Reserpine-induced Dissociation of Canine Pancreatic Secretion

In five dogs, provided with chronic pancreatic and gastric fistulas (Thomas' cannula), the effects on exocrine pancreatic secretion of an intravenous continuous perfusion of gastrin (Eurorga, hog gastrin I-II, 6 μg./kg./hr.) and secretin (GIH, 0.5 C.U./kg./hr.) was studied before and after 48 hours of reserpine treatment (0.1 mg./kg./24 hr.). When compared with the pretreated plateau levels, reserpine induced a significant pancreatic secretion dissociation, a depressive of the alkaline and a rising of the protein component. The former phenomenon suggests a participation of catecholamines in the secretin-elicited pancreatic electrolyte secretion. The latter, an enhanced sensitivity of intrapancreatic and/or acinar cells of the "pancreon" to gastrin stimulation.     

Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a substantial amount of work has been done to unravel their biology, thus leading to implications on clinical decision making. Recent genetic profiling of resected human specimens has identified alterations in signaling pathways involving KRAS and GNAS signaling as early events in the pathogenesis of intraductal pancreatic mucinous neoplasms. Progressively, mutations in genes such as TP53, SMAD4, RNF43, and others are thought to characterize invasive and advanced lesions. The role of inflammation in fueling the growth and transformation of these cysts has also begun to be studied with greater interest. A number of promising clinical studies have attempted to integrate these genetic insights into classifying these cysts and treating patients. We have reviewed existing literature on similar lines besides commenting on some useful animal models that recapitulate molecular and phenotypic progression of these cysts.     

在肾动脉下方的腹主动脉上犬同种带瓣主、肺动脉移植模型

目的：建立在肾动脉下方的腹主动脉上犬同种带瓣主、肺动脉移植实验模型，以研究其移植后免疫学、组织活性和超微结构改变以及宿主细胞替换供体组织过程。方法：将犬分为４组，采用犬同种带瓣主、肺动脉沿血流方向移植于异性受体犬肾动脉下方的腹主动脉上的方法。结果：全组２８例均存活，满足实验设计要求。结论：本实验模型具有手术操作容易、成功率高、术后并发症少、费用低廉等优点     

心力衰竭犬血小板功能及血浆血管性血友病因子、内皮素-1改变的实验研究

目的:观察慢性心力衰竭犬血小板聚集功能和血浆血管性血友病因子(vWF)、内皮素-1(ET-1)和血管紧张素Ⅱ(AngⅡ)含量的变化,探讨心力衰竭血栓前状态的形成机制.方法:14只犬随机分为起搏组(8只)和假手术组(6只),起搏组犬植入实验用心室非同步固定频率起搏方式(VOO)型起搏器,行心室快速起搏(220次/分)6周,建立心力衰竭犬模型.起搏组犬于起搏前和起搏后6周,假手术组犬于术前和术后7周采静脉血测定血小板最大聚集率及血浆vWF、ET-1和AngⅡ含量.结果:①假手术组犬术前与术后7周比较,心脏功能、血小板最大聚集率及血浆vWF、ET-1、AngⅡ含量均无明显变化.②快速心室起搏后6周,起搏组所有犬出现心功能不全症状,心脏每搏量、心输出量、左心室射血分数及心脏指数较起搏前明显降低,有显著性差异(P＜0.05～0.01);③起搏组犬快速心室起搏后6周,由二磷酸腺苷、肾上腺素、胶原和花生四烯酸诱导的血小板最大聚集率较起搏前增加,有极显著性差异(P＜0.01);④快速心室起搏后6周,起搏组犬血浆vWF、ET-1及AngⅡ含量较起搏前升高,有极显著性差异(P＜0.01).结论:血小板聚集功能增强、血浆vWF和ET-1含量升高,是导致心力衰竭血栓前状态形成的重要因素之一.     

Effect of Vagotomy on the Canine Pancreatic Secretion after Feeding

The effect of vagotomy on the external pancreatic secretion in response to a meat meal was investigated in 5 dogs with duodenal and gastric Thomas cannulas. Precautions were taken to maintain the normal regulation of neutrality in the duodenum during the post-prandial period. The gastric acid secretion was determined in some experiments. After vagotomy the secretion of gastric acid and pancreatic fluid and bicarbonate were reduced to the same degree, about 85 %, while the pancreatic secretion of protein was only reduced 57 %. Cholinergic stimulation with Urecholine increased the pancreatic secretion of fluid and bicarbonate to pre-vagotomy levels. The protein secretion did not attain that level, indicating an impaired protein secretion.     

