Lack of portal-venous hypertension after an arterioportal fistula in the rat

The hepatic effects of an end-to-side arteriovenous fistula between the right renal artery and the portal vein were studied in rats. Fifty rats underwent surgery and were studied 3, 12, 24 weeks and 1 year later; Another 15 rats were used as controls. Rats did not have any portohepatic abnormality. Portal and caval pressure were measured, and the liver was evaluated histologically. No statistically significant differences were achieved between the control portal (10.37 +/- 0.29 cm H2O) and vena cava pressures (1.22 +/- 0.19 cm H2O) and those of the experimental groups. The overall liver architecture remained unchanged. A progressive enlargement of the intrahepatic portal and hepatic veins was noted. No hypertrophy of the fibrous tissue into the portal triads, hypertrophy of the muscularis of the portal vein radicals, or wall sclerotic thickening was seen. The forward overflow compensatory mechanisms are discussed.     

Liver regeneration after major hepatectomy for biliary cancer

BACKGROUND: The aim of this study was to evaluate serial changes in liver volume after major hepatectomy for biliary cancer and to elucidate clinical factors influencing liver regeneration. METHODS: Serial changes in liver volume were determined, using computed tomography, in 81 patients with biliary cancer who underwent right hepatic lobectomy or more extensive liver resection with or without portal vein resection and/or pancreatoduodenectomy. Possible factors influencing liver regeneration were evaluated by univariate and multivariate analyses. RESULTS: The remnant mean(s.d.) liver volume was 41(8) per cent straight after hepatectomy. This increased rapidly to 59(9) per cent within 2 weeks, then increased more slowly, finally reaching a plateau at 74(12) per cent about 1 year after hepatectomy. The regeneration rate within the first 2 weeks was 16(8) cm3/day and was not related to the extent of posthepatectomy liver dysfunction. On multivariate analysis, the extent of liver resection (P < 0.001), body surface area (P = 0.02), combined portal vein resection (P = 0.024) and preoperative portal vein embolization (P = 0.047) were significantly associated with the liver regeneration rate within the first 2 weeks. In addition, body surface area (P < 0.001) and liver function expressed as plasma clearance rate of indocyanine green (P = 0.01) were significant determinants of final liver volume 1 year after hepatectomy. CONCLUSION: The liver regenerates rapidly in the first 2 weeks after major hepatectomy for biliary cancer. This early regeneration is influenced by four clinical factors. Thereafter, liver regeneration progresses slowly and stops when the liver is three-quarters of its original volume, approximately 6 months to 1 year after hepatectomy.     

经颈内静脉肝内门体分流术治疗肝静脉广泛闭塞型布加综合征

目的探讨经颈内静脉肝内门体分流术(TIPS)治疗肝静脉广泛闭塞型布加综合征的临床疗效。方法采用TIPS治疗11例广泛肝静脉闭塞型布加综合征患者,其中3例为急性,8例为亚急性或慢性。患者表现为食管静脉曲张破裂出血和顽固性腹水,采用超声多普勒、CT或MRI、上消化道钡餐、血管造影和肝活检明确诊断。TIPS将肝内分流道建于肝后下腔静脉与门静脉分支,支架直径为10 mm,随访时间(63±43)个月。结果所有患者均成功完成TIPS,肝门部门静脉分叉处出血1例,1周后出血控制再植内支撑;肝内分流道建立后门体压力梯度由(41．2±10．5)cm H2O(1 cm H2O=0．098 kPa)下降至(12．4±4．7)cm H2O,门静脉血流速度由(11．2±2．8)cm／s增加至(52．2±13．7)cm／s。患者出血控制,腹水渐消退,肝功能指标明显好转。住院期间因肝功能衰竭死亡1例。术后随访,2例分流道狭窄分别行分流道再扩张或再植内支撑,其余8例无相关并发症。结论TIPS是治疗肝静脉广泛闭塞型布加综合征的重要方法,具有良好的远期疗效。     

Contribution of portal systemic shunt to Kupffer cell dysfunction in obstructive jaundice

