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">
			<td height="21" style="height:21px;width:261px;">Suction Container&#160;</td>
			<td>Medline</td>
			<td>DYNDCL03000</td>
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			<td>Administer injectable agents</td>
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		<tr height="21">
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			<td>8881512878</td>
			<td>Administer injectable agents</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">20 mL Syringe</td>
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			<td>8881520657</td>
			<td>Administer injectable agents</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">3 mL Syinge</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>1180300555</td>
			<td>Administer injectable agents</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">6&#160; mL Syringe</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>1180600777</td>
			<td>Administer injectable agents</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">60 mL Syringe</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>8881560125</td>
			<td>Administer injectable agents</td>
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			<td height="21" style="height:21px;">Blower Mister Kit</td>
			<td>Medtronic/Covidien</td>
			<td>22120</td>
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			<td>078919-016-701</td>
			<td>Remove hair from surgery sites</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Hair Clipper</td>
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			<td>Remove hair from surgery sites</td>
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			<td>Pfizer</td>
			<td>00409-1161-01</td>
			<td>Local Anesthetic</td>
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			<td>00409-0805-01</td>
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			<td>Pfizer</td>
			<td>00409-4277-01</td>
			<td>Local Anesthetic/ antiarrthymic</td>
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			<td style="width:223px;">Pfizer</td>
			<td style="width:203px;">00409-6629-02</td>
			<td>Neuromuscular blocking agent</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Anesthesia Monitor</td>
			<td>Phillips&#160; Intellivue&#160;</td>
			<td style="width:203px;">MP70&#160;</td>
			<td>Supports ventilation with inhalant</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Artificial Tears</td>
			<td style="width:223px;">Rugby</td>
			<td style="width:203px;">0536-1086-91</td>
			<td>Lubricate eyes to prevent corneal drying</td>
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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Buprenorphine 0.3 mg/mL</td>
			<td style="width:223px;">Sigma Aldrich</td>
			<td style="width:203px;">B9275</td>
			<td>Pre operative Analgesic for survivial procedures</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Isoflurane</td>
			<td style="width:223px;">Sigma Aldrich</td>
			<td style="width:203px;">CDS019936</td>
			<td>General Anesthestic- Inhalant</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">36&#8221; Pressure monitoring tubing</td>
			<td>Smith&#8217;s Medical</td>
			<td>MX563</td>
			<td>Connect art. Line&#160; to transducer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">48&#8221; Pressure monitoring tubing</td>
			<td>Smith&#8217;s Medical</td>
			<td>MX564</td>
			<td>Connect art. Line&#160; to transducer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Jelco 18 ga IV catheter&#160;</td>
			<td style="width:223px;">Smiths medical</td>
			<td style="width:203px;">4054</td>
			<td>IV access in Revasc, MRI and Term</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Jelco 20 ga IV catheter</td>
			<td style="width:223px;">Smiths medical</td>
			<td style="width:203px;">4059</td>
			<td>IV access in the MRI</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Jelco 22 ga&#160; IV catheter</td>
			<td style="width:223px;">Smiths medical</td>
			<td>4050</td>
			<td>IV access in Hibernation Procedure</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">OPVAC Synergy II</td>
			<td>Terumo Cardiovascular System</td>
			<td>401-230</td>
			<td>Heart positioner and Stabilizer</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Sternal Saw/ Necropsy Saw</td>
			<td>Thermo Fisher</td>
			<td>812822</td>
			<td>Used to open chest cavity</td>
		</tr>
		<tr height="21">
			<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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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Oxygen Tank E cylinder</td>
			<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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		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Pressure Transducer</td>
			<td>various</td>
			<td>Must adapt to anesthesia monitor</td>
			<td>Monitor direct arterial pressures</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Xylazine 100 mg/mL</td>
			<td style="width:223px;">Vedco</td>
			<td style="width:203px;">468RX</td>
			<td>Pre operative Sedative/ analgesic</td>
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	</tbody>
</table>

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 ...

Research

JoVE Journal

Medicine

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