Name: single-anastomosis duodeno-ileal bypass with sleeve gastrectomy model in mice
Uploaded: 2023-02-10T14:05:00
Description: Watch this Scientific Journal Video about Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice at JoVE.com

We thank Ethicon (Johnson and Johnson surgical technologies) for kindly providing the suture cord and surgical clips. This work was supported by grants from the NExT Talent Project, Universit&#233; de Nantes, CHU de Nantes.

This protocol has been approved by the local French ethical committee for animal experimentation (Comit&#233; d&#39;&#233;thique en exp&#233;rimentation animale; reference CEEA-PdL n 06).
1. Pre-operative preparation
<ol>
	<li>Add gel diet food to the normal diet 3 days before the surgery. Fast the mice 6 h before the surgery.</li>
	<li>Induce anesthesia with 5% isoflurane (1 L/min) in a dedicated chamber with oxygen (1 L/min). Inject the mice subcutaneously with buprenorphi...

<ol>
	<li>Flegal, K. M., Carroll, M. D., Kit, B. K., Ogden, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+of+obesity+and+trends+in+the+distribution+of+body+mass+index+among+US+adults,+1999-2010.">Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.</a> JAMA. 307 (5), 491-497 (2012).</li><li>Sj&#246;str&#246;m, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Association+of+bariatric+surgery+with+long-term+remission+of+type+2+diabetes+and+with+microvascular+and+macrovascular+complications.">Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications.</a> JAMA. 311 (22), 2297-2304 (2014).</li><li>Dyson, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hepatocellular+cancer:+the+impact+of+obesity,+type+2+diabetes+and+a+multidisciplinary+team.">Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team.</a> Journal of Hepatology. 60 (1), 110-117 (2014).</li><li>S&#225;nchez-Pernaute, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proximal+duodenal-ileal+end-to-side+bypass+with+sleeve+gastrectomy:+proposed+technique.">Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy: proposed technique.</a> Obesity Surgery. 17 (12), 1614-1618 (2007).</li><li>Himpens, J., Verbrugghe, A., Cadi&#232;re, G. B., Everaerts, W., Greve, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+results+of+laparoscopic+Roux-en-Y+Gastric+bypass:+evaluation+after+9+years.">Long-term results of laparoscopic Roux-en-Y Gastric bypass: evaluation after 9 years.</a> Obesity Surgery. 22 (10), 1586-1593 (2012).</li><li>S&#225;nchez-Pernaute, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+results+of+single-anastomosis+duodeno-ileal+bypass+with+sleeve+gastrectomy+(SADI-S).">Long-term results of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S).</a> Obesity Surgery. 32 (3), 682-689 (2022).</li><li>Shoar, S., Poliakin, L., Rubenstein, R., Saber, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single+anastomosis+duodeno-ileal+switch+(SADIS):+A+systematic+review+of+efficacy+and+safety.">Single anastomosis duodeno-ileal switch (SADIS): A systematic review of efficacy and safety.</a> Obesity Surgery. 28 (1), 104-113 (2018).</li><li>Rao, R. S., Rao, V., Kini, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+in+bariatric+surgery--a+review+of+the+surgical+techniques+and+postsurgical+physiology.">Animal models in bariatric surgery--a review of the surgical techniques and postsurgical physiology.</a> Obesity Surgery. 20 (9), 1293-1305 (2010).</li><li>Lutz, T. A., Bueter, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+rat+and+mouse+models+in+bariatric+surgery+experiments.">The use of rat and mouse models in bariatric surgery experiments.</a> Frontiers in Nutrition. 3, 25 (2016).</li><li>Baud, 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=Bile+diversion+in+Roux-en-Y+Gastric+Bypass+modulates+sodium-dependent+glucose+intestinal+uptake.">Bile diversion in Roux-en-Y Gastric Bypass modulates sodium-dependent glucose intestinal uptake.</a> Cell Metabolism. 23 (3), 547-553 (2016).</li><li>Blanchard, 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=Sleeve+gastrectomy+alters+intestinal+permeability+in+diet-induced+obese+mice.">Sleeve gastrectomy alters intestinal permeability in diet-induced obese mice.</a> Obesity Surgery. 27 (10), 2590-2598 (2017).</li><li>Ayer, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Techniques+of+sleeve+gastrectomy+and+modified+Roux-en-Y+Gastric+Bypass+in+mice.">Techniques of sleeve gastrectomy and modified Roux-en-Y Gastric Bypass in mice.</a> Journal of Visualized Experiments. (121), e54905 (2017).</li><li>Wang, 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=Comparison+of+diabetes+remission+and+micronutrient+deficiency+in+a+mildly+obese+diabetic+rat+model+undergoing+SADI-S+versus+RYGB.">Comparison of diabetes remission and micronutrient deficiency in a mildly obese diabetic rat model undergoing SADI-S versus RYGB.</a> Obesity Surgery. 29 (4), 1174-1184 (2019).</li><li>Wu, 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=Comparison+of+the+outcomes+of+single+anastomosis+duodeno-ileostomy+with+sleeve+gastrectomy+(SADI-S),+single+anastomosis+sleeve+ileal+(SASI)+bypass+with+sleeve+gastrectomy,+and+sleeve+gastrectomy+using+a+rodent+model+with+diabetes.">Comparison of the outcomes of single anastomosis duodeno-ileostomy with sleeve gastrectomy (SADI-S), single anastomosis sleeve ileal (SASI) bypass with sleeve gastrectomy, and sleeve gastrectomy using a rodent model with diabetes.</a> Obesity Surgery. 32 (4), 1209-1215 (2022).</li><li>Laura, 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=Establishing+a+reproducible+murine+animal+model+of+single+anastomosis+duodenoileal+bypass+with+sleeve+gastrectomy+(SADl-S).">Establishing a reproducible murine animal model of single anastomosis duodenoileal bypass with sleeve gastrectomy (SADl-S).</a> Obesity Surgery. 28 (7), 2122-2125 (2018).</li><li>Meoli, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intestine-specific+overexpression+of+LDLR+enhances+cholesterol+excretion+and+induces+metabolic+changes+in+male+mice.">Intestine-specific overexpression of LDLR enhances cholesterol excretion and induces metabolic changes in male mice.</a> Endocrinology. 160 (4), 744-758 (2019).</li><li>Abu El Haija, 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=Toll-like+receptor+4+and+myeloid+differentiation+factor+88+are+required+for+gastric+bypass-induced+metabolic+effects.">Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.</a> Surgery for Obesity and Related Diseases. 17 (12), 1996-2006 (2021).</li><li>Kumar, S., 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=Lipocalin-type+prostaglandin+D2+synthase+(L-PGDS)+modulates+beneficial+metabolic+effects+of+vertical+sleeve+gastrectomy.">Lipocalin-type prostaglandin D2 synthase (L-PGDS) modulates beneficial metabolic effects of vertical sleeve gastrectomy.</a> Surgery for Obesity and Related Diseases. 12 (8), 1523-1531 (2016).</li><li>Heffron, S. P., 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=Changes+in+lipid+profile+of+obese+patients+following+contemporary+bariatric+surgery:+A+meta-analysis.">Changes in lipid profile of obese patients following contemporary bariatric surgery: A meta-analysis.</a> The American Journal of Medicine. 129 (9), 952-959 (2016).</li><li>Carswell, K. A., Belgaumkar, A. P., Amiel, S. A., Patel, A. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+systematic+review+and+meta-analysis+of+the+effect+of+gastric+bypass+surgery+on+plasma+lipid+levels.">A systematic review and meta-analysis of the effect of gastric bypass surgery on plasma lipid levels.</a> Obesity Surgery. 26 (4), 843-855 (2016).</li><li>Surve, A., Zaveri, H., Cottam, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Retrograde+filling+of+the+afferent+limb+as+a+cause+of+chronic+nausea+after+single+anastomosis+loop+duodenal+switch.">Retrograde filling of the afferent limb as a cause of chronic nausea after single anastomosis loop duodenal switch.</a> Surgery for Obesity and Related Diseases. 12 (4), 39-42 (2016).</li><li>Uysal, 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=Caecum+location+in+laboratory+rats+and+mice:+an+anatomical+and+radiological+study.">Caecum location in laboratory rats and mice: an anatomical and radiological study.</a> Laboratory Animals. 51 (3), 245-255 (2017).</li><li>S&#225;nchez-Pernaute, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Single-anastomosis+duodeno-ileal+bypass+with+sleeve+gastrectomy:+metabolic+improvement+and+weight+loss+in+first+100+patients.">Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy: metabolic improvement and weight loss in first 100 patients.</a> Surgery for Obesity and Related Diseases. 9 (5), 731-735 (2013).</li><li>Wei, J. H., Yeh, C. H., Lee, W. J., Lin, S. J., Huang, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleeve+gastrectomy+in+mice+using+surgical+clips.">Sleeve gastrectomy in mice using surgical clips.</a> Journal of Visualized Experiments. (165), e60719 (2020).</li><li>Ying, L. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technical+feasibility+of+a+murine+model+of+sleeve+gastrectomy+with+ileal+transposition.">Technical feasibility of a murine model of sleeve gastrectomy with ileal transposition.</a> Obesity Surgery. 29 (2), 593-600 (2019).</li><li>Bruinsma, B. G., Uygun, K., Yarmush, M. L., Saeidi, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+models+of+Roux-en-Y+gastric+bypass+surgery+and+sleeve+gastrectomy+in+rats+and+mice.">Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice.</a> Nature Protocols. 10 (3), 495-507 (2015).</li></ol>

Bariatric surgeries, whose techniques are constantly evolving, appear to be currently the most effective treatment for obesity and associated metabolic comorbidities3,19,20. The SADI-S procedure, firstly described in 20074, is a promising procedure associated with greater metabolic effects than other malabsorptive surgeries. Animal models, particularly mice that allow the rapid generation of genetically m...

Obesity is an emerging and endemic situation with increasing prevalence, affecting approximately 1 in 20 adults worldwide1. Bariatric surgery has become the most effective treatment option for the affected adults in recent years, improving both weight loss and metabolic disorders2,3, with variable results depending on the type of surgical procedure used.
There are two main mechanisms that are implicated in the effects of the bariatric procedures: restriction that aims to increase satiety (such as in the sleeve gastrectomy (SG) where 80% of the stomach is removed), and malabsorption. Among the procedures that imply both restriction and malabsorption, the single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has been proposed as an alternative to the Roux-en-Y gastric bypass (RYGB), in which a weight regain is observed in approximately 20% patients4,5. In this technique, a sleeve gastrectomy is associated with a small bowel rearrangment, dividing it into a biliary and a short common limb (one-third of the total small bowel length) (Figure 1A). Technically, the SADI-S has the advantage over the RYGB of requiring only a single anastomosis, reducing the operation time by approximately 30%. In addition, this method preserves the pylorus, which helps to reduce the risk of peptic ulcer disease and limits anastomotic leakage. The SADI-S is also associated with a high rate of metabolic improvement, strongly favoring its use during the last few years6,7.
Since metabolic effects have become increasingly foundational to bariatric procedures, elucidating their mechanisms seems crucial. Therefore, the use of animal models for bariatric procedures is of utmost importance to better understand their metabolic effects and the cellular and molecular pathways involved8. These models contributed, for example, to a better understanding of the change in food intake after SG or RYGB in a controlled environment9 and to the study of glucose or cholesterol fluxes through the intestinal barrier10,11; these informations are rarely available in clinical studies. This knowledge could help to define their optimal surgical indications. We previously described mouse models of SG and RYGB12. However, despite its promising results in clinical practice, the SADI-S has only been developed and described in rats13,14,15. However, given its genetic malleability, the mouse model has been useful in the past to study the various metabolic effects of such procedures16,17,18, and a SADI-S mouse model could be useful to evaluate effects of SADI-S despite the technical difficulty.
In this article, we describe the adaptation of the SADI-S procedure in mice (Figure 1B) in a reproducible manner. Special attention is given to the description of perioperative care.

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			<td>Agagani needle 26 G</td>
			<td>Terumo</td>
			<td>050101B</td>
			<td>26 G needle</td>
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		<tr>
			<td>Betadine dermique&#160;</td>
			<td>Pharma-gdd</td>
			<td>3300931499787</td>
			<td>Povidone solution</td>
		</tr>
		<tr>
			<td>Betadine scrub</td>
			<td>Pharma-gdd</td>
			<td>&#160;3400931499787</td>
			<td>Povidone solution</td>
		</tr>
		<tr>
			<td>Binocular microscope</td>
			<td>Optika Microscopes Italy</td>
			<td>SZN-9</td>
			<td>Binocular stereomicroscope</td>
		</tr>
		<tr>
			<td>Buprecare</td>
			<td>Animalcare</td>
			<td>3760087151244</td>
			<td>Buprenorphin</td>
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		<tr>
			<td>Castroviejo, straight 9 cm</td>
			<td>F.S.T</td>
			<td>12060-02</td>
			<td>Micro scissors</td>
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		<tr>
			<td>Castroviejo, straight 9 cm</td>
			<td>F.S.T</td>
			<td>12060-02</td>
			<td>Needle holder</td>
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			<td>Chlorure de sodium Fresenius 0.9%</td>
			<td>Fresenius Kabi&#160;</td>
			<td>BE182743</td>
			<td>NaCl 0.9%</td>
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			<td>Clamoxyl</td>
			<td>Med&#39;vet</td>
			<td>5414736007496</td>
			<td>Amoxicilline</td>
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		<tr>
			<td>Cotton buds</td>
			<td>Comed</td>
			<td>2510805</td>
			<td>Cotton swabs</td>
		</tr>
		<tr>
			<td>Element HT5</td>
			<td>Scilvet</td>
			<td>Element HT5</td>
			<td>Automated hematology analyzer</td>
		</tr>
		<tr>
			<td>Emeprid</td>
			<td>CEVA</td>
			<td>3411111914365</td>
			<td>Metoclopramid</td>
		</tr>
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			<td>Extra Fine Graefe Forceps, curved (tip width: 0.5 mm)</td>
			<td>F.S.T</td>
			<td>11152-10</td>
			<td>Surgical forceps</td>
		</tr>
		<tr>
			<td>Extra Fine Graefe Forceps, straight (tip width: 0.5 mm)</td>
			<td>F.S.T</td>
			<td>11150-10</td>
			<td>Surgical forceps</td>
		</tr>
		<tr>
			<td>Fercobsang</td>
			<td>Vetoprice</td>
			<td>QB03AE04</td>
			<td>Iron, multivitamins and minerals&#160;</td>
		</tr>
		<tr>
			<td>Forane</td>
			<td>Baxter</td>
			<td>1001936060</td>
			<td>Isoflurane</td>
		</tr>
		<tr>
			<td>Graefe forceps, straight (tip width: 0.8 mm)</td>
			<td>F.S.T</td>
			<td>11050-10</td>
			<td>Forceps</td>
		</tr>
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			<td>Graphpad Prism version 8.0</td>
			<td>GraphPad Software, Inc.</td>
			<td>Version 8.0</td>
			<td>Software for statistical analysis</td>
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			<td>Heat pad</td>
			<td>Intellibio innovation</td>
			<td>A-2101-00300</td>
			<td>Heat pad</td>
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			<td>Incubator</td>
			<td>Bioconcept Technologies</td>
			<td>Manufactured on demand</td>
			<td>Incubator&#160;</td>
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			<td>Lighting</td>
			<td>Optika Microscopes Italy</td>
			<td>CL-30</td>
			<td>Lighting for microscopy</td>
		</tr>
		<tr>
			<td>Ocrygel</td>
			<td>Med&#39;vet</td>
			<td>3700454505621</td>
			<td>Carboptol 980 NF</td>
		</tr>
		<tr>
			<td>Pangen 2.5 cm x 3.5 cm</td>
			<td>Urgovet</td>
			<td>A02978</td>
			<td>Haemostatic collagen compress</td>
		</tr>
		<tr>
			<td>Prolene 6/0</td>
			<td>B.Braun</td>
			<td>3097915</td>
			<td>Optilene 6/0 (0.7 metric) 75 cm 2XDR13 CV2 RCP, suture cord</td>
		</tr>
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			<td>Prolene 8/0</td>
			<td>Ethicon</td>
			<td>8732</td>
			<td>2 x BV175-6 MP, 3/8 Circle, 8 mm,&#160; suture cord</td>
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			<td>Scissors</td>
			<td>F.S.T</td>
			<td>146168-09</td>
			<td>Surgical scissors</td>
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			<td>Sterile compresses&#160;</td>
			<td>Laboartoire Sylamed</td>
			<td>211S05-50</td>
			<td>Non-woven sterile compressed</td>
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			<td>Terumo Syringe</td>
			<td>Terumo</td>
			<td>50828</td>
			<td>1 mL syringe</td>
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		<tr>
			<td>Titanium hemostatic clip</td>
			<td>P&#233;ters Surgical</td>
			<td>B2180-1</td>
			<td>Surgical clip</td>
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			<td>Vannas Wolff</td>
			<td>F.S.T</td>
			<td>15009-08</td>
			<td>Micro scissors</td>
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			<td>Vita Rongeur</td>
			<td>Virbac</td>
			<td>3597133087611</td>
			<td>Vitamin supplementation</td>
		</tr>
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			<td>Vitaltec stainless</td>
			<td>P&#233;ters Surgical</td>
			<td>PB 220-EB Medium</td>
			<td>Surgical clip applier</td>
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single-anastomosis duodeno-ileal bypass with sleeve gastrectomy model in mice

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, cardiovascular events, and cancers) through restrictive and malabsorptive mechanisms. Understanding the mechanisms by which these procedures allow such improvements often require their transposition into animals, especially in mice, because of the ease of generating genetically modified animals. Recently, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has emerged as a procedure that uses both restrictive and malabsorptive effects, which is being used as an alternative to gastric bypass in case of major obesity. Thus far, this procedure has been associated with strong metabolic improvements, which has led to a marked increase in its use in daily clinical practice. However, the mechanisms underlying these metabolic effects have been poorly studied as a result of a lack of animal models. In this article, we present a reliable and reproducible model of SADI-S in mice, with a special focus on perioperative management. The description and use of this new rodent model will be helpful for the scientific community to better understand the molecular, metabolic, and structural changes induced by the SADI-S and to better define the surgical indications for clinical practice.

Learning curve 
The learning curve for this model is displayed in Figure 6. A progressive decrease in the operating time is observed, reaching approximately 60 min of surgery after 4 weeks of intensive training (Figure 6A). The 5-day postoperative survival also improved with time, reaching 77% during regular practice (Figure 6B). The most frequent causes of mortality were anastomotic leaks and an afferent loop ...

Watch this Scientific Journal Video about Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice at JoVE.com

Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice

Single-anastomosis duodeno-ileal bypass (SADI-S) is an emerging bariatric procedure with important metabolic effects. In this article, we present a reliable and reproducible model of SADI-S in mice.

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes ...

So this protocol is the first description of CDS in mice, allowing us to mimic the surgery performed in clinical practice and to decipher the metabolic cellular and molecular mechanisms in a more predictable manner. This procedure requires less anastomosis than the gastric bypass, thus the operation is shortened and the survival rate is improved with similar metabolic benefits to the gastric bypass. Begin by administering buprenorphine, amoxicillin, metoclopromide, and iron subcutaneously.From the xiphoid process, shave the first two thirds of the mouse's abdomen using an electric razor and disinfect the mouse's abdomen using an iodine povidone solution twice. Then place the mouse supine on a dedicated heat pad covered with a clean underpad. Check the depth of anesthetization using the toe pinch test, and cover the mouse in sterilized plastic wrap.Next, hyper extend the mouse's abdomen by fixing the lower core and placing a one milliliter syringe or equivalent behind the mouse's back. Cut a window sized opening as the future incision site in a sterile compress, and use it as an operating field to cover the mouse. Perform a median laparotomy with scissors by opening the abdominal skin from the xiphoid process to the middle of the abdomen.Then use scissors to open the abdominal wall along the linear alba between the abdominal muscles. Using a moistened cotton swab, gently mobilize the duodenum from the abdominal cavity to see its anterior and posterior sides. Then localized the main bile duct, which is immediately visible under the binocular microscope on the posterior side of the lesser omentum and the duodenum.Under the binocular microscope, visualize an area approximately from the main bile duct between the duodenum arteries, and penetrate this area using curved micro forceps from one side of the duodenum to the other. Next, perform a duodenal negation between the arteries using a 6.0 non-absorbable suture. Use a moistened cotton swab and a non-traumatic clamp to mobilize the stomach from the abdominal cavity and separate it from the surrounding organs using micro scissors.Then separate the greater omentum, cut the short gastric arteries between the stomach and the spleen and the lipoma linking the stomach to the lower part of the esophagus. Using micro scissors, perform a five millimeter gastrotomy by opening the fundus and removing the residual food using a cotton swab. Apply surgical clips along the stomach's greater curvature to exclude approximately 80%of the stomach, and remove the excluded stomach by cutting it with micro scissors.Now, anchor the surgical clips to a certain impermeability by performing a running suture from the beginning to the end of the stomach resection. Under the binocular microscope, visualized the last ileal loop situated just before the cecum. Gently mobilized the small intestine outside the abdominal cavity from the last ileal loop, and dispose the small bowel so the last ileal loop is located on the left side.Using a previously sized suture cord, measure 10 centimeters from the last ileal loop. To ensure that the future biliary limb comes to the anastomosis side from its left side, make a large loop of the small intestine around the side of the future anastomosis. At this point, perform a four millimeter enterotomy by opening the small bowel using micro scissors.Perform a four millimeter enterotomy on the duodenum immediately after the pylorus between the stomach and the ligation performed earlier. Then place an absorbable hemostatic collagen compress to favor homeostasis. Using a non-absorbable 8.0 suture, perform a side to side duodenal ilealanal anastomosis starting from the posterior side to the anterior side, and display the small bowel in the abdominal cavity as described in the manuscript.Rehydrate the mouse with 500 microliters of 37 degrees celsius saline solution by infusing it into the abdominal cavity using a one milliliter syringe. Now use a single 6.0 non-absorbable running suture to close the musculoaponeurotic neurotic layer, and close the abdominal skin using 6.0 non-absorbable separated sutures. After four weeks of intensive training, a progressive decrease in the operating time is observed, reaching approximately 60 minutes.The five day post-operative survival also improved with time, reaching 77%during regular practice. From the fourth post-operative day, SADI-S mice experienced significant weight loss compared to the Sham mice. A significant increase in daily food intake was observed in SADI-S mice.However, after iron supplementation, no significant difference was observed in the hemoglobin concentration between the Sham and SADI-S groups. When performing the anastomosis, it is crucial to dispose the bowel in a way that bile and food do not oppose each other to avoid an afferent loop syndrome.

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Research

JoVE Journal

Medicine

Modeling Stroke in Mice - Middle Cerebral Artery Occlusion with the Filament Model

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are very limited. To meet the need for novel therapeutic approaches, experimental stroke research frequently employs rodent models of focal cerebral ischaemia. Most researchers use permanent or transient occlusion of the middle cerebral artery (MCA) in mice or rats.
Proximal occlusion of the middle cerebral artery (MCA) via the intraluminal suture technique (so called filament or suture model) is probably the most frequently used model in experimental stroke research. The intraluminal MCAO model offers the advantage of inducing reproducible transient or permanent ischaemia of the MCA territory in a relatively non-invasive manner. Intraluminal approaches interrupt the blood flow of the entire territory of this artery. Filament occlusion thus arrests flow proximal to the lenticulo-striate arteries, which supply the basal ganglia. Filament occlusion of the MCA results in reproducible lesions in the cortex and striatum and can be either permanent or transient. In contrast, models inducing distal (to the branching of the lenticulo-striate arteries) MCA occlusion typically spare the striatum and primarily involve the neocortex. In addition these models do require craniectomy. In the model demonstrated in this article, a silicon coated filament is introduced into the common carotid artery and advanced along the internal carotid artery into the Circle of Willis, where it blocks the origin of the middle cerebral artery. In patients, occlusions of the middle cerebral artery are among the most common causes of ischaemic stroke. Since varying ischemic intervals can be chosen freely in this model depending on the time point of reperfusion, ischaemic lesions with varying degrees of severity can be produced. Reperfusion by removal of the occluding filament at least partially models the restoration of blood flow after spontaneous or therapeutic (tPA) lysis of a thromboembolic clot in humans.
In this video we will present the basic technique as well as the major pitfalls and confounders which may limit the predictive value of this model.

Filamentous occlusion of the Middle cerebral artery is a common model for studying ischemic stroke in mice.

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are ...

Roux-en-Y Gastric Bypass Operation in Rats

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery1,2. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation3. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation4,5, increased energy expenditure6,7, altered preference for food high in fat and sugar8,9, altered salt and water handling of the kidney10 as well as alterations in gut microbiota11. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating12.
During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail 13-15. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%15. Furthermore, surgery has been carried out almost exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly.
Technical and experimental variations in published gastric bypass rat models complicate the comparison and identification of potential physiological mechanisms involved in gastric bypass. There is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data. This article therefore aims to summarize and discuss technical and experimental details of our previously validated and published gastric bypass rat model.

Numerous studies using gastric bypass rat models have been recently conducted to uncover the underlying physiological mechanisms of Roux-en-Y gastric bypass operations. This article aims to demonstrate and discuss the technical and experimental details of our published gastric bypass rat model to understand advantages and limitations of this experimental tool.

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality ...

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 ...

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. ...

Techniques of Sleeve Gastrectomy and Modified Roux-en-Y Gastric Bypass in Mice

Obesity is a major public health issue, with a prevalence of 4 to 28% for men and 6.2 to 36.5% for women in Europe (from 2003 to 2008). Morbid obesity is frequently associated with metabolic complications, such as type 2 diabetes, hypertension, and dyslipidemia, reducing life expectancy and quality. In the absence of any effective noninvasive treatments, bariatric surgery is a valuable therapeutic option for patients with morbid obesity (body mass index (BMI) &#62;40 kg/m2), leading to long-term, sustained weight loss and improvements in metabolic complications. However, the underlying cellular and molecular mechanisms sustaining the beneficial effects of bariatric surgery are not yet fully understood. Due to the numerous genetically-modified strains available, the mouse model is the most convenient animal model to explore the molecular mechanisms behind the pleiotropic beneficial effects of bariatric surgeries. Here, we detailed the optimized healthcare methods and surgical protocols in mice for the two most widely-used bariatric surgeries: the sleeve gastrectomy and the modified Roux-en-Y gastric bypass. Deciphering the molecular mechanisms underlying the therapeutic effects of bariatric surgeries offers the promise of identifying new therapeutics targets.

Bariatric surgery is the most efficient way to reduce body weight and the deadly metabolic complications (diabetes, obesity, and dyslipidemia) frequently associated with morbid obesity. Mouse models of bariatric surgery represent a unique asset for deciphering molecular mechanisms behind the beneficial effects of these surgeries on diabetes, hypertension, and dyslipidemia.

Obesity is a major public health issue, with a prevalence of 4 to 28% for men and 6.2 to 36.5% for women in Europe (from 2003 to 2008). Morbid obesity is ...

Using the Sleeve Technique in a Mouse Model of Aortic Transplantation - An Instructional Video

Orthotopic aortic transplantation using the sleeve technique reduces injury to the aorta with failure rate of only 10-20%. The time to anastomose the aorta in mice using the sleeve method was short and easy averaging 20 min, permitting studies of iso/allo grafts. The following article describes the aortic transplantation procedure used in our laboratory. The mice were anesthetized with a mixture of 1.5% volume isoflurane and 100% oxygen through a face mask. At this point, the segment of the aorta between the renal arteries and its bifurcation was separated from the vena cava, freely prepared and clampedat the proximal and distal segments with a single silk suture. Prior to the removal of the aorta, a saline solution containing heparin was injected into the inferior vena cava. Then the aorta was cut between the clamps and a saline heparin solution was used to flush the lumen. The sleeve technique with monofilament sutures was used in order to transplant the abdominal aorta in the orthotopic position.

We present an orthotopic aortic transplantation model using the sleeve technique in mice. It is a very rapid anastomosis method, which can be employed in studies of vascular disease.

Orthotopic aortic transplantation using the sleeve technique reduces injury to the aorta with failure rate of only 10-20%. The time to anastomose the ...

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities.

This paper describes how to perform cardiopulmonary bypass in mice. This novel model will facilitate the investigation of the molecular mechanisms involved in organ damage.

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

One-anastomosis Gastric Bypass (OAGB) in Rats

The goal of this protocol is to set up a preclinical model of bariatric surgery and, more specifically, OAGB in obese rats. Based on this preclinical model, longitudinal studies can be carried out to provide an improved understanding of the mechanisms underlying the outcomes seen after bariatric surgery in humans. For this purpose, rats are operated on through a laparotomy under general anesthesia with isoflurane. First, the surgeon creates a long and tubular gastric pouch: after greater curve and hiatal dissection, the nonglandular stomach is stapled and removed. Then, the remaining stomach is also stapled in order to create a gastric tube and exclude the antrum of the stomach. After that, the surgeon performs a single end-to-side gastrojejunostomy 35 cm from the duodenojejunal angle. This limb length has been chosen in order to reproduce the same ratio between the biliopancreatic limb (BPL) and common limb (CL) length as in human bariatric surgery. The operation ends by aponeurotic and cutaneous closure. The early postoperative management consists of subcutaneous hydration, an intramuscular prophylactic antibiotic injection, a parietal injection of xylocaine, the administration of painkillers, and a progressive reintroduction of diet.

One-anastomosis Gastric Bypass OAGB in Rats

This protocol is for the performance of one-anastomosis gastric bypass (OAGB) on rat. The operator performs a long and tubular-stapled gastric pouch followed by hand-sewn anastomosis. For this model, the operator reproduces the same ratio between biliopancreatic and common limb in humans; therefore, the biliopancreatic limb measures 35 cm.

The goal of this protocol is to set up a preclinical model of bariatric surgery and, more specifically, OAGB in obese rats. Based on this preclinical ...

Sleeve Gastrectomy in Mice using Surgical Clips

The number of people who are overweight and obese is continually increasing both in the adult and adolescent populations. This coincides with the increased universal phenomenon of type 2 diabetes (T2D) and other metabolic problems. Bariatric surgery, such as SG, is currently one of the most effective and commonly used long-term treatment for obesity and T2D, but the association between them is not completely explored yet. The mechanisms underlying the outcomes seen after bariatric surgery in humans can be investigated based on preclinical animal studies. The SG reduces body weight, glucose levels and many metabolic parameters, and is easy to perform with a low incidence of complications. The goal of this work is to provide a simple method and an uncomplicated preclinical model of bariatric surgery in animals for researchers.

The prevalence of diabetes and obesity is continuously increasing worldwide. The mechanisms between diabetes, obesity and their associated mortality and co-morbidities need to be further investigated. Here, we present a protocol for sleeve gastrectomy (SG) in animals as an uncomplicated preclinical model of bariatric surgery.