Previous animal models of biliary tract obstruction have shown that hepatic phagocytic activity is impaired secondary to Kupffer cell dysfunction. Biliary tract obstruction leads to portal hypertension and an associated portal systemic shunt. Forty-eight Sprague-Dawley rats were studied to determine the contribution of portal systemic shunt to Kupffer cell dysfunction after 21 days of obstructive jaundice or sham operation. Liver uptake of radiolabeled Escherichia coli decreased from 76.1 +/- 1.4% (sham) to 63.1 +/- 6.1% in the common duct ligation (CDL) rats (P less than 0.05); lung uptake increased from 4.0 +/- 0.6% (sham) to 20.2 +/- 4.5 (CDL) (P less than 0.05). Portal systemic shunt, determined using radioactive microspheres, increased from 2.0 +/- 1.0% (sham) to 46.6 +/- 13.1% (CDL), P less than 0.05. Although a significant portal systemic shunt does exist in this 21-day model of obstructive jaundice, it does not appear to be the only mechanism underlying Kupffer cell dysfunction.     

Angiotensin II increases portosystemic collateral resistance in portal hypertension

The decreased vasoconstrictive response of the splanchnic vasculature in portal hypertension (PHT) to angiotensin II (ANGII) is newly established. This could explain the limited ability of PHT patients to compensate in hypovolemic shock. However, the effect of ANGII upon portosystemic collateral resistance (Rc) is not known. We hypothesized that ANGII could directly effect Rc and thus change portal venous pressure (PVP). Chronic PHT was induced in New Zealand white rabbits by partial portal vein ligation 3 weeks prior to study. Splanchnic blood flow and portosystemic shunt (PSS) were measured simultaneously in six normal rabbits and then in six PHT rabbits at baseline and during intravenous ANGII infusion at 1.0 microgram/kg/min. Flow and resistance were standardized to 100 g small intestine weight. Superior mesenteric artery flow (Qsma) in normal rabbits was 64.9 +/- 3.6 ml/min, increased to 134.6 +/- 13.5 ml/min in the PHT animals (P less than 0.001) and was reduced 30% (P less than 0.05 vs PHT baseline) with ANGII. Concomitantly, PVP in the PHT animals was twice normal, 7.0 +/- 0.32 vs 14.4 +/- 0.55 mm Hg (P less than 0.001) and rose slightly with ANGII. The high PSS in PHT (84 +/- 6.0%, P less than 0.001 vs normal) was not affected significantly by ANGII infusion. Rc in the PHT rabbits rose 50% from 0.06 +/- 0.001 to 0.09 +/- 0.01 mm Hg/ml/min (P less than 0.001) with ANGII. This is the first evidence for a vasoconstrictive response in portosystemic collaterals during ANGII infusion. This change in collateral resistance causes both PVP and PSS to remain pathologically elevated in PHT despite a fall in portal inflow, thus predisposing to repeat variceal bleeding.     

Biliary fibrosis in microsurgical extrahepatic cholestasis in the rat

A new model of extrahepatic cholestasis, using a microsurgical technique, is performed as an alternative to the traditional model of the bile duct ligated-rat, in order to study the stage of fibrosis in the long-term. Male Wistar rats were divided into two groups: I (Sham-operated, n = 9) and II [Microsurgical Cholestasis (MC), n = 10]. After 4 weeks, portal pressure, types of portosystemic collateral circulation, mesenteric venous vasculopathy, hepatic function test, and liver histopathology were studied by using the Knodell index and fibrosis was determined by reticulin and Sirius red stains. The animals with MC presented portal hypertension with extrahepatic portosistemic collateral circulation, associated with mesenteric venous vasculopathy and increased plasma levels of bilirubin (6.30 +/- 1.80 vs. 0.22 +/- 0.37 mg/dL; P = 0.0001), alkaline phosphatase (293.00 +/- 82.40 vs. 126.30 +/- 33.42 U/L; P = 0.001), AST (380.00 +/- 78.50 vs. 68.33 +/- 11.74 IU/L; P = 0.0001), ALT (87.60 +/- 22.32 vs. 42.22 +/- 7.89 IU/L; P = 0.0001), and LDH (697.76 +/- 75.13 vs. 384.80 +/- 100.03 IU/L; P = 0.0001). On the contrary, plasma levels of albumin decreased (2.72 +/- 0.12 mg/dl vs. 2.99 +/- 0.10; P = 0.001). The microsurgical resection of the extrahepatic biliary tract in the rat produces an experimental model of hepatic inflammation, characterized by a high Knodell hepatic activity index (4), bile proliferation, and fibrosis.     

