Portacaval anastomosis

De Waele, J. P., Audet, R. M., Leong, D. K. and Butterworth, R. F. Portacaval anastomosis induces region-selective alterations of the endogenous opioid system in the rat brain. Hepatology 24 895-901,1996. 

Suarez I., Bodega G., and Fernandez B. (2000). Modulation of glutamate transporters (GLAST, GLT-1 and EAAC1) in the rat cerebellum following portacaval anastomosis. Brain Res. 

The ammonia tolerance test (C. van Caulaert et al., 1932 E. Kirk, 1936) is carried out with the oral administration of 4—5 g ammonium acetate or 3 g ammonium chloride. Normally, there is no significant elevation of ammonia levels after 30, 60 and 120 minutes. In hepatic cirrhosis and in portacaval anastomosis, there is a clear elevation with delayed normalization. (49)... 

Following the first portacaval anastomosis on a human being carried out by E. Vidal in 1910 (this operation had already been successfully performed on an animal by N.V. Eck in 1877), this technique was then used to treat ascites. Here, side-to-side anasto-... 

Anorectal varices originate from the superior rectal vein, which is connected to the portal vein system. This portacaval anastomosis drains the blood into the iliac vein. Occasionally, massive bleeding may occur from rectal varices. Endoscopy is required for diagnosis and sclerotherapy. (70) (s. p. 256)... 

Patients with familial hypercholesterolaemia exhibit lower levels of plasma cholesterol after an operation for portacaval anastomosis, and it has now been shown in rats that such an operation causes an increase in HMG-CoA reductase and cholesterol 7a -hydroxylase activities. Many transplantable human and rodent hepatomas do not control the rate of sterol biosynthesis and HMG-CoA reductase levels in response to dietary cholesterol as normal liver cells do. However, certain hepatoma cells have now been found that, although lacking feedback regulation of choles-terologenesis in vivo, retain their regulatory ability in vitro It thus appears that malignant transformation is not necessarily linked to the loss of regulation by the cell of HMG-CoA reductase activity or sterol synthesis. 

U., and Angelico, M., Sulfated bile acids in serum, bile and urine of cirrhotic patients before and after portacaval anastomosis. Dig. Dis. Sci. 26, 513-517 (1981). 

James, J. H., Escourrou, J., and Fischer, J. E., Blood-brain neutral amino acid transport activity is increased after portacaval anastomosis, Science, 200, 1395, 1978. 

Portacaval anastomosis decreases BSP disposal (Bl, B42, L3). There was a fall in the hepatic blood flow in all 12 patients who imderwent portacaval anastomoses for portal hypertension, but the BSP extraction ratio was increased (B42). Formation of Eck fistulae in dogs reduces BSP clearance (S27). Portacaval transposition does not affect the hepatic blood flow or the extraction ratio (S35). 

B43. Bradley, S. E., MacPherson, A. I., Gammeltofti, A., and Blakemore, A. H., Effect of portacaval anastomosis on hepatic oxygen extraction and estimated hepatic blood flow in patients with cirrhosis. J. Clin. Invest. 30, 630-634 (1951). 

Blei AT, Olafsson S, Therrien G, et al. 1994. Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis. Hepatology 19(6) 1437-1444. 

Cdrdoba J, Crespin J, Gottstein J, et al. 1999. Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. Gastroenterology 116(3) 686-693. 

The injected bolus (02mL) contained lOOfiM ammonium chloride (20-100 mCi/mL) in lOmAf potassium phosphate buffer, pH 72, or in lOmAf HEPES-HCl buffer, pH 8.6. The values are the means SEM n = number of determinations. Controls were normal awake male Wistar rats weighing approximately 300 g. Portacaval shunts were animals in which a portacaval anastomosis had been surgically constructed according to the method of Lee and Fisher (46) eight weeks prior to the BUI determination. 

Evidence of an association between HE and ammonia dates back over a century to the studies of Eck, who described the effects of portacaval anastomosis in dogs. Feeding of meat to shunted dogs led to severe neurological impairment progressing... 

Fig. 9.5 Decreased expression of EAAT-2 in brain in experimental ALF. Decreased EAAT-2 mRNA (panel A) and EAAT-2 protein (panel B) in rats with ALF resulting from hepatic devascu-larization (portacaval anastomosis followed by hepatic artery ligation). Rats had severe HE and brain edema. Panel C shows decreased uptake of the glutamate analogue H-D-Aspartate by cortical shces from ALF tats (Data from Knecht et al., 1997)...

