We would like to acknowledge Rachel O&#39;Connell,&#160;and Jessica Lee for their assistance with the animal studies. We would also like to acknowledge Maj. General Harold Timboe, MD, MPH, U.S. Army (Ret.), who has been an advisor and mentor for this project.

<ol>
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K., 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+role+of+intra-aortic+balloon+occlusion+in+penetrating+abdominal+trauma.">The role of intra-aortic balloon occlusion in penetrating abdominal trauma.</a> Journal of Trauma. 29 (6), 861-865 (1989).</li><li>Inoue, J., 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=Resuscitative+endovascular+balloon+occlusion+of+the+aorta+might+be+dangerous+in+patients+with+severe+torso+trauma:+A+propensity+score+analysis.">Resuscitative endovascular balloon occlusion of the aorta might be dangerous in patients with severe torso trauma: A propensity score analysis.</a> Journal of Trauma and Acute Care Surgery. 80 (4), 559-566 (2016).</li><li>Russo, R. 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=Extending+the+golden+hour:+Partial+resuscitative+endovascular+balloon+occlusion+of+the+aorta+in+a+highly+lethal+swine+liver+injury+model.">Extending the golden hour: Partial resuscitative endovascular balloon occlusion of the aorta in a highly lethal swine liver injury model.</a> Journal of Trauma and Acute Care Surgery. 80 (3), 378-380 (2016).</li><li>Russo, R. 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=Partial+Resuscitative+Endovascular+Balloon+Occlusion+of+the+Aorta+in+Swine+Model+of+Hemorrhagic+Shock.">Partial Resuscitative Endovascular Balloon Occlusion of the Aorta in Swine Model of Hemorrhagic Shock.</a> Journal of the American College of Surgeons. 223 (2), 359-368 (2016).</li><li>Williams, T. 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E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Seldinger+technique.">The Seldinger technique.</a> Journal of Cardiothorac Anesthesia. 2 (3), 403 (1988).</li><li>Halaweish, I., 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=Addition+of+low-dose+valproic+acid+to+saline+resuscitation+provides+neuroprotection+and+improves+long-term+outcomes+in+a+large+animal+model+of+combined+traumatic+brain+injury+and+hemorrhagic+shock.">Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock.</a> The Journal of Trauma and Acute Care Surgery. 79 (6), 911-919 (2015).</li><li>Alam, H. B., 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=Surviving+blood+loss+without+blood+transfusion+in+a+swine+poly-trauma+model.">Surviving blood loss without blood transfusion in a swine poly-trauma model.</a> Surgery. 146 (2), 325-333 (2009).</li><li>Jin, 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=Traumatic+brain+injury+and+hemorrhagic+shock:+evaluation+of+different+resuscitation+strategies+in+a+large+animal+model+of+combined+insults.">Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.</a> Shock. 38 (1), 49-56 (2012).</li><li>Nikolian, V. 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=Valproic+acid+decreases+brain+lesion+size+and+improves+neurologic+recovery+in+swine+subjected+to+traumatic+brain+injury,+hemorrhagic+shock,+and+polytrauma.">Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma.</a> The Journal of Trauma and Acute Care Surgery. 83 (6), 1066-1073 (2017).</li><li>Langeland, H., Lyng, O., Aadahl, P., Skjaervold, N. 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D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+significance+of+splenectomy+in+experimental+swine+models+of+controlled+hemorrhagic+shock.">The significance of splenectomy in experimental swine models of controlled hemorrhagic shock.</a> The Journal of Trauma and Acute Care Surgery. 75 (5), 920 (2013).</li><li>Georgoff, P. E., 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=Alterations+in+the+human+proteome+following+administration+of+valproic+acid.">Alterations in the human proteome following administration of valproic acid.</a> Journal of Trauma and Acute Care Surgery. 81 (6), 1020-1027 (2016).</li><li>Dekker, S. 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This work is supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-16-C-0102. The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy, or decision unless so designated by other documentation.

