Name: complete and partial aortic occlusion for the treatment of hemorrhagic shock in swine
Uploaded: 2018-08-24T14:45:00
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.

In conducting research using animals, the investigators adhered to the Animal Welfare Act Regulations and other Federal statutes relating to animals and experiments involving animals and the principles set forth in the current version of the Guide for Care and Use of Laboratory Animals of the National Research Council. This study protocol was approved by the University of Michigan Institutional Animal Care and Use Committee (IACUC). The experiments were conducted in compliance with all regulations and guidelines regardin...

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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+role+of+REBOA+in+the+control+of+exsanguinating+torso+hemorrhage.">The role of REBOA in the control of exsanguinating torso hemorrhage.</a> Journal of Trauma and Acute Care Surgery. 78 (5), 1054-1058 (2015).</li><li>Manzano Nunez, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+meta-analysis+of+resuscitative+endovascular+balloon+occlusion+of+the+aorta+(REBOA)+or+open+aortic+cross-clamping+by+resuscitative+thoracotomy+in+non-compressible+torso+hemorrhage+patients.">A meta-analysis of resuscitative endovascular balloon occlusion of the aorta (REBOA) or open aortic cross-clamping by resuscitative thoracotomy in non-compressible torso hemorrhage patients.</a> World Journal of Emergency Surgery. 12, 30 (2017).</li><li>Gupta, B. 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. 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=Ventral+recumbency+is+crucial+for+fast+and+safe+orotracheal+intubation+in+laboratory+swine.">Ventral recumbency is crucial for fast and safe orotracheal intubation in laboratory swine.</a> Laboratory Animals. 43 (1), 96-101 (2009).</li><li>Li, Y., Alam, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+acetylation:+creating+a+pro-survival+and+anti-inflammatory+phenotype+in+lethal+hemorrhagic+and+septic+shock.">Modulation of acetylation: creating a pro-survival and anti-inflammatory phenotype in lethal hemorrhagic and septic shock.</a> Journal of Biomedicine and Biotechnology. 2011, 523481 (2011).</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>Dekker, S. 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=Normal+saline+influences+coagulation+and+endothelial+function+after+traumatic+brain+injury+and+hemorrhagic+shock+in+pigs.">Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs.</a> Surgery. 156 (3), 556-563 (2014).</li><li>Causey, M. W., McVay, D. P., Miller, S., Beekley, A., Martin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+efficacy+of+Combat+Gauze+in+extreme+physiologic+conditions.">The efficacy of Combat Gauze in extreme physiologic conditions.</a> The Journal of Surgical Research. 177 (2), 301-305 (2012).</li><li>Frankel, D. 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. 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=A+porcine+model+for+evaluating+the+management+of+noncompressible+torso+hemorrhage.">A porcine model for evaluating the management of noncompressible torso hemorrhage.</a> Journal of Trauma. 71, S131-S138 (2011).</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=Putting+life+on+hold-for+how+long?+Profound+hypothermic+cardiopulmonary+bypass+in+a+Swine+model+of+complex+vascular+injuries.">Putting life on hold-for how long? Profound hypothermic cardiopulmonary bypass in a Swine model of complex vascular injuries.</a> Journal of Trauma. 64 (4), 912-922 (2008).</li><li>Bebarta, V. S., Daheshia, M., Ross, J. 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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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&#34; 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&#39;&#39; 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&#39;&#39; 45 cm</td>
			<td>Ethicon</td>
			<td>A185H</td>
			<td></td>
		</tr>
		<tr>
			<td>3-0 Vicryl 36&#39;&#39; 90 cm</td>
			<td>Ethicon</td>
			<td>J344H</td>
			<td></td>
		</tr>
		<tr>
			<td>3-0 Nylon 18&#39;&#39; 45 cm</td>
			<td>Ethicon</td>
			<td>663G</td>
			<td></td>
		</tr>
		<tr>
			<td>4-0 Prolene 30&#39;&#39; 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 ...

