Name: surgical swine model of chronic cardiac ischemia treated by off-pump coronary artery bypass graft surgery
Uploaded: 2018-03-27T13:00:00
Description: Watch this Scientific Journal Video about Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery at JoVE.com

This work was supported by the VA Merit Review #I01 BX000760 (RFK) from the United States (U.S.) Department of Veterans Affairs BLR&amp;D. The contents of this work do not represent the views of the U.S. Department of Veterans Affairs of the United States Government.

All animal studies were approved by the Institutional Animal Care and Use Committees of the Minneapolis VA Medical Center and the University of Minnesota. Follow current National Institutes of Health guidelines for the use and care of laboratory animals.
1. Hibernation Surgery
<ol>
	<li>Animal Preparation
	<ol>
		<li>To create a model of hibernating myocardium, use 5-week old, female, Yorkshire pigs, which weigh in the range of 8-10 kg with 9.2 kg as the average weight.</li>
		<li>For pre-su...

<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+A+Report+From+the+American+Heart+Association.">Heart Disease and Stroke Statistics-2016 Update A Report From the American Heart Association.</a> Circulation. 133 (4), 350 (2015).</li><li>Di Carli, M. F., 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=Value+of+metabolic+imaging+with+positron+emission+tomography+for+evaluating+prognosis+in+patients+with+coronary+artery+disease+and+left+ventricular+dysfunction.">Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction.</a> Am J Cardiol. 73 (8), 527-533 (1994).</li><li>Gerber, B. L., 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=Prognostic+value+of+myocardial+viability+by+delayed-enhanced+magnetic+resonance+in+patients+with+coronary+artery+disease+and+low+ejection+fraction:+impact+of+revascularization+therapy.">Prognostic value of myocardial viability by delayed-enhanced magnetic resonance in patients with coronary artery disease and low ejection fraction: impact of revascularization therapy.</a> J Am Coll Cardiol. 59 (9), 825-835 (2012).</li><li>McFalls, 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=Regional+glucose+uptake+within+hypoperfused+swine+myocardium+as+measured+by+positron+emission+tomography.">Regional glucose uptake within hypoperfused swine myocardium as measured by positron emission tomography.</a> Am J Physiol-Heart C. 272 (1), 343-349 (1997).</li><li>Velazquez, E. 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=Coronary-artery+bypass+surgery+in+patients+with+left+ventricular+dysfunction.">Coronary-artery bypass surgery in patients with left ventricular dysfunction.</a> New Engl J Med. 364 (17), 1607-1616 (2011).</li><li>Canty, J. M., Fallavollita, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hibernating+myocardium.">Hibernating myocardium.</a> J Nucl Cardiol. 12 (1), 104-119 (2005).</li><li>Joyce, 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=Revascularization+and+ventricular+restoration+in+patients+with+ischemic+heart+failure:+the+STICH+trial.">Revascularization and ventricular restoration in patients with ischemic heart failure: the STICH trial.</a> Curr Opin Cardiol. 18 (6), 454-457 (2003).</li><li>Shah, B. N., Khattar, R. S., Senior, 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+hibernating+myocardium:+current+concepts,+diagnostic+dilemmas,+and+clinical+challenges+in+the+post-STICH+era.">The hibernating myocardium: current concepts, diagnostic dilemmas, and clinical challenges in the post-STICH era.</a> Eur Heart J. 34 (18), 1323-1336 (2013).</li><li>Stone, L. L. H., 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=Magnetic+resonance+imaging+assessment+of+cardiac+function+in+a+swine+model+of+hibernating+myocardium+3+months+following+bypass+surgery.">Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery.</a> J Thorac Cardiov Sur. , (2016).</li><li>Kukulski, T., 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=Implication+of+right+ventricular+dysfunction+on+long-term+outcome+in+patients+with+ischemic+cardiomyopathy+undergoing+coronary+artery+bypass+grafting+with+or+without+surgical+ventricular+reconstruction.">Implication of right ventricular dysfunction on long-term outcome in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting with or without surgical ventricular reconstruction.</a> J Thorac Cardiov Sur. 149 (5), 1312-1321 (2014).</li><li>Rahimtoola, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hibernating+myocardium.">The hibernating myocardium.</a> Am Heart J. 117 (1), 211-221 (1989).</li><li>Fallavollita, J. A., Logue, M., Canty, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stability+of+hibernating+myocardium+in+pigs+with+a+chronic+left+anterior+descending+coronary+artery+stenosis:+absence+of+progressive+fibrosis+in+the+setting+of+stable+reductions+in+flow,+function+and+coronary+flow+reserve.">Stability of hibernating myocardium in pigs with a chronic left anterior descending coronary artery stenosis: absence of progressive fibrosis in the setting of stable reductions in flow, function and coronary flow reserve.</a> J Am Coll Cardiol. 37 (7), 1989-1995 (2001).</li><li>White, F. C., Carroll, S. M., Magnet, A., Bloor, 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=Coronary+collateral+development+in+swine+after+coronary+artery+occlusion.">Coronary collateral development in swine after coronary artery occlusion.</a> Circ Res. 71 (6), 1490-1500 (1992).</li><li>Viscardi, A. V., Hunniford, M., Lawlis, P., Leach, M., Turner, P. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+Piglet+Grimace+Scale+to+Evaluate+Piglet+Pain+Using+Facial+Expressions+Following+Castration+and+Tail+Docking:+A+Pilot+Study.">Development of a Piglet Grimace Scale to Evaluate Piglet Pain Using Facial Expressions Following Castration and Tail Docking: A Pilot Study.</a> Front Vet Sci. 4, 51 (2017).</li><li>Holley, C. T., Long, E. K., Lindsey, M. E., McFalls, E. O., Kelly, R. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+hibernating+myocardium:+what+is+the+role+of+surgical+revascularization.">Recovery of hibernating myocardium: what is the role of surgical revascularization.</a> J Cardiac Surg. 30 (2), 224-231 (2015).</li><li>Cooper, H. A., Braunwald, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+importance+of+stunned+and+hibernating+myocardium.">Clinical importance of stunned and hibernating myocardium.</a> Coronary Artery Dis. 12 (5), 387-392 (2001).</li><li>McFalls, E. O., 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=Utility+of+positron+emission+tomography+in+predicting+improved+left+ventricular+ejection+fraction+after+coronary+artery+bypass+grafting+among+patients+with+ischemic+cardiomyopathy.">Utility of positron emission tomography in predicting improved left ventricular ejection fraction after coronary artery bypass grafting among patients with ischemic cardiomyopathy.</a> Cardiology. 93 (1-2), 105-112 (2000).</li><li>Pasquet, 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=Prediction+of+global+left+ventricular+function+after+bypass+surgery+in+patients+with+severe+left+ventricular+dysfunction.+Impact+of+pre-operative+myocardial+function,+perfusion,+and+metabolism.">Prediction of global left ventricular function after bypass surgery in patients with severe left ventricular dysfunction. Impact of pre-operative myocardial function, perfusion, and metabolism.</a> Eur Heart J. 21 (2), 125-136 (2000).</li></ol>

