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>1180300555</td>
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			<td>Neuromuscular blocking agent</td>
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			<td style="width:203px;">0536-1086-91</td>
			<td>Lubricate eyes to prevent corneal drying</td>
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			<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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>
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		<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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			<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>
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		<tr height="21">
			<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.

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