Postoperative course after portacaval anastomosis in rats is determined by the portacaval pressure gradient

Abstract

Variability in experimental results have led to criticism regarding the validity of the rat after portacaval anastomosis (PCA) as a model of changes induced by portal-systemic shunting (PSS). A nonsuture technique using cyanoacrylate glue has been reported to yield a better experimental preparation. To investigate if variations in splanchnic hemodynamics could explain different outcomes after the procedure, male rats received either an end-to-side PCA or sham operations (16 rats each). The PCA was constructed using the "suture" or "glue" technique (8 rats each). Beginning on postoperative day 24 under methoxyflurane and ketamine anesthesia, pressures were recorded from the portal vein, inferior vena cava, and femoral artery. Blood flow to the splanchnic organs and the percent PSS were assessed using the microsphere technique. The rate of delivery of NH3 from the portal vein to the systemic circulation and the concentration of glutamine in the cerebrospinal fluid were determined. In PCA rats, weight gain was significantly impaired, and all animals had evidence of liver atrophy (in both suture and glue groups) when compared with sham animals; a trend toward greater weight gain was seen in glue rats. Portal vein inflow, PSS, NH3 delivery, and CSF glutamine were significantly increased in both PCA-suture and PCA-glue animals compared with sham rats, although no significant differences were seen between the two PCA techniques. When PCA rats from either technique were grouped according to the pressure gradient between portal vein and inferior vena cava, striking differences between animals were now evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration in body composition in the portacaval anastamosis rat is mediated by increased expression of myostatin

“…An increased phosphorylation and activation of skeletal muscle AMP kinase (AMPK)-␣, a critical cellular energy sensor, suggests that lower energy supplies may be responsible for impaired muscle protein synthesis following PCA (12,19). The contribution of the reduction in fat mass to the changes in body composition and the mechanisms responsible for this following PCA are not known (10,11,15). Adipose tissue is the major energy store in the body, and reduction in fat mass is likely to contribute to reduction in whole body energy supplies (32).…”

Experimental models for hepatic encephalopathy

“…In a study performed by our group where 24 rats were used, 8 and 16 under PCS in two control groups of 8 each (control and sham), the values of ammonia plasma of operated rats were found 4 to 5-fold higher than control animals (49). Because of the details of the surgical technique, such as the extent of the stoma between the portal and cava veins, often have important results regarding the ability to reproduce the hyperammonemia in the liver (20,21), we thought that perhaps there were some problems in the surgical technique, leading to the low levels of plasma ammonia in rats reported in the study, responsible for abnormal brain histology.…”

“…It should be remembered, however, that the mere fact of subjecting rats to a PCS cannot guarantee the development of behavioral changes. Aspects such as the surgical technique employed or the size of the stoma of the microvascular anastomosis, which can have a significant influence on the shunt pressure gradient; or the diet provided, the time from the intervention until the study is performed in rats and even the age and weight of animals, may affect the ability of researchers to detect significant changes (20,21). Furthermore, it should be noted that hepatic neovascularization may occur spontaneously developing hepatopedal shunts, which are associated with recovery of weight and decrease in HAM and sub-clinical HE in these animals.…”

“…This would suggest that the microsurgery anastomosis maintain a rate of long-term viability higher than the alternative shunts, which presented higher gradients because of their greater tendency to be in the postoperative period. This would explain the variability of results that had been previously described using these alternative surgical techniques (20). Numata published in 1983 a modification of the technique that greatly simplifies and makes it easier and more reproducible to minimize the operative time, a key issue in the viability of the animal after the intervention (25).…”

Pathogenesis of Hepatic Encephalopathy: Potential Future Approaches

“…Instead we have a liver mass that is reduced (= 50%) and a total postsystemic shunt. Second we have not solved the issue of standardized production of the model as pointed out in a set of important experiments by the Northwestern University group of investigations [10]. Thirdly the behavioral changes require relatively sophisticated and somewhat expensive equipment to detect.…”