选择性脾胃区减断分流术对肝脾血流动力学的影响

目的 探讨肝硬化门静脉高压患者行选择性脾胃区减断分流术(SDDS-GSR)后肝脾血流动力学的改变及临床意义.方法 前瞻性收集41例行SDDS-GSR术治疗患者的超声检查资料,按术前、术后2周及术后1年分为3期,并以21例正常体检患者为对照进行研究.结果 (1)脾脏厚度在术后2周(47±8)mm及术后1年(46±8)mm较术前(60±9)mm显著减小(P<0.01).(2)术后2周门静脉直径(1.13±0.19)cm较术前显著变窄(P<0.01),脾动脉直径(0.49±0.08)cm较术前显著变窄(P<0.05),肝动脉直径(0.40±0.07)cm较术前显著增宽(P<0.05).术后1年门静脉直径(0.89±0.17)cm均较术前显著变窄(P<0.01).(3)术后2周门静脉血流量(649±294)ml/min和脾动脉血流量(446±254)ml/min较术前显著减小(P<0.01),肝动脉血流量(612±295)ml/min较术前显著增加(P<0.01).术后1年肝动脉血流量(401±152)ml/min与术前和正常组比较差异均无统计学意义(P>0.05).结论 肝硬化门静脉高压症患者肝脾血流动力学参数发生异常变化;SDDS-GSR有助于纠正肝硬化门静脉高压症患者肝脾血流动力学的紊乱状态.     

Short-term hemodynamic effects of transjugular retrograde obliteration of gastric varices with gastrorenal shunt

OBJECTIVES: The purpose of this study was to investigate the short-term effects on portal hemodynamics of transjugular retrograde obliteration (TJO) of gastric varices with gastrorenal shunt. METHODS: Thirty patients with gastric varices and a gastrorenal shunt were included in this study. The patients ranged in age from 42 to 75 years (16 men and 14 women), and according to Child's classification, class A, B and C cirrhosis was seen in 1, 13 and 16 patients, respectively. The portal blood flow was measured by an ultrasonic duplex Doppler system, and the wedged hepatic venous pressure was measured by hepatic venous catheterization, before and after TJO. RESULTS: Complete obliteration of the gastrorenal shunt and gastric varices was revealed by retrograde inferior phrenic venography and computed tomography after TJO in all cases. The wedged hepatic venous pressure was significantly increased the day after TJO compared with that before therapy (257 +/- 71 vs. 307 +/- 73 mm H(2)O, p < 0.01). The portal venous flow was significantly increased 1 week after TJO compared with that before therapy (744 +/- 190 vs. 946 +/- 166 ml/min, p < 0.01). The serum albumin levels before and after TJO were 3.0 +/- 0.4 and 3.1 +/- 0.5 g/dl, respectively, and the total bilirubin levels were 1.5 +/- 0.7 and 1. 5 +/- 0.8 mg/dl, respectively, neither of these parameters changing significantly. The plasma ammonia levels before and after TJO were 109 +/- 62 and 67 +/- 31 microg/dl, and the indocyanine green retention rates at 15 min were 31 +/- 13 and 24 +/- 13%, both showing a significant change (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: We conclude that TJO increases portal blood flow which contributes to the decrease in plasma ammonia levels and the indocyanine green retention rate, although increasing the wedged hepatic venous pressure.     