In this protocol, we highlighted a hemorrhagic shock model in swine. This model has been shown to be both reliable and reproducible16,17,18,19. Models similar to this have been employed in several scientific studies investigating the effects of hemorrhagic shock on animal physiology16,20. Furthermore, this model has also been used for t...

Hemorrhage continues to be the dominant cause of preventable deaths in patients undergoing traumatic events, accounting for 90% of trauma-related deaths in the military setting and 40% of post-traumatic deaths in the civilian population1,2. Although direct pressure can treat compressible hemorrhage, non-compressible torso hemorrhage remains difficult to treat and can be lethal without prompt hemostatic control. The historical approach of resuscitative thoracotomy or laparotomy with aortic cross-clamping has proved to be extremely invasive3,4. This intervention also requires a complex selection algorithm to determine the candidacy of patients that have undergone traumatic insults5.
In recent years, there has been a resurgence of interest in a previously described approach&#8212;resuscitative endovascular balloon occlusion of the aorta (REBOA)6,7,8. Although REBOA has conferred a short-term survival advantages in hemorrhage, a prolonged complete occlusion of the aorta during balloon inflation poses serious concerns that include irreversible end-organ ischemia9,10. In an attempt to overcome this potential morbidity, alternative endovascular strategies to manage hemorrhage are being devised. One such strategy that has seen a growing attention is a partial occlusion of the aorta11,12. The idea of partial aortic balloon occlusion affords the perfusion of vascular beds distal to the site of occlusion, improved physiologic proximal aortic MAPs, and a gradual afterload reduction following the balloon deflation. These changes in parameters are desired modifications to the physiological characteristics of a bleeding animal. Prior to this method&#39;s translation to humans, complete and partial aortic balloon occlusion catheters have been heavily tested in swine models of hemorrhagic shock11,12,13.
Swine have been used in studies entailing hemorrhagic shock for many years. Most of the current understanding of the pathophysiology of hemorrhagic shock is derived from studies that have utilized animal models, including swine. Their physiology and homeostatic responses in the setting of pathologic volume depletion following hemorrhage, especially those pertaining to blood clotting and cardiovascular responses, have been well-documented and are like those in humans14. Swine models of hemorrhagic shock also provide opportunities to investigate treatment strategies for hemorrhagic shock and other traumatic injuries.
In this study, we demonstrate a clinically realistic model of hemorrhagic shock in swine to evaluate endovascular treatment strategies, including complete and partial aortic balloon occlusion. We hypothesize that a partial occlusion of the aorta results in a better physiologic and laboratory profile compared to a complete occlusion of the aorta in swine undergoing a controlled fixed-volume hemorrhage.
We aimed to compare the physiologic effects of partial and complete aortic occlusion as a treatment for hemorrhagic shock in a swine model. Partial aortic occlusion was achieved using a selective aortic balloon occlusion in trauma (SABOT) catheter (Figure 1). The SABOT catheter is a two-balloon system that allows intra-luminal blood flow, thereby providing a partial aortic flow to the vascular beds distal to the occlusion. Complete aortic occlusion was achieved using a single-balloon aortic occlusion catheter (e.g.,CODA) (Figure 1). Treatment groups were randomized to undergo resuscitative aortic occlusion either with the complete or with the partial aortic balloon occlusion catheters (n = 2/group).
The major steps of the model include the induction of anesthesia and intubation, the maintenance of anesthesia, instrumentation, 35% TBV hemorrhage (20 min total; half over the first 7 min, and half over the remaining 13 min), aortic balloon occlusion and whole-blood resuscitation (60 min of occlusion; 20% whole-blood resuscitation during the last 20 min of the occlusion), critical care monitoring (240 min) with hemodynamic observation, and euthanasia with tissue harvesting. Figure 2 demonstrates the model utilized in this experiment.

