Modeling Cardiovascular Disease Using Canine Models Rodney A White, - PowerPoint PPT Presentation

Modeling Cardiovascular Disease Using Canine Models Rodney A White, MD Medical Director, Vascular Services MemorialCare Heart & Vascular Institute Long Beach Memorial Hospital Long Beach, California Vascular Surgeon, Harbor-UCLA Medical Emeritus Prof. of Surgery, UCLA School of Medicine

Disclosures Speaker name: Rodney A. White, MD .................................................................................  I have the following potential conflicts of interest to report: • Clinical & Research Support: Bolton Turomo Medtronic Consultant & Speakers Bureau: • Bolton Turomo, Cardiatis, Medtronic Advisory Boards • AneuMed, Intact Vascular

 Present state of the art  Recent accomplishments/advancements in last 5-10 years  Likelihood of replacing dogs as the preferred model for CV disease  Additional safeguards or requirements that should be established?

Historical perspective of canine research on development and clinical introduction of endovascular technologies, i.e., catheters , wires, imaging devices, stents and endografts Issues favoring canine use Somewhat similar to human healing of implanted devices 1. Appropriate size access (peripheral) and deployment vessel size, i.e., 2. aorta Stabile size for long-term studies compared to rapid growth of pigs 3. May be better suited for smaller device development, i.e., for women 4. with smaller aortic anatomy (sheep too large) Recent consideration of canine model to address new issues with long- 5. term failure mechanisms of human implants, i.e., Type 2 endoleaks

Issues against canine use  Other species sometimes appropriate, ie., sheep (larger vessels) & pigs (limited by small access vessels and rapid growth over time limiting long-term use)  Ethical & social issues, cost of acquisition & housing of dogs

 Atherosclerotic lesion models have completely evolved to other species, even though dogs can develop intimal lesions with saturated-fat, essential fatty acid deficient diets  pigs and smaller animal models used for pharmaceutical and dietary studies

Anterior Patch Aneurysm Model

 Over time, endograft testing, particularly thoracic endografts, migrated to sheep because of larger aorta and desired migration away from dogs when possible - pigs access vessels too small  Little publication of this data -relevant for regulatory approval

 Cardiac Implants & Antiarrhythmic Devices -Extensive literature documenting this as preferred model for several applications *Similarities in conduction system to humans & size to accompany long-term implantation

 What is the likelihood of replacing dogs as the preferred model for cardiovascular devices going forward?  What are the tradeoff of doing so? - Evaluate aortic devices as “first -in- man” trials - ? Effect on cardiac electrophysiological drug & device development  Would replacing dogs with another species compromise the quality or timelines of future advances? - probably, also could effect outcomes of larger, sheep model device implant studies

What, if any, additional safeguards or requirements should be in place with regard to the use of dogs in research? Future publications clearly address the reasons for use of  canines, and delineate the key findings of the study that would be compromised, or not possible, using another species. Future publications discuss the efforts to use another  species, why this was not possible & what can be done to address the ethical issues regarding canine research VA could consider reporting patient testimonials regarding  these advances so public is aware of information regarding consideration of the ethical issues