氨利酮电生理作用的实验研究

为探讨氨利酮抗心律失常及致心律失常作用，观察１５只犬静脉注射氨利酮（４ｍｇ／ｋｇ）前后心肌电生理参数的改变。实验结果表明：（１）血压轻度下降；（２）窦律周期、窦房结恢复时间和校正窦房结恢复时间分别缩短１５．３１％、８．００％及１５．５６％，窦房传导时间变化不大；（３）Ｐ－Ｒ、Ａ－Ｈ间期及房室结有效不应期缩短，对心房肌、希浦系统，心室有效不应期无明显作用。用药前后Ｈ、Ｈ－Ｖ、ＱＲＳ、Ｑ－Ｔ间期亦无显著变化；（４）有４只犬出现频发室性早搏，数分钟内自行消失。讨论了此药电生理作用机制及临床意义。     

Medullary Ischaemia in Experimental Analgesic Nephropathy—The Pathogenesis of Renal Papillary Necrosis*

Summary: Medullary blood flow has been assessed in 29 analgesic-fed rats and nine matched control animals and has been correlated with renal medullary histological changes and tests of glomerular and tubular function. The animals were gavage-fed a variety of common non-steroid anti-inflammatory analgesic compounds over 20 weeks. Medullary perfusion was significantly reduced in analgesic-fed animals and was further lowered in animals subjected to hypovolaemic shock. Dehydration, however, did not appear to influence medullary blood flow in analgesic-fed rats. Medullary ischaemia appeared to be the earliest analgesic induced renal damage and developed before histological renal papillary necrosis. Ischaemia correlated with tests of medullary dysfunction — renal concentrating capacity and sodium conservation, but not with tests of glomerular function. On the basis of these findings the pathogenesis of analgesic induced renal papillary necrosis is discussed.     

低通气量犬心房颤动模型的建立

为了对心房颤动（简称房颤）进行电生理检查和治疗的研究，对２８只犬建立低通气量房颤模型。所有犬于麻醉状态下气管插管，以低于所测潮气量１０％～１５％的通气量通气３０ｍｉｎ后，经高位右房远端电极分别给予程序刺激和Ｂｕｒｓｔ刺激诱发房颤。２只犬没能诱发房颤，２６只犬被诱发，持续时间为１ｓ～３４ｍｉｎ，诱发率为９２．８６％（２６／２８）。有４只犬房颤持续在３０ｍｉｎ以上。３只犬只能被程序刺激诱发、９只犬只能被Ｂｕｒｓｔ刺激诱发，其余１４只犬两种刺激方式均可诱发。Ｂｕｒｓｔ刺激时６００ｐｐｍ最易诱发房颤，其次为７００ｐｐｍ，其余频率范围诱发率较低。程序刺激Ｓ１Ｓ２间期诱发范围８８．８２±９．２７（７０～１００）ｍｓ。窦性心律下和房颤持续时的动脉压无明显差异，但房颤时心室率却明显增快（２５９．６±２１．３ｂｐｍｖｓ１８０．７±１８．５ｂｐｍ，Ｐ＜０．０１）。结果表明：低通气量房颤模型的制作方法简便、费用低廉、诱发率高、重复性良好。     

The Lieber‐DeCarli Diet—A Flagship Model for Experimental Alcoholic Liver Disease

Alcoholic liver disease (ALD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. Understanding the pathophysiology and successful treatment for ALD is closely associated with the suitability of the animal model, which fully reflects all aspects of the pathogenesis and typical histological findings. This study reviews one of the most widely used experimental models of ALD in rodents—the Lieber‐DeCarli (LDC) liquid diet. It is an easy, accurate, reliable, and inexpensive model to study the pathogenesis of early stages of ALD. Here, we discuss the historical background and provide an overview of the advantages and disadvantages of the classical LDC as well as modified “second‐hit” models. We also provide a comprehensive protocol for the application of the LDC diet to perform it successfully, reliably, and reproducibly in mice.     

