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-surgical health monitoring, weigh the animal within 3 days prior to surgery.</li>
		<li>Fast the animal for 12 h before starting anesthesia. Ensure that water is available at all times for fasting animals.</li>
		<li>Give SR Buprenorphine 0.18 mg/kg IM 24 h prior to the surgery.</li>
	</ol>
	</li>
	<li>Induction
	<ol>
		<li>Sedate the animal with 6.6 mg/kg tiletamine-zolazepam and xylazine cocktail given intramuscularly. Allow 5-15 min for the drug cocktail to take effect.</li>
		<li>Prepare the ear vein aseptically by wiping three times with 70% isopropyl alcohol for IV catheter placement. 
		NOTE: If an ear vein is not adequate, another peripheral vein may be used (i.e. cephalic).</li>
		<li>Apply ophthalmic ointment to both eyes to prevent corneal drying.</li>
		<li>If necessary, induce anesthesia by administering 1-2 mg/kg of propofol IV or masked with 3 L/min of oxygen and 3% isoflurane, to allow for tracheal intubation. 
		&#8203;NOTE: The animal is considered appropriately anesthetized when the blink reflex or jaw tone is absent.</li>
		<li>Intubate the animal with an appropriately sized endotracheal tube.</li>
	</ol>
	</li>
	<li>Surgery
	<ol>
		<li>Once the animal is anesthetized, shave the left thoracic area for the surgery.</li>
		<li>Initiate the mechanical ventilation at 10-15 breaths per min. Set oxygen at 1-4 L/min, and isoflurane between 1.0 and 3.0% as needed to maintain a surgical plane of anesthesia.</li>
		<li>Place the monitoring devices on the animal. Monitoring devices should include ECG, blood pressure, temperature, and pulse oximeter.</li>
		<li>Connect the IV catheter to an IV drip with 0.9% normal saline at a rate of 5-10 mL/kg/h.</li>
		<li>Aseptically prepare the left lateral chest with an FDA approved surgical scrub.</li>
		<li>Evaluate the depth of anesthesia every 5-15 min. Record the baseline vital signs (heart rate, ECG, SpO2, NIBP, ETCO2 and temperature) every 15 min. 
		NOTE: The animal is considered appropriately anesthetized when the blink reflex or jaw tone is absent.</li>
		<li>With the animal laying on its right side, place sterile drapes the left side of the chest from the spine to the scapula centering the third rib space in the sterile field. 
		NOTE: The sterile field involves left front shoulder including the axillary area continuing to the sternum to the sixth rib space cranially.</li>
		<li>Gently scrub the field with an FDA approved surgical method such as chlorhexidine gluconate or an iodine surgical scrub for 2 min using a target pattern.</li>
		<li>Rinse the field with water and wash it two more times with an FDA approved method as above for 2 min. Rinse the surgical field with water in between washes, then pat dry with sterile toweling or 4 x 4 cm gauze sponges.</li>
		<li>Spray the area with an iodine solution and drape the entire animal (except the surgical field) with sterile drapes. Use steam or gas sterilization to sterilize the instruments, gowns, and drapes for the procedure.</li>
		<li>Administer an intercostal nerve block using 0.3 mL of 0.5% bupivicaine at the 2nd, 3rd and 4th ribs.</li>
		<li>Give 125 mg of cefazolin IV before opening the chest. 
		NOTE: 1.5 mg/kg succinylcholine IV may be given as a paralytic agent to reduce muscle movement per surgeon&#39;s request during the opening of the chest cavity.</li>
		<li>Expose the heart via a left thoracotomy. Prior to heart manipulation, give a 2 mg/kg IV bolus of lidocaine to prevent arrhythmia. Make the lateral 3rd space thoracotomy incision with monopolar electrocautery. The incision should extend from the cranial aspect of the scapula to the axillary area for approximately 10 cm. Use a cautery to incise the skin and underlying musculature to allow the entry into the chest cavity.</li>
		<li>Place a finochietto rib retractor and enter the pleural space at the third intercostal space to retract the lung.</li>
