Name: complete and partial aortic occlusion for the treatment of hemorrhagic shock in swine
Uploaded: 2018-08-24T14:45:00.000+00:00
Duration: 9 min 37 s
Description: Watch this Scientific Journal Video about Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine at JoVE.com

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. 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=Extending+resuscitative+endovascular+balloon+occlusion+of+the+aorta:+Endovascular+variable+aortic+control+in+a+lethal+model+of+hemorrhagic+shock.">Extending resuscitative endovascular balloon occlusion of the aorta: Endovascular variable aortic control in a lethal model of hemorrhagic shock.</a> The Journal of Trauma and Acute Care Surgery. 81 (2), 294-301 (2016).</li><li>Hannon, J. P., 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=Hemorrhage+and+hemorrhagic-shock+in+swine:+A+review.">Hemorrhage and hemorrhagic-shock in swine: A review.</a> Swine as Models in Biomedical Research. , 197-245 (1992).</li><li>Garry, B. P., Bivens, H. 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. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+coherence+of+macrocirculation,+microcirculation,+and+tissue+metabolic+response+during+nontraumatic+hemorrhagic+shock+in+swine.">The coherence of macrocirculation, microcirculation, and tissue metabolic response during nontraumatic hemorrhagic shock in swine.</a> Physiological Reports. 5 (7), (2017).</li><li>Johnson, M. 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=The+effect+of+resuscitative+endovascular+balloon+occlusion+of+the+aorta,+partial+aortic+occlusion+and+aggressive+blood+transfusion+on+traumatic+brain+injury+in+a+swine+multiple+injuries+model.">The effect of resuscitative endovascular balloon occlusion of the aorta, partial aortic occlusion and aggressive blood transfusion on traumatic brain injury in a swine multiple injuries model.</a> Journal of Trauma Acute Care Surgery. 83 (1), 61-70 (2017).</li><li>Theisen, M. 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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=Physiologic+response+to+hemorrhagic+shock+depends+on+rate+and+means+of+hemorrhage.">Physiologic response to hemorrhagic shock depends on rate and means of hemorrhage.</a> The Journal of Surgical Research. 143 (2), 276-280 (2007).</li><li>Morrison, J. 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=The+inflammatory+sequelae+of+aortic+balloon+occlusion+in+hemorrhagic+shock.">The inflammatory sequelae of aortic balloon occlusion in hemorrhagic shock.</a> The Journal of Surgical Research. 191 (2), 423-431 (2014).</li><li>White, J. 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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 ...

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10.4K 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

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

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 ...

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 ...

Swine Models of Aneurysmal Diseases for Training and Research

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper describes two different aneurysmal swine models that may help researchers to study new therapies for aneurysmal diseases. These aneurysmal models are created by surgically adding a pouch of tissue to carotid arteries in swine. When the model is used for research, the pouch must be autologous; for training purposes, a synthetic pouch suffices.
First, the right external jugular vein (EJV) and right common carotid artery (CCA) must be surgically exposed. The EJV is ligated and a vein pouch fashioned from a short segment. This pouch is then sutured to an elliptical arteriotomy performed in the CCA. Animals must be kept heparinized during model creation, and local vasodilators may be used to decrease vasospasms. Once the suture is completed, correct blood flow should be inspected, checking for bleeding from the suture line and vessel patency. Finally, the surgical incision is closed by layers and an angiography performed to image the aneurysmal model.
A simplification of this aneurysmal carotid model that decreases invasiveness and surgical time is the use of a synthetic, rather than venous, pouch. For this purpose, a pouch is tailored in advance with a segment of a polytetrafluoroethylene (PTFE) prosthesis, one end of which is sutured close using polypropylene vascular suture and sterilized prior to surgery. This "sac" is then attached to an arteriotomy performed in the CCA as described. 
Although these models do not reproduce many of the physiopathological events related to aneurysm formation, they are hemodynamically similar to the situation found in the clinical setting. Therefore, they can be used for research or training purposes, allowing physicians to learn and practice different endovascular techniques in animal models that are close to the human system.

Description of two different aneurysmal swine models for neuroradiology training courses and research studies. This study provides evidence of the feasibility of these aneurysm porcine model creations and the reproducible methods that are close to the clinical setting.

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper ...

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 ...

Ascending Aortic Banding for Studying Pressure-Overload Induced Heart Failure

A Minimally Invasive Model of Aortic Stenosis in Swine

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological similarities to humans. Efforts have been dedicated to creating a model of pressure-overload induced heart failure, and ascending aortic banding while still supra-coronary and not a perfect mimic of aortic stenosis in humans, closely resembling the human condition.
The purpose of this study is to demonstrate a minimally invasive approach to induce left ventricular pressure overload by placing an aortic band, precisely calibrated with percutaneously introduced high-fidelity pressure sensors. This method represents a refinement of the surgical procedure (3Rs), resulting in homogenous trans-stenotic gradients and reduced intragroup variability. Additionally, it enables swift and uneventful animal recovery, leading to minimal mortality rates. Throughout the study, animals were followed for up to 2 months after surgery, employing transthoracic echocardiography and pressure-volume loop analysis. However, longer follow-up periods can be achieved if desired. This large animal model proves valuable for testing new drugs, particularly those targeting hypertrophy and the structural and functional alterations associated with left ventricular pressure overload.

Author Spotlight: Development of a Minimally Invasive Large-Animal Model for Reliable and Reproducible Cardiovascular Research 

This protocol describes a minimally invasive surgical procedure for ascending aortic banding in swine.

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological ...

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 ...