Name: improvement of a closed chest porcine myocardial infarction model by standardization of tissue and blood sampling procedures
Uploaded: 2018-03-12T14:30:00
Description: Watch this Scientific Journal Video about Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures at JoVE.com

The authors wish to acknowledge Professor Christian Heinis for providing the FXIIa inhibitor and the respective control. We also gratefully acknowledge Olgica Beslac, Dr. Daniel Mettler and Kay Nettelbeck from the Experimental Surgery Unit, Department for Biomedical Research, University of Bern for technical support. Celine Guillod and Matthias Rausch from the Department for Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, Inselspital provided support with the X-ray equipment and techniques.This project was funded by the Swiss National Science Foundation, project no. 320030_156193.&#160;We also would like to thank Mr. Reto Haenni from communication and marketing, Bern University Hospital, Inselspital for video recording our experiment.

1. Animals:
All animals were treated according to the guidelines of the Swiss national laws. The study was approved by the local animal experimentation committee of the Canton of Bern (permission no. BE 25/16).
Use large white pigs of both sexes (~30 &#177;&#160;5 kg). Divide the animals blindly into two groups, one group receiving a bicyclic (80 kDa protease) inhibitor of FXIIa or treatment of choice and the other an inactive control.
2. Sur...

<ol>
	<li>Mozaffarian, D., 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=Heart+Disease+and+Stroke+Statistics-2016+Update.">Heart Disease and Stroke Statistics-2016 Update.</a> Circulation. 133, e338-e360 (2016).</li><li>Miller, T. D., 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=Infarct+size+after+acute+myocardial+infarction+measured+by+quantitative+tomographic+99mTc+sestamibi+imaging+predicts+subsequent+mortality.">Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality.</a> Circulation. 92, 334-341 (1995).</li><li>Ovize, 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=Postconditioning+and+protection+from+reperfusion+injury:+where+do+we+stand?+Position+Paper+from+the+Working+Group+of+Cellular+Biology+of+the+Heart+of+the+European+Society+of+Cardiology.">Postconditioning and protection from reperfusion injury: where do we stand? Position Paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology.</a> Cardiovasc Res. 87, 406-423 (2010).</li><li>Neri, M., Riezzo, I., Pascale, N., Pomara, C., Turillazzi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ischemia/Reperfusion+Injury+following+Acute+Myocardial+Infarction:+A+Critical+Issue+for+Clinicians+and+Forensic+Pathologists.">Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists.</a> Mediators Inflamm. 2017, 1-14 (2017).</li><li>Yang, Q., He, G. -. W., Underwood, M. J., Yu, C. -. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cellular+and+molecular+mechanisms+of+endothelial+ischemia/reperfusion+injury:+perspectives+and+implications+for+postischemic+myocardial+protection.">Cellular and molecular mechanisms of endothelial ischemia/reperfusion injury: perspectives and implications for postischemic myocardial protection.</a> Am J Transl Res. 8, 765-777 (2016).</li><li>Massberg, S., 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=Platelet-Endothelial+Cell+Interactions+During+Ischemia/Reperfusion:+The+Role+of+P-Selectin.">Platelet-Endothelial Cell Interactions During Ischemia/Reperfusion: The Role of P-Selectin.</a> Blood. 92, 507-515 (1998).</li><li>Wang, 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=Antithrombin+is+protective+against+myocardial+ischemia+and+reperfusion+injury.">Antithrombin is protective against myocardial ischemia and reperfusion injury.</a> J Thromb and Haemost. 11, 1020-1028 (2013).</li><li>Hopp, S., 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=Targeting+coagulation+factor+XII+as+a+novel+therapeutic+option+in+brain+trauma.">Targeting coagulation factor XII as a novel therapeutic option in brain trauma.</a> Ann Neurol. 79, 970-982 (2016).</li><li>Crick, S. J., Sheppard, M. N., Ho, S. Y., Gebstein, L., Anderson, R. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomy+of+the+pig+heart:+comparisons+with+normal+human+cardiac+structure.">Anatomy of the pig heart: comparisons with normal human cardiac structure.</a> J Anat. 193 (Pt 1), 105-119 (1998).</li><li>Heusch, G., Skyschally, A., Schulz, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+in-situ+pig+heart+with+regional+ischemia/reperfusion+-+ready+for+translation.">The in-situ pig heart with regional ischemia/reperfusion - ready for translation.</a> J Mol Cell Cardiol. 50, 951-963 (2011).