The effect of different types of hepatic injury on the estrogen and androgen receptor activity of liver

Mammalian liver contains receptors for both estrogens and androgens. Hepatic regeneration after partial hepatectomy in male rats is associated with a loss of certain male-specific hepatic characteristics. In this study we investigated the effects of lesser forms of hepatic injury on the levels of estrogen and androgen receptor activity in the liver. Adult male rats were subjected to portacaval shunt, partial portal vein ligation, hepatic artery ligation, or two-thirds partial hepatectomy. Another group of animals was treated with cyclosporine. At the time of sacrifice the livers were removed and used to determine the estrogen and androgen receptor activity in the hepatic cytosol. A significant reduction (p less than 0.05) in the hepatic cytosolic androgen receptor activity and a slight increase in the estrogen receptor activity occurred following total portosystemic shunting. Partial ligation of the portal vein, which produces a lesser degree of portosystemic shunting, had no effect on the levels of the estrogen and androgen receptor activity present within hepatic cytosol. Cyclosporine-treated animals had significantly greater (p less than 0.01) levels of estrogen receptor activity in the hepatic cytosol compared to vehicle-treated control animals. Levels of estrogen and androgen receptor activity within the hepatic cytosol remained unchanged after ligation of the hepatic artery. The reduction in the cytosolic estrogen and androgen receptor activity in the liver after partial hepatectomy was confirmed. In summary, certain types of hepatic injury are associated with profound changes in the estrogen and androgen receptor content within the liver.     

An experimental study on the pathophysiology of stenosis and occlusion in portal vein reconstruction in resection of cancer of the hepatic hilus

An experimental study using mature mongrel dogs was performed to clarify the pathophysiology of stenosis and occlusion of portal vein reconstruction accompanied with hepatectomy. All the animals underwent partial (53%) hepatectomy. They were arbitrarily divided into three groups: Non-stenosis Group I with hepatectomy only, Stenosis Group II with partial '70%) stenosis of the portal vein, and Occlusion Group III with ligation of the portal vein. All cases of Group III died within about 122 minutes. The blood flow and pressure of the portal vein, portography, ICG Rmax and the residual liver weight were serially examined until the fourth week following the operation in Group I and Group II. Two principal results were derived: 1) In Group I, portal circulation was sufficiently restored and the residual liver showed adequate regeneration. 2) In Group II, hepatofugal collateral vessels developed. However, the portal pressure remained significantly high (p less than 0.002) and, the portal blood flow and liver tissue blood flow were markedly reduced (p less than 0.001) for 1 week after operation. The residual liver weight and liver function (ICG Rmax) were significantly decreased even in the fourth week. Recently, portal vein resection accompanied with hepatectomy has been accepted as a procedure for advanced carcinoma of the hepatic hilus. This study suggests that stenosis or occlusion of the portal vein should be avoided in the procedure.     

Beneficial effects of arterialization of the portal vein on extended hepatectomy

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.     

Study on splanchnic circulation: measurement of the liver blood flow

In anesthetized patients during abdominal surgery, hepatic artery and portal vein flows were measured simultaneously utilizing an ultrasonic transit-time volume flowmeter. The total hepatic blood flow was 994.6 +/- 52.4 ml/min. The hepatic artery flow and the portal vein flow were 260.0 +/- 23.8 ml/min and 730.8 +/- 41.3 ml/min, respectively. The ratio of hepatic artery flow to portal vein flow was 0.37 +/- 0.04. A significant increase in hepatic artery flow (p less than 0.01) followed portal vein occlusion, whereas no significant change was observed in portal vein flow after hepatic artery occlusion. Common hepatic artery occlusion resulted in a significant decrease in hepatic artery flow (p less than 0.05), but no significant change was observed in portal vein flow. The present study firstly demonstrated that ultrasonic transit-time volume flowmeter is a device to quantitatively assess hepatic artery and portal vein flows with good reproducibility and stability in human subjects. This easy and simple technique seemed to have wide clinical application to abdominal surgery and would have a promising in studying splanchnic blood flows in various situations such as in cases of hepatectomy and portal hypertension.     

Constriction rate variation produced by partial ligation of the portal vein at pre-hepatic portal hypertension induced in rats

Background

Partial portal vein ligation causes an increase in portal pressure that remains stable even after the appearance of collateral circulation, with functional adaptation to prolonged decrease in portal blood flow.

Aim

To assess whether different constriction rates produced by partial ligation of the vein interfere with the results of this experimental model in rats.

