We would like to acknowledge the support of the Army, Navy NIH, Air Force, VA, and Health Affairs regarding the AFIRM II effort under award CTA05: W81XWH-13-2-0052 and CTA06: W81XWH-13-2-0053. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014, is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. In addition, we would like to acknowledge support from the Department of Defense Congressionally Directed Medical Research Programs (CDMRP), Reconstructive Transplantation Research Program (RTRP), through awards W81XWH-17-1-0280, W81XWH-17-1-0624, W81XWH-17-1-0287, and W81XWH18-1-0795. We would also like to acknowledge the Department of Plastic and Reconstructive Surgery and the Johns Hopkins University School of Medicine. Additionally, we would like to acknowledge the entire veterinary staff, including Melanie Adams, Karen Goss, Haley Smoot, Kayla Schonvisky, and Victoria Manahan.

Hickman Catheter for Long-Term Vascular Access in Swine

<ol>
	<li>Pontes, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidents+related+to+the+Hickman&#174;+catheter:+identification+of+damages.">Incidents related to the Hickman&#174; catheter: identification of damages.</a> Revista Brasileira de Enfermagem. 71 (4), 1915-1920 (2018).</li><li>Kolikof, J., Peterson, K., Baker, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+Venous+Catheter.">Central Venous Catheter.</a> StatPearls. , (2022).</li><li>Central venous catheters: how, when, why? (Proceedings). DVM 360 Available from: <a target="_blank" href="https://www.dvm360.com/view/central-venous-catheters-how-when-why-proceedings">https://www.dvm360.com/view/central-venous-catheters-how-when-why-proceedings</a> (2011)</li><li>Abrams-Ogg, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+an+implantable+central+venous+(Hickman)+catheter+for+long-term+venous+access+in+dogs+undergoing+bone+marrow+transplantation.">The use of an implantable central venous (Hickman) catheter for long-term venous access in dogs undergoing bone marrow transplantation.</a> Canadian Journal of Veterinary Research. 56 (4), 382-386 (1992).</li><li>Florescu, M. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+technique+of+placement+of+an+external+jugular+tunneled+hemodialysis+catheter+in+a+large+pig+model.">Surgical technique of placement of an external jugular tunneled hemodialysis catheter in a large pig model.</a> The Journal of Vascular Access. 19 (5), 473-476 (2018).</li><li>. Central Venous Catheter Placement: Modified Seldinger Technique Available from: <a target="_blank" href="https://www.cliniciansbrief.com/article/central-venous-catheter-placement-modified-seldinger-technique">https://www.cliniciansbrief.com/article/central-venous-catheter-placement-modified-seldinger-technique</a> (2015)</li><li>Perondi, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bacterial+colonization+of+non-permanent+central+venous+catheters+in+hemodialysis+dogs.">Bacterial colonization of non-permanent central venous catheters in hemodialysis dogs.</a> Heliyon. 6 (1), e03224 (2020).</li><li>Faulkner, R. T., Czajkowski, W. P., Rayfield, E. J., Hickman, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technique+for+portal+catheterization+in+rhesus+monkeys+(Macaca+mulatta).">Technique for portal catheterization in rhesus monkeys (Macaca mulatta).</a> American Journal of Veterinary Research. 37 (4), 473-475 (1976).</li><li>Moss, J. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+venous+access+devices+for+the+delivery+of+systemic+anticancer+therapy+(CAVA):+a+randomised+controlled+trial.">Central venous access devices for the delivery of systemic anticancer therapy (CAVA): a randomised controlled trial.</a> Lancet. 398 (10298), 403-415 (2021).</li><li>Dai, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+tunneled+and+nontunneled+peripherally+inserted+central+catheter+placement:+A+randomized+controlled+trial.">Effect of tunneled and nontunneled peripherally inserted central catheter placement: A randomized controlled trial.</a> The Journal of Vascular Access. 21 (4), 511-519 (2020).</li><li>Wu, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tunneled+peritoneal+catheter+vs+repeated+paracenteses+for+recurrent+ascites:+a+cost-effectiveness+analysis.">Tunneled peritoneal catheter vs repeated paracenteses for recurrent ascites: a cost-effectiveness analysis.</a> Cardiovascular and Interventional Radiology. 45 (7), 972-982 (2022).