<table><tbody><tr><td>Yorkshire-Landrace Swine</td><td>Michigan State University Veterinary Farm</td><td></td><td></td></tr><tr><td>Anesthesia: Telazol</td><td>Pfizer</td><td></td><td>Dose: 2-8 mg/kg; IM</td></tr><tr><td>Anti-cholinergic: Atropine</td><td>Pfizer</td><td></td><td>Dose: 1mg, IM</td></tr><tr><td>Anesthesia: Isoflurane</td><td>Baxter</td><td></td><td>Dose: 1-5%, INH</td></tr><tr><td>Betadine</td><td>Humco</td><td></td><td></td></tr><tr><td>Alcohol 70%</td><td>Humco</td><td>NDC 0395-4202-28</td><td></td></tr><tr><td>Datex-Aespire Anesthesia Machine</td><td>GE Healthcare</td><td>7900</td><td></td></tr><tr><td>Endotracheal tube</td><td>DEE Veterinary</td><td>20170518</td><td>Appropriate size for animal (6.5 or 7.0F)</td></tr><tr><td>Laryngoscope</td><td>Miller</td><td>85-0045</td><td></td></tr><tr><td>Stylet</td><td>Hudson RCI</td><td>5-151--1</td><td></td></tr><tr><td>Jelco 20G IV Catheter</td><td>Smiths Medical</td><td>4054</td><td></td></tr><tr><td>Operating Room Monitor (Vital Signs Monitor)</td><td>SurgiVet Advisor</td><td>V9201</td><td>May require at least 2</td></tr><tr><td>Surgical Gowns</td><td>Kimberly Clark</td><td>90142</td><td>Use appropriate size for surgeon.</td></tr><tr><td>Sterile surgical gloves</td><td>Cardinal Health (Allegiance)</td><td>22537-570</td><td>Use appropriate size for surgeon.</td></tr><tr><td>Cautery Pencil</td><td>Medline</td><td>ESPB 2000</td><td></td></tr><tr><td>Suction tubing</td><td>Medline</td><td>DYND50251</td><td></td></tr><tr><td>Sunction tip: Yankauer</td><td>Medline</td><td>DYND50130</td><td></td></tr><tr><td>Bovie Aaron 1250 Electrocautery Unit</td><td>Bovie Medical Co. FL</td><td>BOV-A1250U</td><td></td></tr><tr><td>Salpel Blade - Size #10</td><td>Cardinal Health (Allegiance)</td><td>32295-010</td><td></td></tr><tr><td>Scalpel Handle</td><td>Martin</td><td>10-295-11</td><td></td></tr><tr><td>Debakey Forceps</td><td>Roboz</td><td>RS-7562</td><td></td></tr><tr><td>Weitlander Retractor</td><td>Roboz</td><td>RS-8612</td><td></td></tr><tr><td>Mayo Scissors</td><td>Roboz</td><td>RS-76870SC</td><td></td></tr><tr><td>Army-navy Retractor</td><td>Teleflex</td><td>164715</td><td></td></tr><tr><td>Mixter Right-angle Forceps</td><td>Teleflex</td><td>175073</td><td></td></tr><tr><td>5F (1.7 mm) 11 cm Insertion Sheath with 0.35&quot; Guidewire</td><td>Boston Scientific</td><td>16035-05B</td><td></td></tr><tr><td>8F (2.7 mm) 11 cm Insertion Sheath with 0.35&#039;&#039; Guidewire</td><td>Boston Scientific</td><td>16035-08B</td><td></td></tr><tr><td>20G