Acute portal vein stenosis. An experimental study on portal circulation and hepatosplenic function

Portal hypertension was mechanically induced in rats by acute constriction of the portal vein. Using a new "button" technique, a stricture 0.9 mm in diameter was found to be compatible with life in more than 90% of the rats. Angiographic and anatomic studies of portosystemic collaterals confirmed observations in earlier experiments. Oesophageal varices were not seen, despite sustained elevation of portal venous pressure during the four weeks following induction of portal hypertension. Development of paraportal veins bridging the obstacle is suggested to be responsible for maintenance of normal liver structure and for recovery from the transient hepatic dysfunction. Increase of phagocytosis in the germinal centres of the enlarged spleens was found after four weeks, suggesting immunologic changes caused by portal hypertension and/or portosystemic shunt circulation.     

不同手术方式对门体分流率和肝功能影响的实验研究

目的　通过动物实验检测肠腔侧侧分流术 (MCS)、远端脾腔分流术 (DSCS)及门奇断流术 (PAD)对门体分流率和肝功能的影响 ,为合理选择手术方式提供理论依据。方法　采用CCl4/乙醇诱导的肝硬变门脉高压大鼠模型行肠腔侧侧分流术 (MCS)、远端脾腔分流术 (DSCS)及门奇断流术(PAD)。观察术前及术后 1、2、3周时的自由门脉压力 (FPP)、门体分流率 (PSS)和肝脏功能的变化。结果　MCS组术后FPP明显下降 ,PSS显著升高 ,肝脏功能进一步恶化 ,至术后 3周仍未恢复 ;DSCS组和PAD组术后FPP及PSS变化较小 ;DSCS组肝脏功能无明显下降 ;PAD组术后 1周肝功能明显下降 ,2周后逐渐恢复到术前状态。结论　远端脾腔分流 (同时施行彻底的脾胰断流 )术有助于维持向肝血流 ,保护肝功能     

Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet.

The aim of this study was to understand by which intrahepatic mechanism metformin (Met) may inhibit basal hepatic glucose production (HGP) in type 2 diabetes. We studied rats that were fed for 6 weeks a high-fat (HF) diet, supplemented (HF-Met) or not (HF) with Met (50 mg x kg(-1) x day(-1)). Basal HGP, assessed by 3-[(3)H]glucose tracer dilution, was lower by 20% in HF-Met rats compared with HF-rats: 41.6 +/- 0.7 vs. 52 +/- 1.5 micromol x kg(-1) x min(-1) (means +/- SE, n = 5; P < 0.01). Glucose-6 phosphatase (Glc6Pase) activity, assayed in a liver lobe freeze-clamped in situ, was lower by 25% in HF-Met rats compared with HF-rats (7.9 +/- 0.4 vs. 10.3 +/- 0.9 micromol x min(-1) x g(-1) wet liver; P < 0.05). Glucose-6 phosphate and glycogen contents, e.g., 42 +/- 5 nmol/g and 3.9 +/- 2.4 mg/g, respectively, in HF-rats were dramatically increased by three to five times in HF-Met rats, e.g., 118 +/- 12 nmol/g and 19.6 +/- 4.6 mg/g (P < 0.05 and P < 0.01, respectively). Glucose-6 phosphate dehydrogenase activity was increased in HF-Met compared with HF rats (1.51 +/- 0.1 vs. 1.06 +/- 0.08 micromol x min(-1) x g(-1); P < 0.01). Intrahepatic lactate concentration tended to be lower in the Met-group (-30%; NS), whereas plasma lactate concentration was higher in HF-Met rats (1.59 +/- 0.15 mmol/l) than in HF rats (1.06 +/- 0.06 mmol/l; P < 0.05). We concluded that Met decreases HGP in insulin-resistant HF-fed rats mainly by an inhibition of hepatic Glc6Pase activity, promoting glycogen sparing. Additional mechanisms might involve the diversion of glucose-6 phosphate into the pentose phosphate pathway and an inhibition of hepatic lactate uptake.     

Portal diversion for portal hypertension in early childhood.

