Models of Human Vascular Disease: Is There an Animal of La Mancha?

Abstract

Cervantes understood that models–be they physical or moral lessons–are valid only in as much as they mirror that which they seek to mimic. This is the essential issue presented by Diego et al. in the article published in Revista Española de Cardiología. Drug-eluting stents have changed the practice of medicine and are perhaps the most common intervention used today. Millions of stents are placed each year and yet critical questions remain as to whether one design is better than another. The challenge in major part is that, though device designs may be significantly different one from another, detection of a clinical difference is difficult given the rarity of side effects. Human clinical trials are too small and too short to detect differences even in fatal events that occur in 1 in 100 patients per year. The natural fallback is to rely on animal model systems and yet it is unclear how best to use them. Diego et al. describe a study that compares the proliferative response elicited after deployment of paclitaxel-eluting and bare metal stents in porcine coronary arteries. They suggest that the ability of a stent platform to significantly impact late vascular healing depends upon the degree of injury that is created at the time of implantation. Such a result has profound impact on how we consider animal model systems for critical technologies, our view of vascular biology and vascular repair, and our appreciation of the history of work in this field. Moreover, the study shows how a difficult parameter rarely controlled in human interventions–the extent of injury–is such a powerful regulator of clinical effect and restenotic side effect.