angled Introducer Needle</td><td>Arrow</td><td>AK-09903-S</td><td></td></tr><tr><td>14F (4.78 mm) 13 cm Insertion Sheath with 10F dilator</td><td>Cook Medical</td><td>G08024</td><td></td></tr><tr><td>2-0 Silk 18&#039;&#039; 45 cm</td><td>Ethicon</td><td>A185H</td><td></td></tr><tr><td>3-0 Vicryl 36&#039;&#039; 90 cm</td><td>Ethicon</td><td>J344H</td><td></td></tr><tr><td>3-0 Nylon 18&#039;&#039; 45 cm</td><td>Ethicon</td><td>663G</td><td></td></tr><tr><td>4-0 Prolene 30&#039;&#039; 75 cm</td><td>Ethicon</td><td>8831H</td><td></td></tr><tr><td>20 ml syringe</td><td>Metronic/Covidien</td><td>8881512878</td><td></td></tr><tr><td>3 mL syringe</td><td>Metronic/Covidien</td><td>1180300555</td><td></td></tr><tr><td>6 mL syringe</td><td>Metronic/Covidien</td><td>1180600777</td><td></td></tr><tr><td>1000ml 0.9% Saline</td><td>Baxter</td><td>2B1324X</td><td></td></tr><tr><td>Foley Catheter (18F 30 cc)</td><td>Bard</td><td>0166V18S</td><td></td></tr><tr><td>Urinary Drainage Bag</td><td>Bard</td><td>154002</td><td></td></tr><tr><td>9F 10 cm Insertion Sheath</td><td>Arrow</td><td>AK-09903-S</td><td></td></tr><tr><td>Swan-Ganz pulmonary artery catheter (8F)</td><td>Edwards Lifesciences co. CA</td><td>746F8</td><td></td></tr><tr><td>Carotid Flow Probe System</td><td>Transonic, Ithaca, NY</td><td></td><td>3, 4, or 6 mm probes</td></tr><tr><td>SABOT catheter</td><td>Hayes Inc.</td><td></td><td></td></tr><tr><td>CODA balloon catheter</td><td>Cook Medical</td><td>8379144</td><td></td></tr><tr><td>Ultrasound, M-Turbo</td><td>SonoSite</td><td></td><td></td></tr><tr><td>Amplatz Stiff Guidewire (0.035 inch, 260 cm)</td><td>Cook Medical</td><td>G03460</td><td></td></tr><tr><td>Arterial Blood Gas Syringes</td><td>Smiths Medical</td><td>4041-2</td><td></td></tr><tr><td>Arterial Blood Gas Analyzer</td><td>Nova Biochemical</td><td>ABL800</td><td></td></tr><tr><td>Masterflex Pump</td><td>Cole Palmer</td><td>HV-77921-75</td><td></td></tr><tr><td>Blood Collection Bags</td><td>Terumo</td><td>1BBD606A</td><td></td></tr><tr><td>Macro IV drip set</td><td>Hospira</td><td>12672-28</td><td></td></tr><tr><td>Pentobarbital</td><td>Pfizer</td><td></td><td>Dose: 100 mg/kg; IV</td></tr><tr><td>Eppendorf Tubes</td><td>Sorenson</td><td>11590</td><td></td></tr><tr><td>50 cc conical tubes</td><td>Falcon</td><td>352097</td><td></td></tr><tr><td>Formalin</td><td>Fisherbrand</td><td>431121</td><td></td></tr><tr><td>Bair Hugger Normothermia System</td><td>Arizant Healthcare, Inc.</td><td></td><td></td></tr></tbody></table>

