Name: intra-operative neural monitoring of thyroid surgery in a porcine model
Uploaded: 2019-02-11T14:00:00
Description: Watch this Scientific Journal Video about Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model at JoVE.com

This study was supported by grants from Kaohsiung Medical University Hospital, Kaohsiung Medical University (KMUH106-6R49) and from Ministry of Science and Technology (MOST 106-2314-B-037-042-MY2.), Taiwan

The animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Kaohsiung Medical University, Taiwan (protocol no: IACUC-102046, 104063, 105158).
1. Animal Preparation and Anesthesia
<ol>
	<li>Porcine animal model 
	Note: This study applied the protocol described in the literature to establish a prospective porcine model of IONM11,12,13,<sup class="...

<ol>
	<li>Randolph, G. W., 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=Electrophysiologic+recurrent+laryngeal+nerve+monitoring+during+thyroid+and+parathyroid+surgery:+international+standards+guideline+statement.">Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: international standards guideline statement.</a> Laryngoscope. 121, S1-S16 (2011).</li><li>Barczynski, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=External+branch+of+the+superior+laryngeal+nerve+monitoring+during+thyroid+and+parathyroid+surgery:+International+Neural+Monitoring+Study+Group+standards+guideline+statement.">External branch of the superior laryngeal nerve monitoring during thyroid and parathyroid surgery: International Neural Monitoring Study Group standards guideline statement.</a> Laryngoscope. 123, S1-S14 (2013).</li><li>Chiang, F. Y., 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=The+mechanism+of+recurrent+laryngeal+nerve+injury+during+thyroid+surgery--the+application+of+intraoperative+neuromonitoring.">The mechanism of recurrent laryngeal nerve injury during thyroid surgery--the application of intraoperative neuromonitoring.</a> Surgery. 143 (6), 743-749 (2008).</li><li>Chiang, F. Y., 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=Standardization+of+Intraoperative+Neuromonitoring+of+Recurrent+Laryngeal+Nerve+in+Thyroid+Operation.">Standardization of Intraoperative Neuromonitoring of Recurrent Laryngeal Nerve in Thyroid Operation.</a> World Journal of Surgery. 34 (2), 223-229 (2010).</li><li>Chiang, F. Y., 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=Anatomical+variations+of+recurrent+laryngeal+nerve+during+thyroid+surgery:+how+to+identify+and+handle+the+variations+with+intraoperative+neuromonitoring.">Anatomical variations of recurrent laryngeal nerve during thyroid surgery: how to identify and handle the variations with intraoperative neuromonitoring.</a> The Kaohsiung Journal of Medical Sciences. 26 (11), 575-583 (2010).</li><li>Chiang, F. Y., 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=Intraoperative+neuromonitoring+for+early+localization+and+identification+of+the+recurrent+laryngeal+nerve+during+thyroid+surgery.">Intraoperative neuromonitoring for early localization and identification of the recurrent laryngeal nerve during thyroid surgery.</a> The Kaohsiung Journal of Medical Sciences. 26 (12), 633-639 (2010).</li><li>Chiang, F. Y., 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=Detecting+and+identifying+nonrecurrent+laryngeal+nerve+with+the+application+of+intraoperative+neuromonitoring+during+thyroid+and+parathyroid+operation.">Detecting and identifying nonrecurrent laryngeal nerve with the application of intraoperative neuromonitoring during thyroid and parathyroid operation.</a> American Journal of Otolaryngology. 33 (1), 1-5 (2012).</li><li>Wu, C. W., 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=Vagal+nerve+stimulation+without+dissecting+the+carotid+sheath+during+intraoperative+neuromonitoring+of+the+recurrent+laryngeal+nerve+in+thyroid+surgery.">Vagal nerve stimulation without dissecting the carotid sheath during intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery.</a> Head Neck. 35 (10), 1443-1447 (2013).</li><li>Wu, C. W., 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=Loss+of+signal+in+recurrent+nerve+neuromonitoring:+causes+and+management.">Loss of signal in recurrent nerve neuromonitoring: causes and management.</a> Gland Surgery. 