</li><li>Onwubiko, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+tunneled+central+venous+catheters+as+an+alternative+to+a+standard+hemodialysis+catheter+in+neonatal+patients.">Small tunneled central venous catheters as an alternative to a standard hemodialysis catheter in neonatal patients.</a> Journal of Pediatric Surgery. 56 (12), 2219-2223 (2021).</li><li>da Silva, S. R., Reichembach, M. T., Pontes, L., de Souza, G. d. e. P. E. S. C. M., Kusma, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heparin+solution+in+the+prevention+of+occlusions+in+Hickman&#174;+catheters+a+randomized+clinical+trial.">Heparin solution in the prevention of occlusions in Hickman&#174; catheters a randomized clinical trial.</a> Revista Latino-Americana de Enfermagem. 29, e3385 (2021).</li><li>Landoy, Z., Rotstein, C., Lucey, J., Fitzpatrick, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hickman-Broviac+catheter+use+in+cancer+patients.">Hickman-Broviac catheter use in cancer patients.</a> Journal of Surgical Oncology. 26 (4), 215-218 (1984).</li><li>Bawazir, O. A., Altokhais, T. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hickman+central+venous+catheters+in+children:+open+versus+percutaneous+technique.">Hickman central venous catheters in children: open versus percutaneous technique.</a> Annals of Vascular Surgery. 68, 209-216 (2020).</li><li>Cappello, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+venous+access+for+haemodialysis+using+the+Hickman+catheter.">Central venous access for haemodialysis using the Hickman catheter.</a> Nephrology Dialysis Transplantation. 4 (11), 988-992 (1989).</li><li>Shastri, L., Kj&#230;rgaard, B., Rees, S. E., Thomsen, L. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+central+venous+to+arterial+carbon+dioxide+gap+(PCO2+gap)+in+response+to+acute+changes+in+ventilation.">Changes in central venous to arterial carbon dioxide gap (PCO2 gap) in response to acute changes in ventilation.</a> BMJ Open Respiratory Research. 8 (1), e000886 (2021).</li><li>Smith, A. C., Swindle, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+swine+for+the+laboratory.">Preparation of swine for the laboratory.</a> ILAR Journal. 47 (4), 358-363 (2006).</li><li>Swindle, M. M., Makin, A., Herron, A. J., Clubb, F. J., Frazier, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Swine+as+models+in+biomedical+research+and+toxicology+testing.">Swine as models in biomedical research and toxicology testing.</a> Veterinary Pathology. 49 (2), 344-356 (2012).</li><li>Hughes, H. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Swine+in+cardiovascular+research.">Swine in cardiovascular research.</a> Laboratory Animal Science. 36 (4), 348-350 (1986).</li><li>Svendsen, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+minipig+in+toxicology.">The minipig in toxicology.</a> Experimental and Toxicologic Pathology. 57 (5-6), 335-339 (2006).</li><li>Tumbleson, M. E., Schook, L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Advances in Swine in Biomedical Research. 2, (1996).</li><li>Jensen-Waern, M., Kruse, R., Lundgren, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oral+immunosuppressive+medication+for+growing+pigs+in+transplantation+studies.">Oral immunosuppressive medication for growing pigs in transplantation studies.</a> Laboratory Animals. 46 (2), 148-151 (2012).</li><li>Ibrahim, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+modified+heterotopic+swine+hind+limb+transplant+model+for+translational+vascularized+composite+allotransplantation+(VCA)+research.">A modified heterotopic swine hind limb transplant model for translational vascularized composite allotransplantation (VCA) research.</a> Journal of Visualized Experiments. (80), e50475 (2013).</li><li>Nordstr&#246;m, C. -. H., Jakobsen, R., M&#248;lstr&#248;m, S., Nielsen, T. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+venous+blood+is+not+drained+via+the+internal+jugular+vein+in+the+pig.">Cerebral venous blood is not drained via the internal jugular vein in the pig.</a> Resuscitation. 162, 437-438 (2021).</li><li>Habib, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+imaging+of+the+yucatan+pig+head+and+neck+vasculature.">MR imaging of the yucatan pig head and neck vasculature.</a> Journal of Magnetic Resonance Imaging. 38 (3), 641-649 (2013).</li><li>Flournoy, W. 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None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.