Methods

Three groups of five rats each were used; in group 1 (sham-operated), dissection and measurement of portal vein diameters were performed. Portal hypertension was induced by partial portal vein ligation, reducing its size to 0.9 mm in the remaining 10 animals, regardless of the initial diameter of the veins. Five animals with portal hypertension (group 2) underwent reoperation after 15 days and the rats in group 3 after 30 days. The calculation of the constriction rate was performed using a specific mathematical formula (1 - π r 2 / π R2) x 100% and the statistical analysis with the Student t test.

Results

The initial diameter of the animal''s portal vein was 2.06 mm, with an average constriction rate of the 55.88%; although the diameter of the veins and the constriction rate in group 2 were lower than in group 3 (2.06 mm - 55,25% and 2.08 mm - 56.51%, respectively), portal hypertension was induced in all rats and no significant macroscopic differences were found between the animals that were reoperated after 15 days and after 30 days respectively, being the shorter period considered enough for the evaluation. Comparing the initial diameter of the vein and the rate of constriction performed in groups 2 and 3, no statistic significance was found (p>0.05).

Conclusion

Pre-hepatic portal hypertension in rat can be induced by the reduction of the portal vein diameter to 0.9 mm, regardless the initial diameter of the vein and the vessel constriction rate.     

A Novel Method of Determining Portal Systemic Shunting using Biodegradable TC Labelled Albumin Microspheres

Portal systemic shunting (PSS) and portal pressure were measured in control rats and in animals with portal hypertension induced by partial portal vein ligation (PPVL). The portal pressure in rats with partial portal vein ligation (13.4 +/- 0.5 mm.Hg.) was significantly higher (p < 0.005) than in the control group (9.6 +/- 0.6 mm.Hg.). Portal systemic shunting measured by consecutive injections of radiolabelled methylene diphosphonate (MDP), a non-diffusable marker and albumin microspheres directly into the splenic pulp was significantly increased (P < 0.005) in the portal hypertensive animals (30.8 +/- 2.5%) compared to sham operated rats (2.6 +/- 1.5%). Similarly, in portal hypertensive rats portal systemic shunting measured by intrasplenic injections of radiolabelled cobalt microspheres (37.1 +/- 3.9%) was significantly greater (p < 0.005) than in control animals. There was a good correlation and agreement (r = 00.97) between the two methods of measuring portal systemic shunting. However because the (99)Tc(m)-albumin microspheres are biodegradable the method allows portal systemic shunting to be measured in man. Furthermore since the computer adjusts the baseline to zero after each determination of portal systemic shunting the methodology allows repeated measurements to be made.     

Beneficial effect of syngeneic pancreatic islet transplantation on liver atrophy and hepatocellular function after portacaval shunt.

BACKGROUND. Hepatic insufficiency, which continues to be a source of morbidity after portacaval shunt (PCS), can be prevented by syngeneic pancreatic islet transplantation into the portal vein before PCS. This study investigated the ability of syngeneic pancreatic islet transplantation after PCS to prevent hepatic atrophy and rescue hepatocellular function. METHODS. Approximately 1200 to 1400 syngeneic rat pancreatic islets were transplanted through a heparinized catheter into the left lobes of the liver 3, 7, and 21 days after end-to-side PCS. Normal rats received no treatment, and PCS control rats received PCS only, without islet transplantation. Hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green clearance) were analyzed at 42 and 49 days after PCS. On day 51 after PCS, the left and right lobes of the liver were divided, weighed, and sectioned for histologic studies. RESULTS. Caffeine clearance in the animals at 3 days (p less than 0.05) and at 7 days (p less than 0.05) after end-to-side PCS was significantly improved versus control PCS animals, indicating that hepatocellular function could be rescued after creation of a PCS. Indocyanine green clearance of all groups with PCS was significantly (p less than 0.001) decreased versus normal animals, showing that hepatic blood flow was uniformly decreased by PCS in all groups. The weight of the transplanted left lobes was significantly greater than the untransplanted right lobes of the groups at 3 days (p less than 0.01) and at 7 days (p less than 0.05) after end-to-side PCS compared with control animals, indicating that liver atrophy was prevented in the islet-transplanted lobes but not in those lobes without a transplant. CONCLUSIONS. Islet transplantation early after PCS can prevent liver atrophy and significantly improve hepatocellular function.     