Twenty-three children under 6 years of age with portal hypertention were treated by portal diversion. Fourteen had cavernomatous transformation of the portal vein and 9 had an intrahepatic block due to cirrhosis (8) or congenital hepatic fibrosis (1). Portal-systemic shunts were central splenorenal in 20 patients, side-to-side portacaval in 2 and mesocaval in one. In 20 of the 21 peripheral shunts, the veins used for the anastomosis were less than 10 mm in diameter. There was no operative mortality. Thrombosis of the shunt occurred in 3 children (13%) and was responsible for recurrent bleeding in one who was treated later with success by a mesocaval shunt. The two other children with a thrombosed shunt are waiting, at the present time, for a mesocaval anastomosis. The volume of blood flowing through the shunt was small initially and the fall in pressure gradient was slight: therefore intraoperative angiography appeared to be a better way to assess the patency of shunts done at an early age than pressure or flow measurements. The figures recently reported by Clatworthy, with a mortality rate of 12% directly or indirectly related to repeated hemorrhage, are for us a forceful argument for early adequate management of portal hypertension in children. Until now, portal-systemic shunts have been complicated by a high frequency of thrombosis and have given discouraging results. Our results suggest that it is possible to perform portal diversion successfully on diminutive veins (down to 4 mm). From this experience early portal diversion appears to represent the treatment of choice for portal hypertension in childhood.     

去势对雄性大鼠血管成形术后再狭窄的影响

目的 :系统观察血管外膜细胞在血管成形术 (PTA)后再狭窄过程中的动态变化 ,通过复制去势模型对照观察雄激素对再狭窄的影响 ,并探讨其作用机制。　方法 :复制雄性SD大鼠的去势模型及颈总动脉再狭窄模型 ,于术后 3、7、14、2 8d不同时间点取材 ,行苏木精 伊红染色及免疫组化染色 ,并以电镜观察血管狭窄情况。　结果 :PTA术后 3d增殖细胞首先出现在血管外膜 ,并发生表型转变 ,术后 7d时外膜细胞增殖最明显 ,并向内膜迁移 ,术后 14d外膜细胞增殖减少 ,增殖细胞集中于中膜及新生内膜。各观察时间点 ,去势雄性大鼠的血管外膜面积、新生内膜面积、血管狭窄程度 ,均较未去势组大。以 14d组为例 ,血管外膜面积 [(35 6 6± 337) μm2 vs (2 75 1± 4 0 1) μm2 ,P =0 .0 0 8],新生内膜面积 [(35 5 3± 4 77) μm2 vs (2 75 7± 4 35 ) μm2 ,P =0 .0 2 5 ],血管狭窄程度 [(76± 2 ) %vs (6 0±8) % ,P =0 .0 0 5 ],外膜细胞增殖指数 [(2 9± 2 ) %vs (13± 1) % ,P <0 .0 0 1]。　结论 :PTA术后血管外膜细胞增殖、迁移参与了再狭窄的形成。生理状态下体内雄激素可以减轻血管再狭窄程度 ,其作用机制可能与干预血管外膜细胞活化有关。     

Liver bacterial clearance following hepatic artery ligation and portacaval shunt

The reticuloendothelial system (RES) plays an important role in removing bacteria, endotoxins, and immune complexes from the circulation. Hepatic phagocytosis accounts for more than 80% of RES function. The dual hepatic blood supply (hepatic artery/portal vein) may be altered by pathologic states and surgical procedures. This study evaluates and compares the effect of hepatic artery ligation and portacaval shunt on hepatic trapping of viable Escherichia coli. Thirty rats were placed in three groups: Group I was composed of sham operated controls; Group II underwent end-to-side portacaval shunt (PCS); and in Group III, hepatic artery ligation (HAL) was performed. At 2 weeks following the operation 10(9) 35S-radiolabeled viable E. coli were injected via the tail vein. At 10 min, bacterial distribution in the different organs was determined. Tissue samples were processed for liquid scintillation counting. The final distribution of bacteria was calculated from the input specific activity (dpm/bacteria) and expressed as the mean percentage of injected viable E. coli per gram of tissue and per organ weight. There was a significant decrease of bacterial trapping by the liver in rats following PCS (Group II), 45.0 +/- 10.4% vs controls 77.1 +/- 3.73% (P less than 0.005). This was partially compensated for by a significant increase of bacterial trapping by the lung. The decreased clearance in PCS rats is due to a reduction in liver mass compared to that in controls. Bacterial localization in HAL (Group III) rats was similar to that in controls. These data show that PCS decreases hepatic clearance and increases pulmonary localization of viable E. coli. This phagocytic dysfunction may contribute to increased susceptibility to infection following portacaval shunt.     