While CVCs serve a spectrum of functions in large animal research, current literature lacks a consensus approach for safe and sustainable use in long-term trials over 30 days. This protocol&#39;s stepwise procedure for HC insertion, skin securement, and storage in a handmade pouch has undergone significant adjustments for quality improvement. As such, this protocol presents a technique for HC use that permits efficient and effective intravenous access while ensuring animal welfare and minimizing complications.
<p cla...

The indispensable role of central venous catheters (CVCs) in patient care is owed to their convenience, favorable safety profile, and versatility1. Functions of a CVC include reliable access for total parenteral nutrition, hematopoietic stem cell transplantation, plasmapheresis/apheresis, and efficient fluid, blood, or co-drug administration2. In veterinary medicine, CVCs also minimize animal discomfort via the rapid dilution of irritant drugs and blood sampling without repeated venipuncture3. Despite their broad applications, the use of CVCs in large animal research still presents several considerable challenges4.
Percutaneous CVC placement via a guidewire or introducer catheter can be difficult for non-veterinary researchers, particularly in animals with deep venous structures5. An improper CVC installation technique may result in inadvertent placement into nearby structures, necessitating ultrasound-guided placement or a postprocedure radiography of the positioning6. However, compared to human operating rooms, ultrasounds are not readily available in many large animal research laboratories. Further, long-term use of indwelling catheters can result in line kinking, puncture, infection, or extrication by animals, with the possible disruption of timely treatment, clinical monitoring, and research outcomes4,7. Replacement of the CVC requires additional resources, including material procurement, surgical scheduling, fasting time, and radiographic access. CVC-related complications can therefore create significant technical and financial barriers or a disruption to productive translational research, particularly in swine. Contamination by food or feces, scratching against cage walls, and kicking sites of irritation may compromise a CVC, and the risk of CVC-related complications is amplified by long-term use. Thus, safe and uncomplicated maintenance of a CVC in swine requires careful consideration of CVC choice, placement, securement, protection, sanitation, and surveillance.
The Hickman catheter (HC) used in this protocol is a tunneled CVC with a polyester cuff and one to three lumens, that is commonly used for long-term intravenous access in humans and animals1,4,8,9. The tunneled catheter approach has been associated with lower complication rates and maintenance costs relative to non-tunneled variations10,11,12. The cuff reduces HC extrication by incorporating into the subcutaneous tissues surrounding the skin exit site. The multi-lumen design also enables the separation of medication administration and blood draws, thereby minimizing blood sample contamination and inaccuracy. Despite this, HC use is not without challenges, the most common of which include fracture, migration, occlusion, and infection13,14,15,16. Proper installation and maintenance of a HC are therefore indispensable skills when used in translational research. However, the current literature offers little guidance for best-practices for HC use in swine during long-term trials5,6,17.
The purpose of this study is to outline an optimized approach for HC insertion into the internal jugular vein (IJV), skin securement, and durable protection that minimizes long-term catheter-related complications and discomfort in swine. A discussion of the important considerations for HC use, potential challenges that may be encountered, and modifications that may improve the quality of this approach is included.