Experimental study of partial arterialization of the portal vein on the dearterialized liver

The influence of hepatic arterial obstruction on the hepatic circulation and tissue metabolism was studied between animals with and without partial arterialization of the portal vein. Mongrel dogs were divided into these groups: a group in which the collaterals to the liver were obstructed and the hepatic artery was dissected (hepatic artery ligated group); two groups in which an extracorporeal femoral artery-portal vein shunt was produced, and blood was sent by a Biopump at a rate of 100 or 200 ml/min (100 ml/min and 200 ml/min portal arterialized groups). The hepatic artery ligated group showed CO2 accumulation and acidosis in hepatic venous blood, reduction of oxygen supply, increase of oxygen consumption and marked increase of GOT and GPT. In the portal arterialized groups, sufficient oxygenation of portal blood was noted, and the oxygen demand and supply and tissue metabolism were kept approximately normal. The optimum flow rate for partial arterialization of the portal vein seemed to be 100 ml/min. At the flow rate of 200 ml/min, the original portal blood was reduced, leading to portal hypertension and increase of GOT and GPT. These results indicate that partial arterialization of the portal vein effectively preserves the liver function during the operation and in the early period after dissection of the hepatic artery.     

Hepatic haemodynamic changes after portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats

Radioactive microspheres were used to determine the hepatic haemodynamic response to portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats 20 days after operation, and in normal rats 2 months after operation. After 20 days portacaval anastomosis caused a decrease in liver mass only in normal and cirrhotic animals, whereas hepatic arterial blood flow per unit of mass increased in normal (+488 per cent), cirrhotic (+191 per cent) and prehepatic portally hypertensive rats (+133 per cent). Despite these facts, animals with portacaval anastomosis showed a reduced hepatic total perfusion (arterial plus portal inflow) per unit of mass with respect to controls in normal (-53 per cent) and cirrhotic rats (-68 per cent), but not in those with prehepatic portal hypertension. Comparing studies carried out at 2 months with those performed 20 days after portacaval anastomosis in normal rats, some recovery of liver mass and total liver blood flow was observed. In conclusion, portacaval anastomosis produced a limited increase in hepatic arterial blood flow which was unable to preserve liver mass and its total perfusion in normal and cirrhotic animals. In contrast, portacaval anastomosis did not significantly alter liver mass or its perfusion in animals with chronic prehepatic portal hypertension, as both values were previously diminished in controls. Thus, the risk of liver failure after portacaval anastomosis is higher in normal and cirrhotic rats than in those with chronic prehepatic portal hypertension.     

原位肝移植术中结扎门体分流静脉的临床研究

目的 通过原位肝移植术中结扎经CT确认的粗大的门体分流静脉,探讨结扎该分流静脉的临床意义.方法 根据天津市第一中心医院移植外科2007年1月1日至2008年8月1日原位肝移植术前三维CT检杳35例中,12例无门体分流静脉,23例存在明确的门体分流静脉,并应用门静脉血流仪在术中行门静脉血流量测定,根据测量结果,其中7例未行分流静脉结扎,16例行门体分流静脉结扎.结果 本组中12例无门体静脉分流者的门静脉血流量是(1101±70)ml/min.23例有门体分流静脉中,7例门静脉血流量>1000 ml/min者未行分流静脉结扎,16例血流馈<1000 ml/min者行分流静脉结扎.16例结扎前后门静脉血流量分别是(657±112) ml/min和(1136±161) ml/min,结扎前后门静脉血流量相比差异有统计学意义(P<0.05).本组23例均获得随访,其中19例正常存活,移植物功能良好,血流正常.有2例术后门静脉血栓复发(经抗凝治疗后好转),其中1例出现间断性意识障碍,血氨水平波动在126～194 mmol/L之间,给予降血氨治疗后好转.2例在术后3个月内死亡,其中1例在术后1.5个月因肺部曲霉菌感染导致呼吸功能衰竭死亡,另1例在术后2个月因移植物功能不良导致肝功能衰竭而死亡. 结论原位肝移植术中结合三维CT扫描血管重建及血流动力学数据,结扎门体分流静脉是有意义的.     

Portal hypertension due to hepatic artery-portal vein arteriovenous fistula--a case report.

A case of portal hypertension secondary to traumatic hepatoportal arteriovenous fistula with portal fibrosis was successfully treated by ligation of the afferent hepatic arteries which decreased significantly portal pressure and corrected the abnormal blood inflow to the portal vein via A-V fistula resulting in a recovery of the disturbed liver function. Collateral blood supply from the left hepatic artery into the right hepatic lobe was found to be quite satisfactory after the ligation of the hepatic artery. Hemodynamic data and clinical findings of the present case suggest that the mechanism responsible for the portal hypertension is the inflow block resulting from the interruption of portal venous flow by the inflow of arterial blood via A-V fistula and the subsequent increased blood pressure in portal vein radicals.     

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.     