4 (1), 19-26 (2015).</li><li>Wu, C. W., 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=Recurrent+laryngeal+nerve+injury+with+incomplete+loss+of+electromyography+signal+during+monitored+thyroidectomy-evaluation+and+outcome.">Recurrent laryngeal nerve injury with incomplete loss of electromyography signal during monitored thyroidectomy-evaluation and outcome.</a> Langenbeck's Archives of Surgery. 402 (4), 691-699 (2017).</li><li>Wu, C. W., 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=Investigation+of+optimal+intensity+and+safety+of+electrical+nerve+stimulation+during+intraoperative+neuromonitoring+of+the+recurrent+laryngeal+nerve:+a+prospective+porcine+model.">Investigation of optimal intensity and safety of electrical nerve stimulation during intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective porcine model.</a> Head Neck. 32 (10), 1295-1301 (2010).</li><li>Lu, I. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparison+between+succinylcholine+and+rocuronium+on+the+recovery+profile+of+the+laryngeal+muscles+during+intraoperative+neuromonitoring+of+the+recurrent+laryngeal+nerve:+A+prospective+porcine+model.">A comparison between succinylcholine and rocuronium on the recovery profile of the laryngeal muscles during intraoperative neuromonitoring of the recurrent laryngeal nerve: A prospective porcine model.</a> The Kaohsiung Journal of Medical Sciences. 29 (9), 484-487 (2013).</li><li>Wu, C. W., 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=Intraoperative+neuromonitoring+for+the+early+detection+and+prevention+of+RLN+traction+injury+in+thyroid+surgery:+A+porcine+model.">Intraoperative neuromonitoring for the early detection and prevention of RLN traction injury in thyroid surgery: A porcine model.</a> Surgery. 155 (2), 329-339 (2014).</li><li>Lin, Y. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrophysiologic+monitoring+correlates+of+recurrent+laryngeal+nerve+heat+thermal+injury+in+a+porcine+model.">Electrophysiologic monitoring correlates of recurrent laryngeal nerve heat thermal injury in a porcine model.</a> Laryngoscope. 125 (8), E283-E290 (2015).</li><li>Wu, C. W., 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=Recurrent+laryngeal+nerve+safety+parameters+of+the+Harmonic+Focus+during+thyroid+surgery:+Porcine+model+using+continuous+monitoring.">Recurrent laryngeal nerve safety parameters of the Harmonic Focus during thyroid surgery: Porcine model using continuous monitoring.</a> Laryngoscope. 125 (12), 2838-2845 (2015).</li><li>Dionigi, G., 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=Severity+of+Recurrent+Laryngeal+Nerve+Injuries+in+Thyroid+Surgery.">Severity of Recurrent Laryngeal Nerve Injuries in Thyroid Surgery.</a> World Journal of Surgery. 40 (6), 1373-1381 (2016).</li><li>Wu, C. W., 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=Optimal+stimulation+during+monitored+thyroid+surgery:+EMG+response+characteristics+in+a+porcine+model.">Optimal stimulation during monitored thyroid surgery: EMG response characteristics in a porcine model.</a> Laryngoscope. 127 (4), 998-1005 (2017).</li><li>Dionigi, G., 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=Safety+of+LigaSure+in+recurrent+laryngeal+nerve+dissection-porcine+model+using+continuous+monitoring.">Safety of LigaSure in recurrent laryngeal nerve dissection-porcine model using continuous monitoring.</a> Laryngoscope. 127 (7), 1724-1729 (2017).</li><li>Lu, I. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+of+high-current+stimulation+for+intermittent+intraoperative+neural+monitoring+in+thyroid+surgery:+A+porcine+model.">Safety of high-current stimulation for intermittent intraoperative neural monitoring in thyroid surgery: A porcine model.</a> Laryngoscope. , (2018).</li><li>Lu, I. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversal+of+rocuronium-induced+neuromuscular+blockade+by+sugammadex+allows+for+optimization+of+neural+monitoring+of+the+recurrent+laryngeal+nerve.">Reversal of rocuronium-induced neuromuscular blockade by sugammadex allows for optimization of neural monitoring of the recurrent laryngeal nerve.</a> Laryngoscope. 126 (4), 1014-1019 (2016).