complete and partial aortic occlusion for the treatment of hemorrhagic shock in swine

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.

Hemodynamic and Physiological Parameters:
The MAP decreased immediately after the hemorrhage (Figures 3A - 3D). During the balloon inflation phase, animals in the complete occlusion group experienced a higher proximal MAP compared to the animals in the partial occlusion group (Figures 3A and 3B). The average distal MAP during the balloon inflation was higher in the...

Watch this Scientific Journal Video about Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine at JoVE.com

Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine

Here, we present a protocol demonstrating a hemorrhagic shock model in swine that uses aortic occlusion as a bridge to definitive care in trauma. This model has application in testing a wide range of surgical and pharmacological therapeutic strategies.

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the ...

complete-partial-aortic-occlusion-for-treatment-hemorrhagic-shock

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

10.5K Views.  University of Michigan. Here, we present a protocol demonstrating a hemorrhagic shock model in swine that uses aortic occlusion as a bridge to definitive care in trauma. This model has application in testing a wide range of surgical and pharmacological therapeutic strategies.

Video: Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1, 2, 3, 4, 5 These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). 6, 7, 8, 9 It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. 10 This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions. 11, 12, 13 Advances in the assessment of biological systems, i.e. Systems Biology have enabled the scientific community to further understand complex physiologic networks and cellular communication patterns. 14 Hemorrhagic Shock has proven to be a vital tool for unveiling these cellular communication patterns as they relate to immune function. 15, 16, 17, 18 This procedure can be mastered! This procedure can also be used as either a fixed volume or fixed pressure approach. We adapted this technique in the murine model to enhance research in innate and adaptive immune function. 19, 20, 21 Due to their small size HS in mice presents unique challenges. However due to the many available mouse strains, this species represents an unparalleled resource for the study of the biologic responses. The HS model is an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, i.e. DAMP and PAMP upregulation as it elicits distinct responses that differ from other forms of shock. 22, 23, 24, 25 The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma 26, 27, 28, 29, 30. 
There are numerous resuscitation methods (R) in association with HS and trauma. 31, 32, 33, 34 A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation. 35, 36, 38 This method of resuscitation is proven to be effective in evaluating the effects of HS and trauma 38, 39.

The Hemorrhagic Shock model has been a reliable and reproducible resource facilitating the identification and understanding of signaling cascades associated with inflammation and end-organ damage after trauma. This article provides a step-by-step description of surgical and mechanical aspects associated with the Hemorrhagic Shock experimental procedure in mice.

It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1, ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. This is largely true, but there are a number of important principles that can reduce the difficulty of these procedures and enhance reproducibility. Orthotopic aortic transplantation is an excellent procedure in which to learn these principles because it involves only two end-to-end anastomoses, but requires good suturing technique and handling of the vessels for consistent success. This procedure begins with the procurement of a length of abdominal aorta from a donor animal, followed by division of the native aorta in the recipient. The procured aorta is then placed between the divided ends of the recipient aorta and sutured into place using end-to-end anastomoses. To accomplish this objective successfully requires a high degree of concentration, good tools, a steady hand, and an appreciation of how easily the vasculature of a mouse can be damaged, resulting in thrombosis. Learning these important principles is what occupies most of the beginner's time when learning microsurgery in small rodents. Throughout this protocol, we refer to these important points. This model can be used to study vascular disease in a variety of different experimental systems1-8. In the context shown here, it is most often used for the study of post-transplant vascular disease, a common long-term complication of solid organ transplantation in which intimal hyperplasia occurs within the allograft. The primary advantage of the model is that it facilitates quantitative morphometric analyses and the transplanted vessel lies contiguous to the endogenous vessel, which can serve as an additional control9. The technique shown here is most often used for mice weighing 18-25 grams. We have accumulated most of our experience using the C57BL/6J, BALB/cJ, and C3H/HeJ strains.

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient. This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery

Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of coronary artery disease (CAD) patients have HM, which in addition to causing impaired function, puts them at higher risk for arrhythmia and future cardiac events. The standard treatment for this condition is revascularization, but this has been shown to be an imperfect therapy. The majority of pre-clinical cardiac research focuses on infarct models of cardiac ischemia, leaving this subset of chronic ischemia patients largely underserved. To address this gap in research, we have developed a well-characterized and highly reproducible model of hibernating myocardium in swine, as swine are ideal translational models for human heart disease. In addition to creating this unique disease model, we have optimized a clinically relevant treatment model of coronary artery bypass surgery in swine. This allows us to accurately study the effects of bypass surgery on heart disease, as well as investigate additional or alternate therapies. This model surgically induces single vessel stenosis by implanting a constrictor on the left anterior descending (LAD) artery in a young pig. As the pig grows, the constrictor creates a gradual stenosis, resulting in chronic ischemia with impaired regional function, but preserving tissue viability. Following the establishment of the hibernating myocardium phenotype, we perform off-pump coronary artery bypass graft surgery to revascularize the ischemic region, mimicking the gold-standard treatment for patients in the clinic.