Changes in hepatic hemodynamics and oxygen consumption after partial hepatic congestion in dogs.

The effects of 66% hepatic congestion (group 2, n = 6) on liver blood flow and hepatic oxygen metabolism were investigated in anesthetized dogs using an ultrasonic transit time flowmeter. The results were compared with those for control dogs (group 1, n = 6) and for 60% hepatectomized dogs (group 3, n = 6) wherein almost the same amount of hepatic parenchyma was removed as was congested in group 2. Portal blood flow (PVF) in group 2 and group 3 decreased similarly to 60 and 63% of the baseline values, respectively (p less than 0.05). Cardiac output (CO) in group 2 and group 3 also decreased significantly in proportion to the decrease in PVF. Among the dogs in group 2, hepatic arterial blood flow (HAF) was fairly well maintained at 86% of the baseline value, despite the decrease of cardiac output, whereas the HAF in group 3 decreased to 49% of the baseline value at 1 h after hepatectomy. The calculated hepatic arterial resistance (HAR) in group 3 increased significantly due to the 60% loss of the hepatic arterial vascular bed. The HAR in group 2, by contrast, became lower than that in group 1, suggesting a compensatory decrease of HAR for the obstructed portal flow to the congested area. These results were well consistent with our angiographic findings (n = 3) that the portal flow to the congested segments was completely obstructed and the congested segments received only an arterial blood supply. The centrilobular hepatocytes of the congested segments showed marked vacuolar degeneration and the total hepatic oxygen consumption in group 2 was reduced (p less than 0.05). However, the decrease in oxygen consumption in group 2 was not so severe as in group 3 (p less than 0.05). These data suggest that some parts of the preserved congested segments were still viable and had the capacity of aerobic metabolism even 4 h after the ligation of the drainage vein of those segments. In this study, the importance of the hepatic arterial flow to the congested segment has been demonstrated. When the congested hepatic segment is to be preserved intraoperatively, care must be taken to maintain the hepatic arterial blood flow during the perioperative period.     

Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat

To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n?=?10), 2 [triple partial portal vein ligation (TPVL); n?=?9], 3 (TAA; n?=?11), and 4 (TPVL plus TAA; n?=?9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL?+?TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations.     

Hyperbaric oxygenation after portal vein emobilization for regeneration of the predicted remnant liver

BACKGROUND: Liver failure often develops after extensive liver resection. Preoperative portal vein embolization to induce compensatory hypertrophy in the predicted remnant liver decreases clinical complications after hepatectomy. The aim of this study was to examine whether hyperbaric oxygenation (HBO) after portal vein embolization increases compensatory hypertrophy of the predicted liver remnant. We performed portal vein ligation and HBO in rats to investigate whether HBO after portal vein embolization increases compensatory hypertrophy of the predicted remnant liver. METHODS: Rats were divided into four groups that underwent (1) laparotomy only (control group); (2) right portal vein ligation (RPL group); (3) RPL followed by HBO at 2 atm (HBO-2 atm group; 1 h/day, 5 days/week for 2 weeks); or (4) RPL followed by HBO at 3 atm (HBO-3 atm group). Laparotomy was repeated after 2 weeks in each group; serum levels of albumin and hepatocyte growth factor (HGF) were measured, and the ratio of the weights of nonligated to ligated hepatic segments and the percentage of hepatocytes expressing proliferating cell nuclear antigen (PCNA) in ligated hepatic segments were determined. RESULTS: In rats that had received HBO after RPL, serum levels of HGF, weight ratios of nonligated to ligated hepatic segments, and the percentage of PCNA-positive hepatocytes in nonligated liver were significantly higher than those in the control group. Furthermore, rats that had undergone 3-atm HBO after RPL had significantly higher serum levels of HGF and percentages of PCNA-positive hepatocytes in nonligated hepatic segments. CONCLUSIONS: Preoperative HBO after portal vein embolization may be useful for inducing compensatory hypertrophy of the predicted remnant liver.     

Cyclic AMP- and ATP-mediated stimulation of DNA synthesis following partial hepatectomy by prostaglandin-E1 in D-galactosamine injured liver

D-galactosamine (D-gal) damaged rats were infused with Prostaglandin E1 (PGE1) through a peripheral vein for 40 min. before and after partial hepatectomy. DNA synthesis following 68% partial hepatectomy was severely inhibited by the pretreatment of D-galactosamine. PGE1 infusion (0.5, 1.0 microgram/kg/min) enhanced the DNA synthesis inhibited by D-gal 600 mg/kg significantly (p less than 0.01). After 20 min. of PGE1 infusion cyclic AMP levels of liver tissue was increased as compared with saline infusion in D-gal (600 mg/kg)-damaged rat (p less than 0.05). Also 20 min. and 3 hour after partial hepatectomy. ATP levels of liver tissue was enhanced in PGE1 treated group (p less than 0.05). However the doses of PGE1 infused in this investigation could not increase the hepatic tissue blood flow measured by hydrogen gas clearance method. These results suggest that PGE1 enhance DNA synthesis of injured liver after partial hepatectomy by the mechanism which PGE1 stimulate cyclic AMP production and increase ATP level in hepatic tissue.     