Splanchnic cortisol production in dogs occurs primarily in the liver: evidence for substantial hepatic specific 11beta hydroxysteroid dehydrogenase type 1 activity

Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 +/- 0.1 to 2.4 +/- 0.1 to 1.7 +/- 0.1 microg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 +/- 3 and 28 +/- 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 +/- 0.12 vs. 0.28 +/- 0.11 vs. 0.27 +/- 0.10 microg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 +/- 0.1 microg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 +/- 0.1 microg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 +/- 0.2 microg/min; P < 0.001 vs. liver). Flux through the 11beta hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 +/- 0.03 vs. 0.48 +/- 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 +/- 0.1 microg/min (P = NS vs. zero production) and 0.6 +/- 0.1 microg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11beta HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.     

Hepatic microcirculatory disturbances due to portal vein clamping in the orthotopic rat liver transplantation model

Most modifications and applications of the orthotopic rat liver transplantation (ORLT) model require clamping of the portal vein, thus leading to ischemia of the gut. The purpose of this study was to evaluate the effect of portal vein clamping during ORLT on hepatic microcirculation and leukocyte--endothelial interaction by intravital fluorescence microscopy. ORLT were performed following 1 hr of cold storage in EuroCollins solution without (standard group) and with insertion of a portojugular shunt (shunt group) to minimize intestinal ischemia. ORLT induced reduction of perfused sinusoids (83%) and velocity of leukocytes (311 +/- 4.5 microns/sec; mean +/- SEM) compared with nontransplanted controls (99% and 417 +/- 4.9 microns/sec). Portojugular shunt during ORLT improved hepatic microvascular perfusion (89% and 355 +/- 3.4 microns/sec; P less than 0.05). Furthermore, percentage of permanent and temporary adherent leukocytes decreased significantly when a portosystemic shunt was applied (from 33.5 +/- 1% to 22.1 +/- 1% and 19.7 +/- 1.2% to 14.0 +/- 0.9%; P less than 0.05). The results of the study reveal that intestinal congestion and reperfusion results in a rise in leukocyte adhesion to the sinusoidal wall and in disturbances of the hepatic microcirculation. It seems likely that increased endotoxin concentrations in the portal vein induce an activation of hepatic macrophages that subsequently cause release of chemoattractant mediators. In conclusion, side effects of intestinal ischemia during experimental liver transplantation surgery on liver function due to release of chemoattractant mediators should be considered when experimental data are transferred to clinical settings.     

Viability of long-term cryopreserved human saphenous veins

The feasibility of maintaining long-term viability of human venous allografts by cryopreservation has been investigated. Segments of vein were obtained from 85 patients undergoing a stripping operation for varicose veins. The venous segments were immersed in a dimethylsulfoxide 15% solution, deep frozen at -196 degrees C in liquid nitrogen and preserved for a duration of 1 week to 24 months. Light microscopy (n = 126) failed to demonstrate striking differences between control veins and any of the cryopreserved veins. The types of damage observed at scanning electron microscopy included endothelial cell separation, endothelial cell loss, exposed basement membrane and exposed fibrillar collagen, which were graded on a scale. The score for short term (less than 3 weeks) stored veins was 8.1 +/- 0.9 (mean +/- SEM) and did not differ from the long-term (greater than 10 weeks) stored veins score (6.3 +/- 1.0, p NS). The tissue enzymes LDH, GOT, GPT, CPK were measured in the frozen vein groups (n = 115) after thawing to room temperature. Cryopreservation did not alter any of the tissue enzymes measured when compared to controls. Endothelial fibrinolytic activity (FA) of 58 venous segments cryopreserved for a mean duration of 20 months was 6136.4 +/- 292.1 Tissue Activator Units (TAU) and did not differ from FA of 11 controls (5989.1 +/- 696.8 TAU). Synthesis of 6-Keto-PGF1-alpha-2, a stable breakdown product of PGI2, measured in 10 venous segments cryopreserved for 10 months, was significantly higher than in 13 veins stored in saline for 12 hours at 4 degrees C (2.8 +/- 0.4 vs 0.4 +/- 0.1 PG ml-1mg-1min-1, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of portosystemic shunt patency and function with magnetic resonance imaging