</li><li>Wu, C. -. W., 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=Intraoperative+neural+monitoring+in+thyroid+surgery:+lessons+learned+from+animal+studies.">Intraoperative neural monitoring in thyroid surgery: lessons learned from animal studies.</a> Gland Surgeryery. 5 (5), 473-480 (2016).</li><li>Lu, I. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversal+of+rocuronium-induced+neuromuscular+blockade+by+sugammadex+allows+for+optimization+of+neural+monitoring+of+the+recurrent+laryngeal+nerve.">Reversal of rocuronium-induced neuromuscular blockade by sugammadex allows for optimization of neural monitoring of the recurrent laryngeal nerve.</a> Laryngoscope. , (2016).</li><li>Scott, A. R., Chong, P. S., Brigger, M. T., Randolph, G. W., Hartnick, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Serial+electromyography+of+the+thyroarytenoid+muscles+using+the+NIM-response+system+in+a+canine+model+of+vocal+fold+paralysis.">Serial electromyography of the thyroarytenoid muscles using the NIM-response system in a canine model of vocal fold paralysis.</a> Annals of Otology, Rhinology, and Laryngology. 118 (1), 56-66 (2009).</li><li>Puram, S. V., 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=Vocal+cord+paralysis+predicted+by+neural+monitoring+electrophysiologic+changes+with+recurrent+laryngeal+nerve+compressive+neuropraxic+injury+in+a+canine+model.">Vocal cord paralysis predicted by neural monitoring electrophysiologic changes with recurrent laryngeal nerve compressive neuropraxic injury in a canine model.</a> Head Neck. 38, E1341-E1350 (2016).</li><li>Puram, S. V., 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=Posterior+cricoarytenoid+muscle+electrophysiologic+changes+are+predictive+of+vocal+cord+paralysis+with+recurrent+laryngeal+nerve+compressive+injury+in+a+canine+model.">Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.</a> Laryngoscope. 126 (12), 2744-2751 (2016).</li><li>Brauckhoff, K., 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=Injury+mechanisms+and+electromyographic+changes+after+injury+of+the+recurrent+laryngeal+nerve:+Experiments+in+a+porcine+model.">Injury mechanisms and electromyographic changes after injury of the recurrent laryngeal nerve: Experiments in a porcine model.</a> Head Neck. 40 (2), 274-282 (2018).</li><li>Brauckhoff, K., Aas, T., Biermann, M., Husby, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EMG+changes+during+continuous+intraoperative+neuromonitoring+with+sustained+recurrent+laryngeal+nerve+traction+in+a+porcine+model.">EMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine model.</a> Langenbeck's Archives of Surgery. 402 (4), 675-681 (2017).</li><li>Schneider, R., 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=A+new+vagal+anchor+electrode+for+real-time+monitoring+of+the+recurrent+laryngeal+nerve.">A new vagal anchor electrode for real-time monitoring of the recurrent laryngeal nerve.</a> The American Journal of Surgery. 199 (4), 507-514 (2010).</li><li>Kim, H. Y., 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=Impact+of+positional+changes+in+neural+monitoring+endotracheal+tube+on+amplitude+and+latency+of+electromyographic+response+in+monitored+thyroid+surgery:+Results+from+the+Porcine+Experiment.">Impact of positional changes in neural monitoring endotracheal tube on amplitude and latency of electromyographic response in monitored thyroid surgery: Results from the Porcine Experiment.</a> Head Neck. 38, E1004-E1008 (2016).</li><li>Sterpetti, A. V., De Toma, G., De Cesare, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recurrent+laryngeal+nerve:+its+history.">Recurrent laryngeal nerve: its history.</a> World Journal of Surgery. 38 (12), 3138-3141 (2014).</li><li>Kaplan, E. L., Salti, G. 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Injury to the RLN and EBSLN remains a significant source of morbidity caused by thyroid surgery. Until recently, nerve injury could only be identified by direct visualization of trauma. The use of IONM now enables further functional identification of the RLN by applying stimulation and recording the contraction of the target muscles. Currently, however, both conventional intermittent and continuous IONM systems have some technical limitations in false-positive and false-negative interpretations. Hence, suitable animal mo...