As the PTBR is localized predominantly on astrocytic mitochondria in mammalian brain, it is not surprising that alterations of PTBR expression in HE are associated with altered mitochondrial function. For example, portacaval anastomosis in rats leads to astrocytic mitochondrial proliferation (Fig. 9.2). Mitochondrial proliferation also results from exposure of both cultured astrocytes (Norenberg and Lapham, 1974) and C6 glioma cells (Shiraishi et al., 1990) to PTBR ligands. 

Other neuroactive and neurotoxic metabohtes of tryptophan are also reportedly increased in the brain with chronic hver failure. One such example is quinolinic acid (QUIN) synthesized from tryptophan via the kynurenine pathway. QUIN synthesis is particularly sensitive to increased availability of tryptophan. QUIN has been identified in both rodent and human brain extracts and cerebral cortical QUIN concentrations are elevated in rats following portacaval anastomosis (Moroni et al., 1986a). Eurthermore, QUIN concentrations are increased up to sevenfold in CSF and autopsied frontal cortex of cirrhotic patients who died in hepatic coma (Moroni et al., 1986b). 

Both acute hyperammonemia (Kosenko et al., 1995) and chronic hyperammonemia resulting from portacaval anastomosis (Raghavendra Rao et al., 1997) result in increased expression of nitric oxide synthase (NOS-1 isoform) in the brain. Nitric oxide synthase activities are also increased by an ammonia-induced stimulation of L-arginine uptake into neuronal preparations both in vitro and in vivo (Raghavendra Rao et al 1997). Selective NOS-1 inhibitors, such as nitroarginine, inhibit many of the metabolic and toxic effects of acute hyperammonemia (Kosenko et al., 1995). However, NOS-I inhibitors were ineffective in the prevention of intracranial hypertension in portacaval shunted rats administered ammonium salts (Larsen et al., 2001). 

Exposure of cultured astrocytes to millimolar concentrations of anunonia results in oxidative stress and in protein tyrosine nitration (ScUiess et al., 2002), a process that was dependent upon stimulation of the inducible isoform of NOS (NOS-2). Astrocytic protein tyrosine nitration was also described in the brain of rats following portacaval anastomosis where tyrosine nitration of GS was described (Schliess et al., 2002). Reduced GS enzyme activity resulting from tyrosine nitration offers a cogent explanation for the consistent reports of decreased capacity for ammonia removal in the brain of animals following portacaval anastomosis. 

Butterworth RF, Tonon MC, Desy L, Giguere JF, Vaudry H, Pelletier G. Increased brain content of the endogenous benzodiazepine receptor ligand octadecemeuropeptide (ODN) following portacaval anastomosis in the rat. Peptides, 12, 119-125, 1991... 

Desjardins P, Butterworth RE. The peripheral-type benzodiazepine ( 3) receptor in hyperam-monemic disorders. Neurochem. Int., 41, 109-114, 2002 Desjardins P, Bandeira P, Raghavendra Rao VL, Ledoux S, Butterworth RF. Increased expression of the peripheral-type benzodiazepine receptor-isoquinohne carboxamide binding protein in mRNA brain following portacaval anastomosis. Brain Res., 758, 255-258, 1997 Desjardins P, Rama Rao VK, Michalak A, Rose C, Butterworth RF. Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab. Brain Dis., 14, 273-282, 1999... 

GiguSre JF, Hamel E, Butterworth RF. Increased densities of binding sites for the peripheral-type benzodiazepine receptor ligand H-PKl 1195 in rat brain following portacaval anastomosis. Brain Res., 585, 295-298, 1992... 

Raghavendra Rao VL, Audet RM, Butterworth RF. Selective alterations of extracellultu- brain amino acids in relation to function in experimental portal-systemic encephtilopathy Results of an in vivo microdialysis study. J. Neurochem., 65, 1221-1228, 1995 Raghavendra Rao VL, Audet RM, Butterworth RF. Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis. Brain Res., 765, 169-172, 1997 Rama Rao VK, Desjardins P, Rose C, Therrien G, Butterworth RF. Increased glutamine synthetase expression in skeletal muscle An important alternative pathway for ammonia removal in liver faUure. Hepatology, i0(4), 162A, 7, 1999... 

D. J. McNamara, E. H. Ahrens, Jr., R. Kolb, C. D. Brown, T. S. Parker, N. O. Davidson, P. Samuel and R. M. McVie, Treatment of familial hypercholesterolemia by portacaval anastomosis Effect on cholesterol metabolism and pool sizes. Proc Natl Acad Sci USA 80 564 (1983). 

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