Two cases of hepatic artery interruption after hepatopancreatobiliary surgery treated by prostaglandin E1 infusion via the superior mesenteric artery

In two cases of hepatic arterial flow interruption after hepatopancreatic surgery, continuous PGE₁ infusion from the superior mesenteric artery (SMA) was applied to oxygenate the liver through the portal vein. Case 1 was a 69-year-old woman with a non-functioning islet cell tumor of the pancreas. She underwent pancreatic resection following hepatic arterial infusion of anticancer drugs. Serum alanine aminotransferase (ALT) was elevated to 5500 IU/l on postoperative day (POD) 2; angiography revealed complete celiac artery obstruction. Continuous PGE₁ was administered from SMA at a rate of 0.01 μg/kg/min for 7 days. Serum ALT was normalized within 2 weeks and the peak level of serum total bilirubin (T. Bil) was 4.5 mg/dl. Case 2 was a 66-year-old man suffering from metastatic liver cancer. Complete obstruction of the proper hepatic artery was noted at the time of liver resection after hepatic arterial chemotherapy. Serum ALT was elevated to 2930 IU/l on POD 1, and PGE₁ infusion from SMA was done for the succeeding 7 days. Necrotic area was so vast that serum T. Bil rose to 19 mg/dl. However, it decreased with time. Both cases required 3 months for necrotic liver shrinkage. Doppler ultrasonography revealed that PGE₁ infusion actually increased portal blood flow. In conclusion, based on the preceding experimental backgrounds and clinical experiences, continuous PGE₁ infusion via the SMA can be a useful measure to prevent severe liver damage after hepatic arterial flow interruption through portal blood oxygenation.     

Continuous Arterial Infusion of Prostaglandin E1 via the Superior Mesenteric Artery in the Treatment of Postoperative Liver Failure

Abstract: Impaired hepatic blood flow is one of the causative factors in postoperative liver failure. To restore the hepatic blood flow in case of hepatic artery interruption (HAI), the effect of continuous arterial infusion of prostaglandin E₁ (PGE₁), which has a strong vasodilatory effect on vascular smooth muscles, was assessed experimentally and clinically. Twelve pigs underwent ligation and division of the hepatic artery and were divided into 2 groups. In the control group, saline was infused in the superior mesenteric artery (SMA), and in the PGE₁ group, 0.02 μg/kg/min of PGE₁ was infused continuously in the SMA. Hepatic oxygen delivery (HDo ₂) in the control group was 87.8 ± 8.9 ml/min before HAI and decreased to 43.1 ± 2.6 ml/min at 60 min after HAI, showing 50.9% decrease by HAI. On the contrary, HDo ₂ in the PGE₁ group was 86.7 ± 9.1 ml/min before HAI and was 76.6 ± 12.2 ml/min at 60 min after HAI, showing only 11.6% decrease by HAI. Clinically, a 65‐year‐old female suffering from cholangiocellular carcinoma underwent extended left hepatic lobectomy. At operation, the branch of the hepatic artery to the anterior segment of the liver was ligated, and the right branch of the portal vein became stenotic unavoidably. Postoperatively, severe liver dysfunction developed so that continuous PGE₁ infusion in the SMA was initiated at a rate of 0.01 μg/kg/min on the eighth postoperative day and continued for 9 days. Plasma exchange was performed twice concomitantly. Portal venous flow increased from 612 ml/min to 1,192 ml/min, and bile flow from external biliary drainage tube doubled by the PGE₁ infusion. The liver function was ameliorated after PGE₁ infusion.     