Although thyroidectomy is now a commonly performed procedure worldwide, postoperative voice dysfunction is still common. Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. Additionally, injury to the external branch of the superior laryngeal nerve can cause a major voice change by affecting pitch and vocal projection.
Intraoperative neural monitoring (IONM) during thyroid operations has obtained wide popularity as an adjunct technique for mapping and confirming the RLN, the vagus nerve (VN), and the external branch of the superior laryngeal nerve (EBSLN). Because IONM is useful for confirming and elucidating mechanisms of RLN injury and for detecting anatomic variations in the RLN, it can be used to predict vocal cord function after thyroidectomy. Therefore, IONM adds a new functional dynamic in thyroid surgery and empowers surgeons with information that cannot be obtained by direct visualization alone1,2,3,4,5,6,7,8,9,10.
Recently, many prospective studies have used porcine models to optimize the use of IONM technology and to establish reliable strategies for preventing intraoperative RLN injury11,12,13,14,15,16,17,18,19,20. Porcine models have also been used to provide practitioners with essential education and training in clinical applications of IONM.
Therefore, the combination of animal models and IONM technology is a valuable tool for studying the pathophysiology of RLN injury21. The aim of this article was to demonstrate the use of a porcine model in IONM research. Specifically, the article demonstrates how to induce general anesthesia, perform tracheal intubation, and set up experiments for investigating the electrophysiological characteristics of various RLN injury types.