</li><li>Poirier, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exercise,+heart+rate+variability,+and+longevity:+the+cocoon+mystery?.">Exercise, heart rate variability, and longevity: the cocoon mystery?.</a> Circulation. , 2085-2087 (2014).</li><li>Milani-Nejad, N., Janssen, P. M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+and+large+animal+models+in+cardiac+contraction+research:+advantages+and+disadvantages.">Small and large animal models in cardiac contraction research: advantages and disadvantages.</a> Pharmacol Ther. 141, 235-249 (2014).</li><li>Bloor, C. M., White, F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+development+of+the+coronary+collateral+circulation+during+coronary+artery+occlusion+in+the+conscious+dog.">Functional development of the coronary collateral circulation during coronary artery occlusion in the conscious dog.</a> Am J Pathol. 67, 483-500 (1972).</li><li>Banz, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Locally+targeted+cytoprotection+with+dextran+sulfate+attenuates+experimental+porcine+myocardial+ischaemia/reperfusion+injury.">Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury.</a> Eur Heart J. 26, 2334-2343 (2005).</li><li>Krombach, G. A., Kinzel, S., Mahnken, A. H., G&#252;nther, R. W., Buecker, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Minimally+Invasive+Close-Chest+Method+for+Creating+Reperfused+or+Occlusive+Myocardial+Infarction+in+Swine.">Minimally Invasive Close-Chest Method for Creating Reperfused or Occlusive Myocardial Infarction in Swine.</a> Invest Radiol. 40, 14 (2005).</li><li>Suzuki, Y., Lyons, J. K., Yeung, A. C., Ikeno, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+porcine+model+of+reperfused+myocardial+infarction:+in+situ+double+staining+to+measure+precise+infarct+area/area+at+risk.">In vivo porcine model of reperfused myocardial infarction: in situ double staining to measure precise infarct area/area at risk.</a> Catheter Cardiovasc Interv. 71, 100-107 (2008).</li><li>McCall, F. 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=Myocardial+infarction+and+intramyocardial+injection+models+in+swine.">Myocardial infarction and intramyocardial injection models in swine.</a> Nat Protoc. 7, 1479-1496 (2012).</li><li>Koudstaal, S., 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=Myocardial+infarction+and+functional+outcome+assessment+in+pigs.">Myocardial infarction and functional outcome assessment in pigs.</a> J Vis Exp. , e51269 (2014).</li><li>Kamat, P., 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=Dexrazoxane+Shows+No+Protective+Effect+in+the+Acute+Phase+of+Reperfusion+during+Myocardial+Infarction+in+Pigs.">Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs.</a> PLoS One. 11, e0168541 (2016).</li><li>Carden, D. L., Granger, D. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+of+ischaemia-reperfusion+injury.">Pathophysiology of ischaemia-reperfusion injury.</a> J Pathol. 190, 255-266 (2000).</li><li>P&#233;rez de Prado, 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=Closed-chest+experimental+porcine+model+of+acute+myocardial+infarction-reperfusion.">Closed-chest experimental porcine model of acute myocardial infarction-reperfusion.</a> J Pharmacol Toxicol Methods. 60, 301-306 (2009).</li><li>Lown, B., Levine, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+carotid+sinus.+Clinical+value+of+its+stimulation.">The carotid sinus. Clinical value of its stimulation.</a> Circulation. 23, 766-789 (1961).</li><li>Regueiro-Purri&#241;os, 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=Ventricular+Arrhythmias+and+Mortality+Associated+with+Isoflurane+and+Sevoflurane+in+a+Porcine+Model+of+Myocardial+Infarction.">Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction.</a> J Am Assoc Lab Anim Sci. , (2011).</li><li>Roberts, L. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evans+blue+toxicity.">Evans blue toxicity.</a> Can Med Assoc J. 71, 489-491 (1954).</li><li>Ellenbroek, G. H. 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=Primary+Outcome+Assessment+in+a+Pig+Model+of+Acute+Myocardial+Infarction.">Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction.</a> J Vis Exp. , e54021 (2016).</li></ol>

Myocardial I/R injury has a significant effect on the final infarct size which is directly translated into the patient&#39;s prognosis after acute myocardial infarction3. Understanding the pathophysiology of myocardial I/R injury is the first step to reduce or prevent it. Myocardial I/R injury is an acute condition that occurs directly after reperfusion of the occluded vessels. I/R injury leads to activation of the innate immune response and cellular damage occurs at the site of reperfusion and th...