Efficacy of hepatic arterial infusion of prostaglandin E1 in the treatment of postoperative acute liver failure--report of a case

Prostaglandin E1 (PGE1) has received attention for its protective effects against various types of liver damage. However, it is known that approximately 70% of PGE1 is inactivated during a single passage through the lung. Therefore, direct infusion of PGE1 into the liver bloodstream is preferable to intravenous infusion. A 66-year-old man with hepatocellular carcinoma with liver cirrhosis developed postoperative acute liver failure following posterior segmentectomy under hepatic total vascular exclusion exceeding 1 hour. Because his liver function did not recover in spite of plasma exchange starting on postoperative day 8 and intravenous infusion of PGE1, hepatic arterial continuous infusion of PGE1 at a rate of 0.01 microgram/kg/min was carried out for 7 days from postoperative day 17. Immediately after the start of the arterial infusion, the bile flow significantly increased compared to before the arterial infusion, and the serum total bilirubin level decreased thereafter and finally recovered from the hepatic failure. In addition to its highly efficient drug delivery, the hepatic arterial infusion of PGE1 seems to be more advantageous in oxygen delivery to the liver compared with intravenous infusion. In conclusion, the hepatic arterial infusion of PGE1 may be useful in the treatment of acute liver failure.     

The effect of mechanically enhancing portal venous inflow on hepatic oxygenation, microcirculation, and function in a rabbit model with extensive hepatic fibrosis.

Enhancing the portal venous blood flow (PVBF) has been shown to reduce portal pressure and intrahepatic vascular resistance and to improve liver function in isolated cirrhotic rodent livers in vitro. The aim of this study was to assess the short-term effect of mechanically pumping the portal inflow on hepatic microcirculation (HM), oxygenation, and function in an animal model of extensive hepatic fibrosis. New Zealand white rabbits underwent laparotomy and exposure of the liver: group 1 (n = 7) were normal controls; group 2 (n = 7) had hepatic fibrosis. Total hepatic blood flow (THBF) and HM was measured along with continuous monitoring of intrahepatic tissue oxygenation using near infrared spectroscopy (NIRS). Baseline hepatic hemodynamics and liver function were measured in both groups. PVBF was then increased by 50% over a 3-hour period in the hepatic fibrosis group using a miniature portal pump designed for human implantation, and the hemodynamics were monitored continuously. Liver function tests were repeated after portal pumping. In comparison with normal controls, animals with hepatic fibrosis had a higher portal pressure (13.0 +/- 3.6 vs. 3.7 +/- 1.4 mm Hg, P <.001, mean +/- SD vs. controls), reduced PVBF (52.4 +/- 24.6 vs. 96.9 +/- 21.1 mL/min, P =.003), and increased portal vascular resistance (P =. 001). THBF and flow in the HM was lower than in controls, and liver function tests were abnormal. After a 3-hour period of enhanced portal flow in animals with hepatic fibrosis, the portal pressure greatly reduced (13.0 +/- 3.6 to 2.5 +/- 1.1 mm Hg, P <.001) as did the intrahepatic portal resistance (0.32 +/- 0.18 to 0.04 +/- 0.03 mm Hg/mL/min, P =.006). Flow in the HM improved (143 +/- 16 to 173 +/- 14 flux units, P =.006) and was associated with improved hepatic tissue oxygenation, tissue oxy-hemoglobin (HbO2) and cytochrome oxidase being increased by 24.4 +/- 7.5 and 5.65 +/- 2.30 micromol/L above the baseline value (P <.001), respectively. A 3-hour period of mechanical portal pumping produced a dramatic improvement in liver function, bilirubin (41.1 +/- 25.9 to 10.0 +/- 5.9 micromol/L, P =. 040), aspartate transaminase (AST) (135.5 +/- 52.3 to 56.3 +/- 19.8 U/L, P =.006) and lactate dehydrogenase (LDH) (2,030.1 +/- 796.3 to 1,309.8 +/- 431.6 IU/L, P =.006; prepumping vs. postpumping, all P <. 050). In conclusion, portal pumping in this rabbit model with extensive hepatic fibrosis improved liver parenchymal perfusion, oxygenation, and function.     