<table>
	<tbody>
		<tr>
			<td>Criticare systems</td>
			<td>nGenuity</td>
			<td>8100E</td>
			<td>physiologic monitoring, including capnography, electrocardiography (ECG) and monitoring of oxygenation (SaO2)</td>
		</tr>
		<tr>
			<td>Intraoperative NIM nerve monitoring systems</td>
			<td>Medtronic</td>
			<td>NIM-Response 3.0</td>
			<td>monitor EMG activity from multiple muscles. If there is a change in nerve function, the NIM system may provide audible and visual warnings to help reduce the risk of nerve damage.</td>
		</tr>
		<tr>
			<td>NIM TriVantage EMG Tube</td>
			<td>Medtronic</td>
			<td>8229706</td>
			<td>6 mm ID, 8.2 mm OD. The NIM TriVantage EMG Tube is a standard size, non-reinforced, DEHP-free PVC tube that features smooth, conductive silver ink electrodes and a cross-band to guide placement. It has reduced sensitivity to rotation and movement while offering increased EMG responses that facilitate improved nerve dissection.</td>
		</tr>
		<tr>
			<td>NIM Contact Reinforced EMG Endotracheal Tube</td>
			<td>Medtronic</td>
			<td>8229506</td>
			<td>6 mm ID, 9 mm OD. The NIM Contact EMG Tube continuously monitors electromyography (EMG) 
			activity during surgery. An innovative design allows the tube to maintain contact, 
			even upon rotation. Vocal cords are more easily visible against the white band. 
			Recording electrode leads are twisted pair. Packaged sterile with one green and 
			one white subdermal needle. Single use.</td>
		</tr>
		<tr>
			<td>NIM Standard Reinforced EMG Endotracheal Tube</td>
			<td>Medtronic</td>
			<td>8229306</td>
			<td>6 mm ID, 8.8 mm OD. The NIM Standard EMG Tube continuously monitors electromyography (EMG) 
			activity during surgery. Recording electrode leads are twisted pair. Packaged 
			sterile with one green and one white subdermal needle. Single use.</td>
		</tr>
		<tr>
			<td>NIM Flex EMG Endotracheal Tube</td>
			<td>Medtronic</td>
			<td>8229960</td>
			<td>6 mm. The NIM Flex EMG Tube monitors vocal cord and recurrent laryngeal nerve EMG 
			activity during surgery. An updated, dual-channel design allows the tube to 
			maintain contact with the vocal cords, even upon rotation. Recording electrode 
			leads are twisted pair. Packaged sterile with one green and one white subdermal 
			needle. Single use.</td>
		</tr>
		<tr>
			<td>Standard Prass Flush-Tip Monopolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225101</td>
			<td>Tips and Handles. For locating and mapping cranial nerves in the surgical field, the single-use 
			Standard Prass Monopolar Stimulating Probe features a flush 0.5 mm tip 
			diameter. The probe is insulated to the tip to prevent current shunting. Individually 
			sterile packaged.</td>
		</tr>
		<tr>
			<td>Ball-Tip Monopolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225275/ 8225276</td>
			<td>Tip and Handle, 1.0 mm/ 2.3mm. Featuring a flexible ball tip and flexible shaft, the single-use Ball-Tip Monopolar 
			Stimulating Probe allows greater access to neural structures. The 1.0 mm tip 
			diameter allows atraumatic contact to larger neural structures. The probe is insulated 
			to the tip to prevent current shunting. Individually sterile packaged.</td>
		</tr>
		<tr>
			<td>Yingling Flex Tip Monopolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225251</td>
			<td>Tips and Handles. The highly flexible single-use Yingling Monopolar Stimulating Probe allows 
			stimulation in areas outside the surgeon&#8217;s field of view. The platinum-iridium wire 
			of the probe is fully insulated to the ball tip to prevent current shunting. Individually 
			sterile packaged with one green subdermal electrode.</td>
		</tr>
		<tr>
			<td>Prass Bipolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225451</td>
			<td>The single-use Prass Bipolar Stimulating Probe features a slim, flexible tip that 
			allows greater access to neural structures. The probe tip is 0.5 mm in distance 
			between cathode and anode for minimal shunting. Individually sterile packaged.</td>
		</tr>
		<tr>
			<td>Concentric Bipolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225351</td>
			<td>The single-use Concentric Bipolar Stimulating Probe features a 360&#176; 
			contact area. Insulation is complete to the active tip; cables and handles are 
			polarized. Individually sterile packaged.</td>
		</tr>
		<tr>
			<td>Side-by-Side Bipolar Stimulator Probe</td>
			<td>Medtronic</td>
			<td>8225401</td>
			<td>The single-use Side-by-Side Bipolar Stimulating Probe features probe tips that 
			are 1.3 mm apart, allowing neural structures to be stimulated between the tips. 
			Insulation is complete to the active tip; cables and handles are polarized. 
			Individually sterile packaged.</td>
		</tr>
		<tr>
			<td>APS (Automatic Periodic Stimulation) Electrode*</td>
			<td>Medtronic</td>
			<td>8228052 / 8228053</td>
			<td>2 mm/ 3mm. The APS Electrode offers continuous, real-time monitoring. The electrode is placed 
			on the nerve and can provide early warning of a change in nerve function.</td>
		</tr>
		<tr>
			<td>Neotrode ECG Electrodes</td>
			<td>ConMed</td>
			<td>1741C-003</td>
			<td>The electrode is made of a clear tape material, which allows for continuous observation of the patient&#39;s skin during monitoring.</td>
		</tr>
		<tr>
			<td>LigaSure Small Jaw</td>
			<td>Medtronic</td>
			<td>LF1212</td>
			<td>A FDA-approved 
			electrothermal bipolar vessel sealing system for surgery</td>
		</tr>
	</tbody>
</table>