Magnetic resonance imaging (MRI) was performed in seven patients before and after portosystemic shunting to evaluate venous changes accompanying nonselective and selective shunt construction. The size and number of the intrahepatic portal and hepatic veins, left perirenal veins, and left upper quadrant varices were evaluated at MRI before and after shunt construction. MRI correctly diagnosed patent shunts in all seven patients. A marked decrease in the size of intrahepatic veins after a total or nonselective shunt suggests adequate portal vein and variceal decompression. Dilatation of left perirenal veins in the presence of a patent mesorenal or splenorenal shunt suggests hypertension of the left renal vein and possibly inadequate decompression of esophageal varices.     

Treatment of Budd-Chiari Syndrome by Side-to-Side Portacaval Shunt: Experimental and Clinical Results

The Budd-Chiari syndrome caused by occlusion of the major hepatic veins, often of unknown etiology, is typically characterized by massive ascites, hepatomegaly and abdominal pain due to intense congestion of the liver. The outcome has almost always been fatal. This report describes an evaluation of side-to-side portacaval shunt in dogs with experimental Budd-Chiari syndrome and in six patients with hepatic vein thrombosis. In the animal studies, side-to-side portacaval shunt was very effective in relieving massive ascites, hepatomegaly, hepatic congestion and portal hypertension produced by ligation of the hepatic veins. Only one of 24 dogs with side-to-side anastomosis reformed ascites, 67% of the animals survived until the study was concluded after one year, and liver biopsies showed reversal of the severe pathologic abnormalities. In contrast, all 20 control dogs subjected to a sham laparotomy, and all 20 dogs that underwent end-to-side portacaval shunt reformed massive ascites and died within six months with continued hepatic congestion and necrosis.

All six patients with the Budd-Chiari syndrome due to hepatic vein occlusion had massive ascites (4.4-15.9 l), hepatomegaly, abdominal pain and disturbed liver function. In all six, angiography demonstrated occlusion of the hepatic veins with a patent inferior vena cava (IVC) and a normal IVC pressure, and liver biopsy showed intense centrilobular congestion and necrosis. The most valuable diagnostic study was angiography of the IVC and hepatic veins with pressure measurements. Side-to-side portacaval shunt was performed from four to 14 weeks after the onset of symptoms, and produced dramatic and sustained relief of ascites in five of the six patients during follow-up periods of from eight months to seven years. Liver function returned to normal, hepatosplenomegaly disappeared, none of the survivors developed portal-systemic encephalopathy, and follow-up liver biopsies showed disappearance of congestion and necrosis, but mild to moderate fibrosis. One patient died following an emergency IVC thrombectomy and portacaval shunt, which was undertaken when, during the course of his workup, his condition deteriorated suddenly because the thrombotic process extended from the hepatic veins into the IVC. The everpresent risk of this complication, and the dangers associated with delaying operation were emphasized by this case. It is concluded that side-to-side portacaval shunt, which decompresses the liver by converting the portal vein into an outflow tract, provides effective treatment of the Budd-Chiari syndrome when the occlusive process is confined to the hepatic veins.

     

Role for "uremic toxin" in the progressive loss of intact nephrons in chronic renal failure.

We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)