Ischemic heart disease, in particular acute myocardial infarction (MI), is the main cause of death in developed countries 1. Today, the standard treatment of MI is percutaneous coronary intervention (PCI), the balloon catheter treatment. One of the critical factors that affects quality of life and prognosis of patients after PCI-treated acute MI is the infarction size. The reduction of the size can have a great impact on patient survival and prognosis 2. Myocardial ischemia/reperfusion (I/R) injury has a significant influence on the infarction size so one of the main aims in cardiovascular research is to prevent or reduce myocardial I/R injury 3. The exact mechanisms of I/R injury are still under investigation 4. Activation of the plasma cascades and endothelial cells are hallmarks of I/R injury 5. Activation of the coagulation system is clearly involved 6,7. Recently, the role of FXII, as an early upstream peptide involved in contact phase activation of the coagulation cascade, has been shown in a FXII knock out rat model of cerebral I/R injury 8. Validation of these results in a porcine model is an important step into clinical translation. Therefore, we are testing a novel bicyclic (80 kDa protease) FXIIa inhibitor in the context of myocardial I/R injury in a pilot study.
Animal models, which mimic the clinical situation of acute MI and PCI treatments, are essential to improve our understanding of the pathophysiology of myocardial I/R injury and to test novel treatment options. Pigs represent a good animal model for clinical myocardial I/R injury. This is not only because their hearts are very similar to human hearts with respect to anatomy and coronary circulation, but they also show similar pathophysiological responses to myocardial ischemia and reperfusion 9,10. Other models such as rats and mice do not fulfill these criteria and show considerable differences when compared to human hearts 11,12, whereas dogs for example, have many more collateral coronary vessels as compared with humans 13.
The porcine acute myocardial infarction model has been widely used in cardiovascular research to investigate ischemic heart disease including myocardial I/R injury 14,15,16,17. The latter is an inflammatory condition, because of which minimizing the inflammatory reaction related to sternotomy or thoracotomy used in open-chest surgery is essential. The closed chest model using a clinical C-arm angiography setting overcomes this problem. Furthermore, one of the most important points is that our protocol provides an accurate distinction between ischemic (area at risk, AAR) and non-ischemic areas of the left ventricle (area not at risk, ANR) so that the infarct size (necrotic ischemic tissue, NIT) can be accurately determined. Our aim for this paper is to clearly define a reproducible methodology of a porcine myocardial I/R injury model, in particular with respect to myocardial tissue sampling, which will allow for a more precise analysis of the molecular mechanisms of I/R injury and a clearer picture of the effects of novel drug treatments.