		<li>Sharply incise the pericardium and retract to the side using 2-0 polyglactin stay sutures, exposing the LAD artery and vein. Retract the left atrial appendage with a gauze-covered spatula retractor.</li>
		<li>Using iris scissors, open the adventitia over the LAD.</li>
		<li>Bluntly dissect an approximately 0.25 cm portion of the LAD artery approximately 1 cm distal to the LAD and circumflex artery junction. Use a right-angle clamp to encircle the LAD.</li>
		<li>Place two 4-0 polyester sutures around the artery without placing any tension.</li>
		<li>Place a plastic c-shaped constrictor with an internal diameter of 1.5 mm on the LAD proximal to the first diagonal without occluding the vessel.</li>
		<li>Secure it with two 4-0 polyester ties encircling the LAD.</li>
		<li>Loosely close the pericardium using 2-0 polyglactin suture in a simple interrupted pattern.</li>
		<li>Perform a breath hold to remove air from the chest while the intercostal muscle layer is closed. Carefully monitor the airway pressure manometer on the anesthesia machine to maintain the pressure in a proper range of 20-30 cm of water and release when complete. 
		NOTE: This eliminates the need for a chest tube in the post-operative period.</li>
		<li>Close the muscle and skin layers in the standard fashion using 2-0 and 3-0 absorbable suture.</li>
		<li>Use skin adhesive over the incision for skin closure.</li>
		<li>Administer a total dose of 1 mg/kg bupivacaine intramuscularly at multiple sites along the length of the incision at the end of the procedure. Administer meloxicam 0.2 mg/kg SQ before transport to the recovery area.</li>
		<li>Wean the animal off the ventilator as the skin layer is closed.</li>
		<li>Leave the animal connected to the anesthesia machine until it can spontaneously breathe and protective reflexes begin to return.</li>
		<li>Do not remove the endotracheal tube until the animal can swallow to protect its airway.</li>
		<li>Apply a sterile, non-adherent dressing with triple-antibiotic ointment over the incision.</li>
	</ol>
	</li>
	<li>Post-Surgery
	<ol>
		<li>Record the heart rate, respiration rate, body temperature and mucous membrane color every 15 min until the animal can hold a sternal position unassisted.</li>
		<li>Do not leave the animal unattended until it can lift and hold its head up and can stand unassisted.</li>
		<li>Give meloxicam (0.2 mg/kg) subcutaneously.</li>
		<li>Administer sustained release buprenorphine 6 h following the initial pre-surgical dose.</li>
		<li>Leave the dressing on the incision for up to 3 days, if it remains clean and dry. Replace the dressing if it becomes soiled.</li>
		<li>Monitor the pain level, general well-being and the condition of the incision for 5 days following the procedure. 
		NOTE: A piglet grimace scale is now available to assess the level of pain in these animals post-operatively14. Use half dose meloxicam as needed once per day for breakthrough pain.</li>
		<li>Single-house the animal during the recovery period of 5 day to limit activity and allow the wound to heal.</li>
		<li>Allow 8 weeks to fully develop the hibernating myocardium phenotype.</li>
	</ol>
	</li>
</ol>
2. Revascularization or Off Pump Bypass
<ol>
	<li>Animal Preparation
	<ol>
		<li>Weigh the animal within 3 days prior to surgery.</li>
		<li>Fast the animal for 12 h prior to surgery. Ensure that water is available at all times for fasting animals.</li>
		<li>Give sustained release buprenorphine 0.18 mg/kg intramuscularly 24 h prior to the surgery.</li>
	</ol>
	</li>
	<li>Induction
	<ol>
		<li>Sedate the animal with 6.6 mg/kg tiletamine-zolazepam/xylazine cocktail intramuscularly. 5-15 min after the sedation, prepare the ear vein aseptically for catheter placement. 
		&#8203;NOTE: If an ear vein is not adequate, another peripheral vein may be used (i.e. cephalic).</li>
		<li>Apply ophthalmic ointment to both eyes.</li>
		<li>Induce anesthesia with 1-2 mg/kg of propofol IV.</li>
		<li>Intubate the animal with an appropriately sized endotracheal tube.</li>
	</ol>