Here, we show that our swine model of HM accurately mimics the clinical experience of patients with single vessel disease and preserved left ventricular function. Prior to the revascularization, animals with single vessel HM exhibit minimal impairment in global function as measured by ejection fraction, but show significant reduction in regional wall thickening. Following the revascularization, CMR imaging at one or three months of recovery demonstrates preserved viability and graft patency but persistent regional dysfun...

Coronary heart disease (CHD) affects an estimated 15.5 million people in the United States 1 and is one of the leading causes of death globally. While the mortality rate associated with CHD has gone down in recent years, the incidence and burden on patients and the health care system remain high 1. Primary treatment of severe CAD is revascularization, which improves survival and reduces angina2,3,4. However, cardiac function often remains depressed, especially under increased workload and can progress to heart failure5,6. Clinical trials of coronary artery bypass surgery (CABG) for chronic ischemia demonstrate improvement in survival and symptoms, but ejection fraction shows only modest improvements of 8-10% 7,8. Our innovative and well-characterized swine model of chronic myocardial ischemia is a model of clinical CAD with progressive vascular stenosis. We have demonstrated reduced myocardial contractility resulting from gradual reduction in blood flow 9. The myocardium does not infarct and can remain viable in this scenario. Recovery is possible, though outcomes are variable even with timely revascularization. Chronically ischemic myocardium that remains viable has been characterized by reduced blood flow and function at rest with retained contractile reserve has been termed HM and treatment requires CABG.Although the revascularization of HM should restore contractile function, experimental and clinical observations demonstrate that the recovery is incomplete8,10.
HM is characterized by the presence of viable yet dysfunctional myocardium in the presence of reduced regional blood flow11. Despite impaired contractility and metabolic activity at rest, HM is able to demonstrate functional and metabolic reserve under inotropic stimulation12. HM is suspected in a majority of patients with CAD, and encompasses a broad spectrum of disease. In this protocol, we demonstrate our established swine model of HM bypassed with left internal mammary artery (LIMA) to LAD artery that mimics the clinical scenario. The swine provide an excellent model of heart disease over other large animals as they do not have epicardial bridging collaterals. This allows the stenosis of the LAD alone to result in regional ischemia13.
Here, we describe the surgical method of inducing hibernating myocardium in swine by creating single-vessel stenosis at the LAD artery. Once chronic ischemia has been established (8 weeks post implant of LAD constrictor), we describe the method of recreating the clinical treatment for HM in our swine model: an off-pump coronary artery bypass graft. These surgical methods can be used to not only study a clinically relevant model of chronic cardiac ischemia, but also to investigate the effects of bypass surgery on cardiac ischemia as well as test potential alternate or adjunctive therapies for cardiac ischemia.

