Preclinical Evaluation of Coronary Artery Stents

Summary

New coronary artery stent designs and materials must be tested before clinical use in relevant preclinical models. Here we describe an atherosclerotic rabbit aorta model and a pig coronary artery model for stent research with in vivo and histological analyses.

Abstract

Coronary artery disease is a major contributor to morbidity and mortality worldwide. While lifestyle changes and medication are the cornerstones of treatment, coronary artery balloon angioplasty and stenting are routinely performed on patients with acute coronary syndromes and chronic coronary artery disease who remain symptomatic with optical medical treatment. Several generations of coronary stents have been developed over recent decades. Balloon angioplasty and stenting are supported by the use of pharmaceutical agents applied onto balloons and the stent surface, either to advance the healing properties of the artery post-intervention or to prevent the formation of restenosis. New devices need to be rigorously tested for safety and efficacy before acceptance into clinical practice; thus, there is a continuing need for reliable and reproducible preclinical methods of stent evaluation. We describe here a pig coronary artery model as well as an atherosclerotic rabbit model for coronary artery stent research and describe basic steps in intravascular imaging and stent histology.

Introduction

Atherosclerotic coronary artery disease causes a significant burden on the healthcare systems of countries across the globe¹. Coronary artery balloon angioplasty and stenting are routinely performed on patients suffering from acute coronary syndromes as well as symptomatic patients with stable coronary artery disease². Balloon angioplasty was a revolutionary invention to revascularize narrowed or even occluded coronary arteries. Coronary artery stents further improved the results of percutaneous coronary interventions (PCIs) by preventing acute recoil of the artery following balloon angioplasty

Protocol

All animal experiments were approved by the Animal Experiment Board in Finland. Adult 3.0-4.0 kg New Zealand White (NZW) rabbits were used for the atherosclerotic rabbit model. For the pig coronary study, the animals weighed 30-40 kg at the start of the experiment. The protocol for the rabbit atherosclerotic model and the pig coronary artery model is described separately, followed by the description of how histology can be performed for non-degradable coronary stents, regardless of the in vivo model used.

1. Rabbit atherosclerotic model

NOTE: To induce rapid atherosclerotic changes in the ....

Results

Successful stent expansion must be confirmed with angiography and ideally with intravascular imaging (Figure 3A,B). The pig coronary artery model allows for multiple imaging sessions, and OCT can be used to create follow-up data with frequent imaging. ISR and stent expansion, and possible strut fractures can easily be evaluated from angiographic and OCT imaging. Intravascular imaging also produces data along the length of the whole stent, unlike histology, which usually can .......

Discussion

While the current generation of drug-eluting coronary stents have proven their merits, new devices are being developed to better suit the needs of patients and healthcare professionals. The first round of fully biodegradable coronary scaffolds met several challenges, which further underlines the importance of testing new devices in biologically relevant models⁹. The models presented here provide two options for conducting stent research. The coronary model should be applied and is generally requir.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Angiographic puncture needle	Cordis	12-004943
Aspirin Cardio 100 mg	Bayer
Cholesterol	Sigma-Aldrich	C8667
Plavix	Sanofi		Clopidogrel
Coronary stent (bare metal, drug eluting, biodegradable)			Stent should be selected according to the study plan. Stent length 18-25mm and diameter 2.5-3.5mm
Domitor	Orion		medetomide
Dragonfly Optis OCT catheter	Abbott	C408646	Use catheter compatible with available imaging system
Enoxaparine	Sanofi		Clexane
Ethanol	Sigma-Aldrich	32221-M
Fentanyl	Biocodex
Guide wire, coronary	Cordis	507114
Guide wire, J tip	Cordis	502717
Guiding catheter AR1	Cordis	670-110-00
Guiding catheter AR2	Cordis	670-112-00
Guiding catheter straight	Cordis	55626090
Indeflator	Medtronic	AC3200	Indeflator for stent balloon inflation and deflation
Introducer sheath 5F	Cordis	504605P
Introducer Sheath 6F	Cordis	504606X
Ketalar	Pfizer		Ketamine
Microsurgical set	Mediq	FBL-SET	S&T , basic lab set for example
Paraformaldehyde	VWR	VWRRC28794.295	Prepare 1% and 4% solutions
Propofol	B. Braun
Suture	OneMed	JOH8685H	5-0, nonresorbable
Suture	OneMed	JOHFH1642H	4-0 resorbable
Technovit 9100	Kulzer
Ultrasound with linear transducer	Philips
Vacuum chamber	SP Bel-Art	F42043-0000
X-Ray contrast agent	Iomeron
Xylene	Sigma-Aldrich	534056