<table><tbody><tr><td>#10 blade</td><td>Medline</td><td>MDS15110</td><td></td></tr><tr><td>0.9% Sterile Sodium Chloride</td><td>Baxter&amp;nbsp;</td><td>2F7123</td><td></td></tr><tr><td>0-0 Coated and Braided Nonabsorbable Suture</td><td>Covidien</td><td>S-196</td><td></td></tr><tr><td>0-0 Synthetic, Monofilament, Nonabsorbable Polypropylene Suture</td><td>Ethicon</td><td>8690H</td><td></td></tr><tr><td>1 inch Medical Tape</td><td>3M</td><td>1548S-1</td><td></td></tr><tr><td>10 USP units/mL Heparin flush</td><td>Becton, Dickinson and Company</td><td>306424</td><td></td></tr><tr><td>3-0 Braided Absorbable Suture</td><td>Covidien</td><td>SL-636 (cutting needle), GL-122 (taper needle)</td><td></td></tr><tr><td>3-0 Monofilament Absorbable Suture</td><td>Covidien</td><td>SM-922 (cutting needle), CM-882 (taper needle)</td><td></td></tr><tr><td>4-0 Coated and Braided Non-absorbable Suture Ties</td><td>Ethicon</td><td>A303H</td><td></td></tr><tr><td>70% Ethanol</td><td>Vedco</td><td>VINV-IPA7</td><td></td></tr><tr><td>Adson tissue forceps</td><td>MPM Medical Supply</td><td>132-508</td><td></td></tr><tr><td>Adson-Brown forceps</td><td>MPM Medical Supply</td><td>106-2572</td><td></td></tr><tr><td>Air warming blanket and pad</td><td>3M Bair Hugger</td><td>UPC 00608223595770</td><td></td></tr><tr><td>Backhaus towel clamp</td><td>MPM Medical Supply</td><td>117-5508</td><td></td></tr><tr><td>Brown needle holder</td><td>MPM Medical Supply</td><td>110-1513</td><td></td></tr><tr><td>Buprenorphine</td><td>PAR Pharmaceutical</td><td>3003408B</td><td></td></tr><tr><td>Cefazolin</td><td>Hikma Farmacuetica (Portugal)</td><td>PLB 133-WES/1</td><td></td></tr><tr><td>Chlorhexidine</td><td>Vet One</td><td>501027</td><td></td></tr><tr><td>Clave</td><td>Baxter</td><td>7N8399</td><td></td></tr><tr><td>Cotton Padding</td><td>Medline</td><td>NON6027</td><td></td></tr><tr><td>Debakey forceps</td><td>MPM Medical Supply</td><td>106-5015</td><td></td></tr><tr><td>Elastic Adhesive Bandage Tape</td><td>3M</td><td>XH002016489</td><td></td></tr><tr><td>Halstead mosquito forceps</td><td>MPM Medical Supply</td><td>115-4612</td><td></td></tr><tr><td>Hickman Catheter</td><td>Bard Access Systems</td><td>603710</td><td></td></tr><tr><td>Hickman Catheter Repair Kit, 7Fr, Red and White Connectors</td><td>Bard Access Systems</td><td>0601690 (red), 0601680 (white), 502017</td><td></td></tr><tr><td>Kelly hemostatic forceps</td><td>MPM Medical Supply</td><td>115-7014</td><td></td></tr><tr><td>Ketamine</td><td>Vet One</td><td>383010-03</td><td></td></tr><tr><td>Lactated Ringers</td><td>Baxter</td><td>2B2324X</td><td></td></tr><tr><td>Maropitant Citrate</td><td>Zoetis</td><td>106</td><td></td></tr><tr><td>Mayo scissors</td><td>MPM Medical Supply</td><td>103-5014</td><td></td></tr><tr><td>Metzenbaum scissors</td><td>MPM Medical Supply</td><td>132-711</td><td></td></tr><tr><td>Pantoprazole</td><td>JH Pharmacy</td><td>NDC 0143-9284-10</td><td></td></tr><tr><td>Scalpel blade handle</td><td>Medline</td><td>MDS10801</td><td></td></tr><tr><td>Vein Pick</td><td>SAI infusion technologies</td><td>VP-10</td><td></td></tr><tr><td>Veterinary Ophthalmic Ointment</td><td>Dechra</td><td>IS4398</td><td></td></tr><tr><td>Xylazine</td><td>Vet One</td><td>510004</td><td></td></tr></tbody></table>

hickman catheter use for long-term vascular access in a preclinical swine model

Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood monitoring and reliable intravenous fluid and drug administration. Specifically, the tunneled multi-lumen Hickman catheter (HC) is commonly used in swine models due to its lower extrication and complication rates. Despite fewer complications relative to other CVCs, HC-related morbidity presents a significant challenge, as it can significantly delay or otherwise negatively impact ongoing studies. The proper insertion and maintenance of HCs is paramount in preventing these complications, but there is no consensus on best practices. The purpose of this protocol is to comprehensively describe an approach for the insertion and maintenance of a tunneled HC in swine that mitigates HC-related complications and morbidity. The use of these techniques in &gt;100 swine has resulted in complication-free patent lines up to 8 months and no catheter-related mortality or infection of the ventral surgical site. This protocol offers a method to optimize the lifespan of the HC and guidance for approaching issues during use.