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	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Bair Hugger</td>
			<td style="width:223px;">3M</td>
			<td style="width:203px;">Model 505</td>
			<td style="width:468px;">Patient Warming system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">SR Buprenorphine 10 mg/mL</td>
			<td style="width:223px;">Abbott Labs</td>
			<td style="width:203px;">NADA 141-434</td>
			<td>Post operative Analgesic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Surgical Spring Clip</td>
			<td>Applied Medical</td>
			<td>A1801</td>
			<td>Clamp end of LIMA after takedown</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Arterial Line Kit</td>
			<td>Arrow</td>
			<td>ASK-04510-HF</td>
			<td>Femoral catheter for blood pressure monitoring</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">1000mL 0.9% Sodium chloride</td>
			<td>Baxter</td>
			<td>2B1324X</td>
			<td>IV replacement fluid</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">250 mL 0.9% saline</td>
			<td>Baxter</td>
			<td>&#160;UE1322D</td>
			<td>Replacement IV Fluid&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">500mL 0.9% Sodium chloride</td>
			<td>Baxter</td>
			<td>2B1323Q</td>
			<td>Drug delivery, Provide mist for Blower Mister</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Flo-thru 1.0</td>
			<td>Baxter</td>
			<td>FT-12100</td>
			<td>used to anastomos LIMA to L</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Flo-thru 1.25</td>
			<td>Baxter</td>
			<td>FT-12125</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Flo-thru 1.5</td>
			<td>Baxter</td>
			<td>FT-12150</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Flo-thru 2.0</td>
			<td>Baxter</td>
			<td>FT-12200</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Cloroprep</td>
			<td style="width:223px;">Becton Dickenson</td>
			<td style="width:203px;">260815</td>
			<td>Surgical skin prep</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Meloxicam</td>
			<td>Boehringer Ingelheim Vetmedica, Inc.</td>
			<td>0010-6013-01</td>
			<td>NSAID for analgesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Hypafix</td>
			<td>BSN Medical</td>
			<td>4210</td>
			<td>Secure wound dressing and IV catheters</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">IV Tubing for Blower Mister</td>
			<td>Carefusion</td>
			<td>42493E</td>
			<td>Adapts to IV Fluids for Blower/Mister</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Bovie Cautery hand piece&#160;</td>
			<td>Covidien</td>
			<td>E2516</td>
			<td>Hemostasis&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Chest Tube</td>
			<td>Covidien</td>
			<td>8888561043</td>
			<td>Evacuates air from chest cavity&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Monopolar Cautery&#160;</td>
			<td>Covidien</td>
			<td>Valleylab FT10</td>
			<td>Hemostasis&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Telpha pad</td>
			<td style="width:223px;">Covidien</td>
			<td style="width:203px;">2132</td>
			<td>Sterile wound dressing</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">4-0 Tevdek II Strands</td>
			<td style="width:223px;">Deknatel</td>
			<td style="width:203px;">7-922</td>
			<td>Suture to secure constrictor around LAD</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Propofol</td>
			<td style="width:223px;">Diprivan</td>
			<td style="width:203px;">269-29</td>
			<td>Induction agent</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">&#160;long blade for laryngoscope&#160;</td>
			<td style="width:223px;">DRE</td>
			<td>12521</td>
			<td>Allows for visualization of trachea for intubation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">ECG Pads</td>
			<td>DRE</td>
			<td>1496</td>
			<td>Monitor heart rhythm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">laryngoscope&#160;</td>
			<td style="width:223px;">DRE</td>
			<td>12515</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Anesthesia Machine + ventilator</td>
			<td style="width:223px;">DRE Drager- Fabius Tiro</td>
			<td style="width:203px;">DRE0603FT</td>
			<td>Deliver Oxygen and inhalant to patient</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">&#160;5 Ethibond&#160;</td>
			<td>Ethicon</td>
			<td>MG46G</td>
			<td>Suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">0 Vicryl</td>
			<td>Ethicon</td>
			<td>J208H</td>
			<td>Suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">2-0 Vicryl</td>
			<td>Ethicon</td>
			<td>J317H</td>
			<td>Suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">3-0 Vicryl</td>
			<td>Ethicon</td>
			<td>VCP824G</td>
			<td>Suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">7-0 Prolene</td>
			<td>Ethicon</td>
			<td>M8702</td>
			<td>Suture</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Dermabond</td>