	</li>
	<li>Surgery
	<ol>
		<li>Shave the animal&#39;s sternum, left lateral chest and femoral triangles for the surgery.</li>
		<li>Set mechanical ventilation to 10-15 breaths per minute, oxygen at 1-4 L/min, and isoflurane at 1.0-3.0% as needed to maintain a surgical plane of anesthesia.</li>
		<li>Position the monitoring equipments (heart rate, ECG, SpO2, direct blood pressure, ETCO2 and temperature) on the animal.</li>
		<li>Connect the IV catheter to an IV drip with normal saline or LRS.</li>
		<li>Aseptically prepare the skin with povidone iodine scrub or other FDA approved method.</li>
		<li>Evaluate the animal for the depth of anesthesia. 
		NOTE: The animal is considered deeply anesthetized when the eye or jaw reflex is absent.</li>
		<li>Position the animal dorsally, prepare the skin as previously described and drape the animal with sterile towels.</li>
		<li>Perform a cut down to the femoral artery and cannulation. Use monopolar electrocautery to create an approximately 3 cm skin incision over the femoral artery to expose it for cannulation.</li>
		<li>Perform a femoral nerve block after the incision is made, to allow precise placement of drug. Connect the femoral cannula to a transducer to monitor blood pressures during the surgery.</li>
		<li>Use electro-cautery to incise from the manubrium to the xiphoid process, as well as to incise the muscle, adipose, and connective tissue to the level of the sternum.</li>
		<li>Divide the sternum with an oscillating saw. 
		NOTE: Using an oscillating saw, rather than a standard sternal saw avoids potential myocardial injury from pericardial adhesions as a result of the thoracotomy for constrictor placement on the LAD.</li>
		<li>Administer lidocaine (2 mg/kg IV loading dose, 50 &#181;g/kg/min continuous IV infusion) to prevent arrhythmias. Dilute lidocaine in a 500 mL bag of normal saline at a concentration of 1 mg/mL.</li>
		<li>Divide the posterior sternal plate with straight Mayo scissors.</li>
		<li>Use a chest retractor to expose the thoracic cavity.</li>
		<li>Take down the adhesions with monopolar electro-cautery.</li>
		<li>Using the same retractor, with gentle elevation of the left sternal border by an assistant, dissect the left internal mammary artery free from the chest wall.</li>
		<li>Control the arterial branches with hemoclips.</li>
		<li>Heparinize the animal with 100-300 units/kg of heparin IV.</li>
		<li>After 3 min, divide the artery with the distal end over sewn. Prepare the proximal end for grafting.</li>
		<li>Open and retract the pericardium. Confirm that the length of the LIMA is adequate to reach the appropriate anastomotic site on the LAD.</li>
		<li>Perform the LIMA to LAD anastomosis with 7-0 polypropylene suture using an off pump technique with a cardiac stabilizer, spring form clip, and appropriately sized intraluminal devices.</li>
		<li>Place a chest tube between the ribs on the left lateral chest, externalized and attached to vacuum to remove air from the chest cavity for 15-30 min.</li>
		<li>Approximate the sternum with #5 polyester sutures using a figure eight pattern.</li>
		<li>Close the muscle, subcutaneous and skin layers in the usual fashion as described in the Hibernation surgery. Remove the chest tube while performing a Valsalva maneuver to remove any residual air from the chest cavity and close the incision with one skin suture.</li>
		<li>Apply skin adhesive over the skin to protect the sternal incision. Gently remove the femoral catheter and repair the artery using 7-0 polypropylene suture in a purse string pattern. Close the skin using 2-0 polyglactin suture in a subcuticular pattern.</li>
		<li>Administer a total dose of 1 mg/kg bupivacaine intramuscularly at multiple sites along the length of the incision at the end of the procedure.</li>
		<li>Administer meloxicam 0.2 mg/kg subcutaneously before transport to the recovery area.</li>
		<li>Follow the post-operative protocol in the hibernation procedure.</li>
	</ol>
	</li>
</ol>