<table>
	<tbody>
		<tr>
			<td>ABL 90 Flex, blood gas analyser</td>
			<td>Radiometer</td>
			<td>-</td>
			<td>Blood gas analysis (BGA)</td>
		</tr>
		<tr>
			<td>ACT Plus</td>
			<td>Medtronic</td>
			<td>-</td>
			<td>Activated clotting time</td>
		</tr>
		<tr>
			<td>Atropin</td>
			<td>Sintetica</td>
			<td>-</td>
			<td>Atropinum Sulfas, 0,5mg/ml</td>
		</tr>
		<tr>
			<td>Balance (20-500 Kg)</td>
			<td>NAGATA Scale, Tiwan</td>
			<td>HTB/HTR</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Balance (21-4200 g)</td>
			<td>Mettler toledo, Switzerland</td>
			<td>MS4002SDR</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Blood collection tubes: EDTA, citrate and serum</td>
			<td>S-Monovette, Nuembrecht, Germany</td>
			<td>05.1167.001, 
			05.1071.001 
			and 
			05.1557.001 respectively</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>BV Pulsera mobile C-arm</td>
			<td>Philips</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Centrifuge</td>
			<td>Labcare, UK</td>
			<td>ALC PK120R</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Defibrillator Lifepak 12</td>
			<td>Medtronic</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Dextran from Leuconostoc mesenteroides</td>
			<td>Sigma-Aldrich, Germany</td>
			<td>D3759</td>
			<td>Average M.wt 48000-90000</td>
		</tr>
		<tr>
			<td>Digital single lens reflex camera</td>
			<td>Sony, Thailand</td>
			<td>DSLR-A500/A550</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Dissecting forceps</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>EMPIRA RX PCI dilatation catheter</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>85R15300S</td>
			<td>Diameter 3 mm, length 15 mm, Alternative products can be used</td>
		</tr>
		<tr>
			<td>EMPIRA RX PCI dilatation catheter</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>85R15350S</td>
			<td>Diameter 3.5 mm, length 15 mm, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Evans Blue</td>
			<td>Sigma-Aldrich, Germany</td>
			<td>E2129</td>
			<td>Toxic</td>
		</tr>
		<tr>
			<td>Fabius GS premium respirator</td>
			<td>Dr&#228;ger, L&#252;beck, Germany</td>
			<td>-</td>
			<td>Anesthesia work station, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Fentanyl</td>
			<td>Inselspital ISPI</td>
			<td>-</td>
			<td>Fentanyl 2500mcg/50ml</td>
		</tr>
		<tr>
			<td>Formaldehyde</td>
			<td>Pathology Institute, Bern University</td>
			<td>SI148701</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>FXIIa inhibitor</td>
			<td>Provided by Prof. Christian Heinis&#39; laboratory in EPFL</td>
			<td></td>
			<td>Novel bicyclic peptide</td>
		</tr>
		<tr>
			<td>Galeo, coronary guidewire</td>
			<td>Biotronik, Germany</td>
			<td>125497</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Guidance catheter</td>
			<td>Boston Scientific, Florida, USA</td>
			<td>34356-06</td>
			<td>6F (100 cm, EB3.75). Alternative products can be used</td>
		</tr>
		<tr>
			<td>Heparin Sodium</td>
			<td>Drossapharm, Basel, Switzerland</td>
			<td>-</td>
			<td>Liquemin, 25000 U.I./5 ml</td>
		</tr>
		<tr>
			<td>High end electrosurgery</td>
			<td>BOWA, Germany</td>
			<td>ARC 400</td>
			<td>Electrical source for blood suction. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Hydro-Guardmini breathing filter</td>
			<td>Intersurgical, Lithuania</td>
			<td>1745000</td>
			<td>Filters</td>
		</tr>
		<tr>
			<td>Image J</td>
			<td>National Institute of Health, USA</td>
			<td>1.47v</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Inflation device, Atrion QL2530</td>
			<td>Atrion medical product, Alabama, USA</td>
			<td>96402</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>IntelliVue MP 70</td>
			<td>Philips, Boeblingen, Germany</td>
			<td>-</td>
			<td>Monitor (ECG, heart rate, blood presure and body temperature). Alternative products can be used</td>
		</tr>
		<tr>
			<td>KCl</td>
			<td>Sintetica SA</td>
			<td>-</td>
			<td>Potassium chloride 15%</td>
		</tr>
		<tr>
			<td>Ketamine</td>
			<td>Vetoquinol</td>
			<td>-</td>
			<td>Narketan, 1ml/100mg</td>
		</tr>
		<tr>
			<td>LR-ACT</td>
			<td>Medtronic</td>
			<td>402-01</td>
			<td>ACT special syringes</td>
		</tr>
		<tr>
			<td>Midazolam</td>
			<td>Roche</td>
			<td>-</td>
			<td>Dormicum, 5mg/ml</td>
		</tr>
		<tr>
			<td>Monopolar scalpel</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Needle holder</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>High resolution camera, PathStand Macro Imaging Stand for Grossing</td>
			<td>Spotimaging, USA</td>
			<td></td>
			<td>1080 p HD resolution. Alternative products can be used</td>
		</tr>
		<tr>
			<td>PBS</td>
			<td>In-house preparation</td>
			<td>-</td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Peripheral venous cannula, 18 G</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>PowerLab 4/35 data acquisition system</td>
			<td>Adinstruments, Spechbach, Germany</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotamax120T</td>
			<td>Heidolph, Germany</td>
			<td>544-41200-00</td>
			<td>Shaker. Alternative can be used</td>
		</tr>
		<tr>
			<td>R&#252;schelit-Super Safety Clear Tube</td>
			<td>Teleflex, Dublin, Irland</td>
			<td>112480</td>
			<td>Air way tubing, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Safe Pico Aspirator Syringes</td>
			<td>Radiometer</td>
			<td>956-622</td>
			<td>BGA special syringes</td>
		</tr>
		<tr>
			<td>Saline</td>
			<td>Sintetica Bioren</td>
			<td>-</td>
			<td>NaCl 0,9%. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Sevorane 1.5%</td>
			<td>AbbVie AG</td>
			<td>-</td>
			<td>Sevorane 250ml 100%</td>
		</tr>
		<tr>
			<td>Sheath</td>
			<td>Cordis, Johnson&#38;Johnson, USA</td>
			<td>504-607 A</td>
			<td>AVANTI + / 7 F, Alternative products can be used</td>
		</tr>
		<tr>
			<td>Space infusion pump</td>
			<td>B.Braun Medical AG, Germany</td>
			<td>-</td>
			<td>For infusion of fentanyl. Alternative products can be used</td>
		</tr>
		<tr>
			<td>SPR-350 (Millar catheter)</td>
			<td>Adinstruments, Texas, USA</td>
			<td>840-8166</td>
			<td>MIKRO-TIP, 5F, 120 cm</td>
		</tr>
		<tr>
			<td>Sternotomy saw</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Sutures</td>
			<td>ETHICON, Johnson&#38;Johnson, USA</td>
			<td>Y3110H</td>
			<td>Monocryl 3-0 SH-1 Plus. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Syringes (20, 10 and 5 mL)</td>
			<td>CODAN,Baar, Switzerland</td>
			<td>62.7602, 
			62.6616, 
			62.5607 
			respectively</td>
			<td>Used to inject anesthetic materials intramuscularly or directly into the central venous line. Also to inject heparin or FXIIa or the respective control. Alternative products can be used</td>
		</tr>
		<tr>
			<td>Thorax spreader</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Tissue-tek</td>
			<td>SAKURA, Netherlands</td>
			<td>4583</td>
			<td>O.C.T. compound</td>
		</tr>
		<tr>
			<td>Vascular forceps</td>
			<td></td>
			<td></td>
			<td>Alternative products can be used</td>
		</tr>
		<tr>
			<td>Xenetix 300 contrast media</td>
			<td>Guerbet, Z&#252;rich, Switzerland</td>
			<td>-</td>
			<td>Lobitridol, 300 mg iodide/ml</td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Vetoquinol</td>
			<td>-</td>
			<td>Xylapan, 20mg/1 mL</td>
		</tr>
		<tr>
			<td>2,3,5-Triphenyltetrazolium choride</td>
			<td>Sigma-Aldrich, Austria</td>
			<td>T8877</td>
			<td></td>
		</tr>
		<tr>
			<td>500 &#956;L tubes (eppendorf)</td>
			<td>Trefflab, Switzerland</td>
			<td>96.08185.9.03</td>
			<td>Alternative products can be used</td>
		</tr>
	</tbody>
</table>

