Aby wyświetlić tę treść, wymagana jest subskrypcja JoVE. Zaloguj się lub rozpocznij bezpłatny okres próbny.
Method Article
This protocol describes the surgical methodology for implanting a large animal wireless telemetry device to enable continuous and long-term collection of hemodynamic data, including heart rate, arterial blood pressure, inferior and superior vena cava pressures, and cardiac rhythm.
While the Fontan procedure drastically improves life expectancy for patients with single ventricle, it is well recognized that the resulting circulation causes significant disease burden long term as a consequence of chronically elevated central venous pressures and decreased cardiac output. Chronic Fontan animal models are a valuable asset to studying the late physiological outcomes associated with this operation and a necessary tool in the evaluation of future devices designed to alleviate Fontan failure. However, previous attempts at the creation of chronic Fontan models have been hindered by poor survival rates. Additionally, effective hemodynamic data collection poses a significant challenge in freely moving animals. To this end, the use of wireless implantable telemetry systems provides a novel solution for real-time and long-term monitoring of cardiovascular data. This protocol describes the methodology for surgical implantation of a wireless telemetry device in a Fontan survival ovine model, facilitating the continuous and ongoing recording of several hemodynamic parameters, including heart rate, arterial blood pressure, and localized pressures in the inferior (IVC) and superior vena cava (SVC). Telemetry devices were implanted with cannulation of either the carotid artery and internal jugular vein or femoral artery and vein, for placement of pressure-sensing catheters in the ascending aorta and SVC or abdominal aorta and IVC, respectively. The use of the wireless telemetry systems enabled close postoperative monitoring following a single-stage Fontan operation, which contributed to improved animal welfare and survival.
The development of the Fontan procedure in 1971 led to significant improvements in outcomes for patients with single ventricle1. The purpose of this operation is to separate systemic and pulmonary venous return to the heart, thereby increasing systemic oxygenation and relieving volume load on the systemic ventricle. Since its introduction, numerous modifications have been made to the surgical approach. Currently, total bypass of the right heart is most often achieved through staged reconstruction2,3. Typically, the first stage is performed during the first week of life4. Patients then undergo a second stage, which consists of either the Glenn procedure or hemi-Fontan, to redirect blood flow from the superior vena cava (SVC) to the pulmonary artery (PA)5. This is followed by the Fontan procedure, which involves the creation of an extracardiac conduit or lateral tunnel between the inferior vena cava (IVC) and PA6. Surgical advancements such as those made throughout the history of the Fontan procedure could not have been achieved without the use of animal models7.
While the Fontan procedure drastically improves life expectancy for single ventricle patients, it is well recognized that the resulting circulation, which operates without a subpulmonic pump, causes significant disease burden in the long term as a consequence of chronically elevated central venous pressures (CVP) and decreased cardiac output8,9,10,11,12. Chronic Fontan animal models are a valuable asset to studying the late physiological outcomes associated with this operation13. Active data collection of cardiovascular parameters, such as CVP, heart rate, and other vital signs, to capture the postoperative hemodynamic changes is essential for a comprehensive evaluation of developing pathophysiology. Furthermore, animal models are a necessary tool for testing the capability of novel ventricular assist devices designed to alleviate the hemodynamic shortcomings of the Fontan circulation in vivo14,15,16,17,18,19.
However, effective data collection poses a significant challenge. Invasive catheter-based techniques are limited by their transient nature, associated procedural risks, and the inability to monitor the animal's condition over extended periods. Moreover, previous attempts to create a large animal Fontan model have been hindered by poor survival rates, presumably due to the failure of normal hearts to adapt to the acute establishment of the Fontan circulation7,20. To this end, the use of wireless telemetry systems provides a novel solution for real-time, long-term collection of cardiovascular data in freely moving animals21,22. These devices may also enable close postoperative monitoring, which could lead to improved animal welfare and survival.
Here, we describe the methodology for the successful implantation and use of a wireless telemetry system23 in a chronic Fontan ovine model. This technique provided a robust and reliable means of continuous hemodynamic data collection, enabling the study of venous pressures and other key physiological parameters. Implementation of this technology in preclinical models is critical for advancing our understanding of Fontan physiology and the development of new therapeutic strategies aimed at improving the long-term outcomes of Fontan patients.