Over 100 swine have undergone successful HC insertion in our lab. The HC can be safely and correctly placed and secured in under 1 h with a surgeon, assistant, circulator, and anesthetist. The catheter pouch takes roughly 15-20 min to make. The technique is straightforward and easy to teach and has been performed by veterinarians, surgical residents, and medical students following supervised instructions.
HCs have remained in place without complications or revision for up to 8 months. In a rec...

Watch this Scientific Journal Video about Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model at JoVE.com

Author Spotlight: Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model  

A reliable and reproducible approach for the insertion and maintenance of a tunneled Hickman catheter for long-term vascular access in swine is described. Placement of a central venous catheter allows for convenient daily sampling of whole blood from awake animals and intravenous administration of medication and fluids.

Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model

Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood ...

hickman-catheter-use-for-long-term-vascular-access-preclinical-swine

Research

JoVE Journal

Medicine

3.9K Views.  Johns Hopkins University School of Medicine. Dit protocol beschrijft een betrouwbare en reproduceerbare techniek voor het inbrengen en onderhouden van een Hickman-tunnelkatheter voor langdurige vasculaire toegang in een groot diermodel. De aanpak maakt het mogelijk om dagelijks gemakkelijk volbloed van wakkere dieren te bemonsteren en intraveneuze medicatie en vloeistoffen toe te dienen. Enkele van de belangrijkste uitdagingen voor de centrale veneuze lijnen op lange termijn bij grote dieren zijn infectie en schade.Omdat grote di...

Video: Auteur in de schijnwerpers: Hickman-kathetergebruik voor langdurige vasculaire toegang in een preklinisch varkensmodel  

Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling.

Vascular accesses to measure hemodynamics, provide fluids and perform blood sampling are important to any small animal model study. We present a technique for implanting catheters into the carotid artery and the common jugular vein in an anesthetized rat for connecting to a system to perform monitoring, infusions and sampling.

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. ...

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise.
Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G&#160;catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling.
After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage.
The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study.

Here we present a protocol to assess cardiopulmonary function in awake swine, at rest and during graded treadmill exercise. Chronic instrumentation allows for repeated hemodynamic measurements uninfluenced by cardiodepressive anesthetic agents.

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early ...

Brachial Artery Catheterization in Swine

The video describes in detail the catheterization of the distal brachial artery in swine. This technique enables researchers to measure arterial blood pressure continuously and collect arterial blood samples to assess arterial blood gas measurements. Arterial blood pressures and arterial blood gases are important physiological parameters to monitor during experimental procedures. In swine, four common methods of arterial catheterization have been described, including catheterization of the carotid, femoral, auricular, and medial saphenous arteries. Each of these techniques have advantages, such as ease of access for the auricular artery, and disadvantages that include deep tissue dissection for carotid artery catheterization. The described alternative method of arterial catheterization in swine, the catheterization of the distal aspect of the brachial artery, is a rapid procedure that requires relatively minimal tissue dissection and provides information that is in line with data collected from other arterial catheterization sites. The procedure uses a medial approach along an oblique plane of the lower brachium, positioned between the olecranon and the flexor aspect of the elbow joint, and this approach allows researchers the major advantage of unimpeded freedom for procedures that involve the caudoventral, caudodorsal back, or hind limbs of the pig. Due to the location of the upper forelimb of the catheterized vessel and potential challenges of effective homeostasis following catheter removal from the artery, this technique may be limited to non-recovery procedures.

The video describes in detail the catheterization of the distal brachial artery in swine. This procedure accurately measures arterial blood pressure and is a simple and fast method to collect samples for arterial blood gas measurements.

The video describes in detail the catheterization of the distal brachial artery in swine. This technique enables researchers to measure arterial blood ...