This method can help answer key questions in the field of trauma care, including strategies to treat non-compressible torso hemorrhage. The main advantage of this technique is that it can help test relevant endovascular resuscitative strategies in a clinically realistic large animal model with the physiology that mimics that of humans. The implications of this technique extend towards the treatment of hemorrhagic shock, which is a leading cause of preventable death in trauma.Generally, people new to this method will struggle, because it requires surgical expertise and knowledge of critical care physiology. After confirming an appropriate level of sedation using a hind limb pinch, use a conventional laryngoscope fitted with a 12 inch lighted Miller blade to pass the tip of the blade through the oropharynx of the anesthetized pig. Taking care not to damage the oral mucosa or the teeth, slowly advance the blade tip to the epiglottis, lifting the epiglottis with the blade, and continuing past the laryngeal inlet until a clear view of the larynx is obtained.Place a 6.5 or 7 French endotracheal tube with a stylet between the vocal folds, into the trachea, and inflate the balloon cuff with 10 to 15 cubic centimeters of air to prevent leaking around the cuff or aspiration of the gastric contents. Then, connect the endotracheal tube to the mechanical ventilator through a breathing filter, and secure the tube around the maxilla with cotton tape. For a femoral artery and vein cannulation, scrub the operative sites with a copious volume of povidone iodine for five minutes, and place the sterile surgical towels around the operative sites to preserve the sterility of the surgical fields.Using a scalpel fitted with a number 10 sterile surgical blade, identify the inguinal crease and make a vertical eight centimeter incision in the right groin, four centimeters above and four centimeters below the right inguinal crease. Dissect through the subcutaneous tissue, and place two Weitlaner retractors into the incision. Using Mixter right angle forceps and an electrocautery, dissect through the connective tissues and muscle until the neurovascular bundle is clearly exposed, and cautiously dissect the artery, taking care to preserve the lateral nerve.Use a 20 gauge angled introducer needle to puncture the artery, and advance a round-tipped, 0.35 inch guide wire through the lumen of the angled needle. When the guide wire is in place, withdraw the needle over the guide wire, holding slight pressure over the arteriotomy to prevent bleeding, and insert a 14 French insertion sheath over the guide wire. Then, cannulate the left femoral artery and vein as just demonstrated.For carotid artery and external jugular vein cannulation, use a number 10 blade scalpel to make a six centimeter vertical incision about two centimeters lateral to the midline on the left side of the neck. Use electrocautery to dissect through the subcutaneous tissue until the sternocleidomastoid muscle is exposed, and dissect along the lateral border of the muscle to expose the left external jugular vein. Then, cannulate the vessel with an 8 French catheter as just demonstrated.For left common carotid artery exposure, dissect the medial edge of the sternocleidomastoid muscle, until the carotid triangle, which contains the carotid artery, the vagus nerve, and the internal jugular vein, is observed. Cannulate the carotid artery as previously demonstrated, with a 5 French catheter. For the contralateral dissection, isolate the right external jugular vein and right common carotid artery, as demonstrated for their lateral counterparts.Then, use a 9 French introducer sheath to cannulate the right external jugular vein, and place a four millimeter carotid artery flow probe around the right common carotid artery. Next, insert the pulmonary artery catheter through the 9 French insertion sheath 15 to 18 centimeters into the right external jugular vein. Once the catheter is in place, inflate the balloon with no more than 1.5 cubic centimeters of air.Advance the catheter and observe the monitor to evaluate the transition of the pressure from the right atrium to the right ventricle, to the pulmonary artery, to the pulmonary artery wedge pressure. Then, deflate the balloon and confirm that a pulmonary artery trace returns to the monitor. For cystostomy tube placement, use a number 10 blade scalpel to make a midline five centimeter lower abdominal incision, and extracorporealize the urinary bladder.Using electrocautery, make a small opening in the bladder and suction out the urine, and use a 4-0 polypropylene suture to perform a temporary purse string closure of the bladder. Place an 18 French foley catheter inside the bladder lumen, and use a 10 cubic centimeter syringe to inflate the balloon. Then, tie the suture to secure the catheter within the bladder lumen.For aortic balloon catheter insertion, insert a 0.035 inch, 260 centimeter Amplatz stiff guide wire through the 14 French insertion sheath. Confirm its location in the supraceliac aorta using ultra sonography. Then, insert the balloon occlusion catheter over the guide wire, into the supraceliac aorta.After calculating the total blood volume, use an automated pump to hemorrhage 35%of the total blood volume over 20 minutes, into standard blood collection bags for storage at four degrees Celsius. When all the blood has been stored, inflate the aortic balloon occlusion catheter with 9 to 12 cubic centimeters of air, or until no further decrease in the distal mean arterial pressure following an additional balloon inflation is noted. After 40 minutes of occlusion, use the automated pump to resuscitate the animal, with whole blood equal in volume to 20%of the total blood volume via the left femoral vein catheter over 20 minutes.Then, deflate the balloon incrementally over five minutes. During the balloon inflation phase, animals in the complete occlusion group experience a higher proximal mean arterial pressure, compared to animals in the partial occlusion group, while the average distal mean arterial pressure during the balloon inflation is higher in the partial occlusion group compared to complete occlusion group, reflecting the partial distal aortic flow. Following resuscitation, the proximal and distal mean arterial pressure increases in both groups, and returns to baseline following the balloon deflation for the remainder of the critical care phase.All animals experience reflex tachycardia immediately following the hemorrhage that undergoes an incremental increase during the balloon inflation phase in both groups. Following hemorrhage, the central venous pressure decreases in both groups, undergoing an increase following balloon deflation, and returning to baseline after resuscitation. Similarly, the cardiac output decreases following hemorrhage, increases during balloon inflation, and returns to baseline following balloon deflation in resuscitation in both groups.The carotid flow decreases in both groups immediately following hemorrhage, with the complete occlusion group demonstrating a higher carotid flow rate compared to the partial occlusion group. Following resuscitation and balloon deflation, the carotid flow rate recovers towards baseline in both groups, but at a lower level in the complete occlusion group. After watching this video, you should have a much better understanding of how to use large animal models to test aortic occlusion using endovascular strategies.Also, just like any other surgical operation, you have to be careful in handling the instruments to be able to do it safely.