			<td style="width:223px;">Ethicon</td>
			<td>DNX12</td>
			<td>Skin adhesive</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Ligaclips</td>
			<td>Ethicon</td>
			<td>MSC20</td>
			<td>Surgical Staples for LIMA takedown</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Sterile Saline 20 mL</td>
			<td>Fisher Scientific</td>
			<td>20T700220</td>
			<td>Flush for IV catheters</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Telazol 100 mg/mL</td>
			<td style="width:223px;">Fort Dodge</td>
			<td style="width:203px;">01L60030</td>
			<td>Pre operative Sedative</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Triple Antibiotic Ointment</td>
			<td style="width:223px;">Johnson &#38; Johnson</td>
			<td style="width:203px;">23734</td>
			<td>Topical over wound</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">6.0 mm ID endotracheal tube</td>
			<td>Mallinckrodt</td>
			<td>86049</td>
			<td>Establish airway for Revasc,MRI and Termination</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">1&#34; medical tape</td>
			<td style="width:223px;">Medline</td>
			<td>MMM15271Z</td>
			<td>Secure wound dressing and IV catheters</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">4.0 mm ID endotracheal tube</td>
			<td>Medline</td>
			<td>DYND43040</td>
			<td>Establish airway for Hibernation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">4.5 mm ID endotracheal tube</td>
			<td>Medline</td>
			<td>DYND43045</td>
			<td>Establish airway for Hibernation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">5.0 mm ID endotracheal tube</td>
			<td>Medline</td>
			<td>DYND43050</td>
			<td>Establish airway for Hibernation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">6.5 mm ID endotracheal tube</td>
			<td>Medline</td>
			<td>DYND43065</td>
			<td>Establish airway for Revasc,MRI and Termination</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">7.0 mm ID endotracheal tube</td>
			<td>Medline</td>
			<td>DYND43070</td>
			<td>Establish airway for Revasc,MRI and Termination</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:261px;">Bair Hugger Blanket -&#160; Large size, underbody</td>
			<td>Medline</td>
			<td>AUG55501</td>
			<td>Patient Warming system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Basic pack</td>
			<td style="width:223px;">Medline</td>
			<td style="width:203px;">DYNJP1000</td>
			<td>Sterile drapes and table cover</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Bone Wax</td>
			<td>Medline</td>
			<td>ETHW31G</td>
			<td>Hemostasis of cut bone</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Suction&#160; tubing</td>
			<td>Medline</td>
			<td>DYND50223</td>
			<td></td>
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		<tr height="21">
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			<td>Supports ventilation with inhalant</td>
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			<td height="21" style="height:21px;width:261px;">Isoflurane</td>
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			<td>Smith&#8217;s Medical</td>
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			<td>Smith&#8217;s Medical</td>
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			<td height="21" style="height:21px;width:261px;">Jelco 20 ga IV catheter</td>
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			<td>IV access in the MRI</td>
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			<td height="21" style="height:21px;width:261px;">Jelco 22 ga&#160; IV catheter</td>
			<td style="width:223px;">Smiths medical</td>
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			<td>Terumo Cardiovascular System</td>
			<td>401-230</td>
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			<td>Thermo Fisher</td>
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			<td>Used to open chest cavity</td>
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			<td height="21" style="height:21px;width:261px;">Delrin Constrictor</td>
			<td style="width:223px;">U of MN</td>
			<td style="width:203px;">Custom made</td>
			<td>Creates stenosis of LAD</td>
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			<td>various</td>
			<td>various</td>
			<td>Used for Blower Mister if anesthesia machine doesn&#39;t have auxiliary flow meter</td>
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			<td height="21" style="height:21px;width:261px;">Pressure Transducer</td>
			<td>various</td>
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			<td height="21" style="height:21px;width:261px;">Xylazine 100 mg/mL</td>
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			<td style="width:203px;">468RX</td>
			<td>Pre operative Sedative/ analgesic</td>
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surgical swine model of chronic cardiac ischemia treated by off-pump coronary artery bypass graft surgery

