Endoluminal Atherosclerotic Plaque Debulking Using Enzymatic and Ultrasonic Energy.

Abstract

BACKGROUND:

Current procedures to treat severe atherosclerosis are traumatic to the arterial wall and often result in restenosis due to neointimal hyperplasia. We developed a novel therapy using a specially designed double occlusion balloon catheter, ultrasonic wire, and enzymatic digestion solution to atraumatically debulk atherosclerotic plaques.

MATERIALS AND METHODS:

A combination of different enzymes, chemicals, and treatment conditions were evaluated for its effect at reducing atherosclerotic plaque harvested from human carotid artery endarterectomies ex vivo. The optimized digestion solution was examined in harvested intact human superficial femoral arteries in situ. A conventional Yorkshire/Landrace and a genetically modified Yucatan minipig homozygous for a nonfunctional LDLR mutation were used to evaluate the endovascular therapy in nonatherosclerotic and atherosclerotic environments in vivo.

RESULTS:

Ex vivo, the technology successfully digested human carotid artery plaques by 75%. In situ, the therapy successfully reduced plaque area in harvested superficial femoral arteries by 46%. In vivo, the endovascular therapy was technically feasible and demonstrated initial safety with no thrombosis, dissection, or aneurysmal dilatation in a nonatherosclerotic porcine model. In an atherosclerotic porcine model, the therapy demonstrated initial efficacy by successfully reducing atherosclerotic plaque while preserving the arterial wall with an intact internal elastic lamina.

CONCLUSIONS:

Using human plaque, human artery, and a normal and atherosclerotic pig model, we demonstrated that delivery of our therapy to the vasculature is technically feasible, appears safe, and shows initial efficacy. Our percutaneous plaque debulking method is a unique and promising therapy for the treatment of atherosclerosis and warrants further study.

• Authors: Zheng Wang, Neel A Mansukhani, Zachary M Emond, Vinit N Varu, Amy Chen, Courtney E Morgan, Janet M Vercammen, Melina R Kibbe
• Journal: The Journal of surgical research (J Surg Res) Vol. 233 Pg. 335-344 (01 2019) ISSN: 1095-8673 [Electronic] United States
• PMID: 30502268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, LDL
• Hydrolases

Topics

• Angioplasty, Balloon (instrumentation, methods)
• Animals
• Animals, Genetically Modified
• Atherosclerosis (etiology, pathology, therapy)
• Carotid Arteries (pathology)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Feasibility Studies
• Femoral Artery (pathology)
• Humans
• Hydrolases (administration & dosage)
• Iliac Artery (pathology)
• Male
• Plaque, Atherosclerotic (pathology, therapy)
• Receptors, LDL (genetics)
• Swine
• Swine, Miniature
• Treatment Outcome
• Ultrasonic Therapy (methods)