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

Research

JoVE Journal

Medicine

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, ...

2-Methacryloyloxyethyl Phosphorylcholine Polymer Treatment of Complete Dentures to Inhibit Denture Plaque Deposition

Removable dentures made of poly (methyl methacrylate) (PMMA) are prone to bacterial adherence and dental plaque formation, which is called denture plaque. Denture plaque-associated infection is a source of serious dental and medical complications in the elderly. 2-Methacryloyloxyethyl phosphorylcholine (MPC) is a well-known biomedical material that exhibits marked antithrombogenicity and tissue compatibility because of its high resistance to protein adsorption and cell adhesion. Therefore, MPC polymer coatings are suggested to have the potential to inhibit plaque deposition on the surface of PMMA dentures. However, coating MPC polymer on the surface of a PMMA denture is a complex procedure that requires specialized equipment, which is regarded as a major barrier to its clinical application. 
Here, we introduce a new MPC polymer treatment procedure that uses poly (MPC-co-BMA-co-MPAz) (PMBPAz) to prevent denture plaque deposition on removable dentures. This procedure enables the MPC coating of PMMA denture surfaces in a simple and stable manner that is resistant to various chemical and mechanical stresses due to the MPC layer of PMBPAz that is covalently bound to the PMMA surface by ultraviolet light irradiation. In addition, the procedure does not require any specialized equipment and can be completed by clinicians within 2 min. We applied this procedure in a clinical setting and demonstrated its clinical utility and efficacy in inhibiting plaque deposition on removable dentures.

Removable poly(methyl methacrylate) (PMMA) dentures are prone to bacterial adherence and plaque formation. Denture plaque-associated infection is a source of serious dental and medical complications in the elderly. This paper introduces a novel protocol to treat PMMA dentures with 2-methacryloyloxyethyl phosphorylcholine polymer, poly(MPC-co-BMA-co-MPAz), to suppress plaque deposition on PMMA dentures.

Removable dentures made of poly (methyl methacrylate) (PMMA) are prone to bacterial adherence and dental plaque formation, which is called denture plaque. ...

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via a liver laceration that results in consistent blood loss, hemodynamic alterations, and survival.
Mice undergo a standardized resection of the left-middle lobe of the liver. They are allowed to bleed without mechanical intervention. Hemostatic agents can be administered as pre-treatment or rescue therapy depending on the interest of the investigator. During the time of hemorrhage, real-time hemodynamic monitoring via a left femoral arterial line is performed. Mice are then sacrificed, blood loss is quantified, blood is collected for further analysis, and organs are harvested for analysis of injury. Experimental design is described to allow for simultaneous testing of multiple animals.
Liver hemorrhage as a model of uncontrolled hemorrhage exists in the literature, primarily in rat and porcine models. Some of these models utilize hemodynamic monitoring or quantify blood loss but lack consistency. The present model incorporates quantification of blood loss, real-time hemodynamic monitoring in a murine model that offers the advantage of using transgenic lines and a high-throughput mechanism to further investigate the pathophysiologic mechanisms in uncontrolled hemorrhage.

Uncontrolled hemorrhage, an important cause of mortality among trauma patients, can be modeled using a standard liver laceration in a murine model. This model results in consistent blood loss, survival, and allows for testing hemostatic agents. This article provides the step-by-step process to perform this valuable model.