This protocol presents a surgical large animal model of chronic, single vessel ischemia that results in regional abnormalities but does not create infarct, known as hibernating myocardium. Following establishment of chronic ischemia, animals are treated with off-pump LIMA-LAD coronary artery bypass graft surgery to revascularize the ischemic tissue.

Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of ...

Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an insufficient oxygen supply and irreversible organ failure. The brain exerts only limited compensation capacities and is particularly at high risk of severe hypoxic damage.This article demonstrates the reproducible induction of life-threatening hemorrhagic shock in a porcine model by means of calculated blood withdrawal. We titrate shock induction guided by near-infrared spectroscopy&#160;and extended hemodynamic monitoring to display systemic circulatory failure, as well as cerebral microcirculatory oxygen depletion. In comparison to similar models that primarily focus on predefined removal volumes for shock induction, this approach highlights a titration by means of the resulting failure of macro- and microcirculation.

Hemorrhagic shock is a severe complication in seriously injured patients, which leads to life-threatening oxygen undersupply. We present a standardized method to induce hemorrhagic shock via blood withdrawal in pigs that is guided by hemodynamics and microcirculatory cerebral oxygenation.

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an ...

Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system.
Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta.
This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.

The goal of this protocol is to demonstrate a porcine exsanguination cardiac arrest model and a specifically built selective aortic arch perfusion circuit for translational research.

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Myocardial infarction (MI) animal models that emulate the natural process of the disease in humans are crucial to understanding pathophysiological mechanisms and testing the safety and efficacy of new emergent therapies. Here, we describe an MI swine model created by deploying a percutaneous embolization coil.

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization ...

Complete and Partial Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for hemorrhage control. With the advent of purpose-built devices, REBOA has become increasingly common in civilian trauma and acute care settings. Currently available REBOA catheters were designed as complete aortic occlusion devices. However, the therapeutic window for complete aortic occlusion is time-limited due to ischemia-reperfusion injury. The partial procedure allows blood flow past the level of occlusion while maintaining targeted proximal pressure, which has been shown to reduce distal ischemia and adjunctive resuscitation requirements in preclinical studies with prolonged occlusion times as compared to traditional complete occlusion.
pREBOA-PRO is the first catheter designed to enable partial and complete aortic occlusion and is currently in limited market release at seven Level I trauma centers in North America. This paper will focus on procedural considerations for REBOA, including patient selection criteria and a comparison of complete and partial aortic occlusion in a simulator, along with highlighting critical steps to improve clinical outcomes. Additionally, this paper reviews a contrast-enhanced CT scan from a trauma patient that shows distal perfusion after 2 h of partial aortic occlusion using this newly designed catheter and discusses representative results from the limited market release to highlight the profound effect of technological innovation on outcomes in vascular emergencies.

A commercial catheter was designed to facilitate true partial resuscitative endovascular balloon occlusion of the aorta (REBOA) and address the complications associated with complete aortic occlusion. Initial clinical reports indicate that partial REBOA improves transition to reperfusion, reduction of distal ischemia, and extension of safe occlusion time compared to complete occlusion.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for ...

Description of a Swine Infant Model of Volume-Controlled Hemorrhagic Shock

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to guide resuscitation and comparison between different therapies is difficult in children due to the inherent heterogeneity of this population. As a result, compared to adults, appropriate management of pediatric hemorrhagic shock is still not well established. In addition, the scarcity of pediatric patients with hemorrhagic shock precludes the development of clinically relevant studies. For this reason, an experimental pediatric animal model is necessary to study the effects of hemorrhage in children as well as their response to different therapies. We present an infant animal model of volume-controlled hemorrhagic shock in anesthetized young pigs. Hemorrhage is induced by withdrawing a previously calculated blood volume, and the pig is subsequently monitored and resuscitated with different therapies. Here, we describe a precise and highly reproducible model of hemorrhagic shock in immature swine. The model yields hemodynamic data that characterizes compensatory mechanisms that are activated in response to severe hemorrhage.

This article aims to provide researchers with a detailed and accessible guide to set up an infant porcine model of hemorrhagic shock.

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to ...

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 ...