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

Following the initial hibernation surgery, stenosis greater than 70% should be able to be observed by clinical imaging techniques such as angiography or cardiac MRI (Figure 1A). 8 weeks following the surgical application of the LAD constrictor, analysis of regional function by ECHO or cardiac MRI reveals reduced function under increased workload (Figure 2). This can be tested by stimulating the heart with dobutam...

Watch this Scientific Journal Video about Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery at JoVE.com

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

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

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

The overall goals of this surgical procedure are to create a clinically relevant model of chronic cardiac ischemia and to observe the effects of revascularization in this model using the current clinical therapy of coronary artery bypass graft surgery. This method can help answer key questions in the field of cardiothoracic surgery about how standard surgical treatments of blood flow restoration alter cardiac function and biology. The advantage of this technique is that it accurately mimics the gradual development of clinical atherosclerotic disease in a large animal model of chronic ischemia without infarction.To create a model of hibernating myocardium, place a five-week-old, eight to 10 kilogram female Yorkshire pig onto it's right side and prep and drape the left side of the chest from the spine to the scapula, centering the third rib space in the sterile field. After IV Cefazolin administration, perform an intercostal nerve block at the second, third, and fourth ribs. To expose the heart, use monopolar electrocautery to make a lateral third spaced thoracotomy incision approximately 10 centimeters from the cranial aspect of the scapula to the axcilliary area, followed by an electrocautery incision to the skin and underlying musculature.To prevent arrhythmia, deliver a two milligram per kilogram IV Lidocaine bolus and carefully insert a Finochietto rib retractor at the third intercostal space using gauze to retract the lung. Sharply incise the pericardium and use 2-0 polyglactin stay sutures to retract the pericardium to the side exposing the heart. Using a gauze-covered spatula retractor, retract the left atrial appendage and use Iris scissors to open the adventicia over the left anterior descending artery.Bluntly dissect an approximately quarter centimeter portion of the artery, approximately one centimeter distal to the left anterior artery and the circumflex artery junction. Using a right angle clamp, encircle the left anterior descending artery and loosely place two 4-0 polyester sutures around the artery. Place a plastic c-shaped constrictor onto the left anterior descending artery proximal to the first diagonal, without occluding the vessel, and secure the constrictor with the two 4-0 polyester ties encircling the artery.It is critical that large enough space is dissected around the left anterior descending artery to allow placement of the constrictor. Using a 2-0 polyglactin suture in a simple interrupted pattern, loosely close the pericardium and the intercostal muscle layer performing a breath-hold to remove the air from the chest as the intercostal muscle suture is tied. Carefully monitor the airway pressure manometer on the anesthesia machine to maintain the pressure in the 20 to 30 centimeters of water range, and release when the breath is complete.Then use 2-0 and 3-0 absorbable sutures, respectively, to close the muscle and skin layers according to standard protocols and use skin adhesive over the incision for skin closure. At least eight weeks after constrictor placement surgery, place the chronically ischemic animal in the dorsal position and prepare the pickford surgery as just demonstrated. Using monopolar electrocautery, make an approximately three centimeter skin incision over the femoral artery to expose the artery for cannulation.Connect the femoral cannula to a transducer to monitor the blood pressure during the surgery. Using electrocautery, make an incision from the manubrium to the xiphoid process to expose the sternum and divide the sternum with an oscillating saw. Use straight Mayo scissors to divide the posterior sternal plate and use a chest retractor to expose the thoracic cavity.Remove any adhesions from the thoracotomy by monopolar electrocautery and have an assistant gently elevate the left sternal border. Using the same retractor, dissect the left internal mammary artery free from the chest wall and use hemoclips to control the arterial branches. When fully mobilized, heparinize the animal with 200 to 300 units per killogram of heparin for three minutes.Next, over-sew the distal end of the artery and proximally place an occluder. Then use Iris scissors to create a three millimeter extension in the proximal end of the artery. Open and retract the pericardium and confirm that the length of