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/pubmed?term=((Incidents+related+to+the+Hickman%C2%AE+catheter%3A+identification+of+damages%5BTitle%5D)+AND+%22Revista+Brasileira+de+Enfermagem%22%5BJournal%5D)">Incidents related to the Hickman® 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/pubmed?term=((Central+Venous+Catheter%5BTitle%5D)+AND+%22StatPearls%22%5BJournal%5D)">Central Venous Catheter.</a> StatPearls. , StatPearls Publishing. (2022).</li>
<li>Brainard, B. 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/pubmed?term=((The+use+of+an+implantable+central+venous+%28Hickman%29+catheter+for+long-term+venous+access+in+dogs+undergoing+bone+marrow+transplantation%5BTitle%5D)+AND+%22Canadian+Journal+of+Veterinary+Research%22%5BJournal%5D)">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/pubmed?term=((Surgical+technique+of+placement+of+an+external+jugular+tunneled+hemodialysis+catheter+in+a+large+pig+model%5BTitle%5D)+AND+%22The+Journal+of+Vascular+Access%22%5BJournal%5D)">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>Williams, K., Linklater, A. 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/pubmed?term=((Bacterial+colonization+of+non-permanent+central+venous+catheters+in+hemodialysis+dogs%5BTitle%5D)+AND+%22Heliyon%22%5BJournal%5D)">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/pubmed?term=((Technique+for+portal+catheterization+in+rhesus+monkeys+%28Macaca+mulatta%29%5BTitle%5D)+AND+%22American+Journal+of+Veterinary+Research%22%5BJournal%5D)">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/pubmed?term=((Central+venous+access+devices+for+the+delivery+of+systemic+anticancer+therapy+%28CAVA%29%3A+a+randomised+controlled+trial%5BTitle%5D)+AND+%22Lancet%22%5BJournal%5D)">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/pubmed?term=((Effect+of+tunneled+and+nontunneled+peripherally+inserted+central+catheter+placement%3A+A+randomized+controlled+trial%5BTitle%5D)+AND+%22The+Journal+of+Vascular+Access%22%5BJournal%5D)">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/pubmed?term=((Tunneled+peritoneal+catheter+vs+repeated+paracenteses+for+recurrent+ascites%3A+a+cost-effectiveness+analysis%5BTitle%5D)+AND+%22Cardiovascular+and+Interventional+Radiology%22%5BJournal%5D)">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/pubmed?term=((Small+tunneled+central+venous+catheters+as+an+alternative+to+a+standard+hemodialysis+catheter+in+neonatal+patients%5BTitle%5D)+AND+%22Journal+of+Pediatric+Surgery%22%5BJournal%5D)">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. deP. E. S. C. M., Kusma, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Heparin+solution+in+the+prevention+of+occlusions+in+Hickman%C2%AE+catheters+a+randomized+clinical+trial%5BTitle%5D)+AND+%22Revista+Latino-Americana+de+Enfermagem%22%5BJournal%5D)">Heparin solution in the prevention of occlusions in Hickman® 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/pubmed?term=((Hickman-Broviac+catheter+use+in+cancer+patients%5BTitle%5D)+AND+%22Journal+of+Surgical+Oncology%22%5BJournal%5D)">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/pubmed?term=((Hickman+central+venous+catheters+in+children%3A+open+versus+percutaneous+technique%5BTitle%5D)+AND+%22Annals+of+Vascular+Surgery%22%5BJournal%5D)">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/pubmed?term=((Central+venous+access+for+haemodialysis+using+the+Hickman+catheter%5BTitle%5D)+AND+%22Nephrology+Dialysis+Transplantation%22%5BJournal%5D)">Central venous access for haemodialysis using the Hickman catheter.</a> Nephrology Dialysis Transplantation. 4 (11), 988-992 (1989).</li>
<li>Shastri, L., Kjærgaard, B., Rees, S. E., Thomsen, L. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Changes+in+central+venous+to+arterial+carbon+dioxide+gap+%28PCO2+gap%29+in+response+to+acute+changes+in+ventilation%5BTitle%5D)+AND+%22BMJ+Open+Respiratory+Research%22%5BJournal%5D)">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/pubmed?term=((Preparation+of+swine+for+the+laboratory%5BTitle%5D)+AND+%22ILAR+Journal%22%5BJournal%5D)">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/pubmed?term=((Swine+as+models+in+biomedical+research+and+toxicology+testing%5BTitle%5D)+AND+%22Veterinary+Pathology%22%5BJournal%5D)">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/pubmed?term=((Swine+in+cardiovascular+research%5BTitle%5D)+AND+%22Laboratory+Animal+Science%22%5BJournal%5D)">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/pubmed?term=((The+minipig+in+toxicology%5BTitle%5D)+AND+%22Experimental+and+Toxicologic+Pathology%22%5BJournal%5D)">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://scholar.google.com/scholar?hl=en&safe=off&q=author%3aTumbleson%2C+ME+%22Advances+in+Swine+in+Biomedical+Research%22">Advances in Swine in Biomedical Research</a>. 2, Springer Science & Business Media. (1996).</li>
<li>Jensen-Waern, M., Kruse, R., Lundgren, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Oral+immunosuppressive+medication+for+growing+pigs+in+transplantation+studies%5BTitle%5D)+AND+%22Laboratory+Animals%22%5BJournal%5D)">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/pubmed?term=((A+modified+heterotopic+swine+hind+limb+transplant+model+for+translational+vascularized+composite+allotransplantation+%28VCA%29+research%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments%22%5BJournal%5D)">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>Nordström, C. -H., Jakobsen, R., Mølstrøm, S., Nielsen, T. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cerebral+venous+blood+is+not+drained+via+the+internal+jugular+vein+in+the+pig%5BTitle%5D)+AND+%22Resuscitation%22%5BJournal%5D)">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/pubmed?term=((MR+imaging+of+the+yucatan+pig+head+and+neck+vasculature%5BTitle%5D)+AND+%22Journal+of+Magnetic+Resonance+Imaging%22%5BJournal%5D)">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. S., Mani, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Percutaneous+external+jugular+vein+catheterization+in+piglets+using+a+triangulation+technique%5BTitle%5D)+AND+%22The+International+Journal+of+Laboratory+Animals%22%5BJournal%5D)">Percutaneous external jugular vein catheterization in piglets using a triangulation technique.</a> The International Journal of Laboratory Animals. 43 (4), 344-349 (2009).</li>
<li>Kotsougiani, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Surgical+angiogenesis+in+porcine+tibial+allotransplantation%3A+a+new+large+animal+bone+vascularized+composite+allotransplantation+model%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments%22%5BJournal%5D)">Surgical angiogenesis in porcine tibial allotransplantation: a new large animal bone vascularized composite allotransplantation model.</a> Journal of Visualized Experiments. (126), e55238(2017).</li>
<li>Chuang, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Comparison+of+external+catheters+with+subcutaneous+vascular+access+ports+for+chronic+vascular+access+in+a+porcine+model%5BTitle%5D)+AND+%22Contemporary+Topics+in+Laboratory+Animal+Science%22%5BJournal%5D)">Comparison of external catheters with subcutaneous vascular access ports for chronic vascular access in a porcine model.</a> Contemporary Topics in Laboratory Animal Science. 44 (2), 24-27 (2005).</li>
</ol>