This experimental protocol was approved by the Institutional Animal Care and Use Committee of the Nationwide Children's Hospital Abigail Wexner Research Institute (AR20-00121). All procedures adhered to the guidelines outlined in the National Institute of Health's Guide for the Use and Care of Laboratory Animals. This research followed the Animal Research: Reporting of In Vivo Experiments guidelines. Dorset sheep with a weight range of 23-38 kg and an age range of 2-12 months were housed in a specific pathogen-free environment with free access to food and water for at least 1 week before surgery. The equipment and reagents used in the study are listed in the Table of Materials.
1. Animal preparation
2. Telemetry device preparation
3. Method 1: Femoral artery and vein cannulation
4. Method 2: Carotid artery and internal jugular vein cannulation
5. Recovery
Surgical outcomes
A total of 13 sheep underwent single-stage Fontan surgery involving total cavopulmonary connection with detachment of both the SVC and IVC from the right atrium, direct end-to-side anastomosis of the SVC to PA, and placement of an extracardiac conduit between the IVC and PA. Sheep underwent this procedure at a mean age of 13.3 ± 7.6 months. Of these, 3 sheep underwent wireless telemetry device implantation with placement of pressure-sensing catheters into the abdominal aorta ...
We have developed two surgical methods for the implantation of a wireless telemetry device into an ovine model. The device was successfully implanted in 5 sheep to achieve continuous, long-term monitoring and recording of several cardiovascular parameters, including heart rate, arterial blood pressure, and localized venous pressures from the abdominal IVC and thoracic SVC. All sheep survived the surgery for device implantation without any major complications and went on to undergo a single-stage Fontan operation one mont...
This project was funded by the Additional Ventures Cures Collaborative, Palo Alto, California.
We appreciate the dedicated veterinarian staff at the Animal Research Core. We also wish to express our gratitude to Mary Walker, DVM, MS, for her invaluable expertise and vigilant care throughout the study.
Name | Company | Catalog Number | Comments |
0.9% Sodium Chloride solution | Baxter Healthcare Corporation | Pharmacy | Intraoperative fluid resuscitation and wound rinse |
16 G intravenous catheter | BD | 382259 | For fluid and drug administration |
22 G intravascular catheter | BD | 381423 | For arterial blood pressure monitoring |
70% isopropyl alcohol | Aspen Vet | 11795782 | Topical cleaning solution |
ACT cartridge | Abbot Diagnostics | 03P86-25 | Activated clotting time |
Backhaus towel clamp | Medline | MDS1411111 | To affix sterile drape |
Banamine | Hospira Pharmaceuticals | Pharmacy | Postoperative pain control: concentration 50 mg/mL, dose 2.2 mg/kg |
Blood pressure cuff | Royal Philips | 9.89803E+11 | Non-invasive blood pressure monitoring |
Bupivacaine hydrochloride | Hospira Pharmaceuticals | Pharmacy | Local anesthetic: concentration 2.5 mg/mL, dose 2.5 mg/kg |
Buprenorphine | Hospira Pharmaceuticals | Pharmacy | Postoperative pain control: concentration 0.3 mg/mL, dose 0.03 mg/kg |
Castroviejo needle holder | Medline | MDS0750386 | Needle holder when suturing blood vessels |
Cautery cleaner pad | Cardinal Health | 300-2SS | To clean cautery pencil tip |
Cautery pencil | Medline | ESRK3002L | For dissection using electrocautery |
Cefazolin | Hospira Pharmaceuticals | Pharmacy | Antibiotic prophylaxis |
Cetacaine | Cetylite | 220 | Topical anesthetic spray for intubation |
Chloraprep | BD | 930825 | Topical antiseptic |