intra-operative neural monitoring of thyroid surgery in a porcine model

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.

Electrophysiology study 
Baseline EMG data, minimal/maximal stimulus level, and the stimulus-response curves 
Using a standard monopolar stimulating probe, the obtained minimal stimulation level for VN and RLN stimulation ranges from 0.1 to 0.3 mA, respectively. In general, the stimulus current correlated positively with the resulting EMG amplituderesponse11,17. The EMG amplitude plateaued at the maximal stimula...

Watch this Scientific Journal Video about Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model at JoVE.com

Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model

This study aims to develop a standard protocol of intra-operative neural monitoring of thyroid surgery in a porcine model. Here, we present a protocol to demonstrate general anesthesia, to compare different types of electrodes, and to investigate the electrophysiological characteristics of the normal and injured recurrent laryngeal nerves.

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere ...

This method can help answer key questions about the application of intraoperative neural monitoring during clinical thyroid surgery, and the electrophysiological characteristics of normal and injured that occur in nerves. Some advantages of using the porcine models are that the anatomy and the physiologies are similar to humans. And that the size of the animals enable easy handling.The implications of this technique is stand toward the establishment of reliable strategies for preventing and operating nerve injury. As various occur hydro nerve, injury types can be induced experimentally. Demonstrating procedure will be Pao-Chu Hun, the veterinarian from the laboratory animal center.Hsiu-Ya Chen our nurse specialist, from the anesthesiology department. And Li-Ying Chaung, an assistant from the E&D department. Begin by placing a three to four month old piglet in the prone position on the operating table with the head and body aligned, to facilitate a clear visualization of the upper airway.Have an assistant to apply traction of the upper and lower jaw to maintain an adequate mouth opening, and place the laryngoscope upside down directly into the oral cavity to depress the tongue. Use the laryngoscope to press the epiglottis downward toward the tongue base. Gently advancing the elastic bougie into the trachea when the vocal cords can be clearly visualized.Advance the electromyography, or EMG tube at the corner of the mouth to a depth of 24 centimeters, and use medical tape to fix the tube at the mouth angle. Then connect the EMG tube to the ventilator. Connect the channel leads from the EMG tube to the monitoring system, and set the monitoring system to run a 50 millisecond time window.Set the pulse to stimuli to 100 microseconds, and four hertz, and set the event capture threshold to 100 micro volts. Wearing sterile surgical gloves, use a scalpel to make a 10 to 15 centimeter transverse collar incision to expose the neck and the larynx. And erase the subplot of small flap one centimeter cranially from the clavicle to the hyoid bone.Remove the strap muscles to visualize the tracheal rings and nerves, and use a handheld stimulation probe to carefully expose the external branch of the superior laryngeal nerve, the RLN, and the vagus nerve. Position an automated periodic stimulation electrode on one side of the vagus nerve for stimulation during continuous enter operative neural monitoring, and connect the electrode to the monitoring system. Then set the post stimuli to one hertz 100 microseconds, and one milliamp.To assess the effects of muscle relaxants, and the reversals on nerve responses, apply continuous enter operative neural monitoring. Administer a bolus injection of 0.3 milligrams per kilogram rocuronium in a 10 mg per milliliter volume, and observe the real time EMG changes. Three minutes after injection, perform one injection of two milligrams per kilogram sugammedex in a 100 mg per milliliter volume, as a rapid bolus, and record the recovery profile of the laryngeal EMG.To simulate direct nerve stimulation as occurs during surgery, apply one milliamp stimulation to the exposed external branch of the superior laryngeal nerve, the RLN, and the vagus nerve, and record the EMG responses. To stimulate the indirect mapping and localizing of the nerve position before visual identification during surgery, apply one milliamp stimulation at the overlying fascia, and record the EMG responses. To confirm and compare the patterns of real time changes in a virtual laryngeal EMG signals during and after acute RLN traction injury, wrap a 1.3 milometer wide plastic vascular loop around the RLN, and apply retraction.Using continuous enter operative neural monitoring to monitor the evoked laryngeal EMG signals. After the traction compression RLN injury, use hemostatic forceps to pinch the distal segment of the RLN to stimulate the nerve being inadvertently clamped due to visual misidentification as a vessel during the operation, and record the accompanying EMG signal change. To simulate a thermal injury, activate an energy-based device or EBD at a 5 millimeter distance away from the RLN, and record the EMG response.Pre-gel transcutaneous and trans cartilage electrodes generally record lower EMG amplitudes, compared to EMG tube, and needle electrodes. Changes on the contact between EMG tube electrodes and vocal folds after tracheal displacements significantly changes the recorded EMG signals. When RLN traction stress is experimentally induced EMG tube electrodes on the vocalis muscle and trends cartilage urcutaneous, and transcutaneous electrodes record similar patterns of progressive degradation in EMG amplitude.Typically real time EMG change monitoring during RLN and traction injury reveals the progressive amplitude decrease, combined with a latency increase that gradually recovers after traction release. all RLN'S demonstrate an immediate loss of signal after acute mechanical injury, and no gradual EMG recovery is observed within a short period of time after the injury. After thermal injury, the real time EMG reveals a combined event which then rapidly degrades to a loss of signal that may be related to the dose of thermal stress.Although some date are inapplicable to clinical case, this spoken model provides available research preform, in guiding future experiments to optimize a use of intraoperative neuron monitoring, for the prevention of injuries, to our surgery. Although this measure can provide inside into the Surgey, it can also be used for educational training in clinical applications of inter operative neuron monitoring. Generally individuals.Visual demonstration of this measure is critical. As the animal preparation and the assistant steps. In human surgeries.

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Research

JoVE Journal

Medicine

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration.
Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.

