Name: A Porcine Model of Acute Autologous Pulmonary Embolism (Video) | JoVE Journal
Uploaded: 2024-09-06T14:20:00.000+00:00
Duration: 7 min 44 s
Description: Learn a porcine model of acute autologous pulmonary embolism using autologous blood clots in pigs. This realistic animal model enables investigation of pathophysiology and evaluation of novel pharmacological and interventional treatments.

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We wish to express our sincere gratitude for the tremendous dedication and hard work exhibited by the staff at the Department of Clinical Medicine, Aarhus University, in completing the experiments. Furthermore, we want to thank our collaborators at the Department of Forensic Medicine, Aarhus University, and the Department of Radiology, Massachusetts General Hospital, for the invaluable assistance in conducting and analyzing the CT pulmonary angiography. The work has been supported by Aarhus University Graduate School, Karen Elise Jensen&#39;s Foundation, Danish Heart Foundation, NIH-grant no. 1R01HL168040-01, Novo Nordisk Foundation [NNF17OC0024868], Holger og Ruth Hesse&#39;s Mindefond, Laerdal Foundation [3374], Alfred Benzons Foundation, A.P. M&#248;ller Fonden, Direkt&#248;r Emil C. Hertz og hustru Inger Hertz Fond, P.A. Messerschmidt og Hustrus fond, and Helga og Peter Kornings Fond.

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<li>Lyhne, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Closed+chest+biventricular+pressure-volume+loop+recordings+with+admittance+catheters+in+a+porcine+model%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">Closed chest biventricular pressure-volume loop recordings with admittance catheters in a porcine model.</a> J Vis Exp. 171, e62661(2021).</li>
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<li>Schmitto, J. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Progressive+right+ventricular+failure+is+not+explained+by+myocardial+ischemia+in+a+pig+model+of+right+ventricular+pressure+overload%5BTitle%5D)+AND+%22Eur+J+Cardiothorac+Surg%22%5BJournal%5D)">Progressive right ventricular failure is not explained by myocardial ischemia in a pig model of right ventricular pressure overload.</a> Eur J Cardiothorac Surg. 35 (2), 229-234 (2009).</li>
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<li>Lyhne, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Oxygen+therapy+lowers+right+ventricular+afterload+in+experimental+acute+pulmonary+embolism%5BTitle%5D)+AND+%22Crit+Care+Med%22%5BJournal%5D)">Oxygen therapy lowers right ventricular afterload in experimental acute pulmonary embolism.</a> Crit Care Med. 49 (9), e891-e901 (2021).</li>
<li>Kramer, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Inhaled+nitric+oxide+has+pulmonary+vasodilator+efficacy+both+in+the+immediate+and+prolonged+phase+of+acute+pulmonary+embolism%5BTitle%5D)+AND+%22Eur+Heart+J+Acute+Cardiovasc+Care%22%5BJournal%5D)">Inhaled nitric oxide has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute pulmonary embolism.</a> Eur Heart J Acute Cardiovasc Care. 10 (3), 265-272 (2020).</li>
<li>Lyhne, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Levosimendan%2C+milrinone%2C+and+dobutamine+in+experimental+acute+pulmonary+embolism%5BTitle%5D)+AND+%22Pulm+Circ%22%5BJournal%5D)">Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism.</a> Pulm Circ. 11 (3), 20458940211022977(2021).</li>
<li>Krueger, K., Deissler, P., Coburger, S., Fries, J. W. U., Lackner, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((How+thrombus+model+impacts+the+in+vitro+study+of+interventional+thrombectomy+procedures%5BTitle%5D)+AND+%22Invest+Radiol%22%5BJournal%5D)">How thrombus model impacts the in vitro study of interventional thrombectomy procedures.</a> Invest Radiol. 39 (10), 641-648 (2004).</li>
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</ol>

AA has received speaker honoraria (ABBOTT, Gore Medical, Angiodynamics, EPS Vascular, and Jannsen), and he is a consultant for Inari Medical.

