A Clinically Relevant Swine Model of Chronic Myocardial Ischemia by Ameroid Constrictor Placement with Simultaneous Perfusion Mapping

Summary

The goal of this project is to detail a thoroughly scrutinized protocol of the surgical placement of an ameroid constrictor around the proximal left circumflex coronary artery (LCx), thereby inducing chronic coronary artery disease and precisely mapping the ischemic territory using isotope-labeled microspheres.

Abstract

Despite breakthroughs in medical and procedural therapies for the treatment of cardiovascular disease, the need for translational large animal models has persisted to investigate diagnostic tools and treatment strategies. Swine represent an impeccably accurate and appropriate model for human cardiovascular disease, as their cardiac anatomy and physiology closely resemble that of humans, as well as their metabolic and proteomic profile. The induction of chronic myocardial ischemia to an area of the myocardium by using an ameroid constrictor accurately and easily emulates the common pathophysiologic process of atherosclerosis development in humans and subsequent myocardial response. Ameroid constrictors have been widely studied over the last 50 years providing rigorous evidence for its use; furthermore, we have over two decades of experience in efficiently and uniformly conducting this procedure. An important step within this protocol is performing coronary blood flow mapping to determine the area of greatest ischemia and areas with no ischemia by injecting isotope-labeled microspheres. The ability to perform coronary blood flow mapping precludes the necessary and labor-intensive use of cardiac MRI or PET imaging for perfusion studies and determination of the ischemic territory. The goal of this publication is to detail the correct placement of an ameroid constrictor on the proximal LCx and subsequent coronary perfusion mapping.

Introduction

Globally, ischemic heart disease (IHD) has only grown in its mortality and burden on patients and the healthcare system. According to the American Heart Association, the number of deaths attributable to IHD from 1990 to 2021 has increased by 74% worldwide¹. This is additionally true within the United States, where the Center for Disease Control cites that one in twenty adults has been diagnosed with coronary artery disease (CAD), and about one in five mortalities are due to cardiovascular disease, which is equivalent to a person dying from cardiovascular disease every 33 s². This burden of disease stresses the healthcare....

Protocol

The surgical procedure detailed below was approved by the Institutional Animal Care and Use Committee of Rhode Island Hospital and Brown University.

1. Animal model

1. Use both juvenile female and intact male Yorkshire swine, ideally aged around 11 weeks old, and typically weighing around 15 kg.

2. Pre-surgical procedures

1. Ensure that swine receive daily pre- and postoperative aspirin (10 mg/kg) starting 1 day before the surgery and proceeding to 5 days postoperatively.
2. Ensure that swine are without food on the morning of surgery.
3. On....

Results

Over two decades of performing the above procedure, the survival rate is about 80%^10,11. A majority of mortalities occur around 2 weeks postoperatively, often due to irreversible and spontaneous ventricular arrhythmia at the time of ameroid closure. On multiple prior necropsies, typical findings show a properly placed ameroid with minimal acute scar formation of the left ventricle, confirming the ventricular arrhythmia diagnosis. The arrhythmia leads to sudden ca.......

Discussion

The main advantage of using an ameroid constrictor is the simplicity of the device; however, this presents limitations in the inability to control closure rates or the degree of stenosis around the coronary artery. This can lead to variability in the induction of myocardial ischemia. Alternatives to the use of ameroid constrictors include the use of silk ties, hydraulic occluders, or serial placement of flow probes^{12,13,14,.......}

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
#10 Scalpel	Medline	MDS15310
0.9% Saline	Dechra/Vetivex	17033-492-50	Rate: 5 mL/kg during case
0-Silk Ties	Ethicon	SA76G	Tie off Left Atrial Appendage
1-0 PDS II on a CT Blunt Tip	Ethicon	Z359T	Close rib space
2% Lidocaine	Phoenix		Dosing: 2–5 mg/kg
2-0 Silk Suture on SH Taper	Ethicon	K833H	Tack pericardium
28-guage needle	Patterson Veterinary	78032728	For microsphere injection
3 18G Needles	Patterson Veterinary	78032793	For drawing medication
3-0 Vicryl on an RB Taper	Ethicon	VCP215H	Close pericardium
3-0 Vicryl Reverse Cutting	Ethicon	VCP442H	Close muscular and deep dermal layers
4-0 Monocryl	Ethicon	MCP496G	Close skin
6-0 Polypropylene Suture	SharePoint	JS617N	For emergency repair of atrium
All Surgical Instruments	Steris and Medline	Requires Sales Representative	All Commonly Found in Hospital Operating Rooms
Ameroid Constrictors	Research Instruments SW, Inc.	CS-2.00-TI	Type: titanium (2.0 cm to 3.0 cm)
Analgesia: Buprenorphine	Hospira	Brand Name: Bupredine	Dosing: 0.03 mg/kg
Analgesia: Fentanyl Patch	Covetrus	77870	Dosing: 4 mg/kg
Anesthesia: Telazol	Zoetis	(tiletamine and zolazepam)	Dosing: 4.4 mg/kg
Anesthesia: xylazine (Rompun)	Dechra	N/A	Dosing: 2.2 mg/kg
Chlorhexidine 4%	BD E-Z Scrub	371073	Surgical Prep
Cuffed Endotracheal Tube	RUSCH	7-0 typically	May need different sizes depending on swine size and weight
ECG Monitoring System	MidMark	N/A	Multiparameter Monitor
Electrocautery	Bovie Specialist Pro	1250S
Excede (Ceftiofur)	Covetrus	23814	Single-dose IM injection
Gold STERIspheres	BioPAL, Inc.	C-15H20	Amount: 5cc per surgery
Isoflurane, USP	Dechra		Dosing: 0.75%–3.0%
Mini White Vessel Loops (X-ray Detectable)	DeRoyal	30-711	To isolate the LCx
Multiple 5cc Syringes	Medline	TMOSS05L	For multiple injections
Nitroglycerin	Baxter	Nitroglycerin in 5% dextrose injection (200mcg/mL)	Spray 2–3 cc topically
Red Rubber Catheter	Cardinal Health	888766008	Place into chest to extract air
Sterile Gloves	Encore	820955
Suction System	GOMCO	4042	Better if wall suction of own facility
Suction tip: Yankauer	Medline	DYND50130
Surgical Drapes	Patterson Veterinary General Surgery Pack	78929436	4 small adhesive drapes and one large laparotomy drape
Surgical Lubricant	SurgiLube	0281-0205-43	Must be sterile
Systemic Heparin	Covetrus	82496	Dosage: 80 IU/kg
Yorkshire Swine	CBSET, Inc.	N/A	Ideally around 11-weeks-old