Porcine models of organ transplantation provide an important platform to study mechanisms of organ preservation. This article describes a heterotopic porcine renal autotransplantation model, which allows investigating new approaches to improve the outcome of transplantation using marginal kidney grafts.

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality ...

Surgical Angiogenesis in Porcine Tibial Allotransplantation: A New Large Animal Bone Vascularized Composite Allotransplantation Model

Segmental bone loss resulting from trauma, infection malignancy and congenital anomaly remains a major reconstructive challenge. Current therapeutic options have significant risk of failure and substantial morbidity.
Use of bone vascularized composite allotransplantation (VCA) would offer both a close match of resected bone size and shape and the healing and remodeling potential of living bone. At present, life-long drug immunosuppression (IS) is required. Organ toxicity, opportunistic infection and neoplasm risks are of concern to treat such non-lethal indications.
We have previously demonstrated that bone and joint VCA viability may be maintained in rats and rabbits without the need of long-term-immunosuppression by implantation of recipient derived vessels within the VCA. It generates an autogenous, neoangiogenic circulation with measurable flow and active bone remodeling, requiring only 2 weeks of IS. As small animals differ from man substantially in anatomy, bone physiology and immunology, we have developed a porcine bone VCA model to evaluate this technique before clinical application is undertaken. Miniature swine are currently widely used for allotransplantation research, given their immunologic, anatomic, physiologic and size similarities to man. Here, we describe a new porcine orthotopic tibial bone VCA model to test the role of autogenous surgical angiogenesis to maintain VCA viability.
The model reconstructs segmental tibial bone defects using size- and shape-matched allogeneic tibial bone segments, transplanted across a major swine leukocyte antigen (SLA) mismatch in Yucatan miniature swine. Nutrient vessel repair and implantation of recipient derived autogenous vessels into the medullary canal of allogeneic tibial bone segments is performed in combination with simultaneous short-term IS. This permits a neoangiogenic autogenous circulation to develop from the implanted tissue, maintaining flow through the allogeneic nutrient vessels for a short time. Once established, the new autogenous circulation maintains bone viability following cessation of drug therapy and subsequent nutrient vessel thrombosis.

Currently any kind of vascularized composite allotransplantation depends on long-term-immunosuppression, difficult to support for non-life-critical indications. We present a new porcine tibial VCA model that can be used to study bone VCA and demonstrate the use of surgical angiogenesis to maintain bone viability without the need of long-term immune-modulation.

Segmental bone loss resulting from trauma, infection malignancy and congenital anomaly remains a major reconstructive challenge. Current therapeutic ...

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart failure. Multiple small-animal models of heart transplantation have been used to study the acute and long-term effects of novel therapies. However, few are tested and demonstrated success in clinical trials. It is of critical importance to evaluate new therapies in a clinically relevant large-animal model for efficient and reliable translation of basic studies&#39;&#160;findings. Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and previously used to investigate novel cardioprotective strategies. This procedure focuses on acute ischemia-reperfusion injury and is a reliable method to investigate novel interventions which have been tested and validated in smaller experimental models, such as the murine model. We demonstrate its usefulness in assessing cardiac performance during the early post-transplantation period and other potential possibilities enabled by the model.

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

Fifty-years following the first successful report, cardiac transplantation remains the gold-standard treatment for eligible patients with advanced heart ...

Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called &#946;-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.
Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.
Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% &#177; 47.4% at day 7, 105.4% &#177; 58.1% at day 14, and 113.5% &#177; 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p &#60; 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.
Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.&#160;

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound &#946;-aminopropionitrile administration, which interferes with collagen cross-linking.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal ...

Left Lung Orthotopic Transplantation in a Juvenile Porcine Model for ESLP

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the&#160;in vivo&#160;validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.

This protocol describes a juvenile porcine model of orthotopic left lung allotransplantation designed for use with ESLP research. Focus is made on anesthetic and surgical techniques, as well as critical steps and troubleshooting.

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. ...

