando Marqués and his team will conduct a study that assesses whether using the same catheter for treatment and monitoring influences horses’ diagnostic BLC measurements. The study will include 30 horses that are patients in the WCVM Veterinary Medical Centre. Results of the study will provide equine clinicians with guidelines for collecting and interpreting BLC measurements in horses receiving IV fluids containing LRS.

Will depleting intravascular macrophages help more horses survive after colic surgery?
Drs. Tanya Duke, Stacy Anderson, WCVM

A common cause of death in horses is strangulating intestinal lesions (twisted gut) that lead to severe colic. Horses must undergo emergency abdominal surgery to correct the problem, but they may still become very sick or die after surgery.

Researchers have attempted to find drugs that prevent post-operative sickness in horses. However, little is known about why the immune system seemingly malfunctions, causing horses to become sicker. The culprit could be pulmonary intravascular macrophages (PIMs), certain white blood cells in horses’ lungs that may play an integral role in modulating their systemic inflammatory response.

Dr. Tanya Duke and her team suggest that by depleting the number of intravascular macrophages in a horse’s body, they can significantly reduce the animal’s immune response. A chemical called gadolinium chloride has proven effective in removing these white blood cells.

Using samples from a previous study, the researchers will assess the role of PIMs in horses that had artificially created twisted intestines and subsequent doses of gadolinium chloride to remove the white blood cells. The research team will use several lab tests to assess immune response in tissue samples collected from these horses.

By learning more about the mechanisms of the disease at cellular and molecular levels, researchers hope this information will lead to a more effective, post-operative treatment for horses.

Developing a new analytic tool to create better outcomes for horses after abdominal surgery

Dr. Joe Bracamonte, WCVM; Scott Napper, VIDO-InterVac

Abdominal adhesions are a major complication following equine abdominal surgery, specifically after surgery for small intestinal lesions. Previous experimental and clinical studies have focused on evaluating different methods to reduce adhesion formation in horses, but so far, no one has developed an effective method for preventing adhesions..

Dr. Joe Bracamonte and his team believe that this is in part because of a lack of understanding of how adhesions form at molecular and cellular levels. By learning more about the mechanisms involved in adhesion formation, researchers could make a critical step toward developing effective therapeutic strategies to prevent formation of adhesions in horses.

Peptides are fragments of a protein, and peptide arrays contain critical components of the proteins responsible for regulating communication within a cell. In this study, researchers will apply a promising technique using peptide arrays for kinome analysis. The kinome represents the number of communication pathways in a cell controlled by the kinases (fragments of proteins, or peptides), and these pathways control cell function.

This technique has provided a large amount of information about complex biological problems in people and experimental animals. But so far, no researcher has demonstrated whether the evidence recovered through this method applies to horses.

By collecting samples from live horses after surgery, the researchers will develop equine-specific peptide arrays. They will use these peptide arrays to identify the unique cellular pathways involved in adhesion formation after abdominal surgery. Researchers will use results from this study to develop effective methods to prevent adhesions from forming in horses after surgery.