the left internal mammary artery is adequate to reach the appropriate anastimotic sight on the left anterior descending artery.Using a spring-form clip and cardiac stabilizer, open the adventicia to expose the left anterior descending artery and secure the opening with elastic tape. Place an appropriately-sized intralumenal device into the vessel and release the tape slightly to avoid ischemia. Use a running 7-0 polypropylene suture to anastimose the left internal mammary artery to left anterior descending artery and remove the intralumenal shunt.After tying the suture, remove the occluder from the left internal mammary artery to establish the flow. Hemostasis is critical to the performance of the anastimosis. Have one assistant hold the left internal mammary artery and have another use an air blower device to keep the field dry during the anastimosis.Once hemostatic, place a chest tube between the ribs on the left lateral chest and use suction to remove air from the chest cavity for 15 to 30 minutes. Place a suture around the chest tube and close the incision with number 5 polyester sutures in a figure 8 pattern to approximate the sternum. Close the muscle, subcutaneous, and the skin layers according to standard protocols.When the wound is closed, remove the chest tube while performing a Valsalva maneuver to remove any residual air from the chest cavity and close the chest tube insertion site with one skin suture and an appropriate dressing. Then remove the femoral catheter and close the catheter incision with a 7-0 proline u-stitch closure. Following the initial hibernation surgery, stenosis greater than 70 percent, as well as the patent graft should be able to be visualized by cardiac MRI.Eight weeks after the surgical application of the left anterior descending constrictor, the analysis of regional function by cardiac MRI reveals a reduced function under an increased workload in the left anterior descending artery restricted animals. Following a successful coronary artery bypass surgery, the animal may demonstrate incremental improvements in their regional cardiac function, both at rest and under anitropic stimulation, although these improvements do not restore function back to normal levels. A successful bypass surgery will also eliminate the mortality risk associated with hibernating myocardium.Once mastered, the initial hibernation surgery can be completed in one and a half hours and the revascularization procedure can be completed in three hours if each technique is performed correctly. While attempting this procedure, it is important to remember to maintain a proper sterile technique and anesthetic depth, as well as to administer lidocaine before entering the pleural cavity to prevent arrythmia, and to administer heparin to prevent clotting. Following this procedure, this animal model of cardiac disease can be used to answer questions about disease etiology and to test novel therapies for chronic cardiac ischemia.Generally, individuals new to this method will struggle because it is a highly technical vascular surgery. Surgical skills and loupes for magnification are important for success. After watching this video, you should have a good understanding of how to create a large animal model of chronic cardiac ischemia without infarction that is amenable to revascularization surgery.Visual demonstration of this method is critical as the surgical techniques are complex due to the small size of the vessels. The dissection steps must be precisely completed to reduce the risk of bleeding and ventricular fibrillation.

surgical-swine-model-chronic-cardiac-ischemia-treated-off-pump

Research

JoVE Journal

Medicine

Implantation of Inferior Vena Cava Interposition Graft in Mouse Model

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. The long-term clinical results showed excellent patency rates, however, with significant incidence of stenosis. To investigate the cellular and molecular mechanisms of vascular neotissue formation and prevent stenosis development in tissue engineered vascular grafts (TEVGs), we developed a mouse model of the graft with approximately 1 mm internal diameter. First, the TEVGs were assembled from biodegradable tubular scaffolds fabricated from a polyglycolic acid nonwoven felt mesh coated with &#949;-caprolactone and L-lactide copolymer. The scaffolds were then placed in a lyophilizer, vacuumed for 24 hr, and stored in a desiccator until cell seeding. Second, bone marrow was collected from donor mice and mononuclear cells were isolated by density gradient centrifugation. Third, approximately one million cells were seeded on a scaffold and incubated O/N. Finally, the seeded scaffolds were then implanted as infrarenal vena cava interposition grafts in C57BL/6 mice. The implanted grafts demonstrated excellent patency (&#62;90%) without evidence of thromboembolic complications or aneurysmal formation. This murine model will aid us in understanding and quantifying the cellular and molecular mechanisms of neotissue formation in the TEVG.

