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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
SLIDE 2 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
AneuMed, Intact Vascular
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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?
SLIDE 4 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
1.
Somewhat similar to human healing of implanted devices
2.
Appropriate size access (peripheral) and deployment vessel size, i.e., aorta
3.
Stabile size for long-term studies compared to rapid growth of pigs
4.
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
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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
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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
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Anterior Patch Aneurysm Model
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SLIDE 16 Over time, endograft testing, particularly
thoracic endografts, migrated to sheep because
- f larger aorta and desired migration away
from dogs when possible
- pigs access vessels too small
Little publication of this data
- relevant for regulatory approval
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SLIDE 24 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
SLIDE 25 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
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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