This paper describes a porcine model of acute, intermediate-risk PE using autologous emboli that is minimally invasive and reproducible.
There are some critical steps in this protocol. First, the dilation of the access in the right external jugular vein is crucial for the model as it serves as the access point for the emboli. When advancing the large sheath, it is essential to adhere to the guidance of the stiff wire under continuous fluoroscopy to prevent rupture or dissection of major vessels or right heart chambers. If resistance is encountered, do not apply excessive pressure but instead replace the wire and ensure optimal dilatation of the access. Furthermore, pigs are arrhythmogenic, and the instrumentation can cause atrial fibrillation. It is, therefore, crucial to observe the pig closely.
Second, the model has a hemodynamic phenotype of intermediate-risk PE in the acute phase. The careful titration of the optimal number of emboli can pose a challenge. If the emboli volume surpasses the heart&#39;s capability to withstand high pressure, the pig may experience acute right heart failure and death. The closed-chest approach to PE induction relies on the investigator closely monitoring the hemodynamic response, such as increased mPAP, decreased EtCO2, elevated HR, or reduced systemic arterial pressure, during the embolus induction. If systemic hypotension is severe and prolonged, it suggests that maximal thrombus burden has been reached. By allowing for sufficient time between emboli the risk of sudden collapse is decreased. If there is no apparent response, the embolus may be in transit within the sheath or right-sided chambers of the heart. Then we recommend re-flushing and waiting as an immediate induction of a novel embolus, which could lead to two simultaneous emboli, which can be fatal.
Third, the model is established without the use of heparin. The investigator should pay close attention to always having saline connected to the accesses and remember to draw spill and flush with saline before use. If not done so, embolic material will form and can dislodge, causing smaller emboli to be induced throughout the protocol that can interfere with the results (Figure 4B).
The model contributes to a realistic physiological response, owing to the closed-chest setup but also due to the utilization of autologous embolic material. In the pursuit of developing an acute thromboembolic phenotype in animals, various models have been developed, most requiring the use of inorganic material, pharmacological treatments and/or ligation of the pulmonary artery to induce acute pulmonary hypertension and RV heart failure in a large animal model6,7,8,21,22. Consequently, these models do not mimic the clinical presentation of a patient with PE. One study has created the thromboembolic material in vivo by occlusion of the inferior vena cave to create a deep vein thrombosis (DVT)10. However, the creation of the DVT is time-consuming, and the induction of the DVT is insufficient to create a model with RV dysfunction.
In the present model, the goal was to create a hemodynamic phenotype that is comparable with intermediate-risk PE, which was achieved in the model after 5&#160;&#177; 1 emboli. The clot burden can be changed depending on the scope of the model to achieve a desired hemodynamic phenotype, or one could use a fixed thrombus load. However, a study from our group showed that the hemodynamic changes in pulmonary pressure and RV dysfunction are not directly related to the clot burden alone23. The study found that induction of the first embolus caused the largest increase in mPAP compared to following embolic inductions. However, the RV afterload increased at the induction of the third embolus.
The experimental setup used in this study further provides opportunities to investigate the pathophysiological response in relation to imaging and hemodynamic changes13,14,15. Studies have investigated the acute response of the RV in the first 12 hours after an event of intermediate-risk PE14. Another study has used the model to look at the prolonged response one month after induction of embolic material15. Furthermore, the model has been used to test pharmacological treatments in the acute and subacute phase16,21,22,24,25,26,27. One of the studies found that the use of oxygen therapy at 40% FiO2 decreased the afterload and mechanical work of RV. The model has proven to be versatile.
There are some limitations to the protocol. First, the emboli are formed shortly before induction and created ex vivo, which can be a limitation as the in vitro created thrombus has been found to consist of less fibrin28. However, the benefit is that the clot burden can be controlled while still using autologous material. Second, the animals are fully anesthetized during the protocol, and the anesthesia can affect the hemodynamic response. However, doing repeated measurements equalizes any effect.
The model is established in slaughter pigs and not genetically modified or bred in isolation. The pigs can be prone to diseases that can affect the cardiovascular system and pulmonary pressure29. Therefore, it is essential to perform a baseline evaluation of the hemodynamic status.
In conclusion, we present a pig model using autologous emboli. The model presents a phenotype that is comparable with intermediate-risk PE. This model serves as a valuable tool for testing novel interventional and pharmaceutical treatments, as well as for training medical doctors and professional healthcare workers in interventional procedures.

Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death and is a manifestation of venous thromboembolism (VTE)1. The incidence of VTE ranges between 75 to 269 per 100,000 population per year and is increasing with age2. Initial survivors face a 30-day risk of death ranging from 0.5 % for low-risk patients and up to 22 % for high-risk patients3. The cause of death is right ventricular (RV) failure, which predominantly happens within hours4,5. Even if patients survive, there is still a risk of significant morbidity and chronic disease.
Treatment options in the acute phase of the disease include surgical embolectomy, catheter-based or systemic thrombolysis, low-molecular-weight heparin, and oral anticoagulants1. The number and variety of treatment options are expanding, and new techniques and methods for diagnosis and severity assessment are continuously being developed. Before clinical studies can be performed, the feasibility and safety must be determined in a reproducible and consistent setup, as can be achieved in an animal model. Furthermore, investigating the acute pathophysiology of PE requires an animal model with near-human cardiovascular- and pulmonary physiology. Models in both rodents and larger animals, i.e., pigs, have been developed6. The advantage of a large animal model is the possibility to use clinical techniques and to evaluate equipment and surgical interventions used in clinical practice. However, most of these models use artificial materials, such as plastic spheres or occlusive ballons, or require large invasive procedures for pulmonary arterial banding to mimic acute right heart failure7,8,9. One study used an inferior vena cava filter to create thrombosis in situ10. However, this is time-consuming, and the clot burden is difficult to control. Other studies have created autologous emboli ex vivo, but the PE has been smaller in size11,12. Hence, these models might not be suitable for testing interventional procedures.
There is a need for an animal model that can replicate the human pathology of PE. Based on previous studies conducted by our group13,14,15,16, we aim to present a porcine model of acute PE.

