Implantation of oxygen enhanced, three‐dimensional microporous L‐PLA polymers: A reproducible porcine model of chronic total coronary occlusion

Abstract

We have hypothesized that oxygen enhanced three-dimensional microporous poly-L-lactic acid (L-PLA) bioabsorbable polymer constructs could be implanted to produce a subacute occlusion in a porcine coronary artery, forming a thrombofibrotic occlusion containing microvascular channels. Chronic total occlusion (CTO) is increasingly prevalent in patients who present for percutaneous interventions. No reproducible animal coronary model simulating human CTOs has previously been developed. Swine coronary arteries were cannulated and a microporous L-PLA polymer pledget was advanced into a preselected segment of coronary. The coronary arteries were angiographically re-imaged at day 3, day 10, and day 28, to document the presence or absence of an occlusion. Histopathology was also performed at each time point to evaluate the lesion characteristics. A novel three-dimensional L-PLA microporous polymer construct, when implanted into porcine coronary arteries, reproducibly results in the development of a CTO at day 3. The histopathology in this porcine coronary model of CTO at day 28 closely mimics human coronary CTO, including the presence of microvascular channels and dense collagen and elastic tissue in the occlusion.

The Representative Porcine Model for Human Cardiovascular Disease

“…Early polymeric implants were abandoned as stent platforms because they induced severe inflammatory responses and vessel occlusion [61]. Prosser et al reported placement of a microporous poly L-lactic acid polymer into pig and dog coronary arteries [62]. The polymer is absorbed by 28 days, resulting in a microchanneled occlusion histologically similar to a human CTO.…”

The Pre-Clinical Animal Model in the Translational Research of Interventional Cardiology

“…Early polymeric implants were abandoned as stent platforms because they induced severe inflammatory responses and vessel occlusion (59). Prosser et al (60) reported placement of a microporous poly L-lactic acid polymer into pig and dog coronary arteries. The polymer is absorbed by 28 days, resulting in a microchanneled occlusion histologically similar to a human CTO (60).…”

“…Prosser et al (60) reported placement of a microporous poly L-lactic acid polymer into pig and dog coronary arteries. The polymer is absorbed by 28 days, resulting in a microchanneled occlusion histologically similar to a human CTO (60). Using similar methods, Suzuki et al and our group (61,62) have developed severe calcified CTO in pig coronary arteries (Fig.…”

Importância dos estudos pré-clínicos em animais de experimentação para a cardiologia intervencionista

“…Early polymeric implants were abandoned as stent platforms because they induced severe inflammatory responses and vessel occlusion 69 . Prosser et al 70 reported placement of a microporous poly L-lactic acid polymer into pig and dog coronary arteries. The polymer is absorbed by 28 days, resulting in a microchanneled occlusion histologically similar to a human CTO 70 .…”

“…Prosser et al 70 reported placement of a microporous poly L-lactic acid polymer into pig and dog coronary arteries. The polymer is absorbed by 28 days, resulting in a microchanneled occlusion histologically similar to a human CTO 70 . These animal models may contribute to a deeper understanding of the biology of human CTO and enable new device and pharmacological investigation to improve recanalization success in these challenging lesions.…”