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (from 9.0 +/- 2.1 to 11.7 +/- 2.7 mmHg per liter per min, p less than 0.001), whereas mean arterial pressure did not change (77 vs. 78 mmHg). Propranolol significantly reduced hepatic artery blood flow (from 0.65 +/- 0.20 to 0.55 +/- 0.14 liters per min, p less than 0.01). However, reduction of hepatic artery blood flow (-12.9 +/- 7.3%) was significantly less than reduction of cardiac output (-21.1 +/- 5.2%, p less than 0.01). As a result, the fraction of the cardiac output delivered to the liver was significantly greater after propranolol (8.0 +/- 1.7%) than before (7.3 +/- 1.7%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver.

The role of microcirculation in the pathogenesis of alcoholic liver injury was investigated in isolated perfused livers from fed rats. Infusion of ethanol into the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately on initiation of ethanol load and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury, into the effluent perfusate began to increase after 20 to 30 min of ethanol infusion and continued to increase until the end of the experiment (60 min after the initiation of ethanol infusion). The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100 mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly the ethanol-induced increases in portal pressure and lactate dehydrogenase release by abolishing hepatic vasoconstriction. In histological examinations focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei, was detected predominantly in midzonal and pericentral areas of the liver lobule after 60 min of ethanol infusion. Change in portal pressure during 60 min of ethanol infusion correlated significantly with levels of lactate dehydrogenase after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

经门静脉或肝动脉脐带血干细胞移植治疗失代偿期肝硬化的近期疗效与安全性比较

目的比较经门静脉和肝动脉移植脐带血干细胞治疗失代偿期肝硬化患者的疗效与安全性。方法失代偿期肝硬化患者60例被随机分为门静脉治疗组30例和肝动脉治疗组30例。在基础治疗基础上,经皮经肝门静脉穿刺或经股动脉穿刺至肝固有动脉,注入相同数量的脐带血干细胞。观察两组患者临床症状改善情况及术后不良反应;治疗后8周检测血清ALT、AST、总胆红素、凝血酶原活动度和白蛋白水平。结果两组治疗后第3天全部患者乏力、纳差症状均改善,且两组间均未发现严重的不良反应及并发症;移植治疗后8周,门脉组和肝动脉组血清白蛋白分别升高至36.4±7.8g/L和37.1±9.1g/L,PTA分别上升至57.2±11.8%和55.6±12.5%,而ALT、AST、TBIL、AFP在门脉组分别为46.2±14.6IU/L、53.6±15.4IU/L、30.1±12.0μmol/L、13.2±2.8μg/L,在肝动脉组分别为48.2±10.8IU/L、50.2±13.8IU/L、32.1±10.2μmol/L、16.0±3.0μg/L,两组间观察指标在基线水平、变化值和观察终点水平差异均无显著意义。结论经门静脉和肝动脉移植脐带血干细胞治疗失代偿期肝硬化患者有一定的疗效,且安全可行,两种移植治疗近期疗效无显著性差异。     

Altered hepatic hemodynamics and improved liver function following intrahepatic vascular infusion of prostaglandin E1

Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1 influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we carried out an experimental and a clinical study. PGE1 was continuously administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of 0.01 μg/kg per min in healthy mongrel dogs. In the clinical study, in eight patients PGE1 was administered through the hepatic artery at a rate of 0.01 μg/kg per min after hepatic lobectomy. In the experimental study, hepatic hemodynamics and oxygen metabolism did not change during the administration of PGE1 into the portal vein. During administration of PGE1 into the hepatic artery, hepatic arterial flow increased 1.5-fold after administration compared to the rate before administration (P < 0.01). Hepatic arterial pressure, hepatic arterial resistance, and post-sinusoidal resistance significantly decreased after administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen supply increased significantly (P < 0.01). In the patients, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels remained low after surgery, and the recovery of protein synthesis was improved compared with that in eight hepatectomized patients without PGE1 administration (controls). The intrahepatic arterial infusion of PGE1 was considered useful for the recovery of liver function. (Received Apr. 21, 1997; accepted Sept. 26, 1997)     

Splenic arterial ligation prevents liver injury after a major hepatectomy by a reduction of surplus portal hypertension in hepatocellular carcinoma patients with cirrhosis.