犬左心房心肌细胞动作电位的计算机建模仿真研究

目的构建犬左心房心肌细胞动作电位的计算机仿真模型。方法在Ramirez-Nattel-Courtemanche心房肌细胞模型的基础上,根据离子流数据构建左心房心肌细胞的计算机仿真模型。结果计算机仿真的电流与实验得到的离子流相似,最后得到的动作电位与我们在单个左心房肌细胞记录到的动作电位基本一致。结论我们根据犬左心房肌细胞离子流数据构建的细胞模型较现有模型更符合左心房细胞的特性,为进一步仿真研究心房颤动的机制打下了良好的基础。     

建立犬心房颤动模型的研究

用自制健索钩刀破坏25条犬部分二尖瓣腱索，造成中等程度二尖瓣关闭不全，建立心房颤动（AF）动物模型。术后12周内每2周1次行超声心动图及电生理检查，每次检查后用Burst刺激法诱发AF。术后2周左房前后径增加（22．70±2．31mmvs20．39±3．08mm，P＜0．05），术后4周左房面积增加（7．01±1．91cm2vs5．63±2．05cm2，P＜0．05）。术后4周P波时限延长（61．00±5．07msvs48．75±8．82ms）、高位右房有效不应期缩短（102．67±11．00msvs133．33±14．97ms），P均＜0．01。术后12周80％（8／10）的犬可诱发出持续时间＞5min的AF。左、有房AF波周期无显著差异（102．50±17．89msvs116．60±18．24ms，P＞0．05）。通过破坏二尖瓣腱索造成犬急性二尖瓣关闭不全，手术后随时间延长，动物表现在房扩张及右房有效不应期缩短和心房内传导时间延长，此与临床上瓣膜病引起的AF有一定的对应性，因而是研究AF电生理的良好模型。     

Cholinergic Effect on the Canine Pancreatic Response to Acidification of the Duodenum

On acidification of the duodenum in 3 conscious dogs with duodenal Thomas fistulas and gastrostomies no change in pancreatic secretion was observed after vagotomy. Cholinergic stimulation significantly increased the pancreatic secretion of fluid and bicarbonate in response to hydrochloric acid in the duodenum. The ratio between the pancreatic secretion of bicarbonate and the amount of acid introduced into the duodenum to elicit that response was 1: 3.2. Urecholine stimulation increased the ratio to 1: 1.7.     

A Servo-controlled Canine Model of Stable Severe Ischemic Left Ventricular Failure

Reversible left ventricular failure was produced in conscious dogs by compromise of the coronary circulation. In animals with prior left anterior descending coronary artery occlusion, mean left atrial pressure (LAP) was incorporated into an automatic feedback control system used to inflate a balloon cuff on the circumflex (Cfx) coronary artery. The system could produce stable increases in LAP to 15–20 mm Hg. The dominating system transfer function was the ratio of LAP to balloon volume (BV), which was characterized by a fixed delay (5 s), with LAP/BV = (8e^−jωτ )/(0.02 + jω). The system was stabilized by a phase lead network to reduce oscillations of LAP. A total of seven experiments were conducted in three dogs, and testing of inotropic agents was possible in three experiments under stable conditions with the pump off after an hour or more of operation. Problems encountered were 0.003–0.008 Hz oscillations in LAP in three experiments, which could usually be controlled by reducing the system gain. Late stage ventricular fibrillation occurred in all three animals, but defibrillation was easily accomplished after deflating the Cfx balloon. This system produces reversible left ventricular failure solely due to ischemia, thus closely simulating clinical heart failure due to coronary insufficiency.     

Canine Exocrine Pancreatic Secretory Changes Induced by an Intragastric Ethanol Test Meal

In five dogs with chronic gastric fistulas (Thomas cannula) and a new type of chronic pancreatic fistula which permits collection of pure nonactivated pancreatic juice after ingestion of a test meal, the following series of experiments were performed: In the first series, a test meal (400 gm. canned dog meat) was given with 200 ml. saline simultaneously infused through the gastric cannula. In response to this stimulus, the 20-minute peak pancreatic flow rate and bicarbonate output were respectively 33% and 34%, of the maximal secretion of the pancreatic gland obtained with secretin in six control dogs provided with gastric and the classical Thomas duodenal fistula. The 20-minute peak protein output represented 84% of the maximal secretory capacity attained with dose-response curves to CCK in the same group of control animals.
In the second series either 1.5 or 2.0 gm./kg. ethanol were given instead of saline. Intragastric ethanol induced a dissociation of pancreatic secretion: a significant inhibition of flow rate, of bicarbonate concentration and output and a significant rise of protein concentration; protein output remaining unchanged.
It is postulated that ethanol, acting on the stomach and duodenojejunum, evokes, independently of its gastrin-releasing capacity', an unknown humoral or nervous mechanism that counteracts the ethanol-elicited cholinergic-mediated inhibition of pancreatic protein secretion which has been previously described.     