<ol>
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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. 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The authors have nothing to disclose.

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.

<table border="0" cellpadding="0" cellspacing="0" style="width:1155px;" width="1154">
	<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>
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		<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>
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		<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>
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		<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>
		</tr>
		<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>
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		<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>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Suction Container&#160;</td>
			<td>Medline</td>
			<td>DYNDCL03000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">1 mL Syringe</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>1188100777</td>
			<td>Administer injectable agents</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">12 mL Syringe</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>8881512878</td>
			<td>Administer injectable agents</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">20 mL Syringe</td>
			<td style="width:223px;">Medtronic/Covidien</td>
			<td>8881520657</td>
			<td>Administer injectable agents</td>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Blower Mister Kit</td>
			<td>Medtronic/Covidien</td>
			<td>22120</td>
			<td>Clears surgical field for vessel anastomosis</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Roncuronium</td>
			<td>Mylan</td>
			<td>67457-228-05</td>
			<td>Neuromuscular blocking agent</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;"># 40 clipper blade</td>
			<td>Oster</td>
			<td>078919-016-701</td>
			<td>Remove hair from surgery sites</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Hair Clipper</td>
			<td>Oster</td>
			<td>078566-011-002</td>
			<td>Remove hair from surgery sites</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Bupivicaine</td>
			<td>Pfizer</td>
			<td>00409-1161-01</td>
			<td>Local Anesthetic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Cephazolin</td>
			<td>Pfizer</td>
			<td>00409-0805-01</td>
			<td>Antibiotic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Heparin&#160;</td>
			<td>Pfizer</td>
			<td>&#160;0409-2720-03</td>
			<td>anticoaggulant</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Lidocaine 2%</td>
			<td>Pfizer</td>
			<td>00409-4277-01</td>
			<td>Local Anesthetic/ antiarrthymic</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:261px;">Succinylcholine 20 mg/mL</td>
			<td style="width:223px;">Pfizer</td>
			<td style="width:203px;">00409-6629-02</td>
			<td>Neuromuscular blocking agent</td>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
		<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>
		</tr>
	</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 ...

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

Research

JoVE Journal

Medicine

9.4K Views.  University of Minnesota. 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.

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

A Swine Model of Neonatal Asphyxia

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, perfusion deficit, hypoxic-ischemic encephalopathy, pulmonary hypertension, vasculopathic enterocolitis, renal failure and thrombo-embolic complications. Animal models are developed to help us understand the patho-physiology and pharmacology of neonatal asphyxia. In comparison to rodents and newborn lambs, the newborn piglet has been proven to be a valuable model. The newborn piglet has several advantages including similar development as that of 36-38 weeks human fetus with comparable body systems, large body size (&tilde;1.5-2 kg at birth) that allows the instrumentation and monitoring of the animal and controls the confounding variables of hypoxia and hemodynamic derangements.
We here describe an experimental protocol to simulate neonatal asphyxia and allow us to examine the systemic and regional hemodynamic changes during the asphyxiating and reoxygenation process as well as the respective effects of interventions. Further, the model has the advantage of studying multi-organ failure or dysfunction simultaneously and the interaction with various body systems. The experimental model is a non-survival procedure that involves the surgical instrumentation of newborn piglets (1-3 day-old and 1.5-2.5 kg weight, mixed breed) to allow the establishment of mechanical ventilation, vascular (arterial and central venous) access and the placement of catheters and flow probes (Transonic Inc.) for the continuously monitoring of intra-vascular pressure and blood flow across different arteries including main pulmonary, common carotid, superior mesenteric and left renal arteries. Using these surgically instrumented piglets, after stabilization for 30-60 minutes as defined by Z&lt;10% variation in hemodynamic parameters and normal blood gases, we commence an experimental protocol of severe hypoxemia which is induced via normocapnic alveolar hypoxia. The piglet is ventilated with 10-15% oxygen by increasing the inhaled concentration of nitrogen gas for 2h, aiming for arterial oxygen saturations of 30-40%. This degree of hypoxemia will produce clinical asphyxia with severe metabolic acidosis, systemic hypotension and cardiogenic shock with hypoperfusion to vital organs. The hypoxia is followed by reoxygenation with 100% oxygen for 0.5h and then 21% oxygen for 3.5h. Pharmacologic interventions can be introduced in due course and their effects investigated in a blinded, block-randomized fashion.

Large animal models have good translational values in the examination of physiology and pharmacology of neonatal asphyxia. Using newborn piglets, we develop an experimental protocol to simulate neonatal asphyxia which has advantages of studying the systemic and regional hemodynamics, oxygen transport with biochemical and pathologic pathways and correlations.

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

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 ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

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 ...