A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs

More than half of heart failure (HF) cases are classified as heart failure with preserved ejection fraction (HFpEF) worldwide. Large animal models are limited for investigating the fundamental mechanisms of HFpEF and identifying potential therapeutic targets. This work provides a detailed description of the surgical procedure of descending aortic constriction (DAC) in Tibetan minipigs to establish a large animal model of HFpEF. This model used a precisely controlled constriction of the descending aorta to induce chronic pressure overload in the left ventricle. Echocardiography was used to evaluate the morphological and functional changes in the heart. After 12 weeks of DAC stress, the ventricular septum was hypertrophic, but the thickness of the posterior wall was significantly reduced, accompanied by dilation of the left ventricle. However, the LV ejection fraction of the model hearts was maintained at &gt;50% during the 12-week period. Furthermore, the DAC model displayed cardiac damage, including fibrosis, inflammation, and cardiomyocyte hypertrophy. Heart failure marker levels were significantly elevated in the DAC group. This DAC-induced HFpEF in minipigs is a powerful tool for investigating molecular mechanisms of this disease and for preclinical testing.

The present protocol describes a step-by-step procedure to establish a minipig model of heart failure with preserved ejection fraction using descending aortic constriction. The methods for evaluating cardiac morphology, histology, and function of this disease model are also presented.

More than half of heart failure (HF) cases are classified as heart failure with preserved ejection fraction (HFpEF) worldwide. Large animal models are ...

Establishment and Evaluation of a Porcine Vein Graft Disease Model

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the investigation of disease mechanisms and the development of therapeutic strategies. 
To perform the surgery, we enter the cardiac chamber through the third intercostal space and carefully dissect the internal mammary vein and immerse it in normal saline. The right main coronary artery is then treated for ischemia. The target vessel is incised, a shunt plug is placed, and the distal end of the graft vein is anastomosed. The ascending aorta is partially blocked, and the proximal end of the graft vein is anastomosed after perforation. The graft vein is checked for patency, and the proximal right coronary artery is ligated. 
CABG surgery is performed in minipigs to harvest the left internal mammary vein for its use as a vascular graft. Serum biochemical tests are used to evaluate the physiological status of the animals after surgery. Ultrasound examination shows that the proximal, middle, and distal end of the graft vessel are unobstructed. In the surgical model, turbulent blood flow in the graft is observed upon histological examination after the CABG surgery, and venous graft stenosis associated with intimal hyperplasia is observed in the graft. The study here provides detailed surgical procedures for the establishment of a repeatable CABG-induced VGD model.

In this protocol, novel pig vein bypass grafting was performed through a small incision in the left chest wall without cardiopulmonary bypass. A postoperative pathology study was done, which showed intimal thickening.

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the ...

Investigation of the Electrophysiological and Thermographic Safety Parameters of Surgical Energy Devices During Thyroid and Parathyroid Surgery in a Porcine Model

In thyroid and parathyroid surgery, surgical energy devices (SEDs) provide more efficient hemostasis than conventional clamp-and-tie hemostasis in areas with rich blood supply. However, when a SED is activated near the recurrent laryngeal nerve (RLN), the heat generated by the SED may injure the nerve irreversibly. To safely apply SEDs in thyroid/parathyroid surgery, this article introduces experimental porcine model studies to investigate the activation and cooling safety parameters of SEDs in standardized electrophysiological (EP) and thermographic (TG) procedures, respectively. In the EP safety parameter experiments, continuous intraoperative neuromonitoring (C-IONM) is applied to demonstrate the RLN function in real-time. The EP activation study evaluates the safe activation distance of SEDs; the EP cooling study evaluates the safe cooling time of SEDs. In the TG safety parameter experiment, a thermal imaging camera is used to record the temperature change after activating the SED. The TG activation study evaluates the lateral thermal spread distance after SED activation in a dry or humid environment and whether smoke and splashing are generated; the TG cooling study evaluates the cooling time. This will help establish the safety parameters of newly developed SEDs used in thyroid/parathyroid surgery and provide safety guidelines to avoid RLN injury and related complications.

The safe application of newly developed surgical energy devices in thyroid/parathyroid surgery attracts the attention of surgeons. Animal experimental models can avoid unnecessary trials and errors in human surgery. This report aims to demonstrate electrophysiological and thermographic methods to evaluate the safety parameters of SEDs in thyroid/parathyroid surgery.

In thyroid and parathyroid surgery, surgical energy devices (SEDs) provide more efficient hemostasis than conventional clamp-and-tie hemostasis in areas ...

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.

The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. Female landrace swine received treatment through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump.