Vlad V Simianu, Jonathan G Sham, Andrew S Wright, Skye D Stewart, Mouhamad Alloosh, Michael Sturek, David E Cummings, David R Flum
{"title":"评估减肥手术机制的大型动物生存模型。","authors":"Vlad V Simianu, Jonathan G Sham, Andrew S Wright, Skye D Stewart, Mouhamad Alloosh, Michael Sturek, David E Cummings, David R Flum","doi":"10.4236/ss.2015.68050","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus is thought to result from upper and/or lower gut hormone alterations. Evidence supporting these mechanisms is incomplete, in part because of limitations in relevant bariatric-surgery animal models, specifically the lack of naturally insulin-resistant large animals. With overfeeding, Ossabaw swine develop a robust metabolic syndrome, and may be suitable for studying post-surgical physiology. Whether bariatric surgery is feasible in these animals with acceptable survival is unknown.</p><p><strong>Methods: </strong>Thirty-two Ossabaws were fed a high-fat, high-cholesterol diet to induce obesity and insulin resistance. These animals were assigned to RYGB (n = 8), RYGB with vagotomy (RYGB-V, n = 5), gastrojejunostomy (GJ, n = 10), GJ with duodenal exclusion (GJD, n = 7), or sham operation (n = 2) and were euthanized 60 days post-operatively. Post-operative changes in weight and food intake are reported.</p><p><strong>Results: </strong>Survival to scheduled necropsy among surgical groups was 77%, living an average of 57 days post-operatively. Cardiac arrest under anesthesia occurred in 4 pigs. Greatest weight loss (18.0% ± 6%) and food intake decrease (57.0% ± 20%) occurred following RYGB while animals undergoing RYGB-V showed only 6.6% ± 3% weight loss despite 50.8% ± 25% food intake decrease. GJ (12.7% ± 4%) and GJD (1.2% ± 1%) pigs gained weight, but less than sham controls (13.4% ± 10%).</p><p><strong>Conclusions: </strong>A survival model of metabolic surgical procedures is feasible, leads to significant weight loss, and provides the opportunity to evaluate new interventions and subtle variations in surgical technique (e.g. vagus nerve sparing) that may provide new mechanistic insights.</p>","PeriodicalId":60710,"journal":{"name":"外科学(英文)","volume":"6 8","pages":"337-345"},"PeriodicalIF":0.0000,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871691/pdf/","citationCount":"4","resultStr":"{\"title\":\"A Large Animal Survival Model to Evaluate Bariatric Surgery Mechanisms.\",\"authors\":\"Vlad V Simianu, Jonathan G Sham, Andrew S Wright, Skye D Stewart, Mouhamad Alloosh, Michael Sturek, David E Cummings, David R Flum\",\"doi\":\"10.4236/ss.2015.68050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus is thought to result from upper and/or lower gut hormone alterations. Evidence supporting these mechanisms is incomplete, in part because of limitations in relevant bariatric-surgery animal models, specifically the lack of naturally insulin-resistant large animals. With overfeeding, Ossabaw swine develop a robust metabolic syndrome, and may be suitable for studying post-surgical physiology. Whether bariatric surgery is feasible in these animals with acceptable survival is unknown.</p><p><strong>Methods: </strong>Thirty-two Ossabaws were fed a high-fat, high-cholesterol diet to induce obesity and insulin resistance. These animals were assigned to RYGB (n = 8), RYGB with vagotomy (RYGB-V, n = 5), gastrojejunostomy (GJ, n = 10), GJ with duodenal exclusion (GJD, n = 7), or sham operation (n = 2) and were euthanized 60 days post-operatively. Post-operative changes in weight and food intake are reported.</p><p><strong>Results: </strong>Survival to scheduled necropsy among surgical groups was 77%, living an average of 57 days post-operatively. Cardiac arrest under anesthesia occurred in 4 pigs. Greatest weight loss (18.0% ± 6%) and food intake decrease (57.0% ± 20%) occurred following RYGB while animals undergoing RYGB-V showed only 6.6% ± 3% weight loss despite 50.8% ± 25% food intake decrease. GJ (12.7% ± 4%) and GJD (1.2% ± 1%) pigs gained weight, but less than sham controls (13.4% ± 10%).</p><p><strong>Conclusions: </strong>A survival model of metabolic surgical procedures is feasible, leads to significant weight loss, and provides the opportunity to evaluate new interventions and subtle variations in surgical technique (e.g. vagus nerve sparing) that may provide new mechanistic insights.</p>\",\"PeriodicalId\":60710,\"journal\":{\"name\":\"外科学(英文)\",\"volume\":\"6 8\",\"pages\":\"337-345\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2015-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871691/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"外科学(英文)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4236/ss.2015.68050\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2015/7/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"外科学(英文)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4236/ss.2015.68050","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2015/7/24 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 4
摘要
背景:Roux-en-Y胃旁路术(RYGB)对2型糖尿病的影响被认为是由于上肠和/或下肠激素的改变。支持这些机制的证据是不完整的,部分原因是相关减肥手术动物模型的局限性,特别是缺乏天然胰岛素抵抗的大型动物。在过度饲养的情况下,奥沙巴猪会出现强烈的代谢综合征,可能适合研究手术后生理学。对于这些存活可接受的动物,减肥手术是否可行尚不清楚。方法:采用高脂、高胆固醇饮食诱导小鼠肥胖和胰岛素抵抗。这些动物被分配到RYGB (n = 8), RYGB联合迷走神经切开术(RYGB- v, n = 5),胃空肠吻合术(GJ, n = 10), GJ联合十二指肠切除(GJD, n = 7)或假手术(n = 2),并于术后60天安乐死。报告了术后体重和食物摄入的变化。结果:手术组患者术后平均生存时间为57天,至计划剖检生存率为77%。4头猪出现麻醉下心脏骤停。RYGB组体重下降幅度最大(18.0%±6%),进食量减少幅度最大(57.0%±20%),而RYGB- v组在进食量减少50.8%±25%的情况下,体重仅下降6.6%±3%。GJ猪(12.7%±4%)和GJD猪(1.2%±1%)增重,但低于假对照组(13.4%±10%)。结论:代谢外科手术的生存模型是可行的,可以显著减轻体重,并为评估新的干预措施和手术技术的细微变化(如保留迷走神经)提供了机会,这可能提供新的机制见解。
A Large Animal Survival Model to Evaluate Bariatric Surgery Mechanisms.
Background: The impact of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus is thought to result from upper and/or lower gut hormone alterations. Evidence supporting these mechanisms is incomplete, in part because of limitations in relevant bariatric-surgery animal models, specifically the lack of naturally insulin-resistant large animals. With overfeeding, Ossabaw swine develop a robust metabolic syndrome, and may be suitable for studying post-surgical physiology. Whether bariatric surgery is feasible in these animals with acceptable survival is unknown.
Methods: Thirty-two Ossabaws were fed a high-fat, high-cholesterol diet to induce obesity and insulin resistance. These animals were assigned to RYGB (n = 8), RYGB with vagotomy (RYGB-V, n = 5), gastrojejunostomy (GJ, n = 10), GJ with duodenal exclusion (GJD, n = 7), or sham operation (n = 2) and were euthanized 60 days post-operatively. Post-operative changes in weight and food intake are reported.
Results: Survival to scheduled necropsy among surgical groups was 77%, living an average of 57 days post-operatively. Cardiac arrest under anesthesia occurred in 4 pigs. Greatest weight loss (18.0% ± 6%) and food intake decrease (57.0% ± 20%) occurred following RYGB while animals undergoing RYGB-V showed only 6.6% ± 3% weight loss despite 50.8% ± 25% food intake decrease. GJ (12.7% ± 4%) and GJD (1.2% ± 1%) pigs gained weight, but less than sham controls (13.4% ± 10%).
Conclusions: A survival model of metabolic surgical procedures is feasible, leads to significant weight loss, and provides the opportunity to evaluate new interventions and subtle variations in surgical technique (e.g. vagus nerve sparing) that may provide new mechanistic insights.