Splanchnic Th2 and Th1 Cytokine Redistribution in Microsurgical Cholestatic Rats

García-Domínguez, J M; Aller, María-Ángeles; Garcı́a, Cruz; Vicente, Felipe de; Corcuera, María Teresa; Gómez-Aguado, Fernando; Alonso, María José; Vara, Elena; Árias, Jaime

doi:10.1016/j.jss.2009.06.010

Cited by 13 publications

(8 citation statements)

References 64 publications

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“…Long-term (6 weeks) microsurgical cholestatic rats show a splanchnic redistribution of cytokines, with an increase of Th1 (TNFα and IL-1β) and Th2 (IL-4 and IL-10) production in the small bowel and in the mesenteric lymph nodes [163]. It has been proposed that this splanchnic inflammatory response associated with ascites could be mediated, among others factors, by mast cells.…”

Section: Obstructive Cholestasis In the Rat: A Model Of Decompensatedmentioning

confidence: 99%

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

Aller¹,

Arias²,

Prieto³

et al. 2012

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Prehepatic portal hypertension induces a splanchnic low-grade inflammatory response that could switch to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. The extraembryonic origin of the portal system maybe determines the regression to an extraembryonic phenotype, i.e., vitellogenic and amniotic, during the evolution of both types of portal hypertension. Thus, prehepatic portal hypertension, or compensated hypertension by portal vein ligation in the rat, is associated with molecular mechanisms related to vitellogenesis, where hepatic steatosis and splanchnic angiogenesis stand out. In turn, extrahepatic cholestasis in the rat induces intrahepatic portal hypertension, or decompensated hypertension, with ascites and hepatorenal syndrome. The splanchnic interstitium, the mesenteric lymphatic system, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of ascites. The hypothetical comparison between the ascitic and the amniotic fluid also allows for translational investtigation. The induced regression of the splanchnic system to extraembryonic functions by portal hypertension highlights the great relevance of the extraembryonic structures even during post-natal life.

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Section: Obstructive Cholestasis In the Rat: A Model Of Decompensatedmentioning

confidence: 99%

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

Aller¹,

Arias²,

Prieto³

et al. 2012

ABB

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“…Long-term (6 weeks) microsurgical cholestatic rats show a splanchnic redistribution of cytokines, with an increase of Th1 (TNF- α and IL-1 β ) and Th2 (IL-4 and IL-10) cytokine production in the small bowel and in the mesenteric lymph nodes [118]. It has been proposed that this splanchnic inflammatory response associated with ascites could be mediated, among others factors, by mast cells [111].…”

Section: The Role Of Mesothelial Cells In the Pathophysiology Of Tmentioning

confidence: 99%

The Interstitial Lymphatic Peritoneal Mesothelium Axis in Portal Hypertensive Ascites: When in Danger, Go Back to the Sea

Aller

Prieto

Argudo³

et al. 2010

International Journal of Inflammation

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Portal hypertension induces a splanchnic and systemic low-grade inflammatory response that could induce the expression of three phenotypes, named ischemia-reperfusion, leukocytic, and angiogenic phenotypes.During the splanchnic expression of these phenotypes, interstitial edema, increased lymph flow, and lymphangiogenesis are produced in the gastrointestinal tract. Associated liver disease increases intestinal bacterial translocation, splanchnic lymph flow, and induces ascites and hepatorenal syndrome. Extrahepatic cholestasis in the rat allows to study the worsening of the portal hypertensive syndrome when associated with chronic liver disease. The splanchnic interstitium, the mesenteric lymphatics, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of the portal hypertension syndrome complications. The hypothetical comparison between the ascitic and the amniotic fluids allows for translational investigation. From a phylogenetic point of view, the ancestral mechanisms for amniotic fluid production were essential for animal survival out of the aquatic environment. However, their hypothetical appearance in the cirrhotic patient is considered pathological since ultimately they lead to ascites development. But, the adult human being would take advantage of the potential beneficial effects of this “amniotic-like fluid” to manage the interstitial fluids without adverse effects when chronic liver disease aggravates.

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“…Coadministration with ketamine provides up to 30 minutes of medium planes of surgical anesthesia, with excellent muscle relaxation, smooth recovery, and a moderate degree of postoperative analgesia 18 . Thus, ketamine/xylazine is an injectable anesthetic protocol currently used for this procedure 12,14,16 , although both drugs are hepatotoxic. Ketamine is not associated with mortality, although it still has more side effects -like longer awakening times and higher hepatotoxicity-than isoflurane, which is the least toxic among the commonly used anesthetics 17 .…”

Section: Anesthesia and Analgesiamentioning

confidence: 99%

“…Buprenorphine is currently used for post-operative analgesia 12,16 and also has hepatotoxic effects 17 .…”

Section: Anesthesia and Analgesiamentioning

confidence: 99%

A suitable microsurgical method for obstructive cholestasis in the rat

et al. 2010

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Obstructive cholestasis is characterized clinically by jaundice, discolored urine, pale stools and pruritus 1. The obstruction of the biliary tree, either intrahepatic or extrahepatic, causes a high rate of morbility and mortality in the human clinical field 2. The serious repercussions of cholestasis on the liver and on the systemic level 1,2 have led to the creation of many experimental surgical models so as to better understand its pathogenesis, prophylaxis, and treatment. Comparison between macrosurgical and microsurgical extrahepatic cholestasis Several surgical techniques for developing extrahepatic cholestasis have been described, especially in the rat. The techniques that are generally used to produce obstructive jaundice in the rat are macrosurgical, since they do not require magnification devices to be performed. The macrosurgical extrahepatic cholestasis called common bile duct ligation (BDL) is the most frequently used, and it consists of sectioning the common bile duct between ligatures 3-5. This technique induces potential models of reversible obstructive jaundice, since they imply a high incidence of recanalization of the extrahepatic biliary route 6 , which can be avoided by placing the duodenum and the distal part of the stomach between the two ligated and sectioned ends of the bile duct 6. However, rats with macrosurgical extrahepatic cholestasis by BDL develop an infected hilar biliary pseudocyst by the progressive dilation of the proximal end of the bile duct6. At 16 days of postoperative evolution, the biliary culture of these pseudocysts is positive, the most frequent germs being Escherichia coli and enterococcus 7. Furthermore, the animals generally evolve with hepatic, intraperitoneal and pulmonary abscesses, and their elevated early mortality is attributed to sepsis 8. Microsurgery makes it possible to develop obstructive jaundice in the rat by the resection of the extrahepatic biliary tract that includes both the common bile duct as well as the bile ducts aimed at each of the four hepatic lobes 8. With this technique, the non-existence of the residual proximal extrahepatic biliary tract prevents both the formation of hilar biliary pseudocysts as well as abdominal-thoracic abscesses, and prevents mortality during the evolution in relation to the bile ductligated model 8,9. 3 To achieve reproducible results, a harmonization of the microsurgical technique for extrahepatic cholestasis in the rat is needed. Here, we describe a step-by-step surgical approach to resect the bile ducts that drain the four lobes of the liver in continuity with the common bile duct up to the beginning of its intrapancreatic segment by means of a microsurgical technique 8-11. This protocol is not associated with short-term mortality and has been used to produce data for several publications 12

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Splanchnic Th2 and Th1 Cytokine Redistribution in Microsurgical Cholestatic Rats

Cited by 13 publications

References 64 publications

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

The Interstitial Lymphatic Peritoneal Mesothelium Axis in Portal Hypertensive Ascites: When in Danger, Go Back to the Sea

A suitable microsurgical method for obstructive cholestasis in the rat

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