Measuring Cardiac Output in a Swine Model

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume and cardiac output are essential in this type of research. Contrast ventriculography, thermodilution, and pressure-volume loop (PV-loop) catheters can be used to accurately obtain cardiac performance data depending on which resources and expertise are available. For this study,five Yorkshire swine were anesthetized and intubated. Central venous and arterial access was obtained to place the necessary measurement instruments.A temperature probe was placed in the aortic root. A cold saline bolus was delivered to the right atrium and temperature deflection curve was recorded. Integration of the area under the curve allowed for the calculation of the current cardiac output.A pigtail catheter was percutaneously placed in the left ventricle and 30 mL of iodinated contrast was power injected over 2 seconds. Digital subtraction angiography images were uploaded to volumetric analysis software to calculate the stroke volume and cardiac output. A pressure volume-loop catheter was placed into the left ventricle (LV) and provided continuous pressure and volume data of the LV, which allowed the calculation of both stroke volume and cardiac output.All three methods demonstrated good correlation with each other. The PV-loop catheter and thermodilution exhibited the best correlation with a 3% error and a Pearson coefficient of 0.99, with 95% CI=0.97 to 1.1, (p=0.002). The PV-loop catheter against ventriculography also showed good correlation with a 6% error and a Pearson coefficient of 0.95, 95% CI=0.96 to 1.1 (p=0.01). Finally, thermodilution against ventriculography had a 2% error with r=0.95, 95% CI=0.93 to 1.11, (p=0.01). In conclusion, we state that the PV-loop catheter, contrast ventriculography, and thermodilution each offer certain advantages depending on the researcher's requirements. Each method is reliable and accurate for measuring various cardiac parameters in swine such as the stroke volume and cardiac output.

Thermodilution, pressure-volume loop catheters, and contrast ventriculography are reliable and accurate methods for determining cardiac physiology such as stroke volume and cardiac output in a laboratory setting in swine.

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume ...

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. 
We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. 
The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular ...

Intubation, Central Venous Catheter, and Arterial Line Placement in Swine for Translational Research in Abdominal Transplantation Surgery

Translational surgical research models in swine are crucial for developing safe preclinical protocols. However, the success of the experimental surgeries does not solely rely on the research team's surgical skills; perioperative care and management procedures, like intubation, central venous line, and arterial line placement, are necessary and of the utmost importance for favorable experiment results. As it is uncommon for research teams to have anesthesiologists or any other staff other than the surgical team, the surgical team involved in translational research must acquire and/or develop the skills to perform the perioperative care. The purpose of this paper is to show the techniques of intubation, central venous catheter, and arterial line placement used and perfected at the Toronto Organ Preservation Laboratory over the last 10 years, to be used as a reference for future researchers joining either this team or any other lab performing translational research protocols in swine and/or abdominal transplantation.

To obtain the best possible results, surgeons performing translational research experiments should be proficient at intubation and vascular line placement. This paper describes the techniques used by the Toronto Organ Preservation Laboratory to perform these procedures.

Translational surgical research models in swine are crucial for developing safe preclinical protocols. However, the success of the experimental surgeries ...

Surgical Technique for Lumbar Spinal Catheter Insertion in Pigs Enabling Continuous Access to the Thecal Sac in a Terminal Setup

Pigs are increasingly used as a large animal model for pharmacologic CNS research due to the anatomical and physiological similarities between the porcine and human central nervous systems (CNS). However, accessing the cerebrospinal fluid (CSF) in larger pig breeds by conventional lumbar puncture techniques can be challenging due to an oblique orientation of the spinal spinous processes and a limited interlaminar space. Accordingly, an open surgical procedure for inserting a lumbar spinal catheter for continuous CSF sampling at the L4/L5 level in pigs is thoroughly described in this work. After positioning the pig and identifying the anatomical landmarks, a dorsal midline surgical incision is made to expose the spinous processes. By advancing the introducer needle, the spinal catheter is inserted inside the thecal sac of the spinal canal while leaving the bone structures of the spine intact. This method allows continuous infusion into or sampling from the porcine thecal sac with minimal bleeding or CSF leakage. The procedure is simple, time-efficient, and reproducible across different experimental setups, offering significant potential for various pre-clinical studies, including pharmacokinetic research, surgical training, and spinal cord injury models.

We present a technique for inserting a lumbar spinal catheter at the L4-L5 level in a 3-month-old Danish Landrace pig as part of a terminal research protocol, enabling continuous infusion or CSF sampling from the thecal sac.

Pigs are increasingly used as a large animal model for pharmacologic CNS research due to the anatomical and physiological similarities between the porcine ...

