Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease

Summary

We describe a novel, cost-effective, and efficient technique for percutaneous delivery of three-dimensionally printed coronary implants to create closed-chest swine models of ischemic heart disease. The implants were fixed in place using a mother-and-child extension catheter with high success rate.

Abstract

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

Introduction

Ischemic heart disease continues to be the number one cause of death in the United States¹. Large animal models have been used experimentally to understand and characterize mechanisms driving coronary artery disease (CAD) and associated complications (including myocardial infarction, arrhythmic events, and heart failure), as well as for testing of new therapeutics or diagnostic modalities. Results from these studies have helped to broaden the understanding, diagnosis, and monitoring of ischemic heart disease and to advance clinical practice². Several animal models including rabbits, dogs, and swine have been used. Howeve....

Protocol

We conducted the experiments according to the guidelines by the Animal Welfare Act, the National Institutes of Health, and the American Heart Association on Research Animal Use. Our Institutional Animal Care and Use Committee approved the animal study protocol.

1. Preprocedural preparation of 3D printed coronary stenosis implants

1. Using tweezers, dip-coat the printed implants in a 25% heparin solution to prevent thrombus formation and allow to air dry for 24 h.

2. Preprocedural preparation of animal subjects

1. Have male Yorkshire swine (SNS Farms, 30–45 kg) arrive at the institut....

Results

After initial optimization of the procedure, the intervention component was completed within 30 min. The implants were successfully delivered in all 11 subjects (100%). The implant was retrieved at the autopsy in all 11 subjects (100%). Using the diagonal branches (along the LAD) or obtuse marginal branches (along the LCX) as positional markers, we found the position of the implant at fluoroscopic-guided deployment and at autopsy to be consistent in 10 of the 11 (91%) subjects where the implant was retrievable. In one su.......

Discussion

In this work, we focused on a novel percutaneous deployment strategy for coronary stenosis-inducing implants and showed that a mother-and-child catheter can be repurposed for effective percutaneous delivery of 3D printed coronary implants. Discrete artificial coronary stenoses of variable severity can be created quickly in swine models with a high success rate and in a minimally invasive manner using standard human percutaneous coronary interventional techniques and equipment. These implants were shown to be safe in the .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3D-Printed coronary implants	Study Site Manufactured
Amiodarone IV solution	Study Site Pharmacy
Amplatz Left-2 (AL-2) guide catheter (8F)	Boston Scientific, Marlborough, Massachusetts, USA
Balance Middleweight coronary wire (0.014” 300cm)	Abbott Laboratories, Abbott Park, Illinois, USA
COPILOT Bleedback Control valve	Abbott Laboratories, Abbott Park, Illinois, USA
Esmolol IV solution (1 mg/kg)	Study Site Pharmacy
Formlabs Form 2 3D-printer with a minimum XY feature size of 150 µm	Formlabs Inc., Somerville, Massachusetts, USA
Formlabs Grey Resin (implant material)	Formlabs Inc., Somerville, Massachusetts, USA
Gadobutrol 0.1 mmol/kg	Gadvist, Bayer Pharmaceuticals, Wayne, NJ
GuideLiner catheter (6F)	Vascular Solutions Inc., Minneapolis, Minnesota, USA
Heparin IV solution	Surface Solutions Laboratories Inc., Carlisle, Massachusetts, USA
Ketamine IM solution (10 mg/kg)	Study Site Pharmacy
Lidocaine IV solution	Study Site Pharmacy
Male Yorkshire swine (30-45 kg)	SNS Farms
Midazolam IV solution	Study Site Pharmacy
NC Trek over-the-wire coronary balloon	Abbott Laboratories, Abbott Park, Illinois, USA
Oxygen-isoflurane 1-2% inhaled mixture	Study Site Pharmacy
Rocuronium IV solution	Study Site Pharmacy
Sodium Pentobarbital IV solution (100mg/kg)	Study Site Pharmacy
Triphenyltetrazolium chloride stain	Institution Pathology Lab