<table><tbody><tr><td>12L-RS</td><td>GE Healthcare Japan</td><td>5141337</td><td>Ultrasound probe</td></tr><tr><td>50 mL BD Luer-Lock</td><td>BD Plastipak</td><td>300865</td><td></td></tr><tr><td>Adhesive Aperature Drape (OneMed)</td><td>evercare</td><td>1515-01</td><td>75 cm x 90 cm (hole: 6 cm x 8 cm)</td></tr><tr><td>Alaris GP Guardrails plus</td><td>CareFusion</td><td>9002TIG01-G</td><td>Infusion pump</td></tr><tr><td>Alaris Infusion set</td><td>BD Plastipak</td><td>60593</td><td></td></tr><tr><td>Alcohol swap</td><td>MEDIQ Danmark</td><td>3340012</td><td>82% ethanol, 0.5% chlorhexidin, skin disinfection</td></tr><tr><td>Amplatz Support Wire Guide Extra-Stiff</td><td>Cook Medical</td><td>THSF-25-260-AES</td><td>diameter: 0.025 inches, length: 260 cm</td></tr><tr><td>Aortic Perfusion Cannula</td><td>Edwards Lifesciences</td><td>AA024TFTA</td><td>Size: 24F. Length: 30 cm.</td></tr><tr><td>BD Connecta</td><td>BD</td><td>394601</td><td>Luer-Lock</td></tr><tr><td>BD Emerald</td><td>BD</td><td>307736</td><td>10 mL syringe</td></tr><tr><td>BD Platipak</td><td>BD</td><td>300613</td><td>20 mL syringe</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393204</td><td>20 G</td></tr><tr><td>BD Venflon Pro</td><td>Becton Dickinson Infusion Therapy</td><td>393208</td><td>17 G</td></tr><tr><td>Butomidor Vet</td><td>Richter Pharma AG</td><td>531943</td><td>10 mg/mL</td></tr><tr><td>Chlorhexidine 0.5%</td><td>Meda AB</td><td>N/A</td><td></td></tr><tr><td>Cios Connect S/N 20015</td><td>Siemens Healthineers</td><td>N/A</td><td>C-arm</td></tr><tr><td>CP Oxygenation System Adult With Fusion and Cardioplegia 1/B</td><td>Medtronic</td><td>M450311W</td><td>Custom cardiopulmonary oxygenation system including a cardioplegia line.</td></tr><tr><td>D-LCC12A-01</td><td>GE Healthcare Finland</td><td>N/A</td><td>Pressure measurement monitor</td></tr><tr><td>Durapore</td><td>3M</td><td>N/A</td><td>Adhesive tape</td></tr><tr><td>E-PRESTIN-00</td><td>GE Healthcare Finland</td><td>6152932</td><td>Respirator tubes</td></tr><tr><td>Euthanimal</td><td>Alfasan</td><td>136278</td><td>Pentobarbitalnatrium 400 mg/mL (0.5 mL/kg for euthanasia)&amp;nbsp;</td></tr><tr><td>Favorita II</td><td>Aesculap</td><td>GT104</td><td></td></tr><tr><td>Fentanyl</td><td>B. Braun</td><td>71036</td><td>50 &amp;micro;g/mL</td></tr><tr><td>Glucose isotonic</td><td>SAD</td><td>419358</td><td>55 mg/mL Isotonic glucose (500 mL bag)</td></tr><tr><td>Gore DrySeal Flex Introducer Sheath</td><td>GORE</td><td>DSF2633</td><td>Size: 26 French. Working length: 33 cm.</td></tr><tr><td>Ketaminol Vet</td><td>MSD/Intervet International B.V.</td><td>511519</td><td>100 mg/mL</td></tr><tr><td>Lawton 85-0010 ZK1</td><td>Lawton</td><td>N/A</td><td>Laryngoscope</td></tr><tr><td>Lectospiral</td><td>VYGON</td><td>1159.90</td><td>400 cm (Luer-LOCK)</td></tr><tr><td>MBH qufora</td><td>MBH-International A/S</td><td>13853401</td><td>Urine bag</td></tr><tr><td>Natriumchlorid</td><td>Fresenius Kabi</td><td>7340022100528&amp;nbsp;&amp;nbsp;&amp;nbsp;</td><td>9 mg/mL Isotonic saline</td></tr><tr><td>Noradrenalin&amp;nbsp;</td><td>Macure Pharma</td><td>425318</td><td>1 mg/mL</td></tr><tr><td>PICO50 Aterial Blood Sampler</td><td>Radiometer</td><td>956-552</td><td>2 mL</td></tr><tr><td>Portex Tracheal Tube</td><td>Smiths Medical</td><td>100/150/075</td><td>Cuffed Clear Oral/Nasal Murphy Eye</td></tr><tr><td>Pressure Extension set</td><td>CODAN</td><td>7,14,020</td><td>Tube for anesthetics, 150 cm long, inner diameter 0.9 mm</td></tr><tr><td>Propolipid</td><td>Fresenius Kabi</td><td>21636</td><td>Propofol, 10 mg/mL</td></tr><tr><td>Radiofocus Introducer II</td><td>Radiofocus/Terumo</td><td>RS+B80N10MQ</td><td>7 + 8F sheaths</td></tr><tr><td>Rompun Vet</td><td>Beyer</td><td>86450917</td><td>Xylazin, 20 mg/mL</td></tr><tr><td>R&amp;uuml;sch Brilliant AquaFlate Glycerine&amp;nbsp;</td><td>Teleflex</td><td>178000</td><td>Bladder catheter, size 14</td></tr><tr><td>S/5 Avance</td><td>Datex-Ohmeda</td><td>N/A</td><td>Mechanical ventilator</td></tr><tr><td>Safersonic Conti Plus &amp;amp; Safergel</td><td>SECMA medical innovation</td><td>SAF.612.18120.WG.SEC</td><td>18 cm x 120 cm (Safersonic Sterile Transducer Cover with Adhesive Area and Safergel)&amp;nbsp;</td></tr><tr><td>Standard Dilator</td><td>Cook Medical</td><td>G01212</td><td>Size: 16 French. Length: 20 cm.</td></tr><tr><td>Swan-Ganz CCOmbo</td><td>Edwards Lifesciences</td><td>744F75</td><td>110 cm</td></tr><tr><td>TruWave Pressure Monitoring Set</td><td>Edwards Lifesciences</td><td>T434303A</td><td>210 cm</td></tr><tr><td>Vigilance VGS Patient Monitor</td><td>Edwards Lifesciences</td><td>N/A</td><td></td></tr><tr><td>Vivid iq</td><td>GE Medical Systems China</td><td>Vivid iq</td><td></td></tr><tr><td>Zoletil 50 Vet (tiletamin 125 mg and zolazepam 125 mg)</td><td>Virbac</td><td>83046805</td><td>Zoletil Mix for pigs: 1 vial of Zoletil 50 Vet (dry matter); add 6.25 mL Xylozin (20 mg/mL), 1.25 mL ketamin (100 mg/mL) and 2.5 mL Butorphanol (10 mg/mL). Dose for pre-anesthesia: 0.1 mL/kg as intramuscular injection</td></tr></tbody></table>

