Quantifying Inferior Vena Cava Compliance and Distensibility in an In Vivo Ovine Model Using 3D Angiography

Summary

This protocol allows for the in vivo quantification of venous compliance and distensibility using catheterization and 3D angiography as a survival procedure allowing for a variety of potential applications.

Abstract

Synthetic vascular grafts overcome some challenges of allografts, autografts, and xenografts but are often more rigid and less compliant than the native vessel into which they are implanted. Compliance matching with the native vessel is emerging as a key property for graft success. The current gold standard for assessing vessel compliance involves the vessel's excision and ex vivo biaxial mechanical testing. We developed an in vivo method to assess venous compliance and distensibility that better reflects natural physiology and takes into consideration the impact of a pressure change caused by flowing blood and by any morphologic changes present.

This method is designed as a survival procedure, facilitating longitudinal studies while potentially reducing the need for animal use. Our method involves injecting a 20 mL/kg saline bolus into the venous vasculature, followed by the acquisition of pre and post bolus 3D angiograms to observe alterations induced by the bolus, concurrently with intravascular pressure measurements in target regions. We are then able to measure the circumference and the cross-sectional area of the vessel pre and post bolus.

With these data and the intravascular pressure, we are able to calculate the compliance and distensibility with specific equations. This method was used to compare the inferior vena cava's compliance and distensibility in native unoperated sheep to the conduit of sheep implanted with a long-term expanded polytetrafluorethylene (PTFE) graft. The native vessel was found to be more compliant and distensible than the PTFE graft at all measured locations. We conclude that this method safely provides in vivo measurements of vein compliance and distensibility.

Introduction

Patients with critical cardiac anomalies require reconstructive surgery. Most reconstructive operations require the use of prosthetic materials, including vascular grafts. Potential conduits to bridge this space include synthetic or biologic materials. Initially, homografts were used as the Fontan conduit but have since been abandoned due to a high incidence of calcification and acute phase incidents¹. Currently, synthetic vascular grafts derived from inorganic polymers are used. There remains a challenge that these grafts are less compliant than the native vessel into which they are implanted and have long-term complications, such as stenosis,....

Protocol

The study protocol was approved by the Institutional Animal Care and Use Committee of Nationwide Children's Hospital Abigail Wexner Research Institute (AR22-0004). All animals received humane care in compliance with the Guide for the Care and Use of Laboratory Animals, published by the National Institutes of Health.

1. Animal preparation

1. Have a veterinary team evaluate the sheep 1 week prior to catheterization, including a physical exam and analysis of vital si.......

Discussion

Compliance and distensibility are key properties for blood vessel function, serving as indicators of potential complications and interventions. Precisely quantifying and comparing changes in these parameters is important to assess graft efficacy. Our in vivo method overcomes the limitations of ex vivo analysis and maintains comparable results. Comparing our in vivo data to the ex vivo data presented by Blum et al., both methods demonstrate marked differences between the synthetic graft.......

Materials

Name	Company	Catalog Number	Comments
0.035" x 260 cm Rosen Curved Wire Guide	Cook Medical	G01253	Guide for holding placement swapping caths (Multi-track, IVUS, etc)
0.035"x 150 cm Glidewire	Terumo	GR3507	Guide for JR cath
0.9% Sodium Chloride Saline	Baxter Healthcare Corporation	NCH pharmacy	For diluting norepinpherine, pressure monitoring
10.0 Endotracheal tube	Coviden	86117	To secure airway
16 G IV catheter	BD	382259	To administer fluids and anesthetic drugs
22 G IV catheter	BD	381423	For invasive blood pressure
5Fr x .35" JR2.5	Cook Medical	G05035	Guide for rosen wire
70% isopropyl alcohol	Aspen Vet	11795782	Topical cleaning solution
7Fr x 100 cm Multi-track	B. Braun	615001	Collecting pressure, Administering contrast to specific intravascular location
9Fr Introducer sheath	Terumo	RSS901	Access catheter through skin into vessel for wires to pass through
ACT cartridge	Abbot Diagnostics	03P86-25	Activated Clotting Time
Angiographic syringe w/ filling spike	Guerbet	900103S	For contrast injector
Bag decanter	Advance Medical Designs, LLC	10-102	Punctures saline bag to pour and fill sterile bowl with saline
Butorphanol	Zoetis	NCH pharmacy	Sedation drug: Concentration 10 mg/mL, Dosage 0.1 mg/kg
Cath Research Pack	Cardinal Health	SAN33RTCH6	Cath pack with misc. supplies
Cetacaine	Cetylite	220	Topical anesthetic spray
Chloraprep	BD	930825	Topical cleaning solution
Chlorhexidine 2% solution	Vedco INC	VINV-CLOR-SOLN	Topical cleaning solution
Conform stretch bandage	Coviden	2232	Neck wrap to prevent bleeding
Connection tubing	Deroyal	77-301713	Connects t-port to fluid/drug lines
Diazepam	Hospira Pharmaceuticals	NCH pharmacy	Sedation drug: Concentration 5 mg/mL, Dosage 0.5 mg/kg
EKG monitoring dots	3M	2570
Fluid administration set	Alaris	2420-0007
Fluid warming set	Carefusion	50056
Hemcon Patch	Tricol Biomedical	1102	Patch for hemostasis
Heparin	Hospira, Inc	NCH pharmacy	Angicoagulant: 1,000 USP units/mL
Infinix-i INFX-8000C	Toshiba Medical Systems	2B308-124EN*E	Interventional angiography system
Invasive pressure transducer	Medline	23DBB538	For invasive blood pressure
Isoflurane	Baxter Healthcare Corporation	NCH pharmacy	Anesthetic used in prep room
Ketamine	Hospira Pharmaceuticals	NCH pharmacy	Sedation drug: Concentration 100 mg/mL, Dosage 4 mg/kg
Lubricating Jelly	MedLine	MDS0322273Z	ET tube lubricant
Micropuncture Introducer Set	Cook Medical	G47945	Access through skin into vessel
Needle & syringes	Cardinal Health	309604	For sedation
Norepinpherine Bitartrate Injection, USP	Baxter Healthcare Corporation	NCH pharmacy	1 mg/mL
Optiray 320	Liebel-Flarsheim Company, LLC	NCH pharmacy	Contrast
Optixcare	Aventix	OPX-4252	Corneal lubricant
OsiriX MD	Pixmeo SARL	-	DICOM Viewer and Analysis software
Pressure infusor bag	Carefusion	64-10029	To maintain invasive blood pressure
Propofol	Fresenius Kabi	NCH pharmacy	Anesthetic drug: Concentration 10 mg/mL, Dosage 20-45 mg·kg-1·h-1
Silk suture 3-0	Ethicon	C013D	To secure IV catheter
SoftCarry Stretcher	Four Flags Over Aspen	SSTR-4
Stomach tube	Jorgensen Lab, INC	J0348R	To release gastric juices and gas and prevent bloat
T-port	Medline	DYNDTN0001	Connects to IV catheter
Urine drainage bag	Coviden	3512	Connects to stomach tube to collect gastric juices
Warming blanket	Jorgensen Lab, INC	J1034B