To improve our knowledge of cellular and molecular neotissue formation, a murine model of the TEVG was recently developed. The grafts were implanted as infrarenal vena cava interposition grafts in C57BL/6 mice. This model achieves similar results to those achieved in our clinical investigation, but over a far shortened time-course.

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are often used for reconstructive surgery to treat congenital cardiac anomalies. ...

Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated.

This paper describes a novel nonocclusive coronary anastomotic connector in a porcine off-pump coronary artery bypass (OPCAB) model. This easy-to-use coronary connector has intrinsic potential to facilitate minimally invasive OPCAB surgery.

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the ...

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. 
During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). 
The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. 
The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

Coronary flow reserve (CFR) is useful for assessment of myocardial oxygen demand and evaluation of cardiovascular risk. This study establishes a step-by-step transthoracic Doppler echocardiographic (TTDE) method for longitudinal monitoring of the changes in CFR, as measured from coronary artery in mice, under the experimental pressure overload of aortic banding.

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow ...

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. Research models for bypass graft failure are essential for a better understanding of pathobiological and pathophysiological processes during graft patency loss. Large animal models, such as pigs or sheep, resemble human anatomical structures but require special facilities and equipment. This video describes a rat vein interposition model to investigate vein graft patency loss. Rats are inexpensive and easy to handle. Compared to mouse models, the convenient size of rats permits better operability and enables a sufficient amount of material to be obtained for further diverse analysis. In brief, the inferior epigastric vein of a donor rat is harvested and used to replace a segment of the femoral artery. Anastomosis is conducted via single stitches and sealed with fibrin glue. Graft patency can be monitored non-invasively using duplex sonography. Myointimal hyperplasia, which is the main cause for graft patency loss, develops progressively over time and can be calculated from histological cross sections.

This video demonstrates a model to study the development of myointimal hyperplasia after venous interposition surgery in rats.

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine.
A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. 
After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing.
This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

Brachial Artery Catheterization in Swine

The video describes in detail the catheterization of the distal brachial artery in swine. This technique enables researchers to measure arterial blood pressure continuously and collect arterial blood samples to assess arterial blood gas measurements. Arterial blood pressures and arterial blood gases are important physiological parameters to monitor during experimental procedures. In swine, four common methods of arterial catheterization have been described, including catheterization of the carotid, femoral, auricular, and medial saphenous arteries. Each of these techniques have advantages, such as ease of access for the auricular artery, and disadvantages that include deep tissue dissection for carotid artery catheterization. The described alternative method of arterial catheterization in swine, the catheterization of the distal aspect of the brachial artery, is a rapid procedure that requires relatively minimal tissue dissection and provides information that is in line with data collected from other arterial catheterization sites. The procedure uses a medial approach along an oblique plane of the lower brachium, positioned between the olecranon and the flexor aspect of the elbow joint, and this approach allows researchers the major advantage of unimpeded freedom for procedures that involve the caudoventral, caudodorsal back, or hind limbs of the pig. Due to the location of the upper forelimb of the catheterized vessel and potential challenges of effective homeostasis following catheter removal from the artery, this technique may be limited to non-recovery procedures.

The video describes in detail the catheterization of the distal brachial artery in swine. This procedure accurately measures arterial blood pressure and is a simple and fast method to collect samples for arterial blood gas measurements.

The video describes in detail the catheterization of the distal brachial artery in swine. This technique enables researchers to measure arterial blood ...