a porcine model of acute autologous pulmonary embolism

A Porcine Model of Acute Autologous Pulmonary Embolism

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

In a pooled analysis of pigs included in previous studies, we present the results characterizing the acute PE model described in this protocol15,16. Two pigs died from acute right heart failure following PE. In total, we included 24 pigs.
Hemodynamics 
The response after each embolus is evident in Figure 5. The induction of PE (5 ± 1) caused an immediate increase in mPAP (17 ± 3 mmHg to 33±6 mmHg, p &lt; 0.0001) and HR (50 ± 9 beats·min-1 to 63 ± 6 beats·min-1, p &lt; 0.0003) accompanied by a decrease in CO (5.0 ± 0.8 L/min to 4.5 ± 0.9 L/min, p &lt; 0.037) and EtCO2 (Figure 5 and Figure 6). The MAP was unaltered (79 ± 9 mmHg to 77 ± 11 mmHg, p = 0.1955). (Figure 6). The PE induction resulted in elevated troponin T (TnT)13, increased RV afterload, RV ventriculo-arterial uncoupling, and RV dilatation, making it compatible with intermediate-risk PE (data not shown)1,14.
Imaging 
To evaluate the clot burden, a pulmonary obstruction percentage was calculated as previously described (Figure 7)15. In short, the percentage was calculated as <img alt="Equation for weighted average, Σ(n.d)/74·100, used in statistical analysis calculations." src="/files/ftp_upload/67177/67177eq02.jpg" style="margin: auto;" data-altupdatedat="1788304762000" data-alt="Equation 2">, where n is the presence of segmental embolus, and d is the degree of obstruction on a scale from 0-2, computing with a maximum of 74 points. The CTPA performed at baseline showed no signs of PE (Figure 7A), but after PE induction, multiple emboli in the pulmonary arteries were evident on the CTPA, yielding an increase in the CT obstruction percentage (0 [0 - 0] to 57.1% [IQR 38.8-63.3]) (Figure 7C-E).
<img alt="Blood flow experiment setup with tubes and clamp stand; capillary action analysis." class="xfigimg" src="/files/ftp_upload/67177/67177fig01.jpg" data-altupdatedat="1788304762000" data-alt="Figure 1"> 
Figure 1: Embolus formation. (A) PVC tubes filled with 30 mL blood, each hanging vertically for a minimum 3 h. (B) One formed embolus. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Catheterization procedure setup, step-by-step guide; includes tools, insertion, and X-ray images of catheter placement." class="xfigimg" src="/files/ftp_upload/67177/67177fig02.jpg" data-altupdatedat="1788304762000" data-alt="Figure 2"> 
Figure 2: Insertion of 26 F sheath and right heart catheterization. (A) Table with equipment needed for replacing the 8 F sheath, using a 16 F dilator (red arrow) and long extra-stiff guidewire (white arrow), into a 26 F sheath (black double arrow), including the Swan-Ganz (SG) catheter (arrowhead). (B) The wire with the 16 F dilator. (C) The 26 F sheath in place with napkins under the sterile drape to elevate the end. The SG is inserted into the 26 F sheath. (D) Fluoroscopy showing the 26 F (arrow indicating the radiopaque ring of the sheath) with the dilator (marked by dotted lines) and the wire (dotted arrow). (E) Fluoroscopy showing the 26 F sheath (arrow) with the SG catheter (arrowhead). <a href="https://www.jove.com/files/ftp_upload/67177/67177fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Cardiovascular setup diagram: silicone tubes, connectors; aortic perfusion for fluid flow analysis." class="xfigimg" src="/files/ftp_upload/67177/67177fig03.jpg" data-altupdatedat="1788304762000" data-alt="Figure 3"> 
Figure 3: Embolus device. (A) Unassembled components for part A of the embolus device. (B) Unassembled components for part B of the embolus device. (C) From left to right: assembled part A of the embolus device and part B of the embolus device. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Extracorporeal circulation setup with blood bags and tubing for experimental flow analysis." class="xfigimg" src="/files/ftp_upload/67177/67177fig04.jpg" data-altupdatedat="1788304762000" data-alt="Figure 4"> 