Debakey atraumatic forceps | Medline | MDS1130630F | For tissue handling |
Diazepam | Hospira Pharmaceuticals | Pharmacy | Sedative: concentration 5 mg/mL, dose 0.5 mg/kg |
ECG leads | 3M | 2570 | ECG monitoring |
Endotracheal tube, size 8-9 | Covidien | 86452, 86114, or 86454 | To secure airway |
Hartmann hemostatic forceps | Medline | MDS1221109 | To clamp blood vessels and hold small sutures |
Heparin | Hospira Pharmaceuticals | Pharmacy | Anticoagulant: 1,000 USP units/mL |
Pressure transducer kit | Edwards Lifesciences | VSYPX12N | For arterial blood pressure monitoring |
Pulse oximeter lingual clip | Nellcor | PO736 | For pulse oximetry |
Isoflurane | Baxter Healthcare Corporation | Pharmacy | Anesthetic: dose 1-3% |
Kantrowitz forcep (right angle) | Medline | MDS1243528 | For blunt dissection around blood vessels |
Ketamine | Hospira Pharmaceuticals | Pharmacy | Sedative: concentration 100 mg/mL, dose 4 mg/kg |
Laparotomy drape | Medline | DYNJP3008 | Sterile drape |
Lubricating jelly | Medline | MDS0322273Z | Endotracheal tube lubricant |
Mayo Hegar needle holder | Medline | MDS2418420F | Needle holder when suturing soft tissue |
Mayo scissors | Medline | MDS0816121 | To cut suture |
Metzenbaum curved scissors | Medline | MDS3223226 | For sharp dissection |
Needles and syringes | Cardinal Health | 309604 | For intravenous and subcutaneous drug administration |
Optixcare | Aventix | OPX-4252 | Corneal lubricant |
Perma-Hand silk suture | Ethicon | C016D | For blood vessel ligation and attachment of the telemetry device subcutaneously |
PhysioTel Digital wireless telemetry device | Data Sciences International | L21 model | Wireless telemetry device implant |
Pierce microforceps | Medline | MDG384908 | Small needle handling |
Plastic tourniquet and suture snare | Medtronic | 79013 | To facilitate hemostasis during vessel cannulation |
Pressure bag | Carefusion | 64-10029 | For arterial blood pressure monitoring |
Prolene 6-0 suture | Ethicon | 8307H | Purse string stitch for vessel cannulation |
Propofol | Fresenius Kabi | Pharmacy | Anesthetic: concentration 10 mg/mL, dose 20-45 mg/kg/h |
Scalpel #10 blade | Medline | MDS15310 | For skin incisions |
Scalpel #11 blade | Medline | CISION11CS | For incision into blood vessels |
Schnidt tonsil forceps | Medline | MDS5018719 | For blunt dissection through subcutaneous tissue |
SoftCarry stretcher | Four Flags Over Aspen | SSTR-4 | For animal transportation |
Sterile disposable OR towel | Medline | MDT2168201 | Sterile drape |
Sterile bowl | LSL Industries | 5232 | To hold saline solution |
Sterile cotton X-ray detectable gauze sponge | Medline | NON21430LF | Fluid absorption |
Orogastric tube | Jorgensen Lab, Inc. | J0348R | For stomach and rumen decompression |
T-port | Medline | DYNDTN0001 | Intravenous catheter tubing connector |
Urine drainage bag | Covidien | 3512 | Connects to orogastric tube to collect gastric fluids |
Veterinary trocar with stylet | Braintree Scientific, Inc. | TRO-STY 7B-12 | To guide telemetry wires through subcutaneous tissue |
Vicryl 2-0 suture | Ethicon | VCPB269H | Closure of subcutaneous soft tissue |
Vicryl 3-0 suture | Ethicon | VCPB416H | Closure of deep dermal layer |
Vicryl 4-0 suture | Ethicon | J494H | Closer of subcuticular layer |
Warming blanket | Jorgensen Lab, Inc. | J1034B | To maintain animal's body temperature |
Weitlander retractor | Teleflex Medical | 165358 | For wound retraction |
Yankauer bulb tip suction | Medline | DYND50138 | Sterile waste management |
Zapytaj o uprawnienia na użycie tekstu lub obrazów z tego artykułu JoVE
Zapytaj o uprawnieniaThis article has been published
Video Coming Soon
Copyright © 2025 MyJoVE Corporation. Wszelkie prawa zastrzeżone