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 ...

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4.0K Views.  Johns Hopkins University School of Medicine. 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. 

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

Gene Transfer for Ischemic Heart Failure in a Preclinical Model

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine their efficacy and safety.
Gene therapy using viral vectors is one of the most promising approaches for treating cardiac diseases. Viral delivery of various different genes by changing the carrier gene has immeasurable therapeutic potential.
In this video, the full process of an animal model of heart failure creation followed by gene transfer is presented using a swine model. First, myocardial infarction is created by occluding the proximal left anterior descending coronary artery. Heart remodeling results in chronic heart failure. Unique to our model is a fairly large scar which truly reflects patients with severe heart failure who require aggressive therapy for positive outcomes. After myocardial infarct creation and development of scar tissue, an intracoronary injection of virus is demonstrated with simultaneous nitroglycerine infusion. Our injection method provides simple and efficient gene transfer with enhanced gene expression. This combination of a myocardial infarct swine model with intracoronary virus delivery has proven to be a consistent and reproducible methodology, which helps not only to test the effect of individual gene, but also compare the efficacy of many genes as therapeutic candidates.

A method of gene transfer for the treatment of ischemic heart failure is described using a swine model of myocardial infarction. Our simple and reproducible method enables us to readily evaluate the efficacy of various gene transfers with a very simple and reproducible way.

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine ...

A Swine Model of Neonatal Asphyxia

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, perfusion deficit, hypoxic-ischemic encephalopathy, pulmonary hypertension, vasculopathic enterocolitis, renal failure and thrombo-embolic complications. Animal models are developed to help us understand the patho-physiology and pharmacology of neonatal asphyxia. In comparison to rodents and newborn lambs, the newborn piglet has been proven to be a valuable model. The newborn piglet has several advantages including similar development as that of 36-38 weeks human fetus with comparable body systems, large body size (&tilde;1.5-2 kg at birth) that allows the instrumentation and monitoring of the animal and controls the confounding variables of hypoxia and hemodynamic derangements.
We here describe an experimental protocol to simulate neonatal asphyxia and allow us to examine the systemic and regional hemodynamic changes during the asphyxiating and reoxygenation process as well as the respective effects of interventions. Further, the model has the advantage of studying multi-organ failure or dysfunction simultaneously and the interaction with various body systems. The experimental model is a non-survival procedure that involves the surgical instrumentation of newborn piglets (1-3 day-old and 1.5-2.5 kg weight, mixed breed) to allow the establishment of mechanical ventilation, vascular (arterial and central venous) access and the placement of catheters and flow probes (Transonic Inc.) for the continuously monitoring of intra-vascular pressure and blood flow across different arteries including main pulmonary, common carotid, superior mesenteric and left renal arteries. Using these surgically instrumented piglets, after stabilization for 30-60 minutes as defined by Z&lt;10% variation in hemodynamic parameters and normal blood gases, we commence an experimental protocol of severe hypoxemia which is induced via normocapnic alveolar hypoxia. The piglet is ventilated with 10-15% oxygen by increasing the inhaled concentration of nitrogen gas for 2h, aiming for arterial oxygen saturations of 30-40%. This degree of hypoxemia will produce clinical asphyxia with severe metabolic acidosis, systemic hypotension and cardiogenic shock with hypoperfusion to vital organs. The hypoxia is followed by reoxygenation with 100% oxygen for 0.5h and then 21% oxygen for 3.5h. Pharmacologic interventions can be introduced in due course and their effects investigated in a blinded, block-randomized fashion.

Large animal models have good translational values in the examination of physiology and pharmacology of neonatal asphyxia. Using newborn piglets, we develop an experimental protocol to simulate neonatal asphyxia which has advantages of studying the systemic and regional hemodynamics, oxygen transport with biochemical and pathologic pathways and correlations.

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

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 ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

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 ...

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

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.

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.

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally ...

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 ...