Progress reported on tying up syndrome

01 January 2010, at 12:00am

JOHN BONNER reports on an equine research symposium in Cheltenham

RESEARCHERS at the Royal Veterinary College have developed a test which may reliably identify horses susceptible to exertional rhabdomyolysis syndrome before they enter training.

Dr Richard Piercy, senior lecturer in equine medicine at the RVC, described progress with the project at a symposium at Cheltenham in November focusing on research supported by the Horserace Betting Levy Board.

The condition, also known as setfast or tying up, affects between five and seven per cent of thoroughbred horses in training and has a seriously detrimental effect on racing performance.

It causes repeated episodes of muscle damage, resulting in signs ranging from muscle stiffness to severe myoglobulinuria with a potentially fatal outcome. Its cause is still unknown although it is thought likely to result from a combination of genetic and environmental factors. As well as improving diagnosis, the test may be helpful in identifying the exact cause and in testing novel treatments, he said.

Metabolism defect

Previous studies by US researchers have identified a defect in calcium metabolism in horses with a propensity to develop the condition, which is normally diagnosed in clinical cases by measuring creatine kinase and aspartate aminotransferase levels in the blood.

Muscle fibres taken from these horses show an abnormal sensitivity to the effects of caffeine and other agents which affect muscle contraction by increasing cellular calcium levels. However, this test is based on a biopsy sample from the intercostal muscles which not only leaves a scar, but it can also result in a pneumothorax if the sampling technique is poor.

Dr Piercy’s team have developed a minimally invasive alternative based on small skin biopsy samples which can then be cultured in the laboratory and converted into muscle cells through the action of a muscle-specific transcription agent known as MyoD.

The relevant gene for this protein has been cloned into a virus which is then used to infect the cultured skin cells and change their morphology. Lab tests have shown that these newly created muscle cells have the same response to caffeine and similar agents as normal muscle cells.

A wide range of treatments and nutritional supplements have been marketed to thoroughbred trainers as being protective against the effects of exertional rhabdomyolysis in their animals.

However, the only treatment with proven efficacy is dantrolene, a drug which appears to have an opposite effect to caffeine on the ryanodene receptor involved in calcium transport within muscle cells.

Dantrolene is often given by trainers to horses with a history of the condition to prevent further damage while they build up fitness in preparation for a race, although standard withdrawal times must be observed in order to avoid infringing the rules of racing.

Dietary adjustments, including a high fat, low carbohydrate diet and avoiding sudden changes in the training schedule, have also been suggested as strategies which may protect against muscle damage.

“Other than these recommendations, there is very little convincing evidence that any other management, supplement, drug or diet is beneficial. Our hope is that our new lab-based technique will allow us and others to investigate novel treatments and perhaps even a cure,” he said.

A new laboratory method has also been approved this year for inclusion in the codes of practice for the prevention of contagious equine metritis and other venereal conditions in breeding units, Chris Rea from the Three Counties Equine Hospital in Tewkesbury told the meeting.

Mr Rea sits on the HBLB’s veterinary advisory committee, which has recommended the use of the polymerase chain reaction technique for use in testing swabs taken from mares for the causative organism of CEM, the bacterium Taylorella equigenitalis. It may also be used in testing semen samples for the equine viral arteritis agent.

In the case of the CEM organism, the new test has advantages over traditional culture methods in providing a result within two days rather than seven.

It can also be used on samples that have become too degraded for conventional culture and will distinguish between the pathogenic bacterium and the closely related but benign organism, T. Asinigenitalis, found mostly in donkeys.

This latter benefit is important because it protects the UK’s important export trade from future disruption. The greater precision will dissuade importing countries placing restrictions on admitting horses from states where there have been incidents of samples wrongly classed as positive to T. equigenitalis on culture.

Mr Rea said the code has been a major factor in successfully guarding Britain against major epidemics of equine reproductive diseases over the past 30 years and encouraged vets and horse owners to continue supporting regular sampling from adult horses of all breeds.

Anthelmintic resistance

Testing in equine practice laboratories will also help to protect the UK horse industry against the damage that may be caused by the emergence of anthelmintic-resistant strains of small cyathastome worms, said Professor Jackie Matthews of the Glasgow veterinary school. 

Preventing the further spread of resistance to the only three groups of anthelmintics currently available will depend on the development and use of sustainable worming strategies, she said.

These will be based on routine testing to assess the susceptibility of resident worms to the drug class intended for use. Analyses of the worm burden in individual animals will also help to maintain an effective armoury of drugs by focusing treatment on the 20% of individual animals that carry 80% of the worm burden on any equine premises.

Professor Matthews reviewed progress in developing new, more effective methods for analysing worm counts and assessing the likely efficacy of treatment, including new DNA- based methods for detecting the genes responsible for anthelmintic resistance.

But education of horse owners was an equally important element in persuading owners to pay for susceptibility tests rather than implementing blanket treatment strategies for all horses.

Targeted treatment will reduce the costs of treatment even on holdings where owners would have to pay for individual faecal egg count tests on dozens of animals, she said.