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries. The renal arteries are occluded for 60 min by introducing the balloon-catheters through the femoral and carotid artery and advancing them into the proximal portion of the arteries. Iodinated contrast is injected in the aorta to assess any opacification of the kidney vessels and confirm the success of the artery occlusion. This is furtherly confirmed by the flattening of the pulse waveform at the tip of the balloon catheters. The balloons are deflated and removed after 60 min of bilateral renal artery occlusion, and the animals are allowed to recover for 24 h. At the end of the study, plasma creatinine and blood urea nitrogen significantly increase, while eGFR and urine output significantly decrease. The need for iodinated contrast is minimal and does not affect renal function. Bilateral renal artery occlusion better mimics the clinical scenario of perioperative renal hypoperfusion, and the percutaneous approach minimizes the impact of the inflammatory response and the risk of infection seen with an open approach, such as a laparotomy. The ability to create and reproduce this clinically relevant swine model eases the clinical translation to humans.

This study presents a highly reproducible large animal model of renal ischemia-reperfusion injury in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries for 60 min and reperfusion for 24 h.

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most ...

A Rodent Model of The Ross Operation: Syngeneic Pulmonary Artery Graft Implantation in A Systemic Position

The Ross operation for aortic valve disease has regained new interest due to its outstanding long-term results. Nonetheless, when employed as freestanding root replacement, the possible dilation of the pulmonary autograft and subsequent aortic regurgitation is described. Several animal models have been proposed. However, these are usually limited to ex-vivo models or in-vivo experiments with relatively expensive large animal models. In this study, we sought to establish a rodent model of pulmonary artery graft (PAG) implantation in a systemic position. A total of 39 adult Lewis rats were included. Immediately after euthanasia, the pulmonary root was harvested from a donor animal (n=17). Syngeneic recipient (n=17) and sham-operated (n=5) rats were sedated and ventilated. In the recipient group, the PAG was implanted with an end-to-end anastomosis in infra-renal abdominal aortic position. Sham-operated rats underwent only transection and re-anastomosis of the aorta. Animals were followed with serial ultrasound studies for two months and post-mortem histological analysis. The median PAG diameter in the native position was 3.20 mm (IQR=3.18-3.23). At follow-up, the median diameter of the PAG was 4.03 mm (IQR=3.74-4.13) at 1 week, 4.07 mm (IQR=3.80-4.28) at 1 month, and 4.27 mm (IQR=3.90-4.35) at 2 months (p&lt;0.01). Peak systolic velocity was 220.07 mm/s (IQR=210.43-246.41) at 1 week, 430.88 mm/s (IQR=375.28-495.56) at 1 month, and 373.68 mm/s (IQR=305.78-429.81) at 2 months (p=0.02) and did not differ from the sham-operated group at the end of the experiment (p=0.5). Histological analysis did not show any sign of endothelial thrombosis. This study showed that rodent models may allow for the evaluation of the long-term adaptation of the pulmonary root to a high-pressure system. A systemically placed syngeneic PAG implantation represents a simple and feasible platform for the development and evaluation of novel surgical techniques and drug therapies to further improve the outcomes of the Ross operation.

We demonstrate how to establish a murine model of pulmonary root implantation into the descending aorta to simulate the Ross procedure. This model enables the medium/long-term evaluation of pulmonary autograft remodeling in a systemic position, representing the basis of developing therapeutic strategies to promote its adaptation.

The Ross operation for aortic valve disease has regained new interest due to its outstanding long-term results. Nonetheless, when employed as freestanding ...

Left Coronary Artery Ligation: A Surgical Murine Model of Myocardial Infarction

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In order to explore the pathophysiological changes after myocardial infarction and design future treatments, research models of MI are required. Permanent ligation of the left coronary artery (LCA) in mice is a popular model to investigate cardiac function and ventricular remodeling post MI. Here we describe a less invasive, reliable, and reproducible surgical murine MI model by permanent ligation of the LCA. Our surgical model comprises of an easily reversible general anesthesia, endotracheal intubation that does not require a tracheotomy, and a thoracotomy. Electrocardiography and troponin measurement should be performed to ensure MI. Echocardiography at day 28 after MI will discern heart function and heart failure parameters. The degree of cardiac fibrosis can be evaluated by Masson's trichrome staining and cardiac MRI. This MI model is useful for studying the pathophysiological and immunological alterations after MI.

Presented here is a surgical procedure for permanent ligation of the left coronary artery in mice. This model can be used to investigate the pathophysiology and associated inflammatory response after myocardial infarction.

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In ...