Figure 4: Induction of embolus. (A) From left to right: assembled part B of the embolus device, PVC tube, and part A of the embolus device connected to the infusion set by the 3-way side-port. (B) The PVC tube is attached to part A of the embolus device, and an embolus is placed in the tube. (C) Fully assembled embolus device with an embolus. (D) The embolus device (black dotted arrow) with an embolus (black arrow) is inserted into the 26 F sheath (white arrow) with the Swan Ganz catheter (white dotted arrow) in place. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Heart rate and pressure trends graph; time series showing cardiovascular metrics: HR, SAP, PAP, CO2." class="xfigimg" src="/files/ftp_upload/67177/67177fig05.jpg" data-altupdatedat="1788304762000" data-alt="Figure 5"> 
Figure 5: Acute hemodynamic response. Measurements of heart rate (black), mean systemic arterial pressure (green), mean pulmonary arterial pressure (red), and end-tidal CO2 (blue) from one pig. The vertical dotted lines mark the induction of an embolus (PE). After PE induction, the heart rate increases momentarily (black arrows), together with a persistent increase in the mean pulmonary arterial pressure (black dotted arrow). The mean systemic arterial pressure decreases slightly after each PE, and the decrease becomes bigger after each embolus (white arrows). The end-tidal CO2 decreases abruptly after each PE (white dotted arrows). After the fifth PE the pig receives a bolus of norepinephrine (NA) that causes an increase in heart rate and mean systemic- and pulmonary arterial pressure (red arrows). <a href="https://www.jove.com/files/ftp_upload/67177/67177fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Graphs of heart metrics: pulmonary, arterial pressure, heart rate, cardiac output; baseline vs PE." class="xfigimg" src="/files/ftp_upload/67177/67177fig06.jpg" data-altupdatedat="1788304762000" data-alt="Figure 6"> 
Figure 6: Acute physiological response. Comparison of (A) mean pulmonary arterial pressure, (B) mean arterial pressure, (C) heart rate, and (D) cardiac output at baseline and after induction of pulmonary emboli (PE). Timepoints are compared with paired sample t-tests. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig06large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="CT scan images showing pulmonary embolism; graph of obstruction percentage increase&lt;0.0001." class="xfigimg" src="/files/ftp_upload/67177/67177fig07.jpg" data-altupdatedat="1788304762000" data-alt="Figure 7"> 
Figure 7: CT pulmonary angiography (CTPA). (A) Pig after full instrumentation, receiving only saline. No signs of embolic material. (B) CTPA of a pig after full instrumentation receiving only saline. A non-indented embolus (red arrow) is present. (C,D) Immediately after the induction of emboli (green arrows) from two different pigs. (E) Pulmonary obstruction percentage at baseline compared to after induction of pulmonary emboli (PE). Timepoints are compared with paired sample t-tests. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig07large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Pulmonary embolism in dissected lung; medical pathology demonstration; thrombus visible in arteries." class="xfigimg" src="/files/ftp_upload/67177/67177fig08.jpg" data-altupdatedat="1788304762000" data-alt="Figure 8"> 
Figure 8: Necropsy. Macroscopically findings showing the large autologous emboli in the pulmonary arteries. <a href="https://www.jove.com/files/ftp_upload/67177/67177fig08large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

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

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

a-porcine-model-of-acute-autologous-pulmonary-embolism

Research

JoVE Journal

Medicine

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Learn a porcine model of acute autologous pulmonary embolism using autologous blood clots in pigs. This realistic animal model enables investigation of pathophysiology and evaluation of novel pharmacological and interventional treatments.

A Porcine Model of Acute Autologous Pulmonary Embolism

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