improvement of a closed chest porcine myocardial infarction model by standardization of tissue and blood sampling procedures

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological mechanisms of myocardial I/R injury is essential to develop successful treatments. Large animal experiments are an important step in translational methods. The porcine model of acute myocardial infarction has been established and described by ourselves and others. We aimed to further improve the value of the model by focusing in detail on the sampling techniques for use in future experiments. Furthermore, we emphasize small but important steps that can affect the quality of the final results. To mimic the clinical situation of myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was inserted into the left anterior descending coronary artery (LAD) of an anesthetized pig. &#176;&#176;&#176;This model mimics acute myocardial infarction and PCI treatment in humans with the possibility of accurately determining the area at risk as well as the necrotic- and viable ischemic tissue. Here the model was used to investigate the effect of a bicyclic peptide inhibitor of FXIIa. The model can also be modified to allow longer reperfusion times to study later effects of myocardial infarction.

One animal died prematurely before administration of FXIIa inhibitor or control peptide due to a technical error (sudden drop of blood pressure during ischemia time, before addition of test substance). One animal was excluded from the FXIIa inhibitor group because no ischemia/reperfusion injury was observed due to abnormal anatomy of the left anterior descending artery (LAD). A large part of the left ventricle, including the apex, was perfused by the circumflex artery in this animal. The ...

Watch this Scientific Journal Video about Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures at JoVE.com

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Here we demonstrate a protocol to standardize sampling procedures of an established porcine model of acute myocardial infarction in order to increase its translational value in the understanding of the pathophysiology of myocardial ischemia/reperfusion injury and to test novel drug candidates.

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

Research

JoVE Journal

Medicine

Acute Myocardial Infarction in Rats

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular ...

A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion

Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ...

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 ...

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

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

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in GÃƒÆ’Ã‚Â¶ttingen Minipigs and Landrace Pigs

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