A Novel Canine Model of Esophageal Varices with a Balloon Dilatation Constrictor

Background and objective The canine model of esophageal varices with an agar constrictor has been used for studies of the endoscopic treatment of esophageal variceal bleeding, but it has limitations in both stability and successful rate. This study was designed to enhance the model’s efficiency and success rate by using a novel approach with a balloon dilatation constrictor. Methods We used 22 adult mongrel dogs to establish the model by progressively compressing and constricting the portal vein through a rechargeable balloon dilatation constrictor in combination with side-to-side portocaval shunt and inferior vena cava (IVC) ligation to increase portal vein pressure (PVP). The rechargeable balloon dilatation constrictor was composed of a hyaline polypropylene (PP) ring, a silica gel tube with a balloon, and an injection pedestal (silica gel) in an implantable vascular access port. The effects were evaluated with pre- and post-shunt PVP measurement, weekly gastroscopy, and portocaval venography. Results The mean PVP increased significantly from a preoperative (before side-to-side portocaval shunt and IVC ligation) 12.86 ± 0.18 cmH₂O to 26.75 ± 0.39 cmH₂O after the model had been established (P < 0.05). After the model was established, gastroscopy performed to assess esophageal varix size demonstrated four varicose veins of grade I, six of grade II, eight of grade III and four of grade IV. The portocaval angiography showed that the IVC and portal vein were completely blocked, that the anastomosis stoma was unobstructed and that the blood flow through esophageal varices via splenetic and gastric veins was blocked. Conclusion The novel canine model developed with a rechargeable balloon dilatation constrictor is feasible and reliable for modeling esophageal varices.     

局灶性心房颤动模型的建立及其射频消融

建立一种稳定的局灶性心房颤动 (简称房颤 )的动物模型以探索其电生理特点及射频消融方法与安全性。选用 18只犬开胸直视下以乌头碱在心脏局部肌注加猝发电刺激建立模型。观察房颤射频消融前后的病理、生理、生化及房颤诱发率的变化 ,以及有效靶点的电生理特点。结果 :①所有犬均能以单次用药加猝发刺激诱发房颤 (诱发率 10 0 %)。②消融组犬在电生理标测指导下行单线射频消融 ,消融前房颤持续时间 94 2± 4 80s,消融后房颤诱发率为 13 .8%,持续时间为 7.3± 6.8s ,与消融前比较差异有统计学意义 (P <0 .0 1)。③消融前后窦性心率 ( 163 .9±2 0 .8次 /分vs 15 8.4± 2 3 .3次 /分 )、校正窦房结恢复时间 ( 89.0± 3 9.6msvs 93 .9± 3 8.0ms)、心房有效不应期 ( 14 7.3± 2 0 .9msvs14 0 .3± 18.3ms)及血清磷酸肌酸激酶 ( 5 3 0 .5± 2 0 4 .7U/Lvs 4 73 .5± 2 2 6.1U/L) ,均无明显变化 (P均 >0 .0 5 )。结论 :应用乌头碱制备局灶性房颤方法简单、诱发率高。电生理标测指导下局部消融可终止局灶性房颤。结果初步提示此法能以较少的损伤达到治疗目的 ,是较安全的 ,有一定的临床价值。     

犬心衰动物模型制作现况及进展

心力衰竭是心脏泵血功能衰竭,无法将静脉回流的血液充分泵出以满足全身组织代谢需求的一种病理生理状态及临床综合征。随着老龄化、不健康饮食习惯等危险因素的积累,心力衰竭的发病率逐年增加并对人类健康产生严重威胁。动物模型可间接模拟人体心衰的发生、发展、治疗的过程,但是并不能完全展示心衰整个发展过程及治疗效果。所以选择合适的心衰模型对实验至关重要。本文将对心衰模型的制作方法,适应症及优缺点选择进行综述。