Importance of portal flow diversion in experimental auxiliary partial orthotopic liver transplantation

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has successfully been performed in patients with noncirrhotic metabolic diseases. It remains, however, unclear if intervention in the portal venous inflow is necessary to ensure adequate portal blood flow to graft and host liver. In this experimental study we evaluate the hepatic flow during APOLT. METHODS: Left lateral/medial segmental grafts were transplanted from beagle to dalmatian dogs. Vascular structures were anastomosed end-to-end. The effect of diversion of the portal flow was studied in three groups: in the ligation group (n=3) the host portal vein was tied off, the free flow group (n=6) had random flow to both livers. In the banding group (n=11) the host portal vein was banded with a adjustable strapband to restore the pretransplantation flow distribution. RESULTS: After reperfusion the blood flow through the common portal vein decreased from 49 to 36 ml/kg/min (P<0.03) in all animals. Flow through the left portal vein decreased from 26 to 5 ml/kg/min (P<0.0001). Banding restored the flow in the left portal vein to 12 ml/kg/min, although the flow in the free-flow group remained 4 ml/kg/min. In the ligation group the total portal flow was forced toward the graft leading to the highest perfusion: 24 ml/kg/min (P<0.005). Adverse effect of this ligation was the development of portal hypertension. CONCLUSIONS: This experimental study confirms that diversion of the portal flow is necessary for adequate graft perfusion in APOLT. Banding can restore the pretransplantation flow distribution, without compromising the flow in the common portal vein.     

Effect of Portocaval Shunt on Residual Extreme Small Liver after Extended Hepatectomy in Porcine

Background When residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs. Methods Fourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava. Results In the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 ± 3.8 mmHg in the group without a shunt and 10.5 ± 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt. Conclusions These results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury. This study was presented at the Fourth International Meeting on Hepatocellular Carcinoma: Eastern and Western Experiences, Hong Kong, China, December 14–16, 2004     

Effects of nonshunting operations on portal venous pressure and hepatic blood flow

A comparative analysis has been presented of the effect of the nonshunting operation on portal venous pressure and effective hepatic blood flow in patients with liver cirrhosis and idiopathic portal hypertension. A reduction of portal pressure after splenectomy with esophagogastric devascularization in 17 patients with idiopathic portal hypertension was significantly greater than that in 79 patients with liver cirrhosis (-21 +/- 4.1 percent versus -8.9 +/- 1.6 percent, p less than 0.01). Clearance of galactose from the blood, which approximates effective hepatic blood flow, was decreased after the nonshunting operation by 6.7 percent in five patients with liver cirrhosis (p value not significant). On the other hand, there was a 19.4 percent reduction (statistically significant) in galactose clearance in four patients with idiopathic portal hypertension (p less than 0.05). Based on these data, we suggest that in patients with idiopathic portal hypertension, the splenic circuit largely contributes to the portal hypertension, the effective hepatic blood flow, or both. We recommend a nonshunting operation for the treatment of esophageal varices from the hemodynamic viewpoint in cirrhotic patients.     

Increased duodenal mucosa infiltration by mast cells in rats with portal hypertension

BACKGROUND: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. Aims: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. METHODS: Five rats in each group (male Wistar, 230-255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. RESULTS: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 +/- 3.16 vs. 18.60 +/- 1.52), their diameter (20.09 +/- 2.90 vs. 12.61 +/- 3.97 microm, p < 0.05) and consequently their total area (12,749.30 +/- 2,298.26 vs. 3,455.82 +/- 1,702.33 microm2) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 +/- 12.88, p < 0.05; 22.92 +/- 6.72 microm, p < 0.05 and 51,376.95 +/- 43,732.24 miccrom2, p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 +/- 1.18 in controls to 10.74 +/- 1.47, p < 0.01 and 22.50 +/- 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 +/- 1.78 vs. 17.40 +/- 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 +/- 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 +/- 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 +/- 0.09%, p < 0.01). CONCLUSIONS: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.