Modeling Cardiovascular Disease Using Canine Models

Rodney A White, MDMedical Director, Vascular Services

MemorialCare Heart & Vascular InstituteLong Beach Memorial Hospital

Long Beach, CaliforniaVascular Surgeon, Harbor-UCLA Medical

Emeritus Prof. of Surgery, UCLA School of Medicine

Disclosures

Speaker name: Rodney A. White, MD

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I have the following potential conflicts of interest to report:

• Clinical & Research Support:Bolton Turomo Medtronic

• Consultant & Speakers Bureau:Bolton Turomo, Cardiatis, Medtronic

• Advisory BoardsAneuMed, 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 use1. Somewhat similar to human healing of implanted devices2. Appropriate size access (peripheral) and deployment vessel size, i.e.,

aorta 3. Stabile size for long-term studies compared to rapid growth of pigs4. May be better suited for smaller device development, i.e., for women

with smaller aortic anatomy (sheep too large)5. Recent consideration of canine model to address new issues with long-

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