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via ...

Reproducible Motor Deficit Following Aortic Occlusion in a Rat Model Of Spinal Cord Ischemia

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing and treating this complication using experimental models of spinal cord ischemia. The model described here demonstrates varying degrees of paraplegia that relate to the length of occlusion following thoracic aortic occlusion in a rat spinal cord ischemia model.
A 2-Fr. balloon-tipped catheter was advanced through the femoral artery into the descending thoracic aorta until the catheter tip was placed at the left subclavian artery in anesthetized male Sprague-Dawley rats. Spinal cord ischemia was induced by inflating the catheter balloon. After a set period of occlusion (9, 10, or 11 min), the balloon was deflated. Neurologic assessment was performed using the motor deficit index at 24 h after surgery, and the spinal cord was harvested for histopathological examination.
Rats that underwent 9 min of aortic occlusion showed mild and reversible motor impairment in the hind limb. Rats subjected to 10 min of aortic occlusion presented with moderate but reversible motor impairment. Rats subjected to 11 min of aortic occlusion displayed complete and persistent paralysis. The motor neurons in the spinal cord sections were more preserved in rats subjected to shorter duration of aortic occlusion.
Researchers can achieve a reproducible hind limb motor deficit following thoracic aortic occlusion using this spinal cord ischemia model.

This study demonstrates the technique to make a minimally invasive and easily reproducible model of spinal cord ischemia in rats. Various degrees of hind limb motor deficit can be produced by controlling the aortic occlusion time.

Spinal cord ischemia is a fatal complication following thoracoabdominal aortic aneurysm surgery. Researchers can investigate the strategies for preventing ...

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 ...

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 ...

Vascular Cannulation with Hemorrhagic Shock Induction in Rats

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic shock, i.e., organ failure due to rapid loss of a large volume of blood, is associated with a highly complex pathophysiology involving several pathways. Numerous existing animal models of hemorrhagic shock strive to replicate what happens in humans, but these models have limits in terms of clinical relevance, reproducibility, or standardization. The aim of this study was to refine these models to develop a new model of hemorrhagic shock. Briefly, hemorrhagic shock was induced in male Wistar Han rats (11-13 weeks old) by a controlled exsanguination responsible for a drop in the mean arterial pressure. The next phase of 75 min was to maintain a low mean arterial blood pressure, between 32 mmHg and 38 mmHg, to trigger the pathophysiological pathways of hemorrhagic shock. The final phase of the protocol mimicked patient care with an administration of intravenous fluids, Ringer Lactate solution, to elevate the blood pressure. Lactate and behavioral scores were assessed 16 h after the protocol started, while hemodynamics parameters and plasmatic markers were evaluated 24 h after injury. Twenty-four hours post-hemorrhagic shock induction, the mean arterial and diastolic blood pressure were decreased in the hemorrhagic shock group (p&#160;&#60; 0.05). Heart rate and systolic blood pressure remained unchanged. All organ damage markers were increased with the hemorrhagic shock (p &#60; 0.05). The lactatemia and behavioral scores were increased compared to the sham group (p &#60; 0.05). In conclusion, we demonstrated that the protocol described here is a relevant model of hemorrhagic shock that can be used in subsequent studies, particularly to evaluate the therapeutic potential of new molecules.

Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research

Hemorrhagic shock kills 1.9 million people worldwide every year. Small animals are frequently used as hemorrhagic shock models but are associated with issues of standardization, reproducibility, and clinical significance, thus limiting their relevance. This article describes developing a new clinically relevant hemorrhagic shock model in rats.

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic ...

Arterial Cannulation for Ascending Aortic Banding in Swine 

To begin, identify the puncture site for arterial cannulation in an anesthetized pig. Using the vascular probe, identify the common femoral artery and confirm the position of the ultrasound marker and correct depth. Before assembling the introducer sheath, flush the introducer and dilator with heparinized saline.Under ultrasound guidance, insert an echogenic arterial needle into the femoral artery. Once the arterial lumen is reached and pulsating arterial blood comes out from the needle hub, advance a J-tip guidewire into the artery. While maintaining pressure on the puncture site, remove the needle, and advance the introducer and dilator assembly into the artery.Next, remove the dilator and aspirate the blood from the side port of the introducer to confirm the correct positioning of the introducer. Sequentially flush the introducer with sterile saline. Finally, connect an arterial pressure line to the side port of the femoral artery introducer to monitor blood pressure.