"A better model is within reach."

Rabbit Models of Endocarditis

Rabbit Models of Endocarditis

Infective endocarditis (IE) is a life-threatening disease caused by bacteria that enter the bloodstream and settle in the heart lining, a heart valve, or a blood vessel. If not treated quickly, IE can damage or destroy the heart valves. The heart valves are not supplied directly with blood, which means the body’s immune system cannot directly reach the valves through the bloodstream. This makes it difficult to fight the infection through the body’s own immune system or through medications, which rely on the blood system for delivery.

People at the greatest risk of IE usually have damaged heart valves, artificial heart valves or other heart defects – which could affect people young to old. Due to the complex and often indecisive presentation of the disease, the mortality rate for IE is about 40% – 50%. Rising patient ages, antibiotic-resistant strains of bacteria such as MRSA, and increased usage of cardiac device implants have all contributed to an increased risk for IE, especially in healthcare settings.

Since there are many ways to develop endocarditis, it can be tough to determine exactly what causes this condition. Some ways to develop IE include everyday oral activities such as brushing one’s teeth, an infection, catheter usage, needles for tattoos and body piercing, IV drug use, and certain dental procedures – all of which could allow bacteria to enter into the bloodstream and settle into the heart. If caught early enough IE can be treated with antibiotics. However, IE can go unnoticed for a while and once noticed, different bacteria respond to different treatments. Along with the rise in antibiotic resistance, it can be tricky to pinpoint which treatment is best before heart damage is done. The key to fighting the disease is prevention. Despite intensive research on IE and gained knowledge of the fundamental mechanisms of the disease, there is much room for improvement in diagnosis and treatment. Rabbit models of endocarditis have helped our understanding of what causes the disease, how it progresses and potential new treatment options.

Animal models of IE

To improve our understanding on the development of disease and to address the urgent need for better diagnosis and treatment, several experimental animal models of S. aureus, the predominant bacteria that leads to IE, have been established. Although there are some non-animal models that help tell us more about IE, in vivo animal models are at times required, especially when scientists want to study the host immune response within the context of a whole working body. In earlier days circa the 1950s, larger animal models such as dogs were used to study IE, but the trauma that needed to be used in order to induce the disease made the reliability of the results questionable. Two decades later, the use of catheters allowed smaller animals to be used, for example rabbit models of endocarditis. In these animals, bacteria could be detected easily on the heart valves and could be removed for further investigations. Although still smaller than dogs, the body size of the rabbit still required the use of high amounts of drug candidates which often led to experimental limitations. Nowadays, investigations on IE are primarily performed on mouse models of endocarditis due to their smaller size, rapid reproduction and more economical housing requirements. Also the ability to make gene knockouts and knockins related to IE was easier to perform up until recently in mice. However, mouse models are not without limitations. There is increasing evidence that S. aureus superantigens, exotoxins, and adhesins display high specificity towards their human targets, questioning how well infectious disease mouse models actually mimic the human inflammatory stress response. Also, because of the small size of the carotid artery, the mouse is a technically challenging model for the study of IE. This makes rabbit models a better choice for endocarditis studies because the rabbit immune and cardiovascular system is more similar to humans and the rabbit carotid artery is easier to work with.

Conclusion

Despite the research that has facilitated our understanding of IE, management of IE still exhibits many challenges to be overcome. Continued research on appropriate animal models will allow for better treatment options to be uncovered. With advancements in gene targeting and editing technologies such as CRISRP/Cas9, gene modifications that have been studied in mice can now be applied to rabbits in order to provide an animal model of choice that is most similar to the human condition.

References