Neuroscience

A Porcine Model of Acute Autologous Pulmonary Embolism

Acute pulmonary embolism (PE) is a potentially life-threatening condition that causes abrupt obstruction of the pulmonary arteries, leading to acute right heart failure. Novel diagnostic methods and catheter-directed therapies are being developed rapidly, and there is an obvious need for a realistic PE animal model that can be used for pathophysiological evaluation and preclinical testing.
This protocol introduces a porcine model employing large autologous pulmonary emboli. Instrumentations are performed with minimally invasive techniques, creating a close-chest model that enables the investigation of various treatment options with high reproducibility. Three hours after drawing blood to create autologous emboli ex vivo, the induction of PE caused an immediate increase in the mean pulmonary arterial pressure (17&#160;&#177; 3 mmHg to 33&#160;&#177; 6 mmHg, p &#60; 0.0001) and heart rate (50&#160;&#177; 9 beats&#183;min-1 to 63&#160;&#177; 6 beats&#183;min-1,&#160;p &#60; 0.0003) accompanied by a decreased cardiac output (5.0&#160;&#177; 0.8 L/min to 4.5&#160;&#177; 0.9 L/min, p &#60; 0.037) compared to baseline. The CT pulmonary angiography revealed multiple emboli, and the pulmonary obstruction percentage was increased compared to baseline (0% [0-0] to 57.1% [38.8-63.3], p &#60; 0.0001). In the acute phase, the phenotype is comparable to intermediate-risk PE.
The model represents a realistic and well-characterized phenotype of intermediate-risk PE and creates an opportunity to test novel diagnostic methods, interventional and pharmaceutical treatments, and hands-on training for healthcare workers in interventional procedures.

This study presents a porcine model of pulmonary embolism (PE) using large autologous emboli that replicate acute intermediate-risk PE. The model is well-suited for the evaluation of both pathophysiology and treatment responses.

Acute pulmonary embolism (PE) is a potentially life-threatening condition that causes abrupt obstruction of the pulmonary arteries, leading to acute right ...

Swine Axillary Artery Injury Model for Testing Pre-Hospital Hemostatic Products

A New Hybrid Quantitative Evaluation Model for Axillary Junctional Hemorrhage in Swine

In this study, we developed and validated a hybrid quantitative model for simulating upper extremity junctional hemorrhage in swine, aiming to advance the development of pre-hospital hemostatic products. Utilizing 12 healthy 8-month-old male Yorkshire swine, we demonstrated the feasibility of a swine axillary artery injury model for evaluating hemostatic efficacy. Animals were divided into three groups to undergo volume-controlled hemorrhage (VCH), mimicking Class I-III hemorrhagic shock by withdrawing blood at different rates. Subsequent external compression was applied using a novel device consisting of a mechanical arm and an inflatable hemostatic balloon, achieving controlled pressure to enhance clot formation. Hemodynamic parameters, including heart rate and blood pressure, were continuously monitored, highlighting the impact of controlled hemorrhage and external compression on physiological responses. The findings suggest that the combination of VCH with targeted external compression effectively simulates clinical scenarios of axillary artery injury, providing a valuable model for testing hemostatic interventions in a controlled, standardized manner. This study underscores the potential of the model in facilitating the development and evaluation of new hemostatic agents and devices for managing junctional hemorrhages.

This study presents a hybrid quantitative model for axillary junctional hemorrhage in swine, enhancing pre-hospital hemostatic intervention evaluation.

In this study, we developed and validated a hybrid quantitative model for simulating upper extremity junctional hemorrhage in swine, aiming to advance the ...

Seldinger Technique Based Pulmonary Artery Catheterization: A Procedure to Insert Pulmonary Artery Catheter Through the Jugular Vein in a Porcine Model

Source: Lyhne, M. D., et al. <a href="https://www.jove.com/v/62661">Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model</a> J. Vis. Exp. (2021).
In this video, we have demonstrated a step-by-step procedure of pulmonary artery catheterization by inserting an intravascular catheter through jugular vein and reach the pulmonary artery to measure the cardiac chamber pressure in porcine model.

Source: Lyhne, M. D., et al. Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model J. Vis. Exp. (2021).
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Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model

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