BACKGROUND/AIMS: In this study, we investigated whether a reduction of surplus portal hypertension after a major hepatectomy by SPL (splenic arterial ligation) prevents a liver injury in cirrhotic patients with hepatocellular carcinoma. METHODOLOGY: Six hepatocellular carcinoma patients (SPL group) with liver cirrhosis (67 +/- 10 years old, ICGR15: 21.0 +/- 9.8%, T.Bil: 1.1 +/- 1.2 mg/dL) underwent major hepatectomy with splenic arterial ligation in order to reduce excessive portal hypertension after hepatectomy from 1998 to 2000, July. The patients (n = 15, 60 +/- 9 years old, ICGR15: 11.5 +/- 5.9%, T.Bil: 0.66 +/- 0.15 mg/dL) who underwent liver resection above subsegmentectomy in the same period (control group) served as the control for SPL group. RESULTS: In the SPL group, the portal pressures before hepatectomy were 26 +/- 7 cm H2O and those after hepatectomy were 29 +/- 6 cm H2O. The portal pressure after splenic arterial ligation decreased to 24.5 +/- 6.3 cm H2O. The splenic tissue blood flows before SPL were 16.8 +/- 5.6 mL/min/100 g, while those after SPL were 7.2 +/- 2.2 mL/min/100 g. The portal pressures before hepatectomy were 17 +/- 2 cm H2O and those after hepatectomy were 19 +/- 2 cm H2O in the six control patients. At the peak levels of liver function after surgery, T.Bil was 2.6 +/- 1.5 mg/dL, GOT was 165 +/- 59 IU/L, and GPT was 107 +/- 49 IU/L. All patients could discharge without complications except for one case with bile leakage in SPL. At the peak levels of liver function in control group, T.Bil was 3.7 +/- 1.9 mg/dL, GOT was 404 +/- 227 IU/L, and GPT was 322 +/- 171 IU/L. At the peak levels of liver function after surgery, T.Bil was 3.4 +/- 1.3 mg/dL, GOT was 398 +/- 289 IU/L, and GPT was 319 +/- 220 IU/L. Conversely, there were 11 episodes of complications (11/15), including two cases of hospital death resulting from liver failure in patients who underwent right lobectomy, in the control patients. CONCLUSIONS: The decompression of surplus portal hypertension by SPL might be effective in the prevention of post hepatectomized liver injury and the improvement of postoperative mortality and morbidity.     

Tumor Necrosis Factor in Alcohol Enhanced Endotoxin Liver Injury

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

The intrahepatic biliary epithelium in the guinea pig: is hepatic artery blood flow essential in maintaining its function and structure?

To determine whether hepatic artery blood flow is essential in maintaining the function and structure of bile ductules/ducts, the acute effects of hepatic artery ligation on bile secretion and hepatic ultrastructure were examined in anesthetized, bile duct-cannulated guinea pigs. Sixty minutes after hepatic artery ligation, spontaneous bile flow (5.08 +/- 0.4 microliter per min per gm liver) was virtually the same as that before hepatic artery ligation (5.31 +/- 0.3 microliter per min per gm), as were the choleretic effects of 10 CU per kg per 30 min secretin (7.14 +/- 0.9 vs. 7.21 +/- 0.9 microliter per min per gm), 300 micrograms per kg per 30 min glucagon (6.72 +/- 0.9 vs. 6.59 +/- 0.8 microliter per min per gm) and 60 mumoles per kg per 30 min glycochenodeoxycholate (6.43 +/- 0.6 vs. 6.45 +/- 0.6 microliter per min per gm). The failure of hepatic artery ligation to affect bile secretory function could not be attributed to the existence of collateral arterial blood flow to the liver. First of all, hepatic artery ligation resulted in diminishing significantly hepatic venous, but not portal, oxygen content. More importantly, in isolated guinea pig livers, perfused through the portal vein alone, secretin, glucagon and glycochenodeoxycholate produced changes in bile flow and composition similar to those seen in vivo. Electron microscopy showed no major ultrastructural changes of hepatic parenchyma and biliary epithelium 2 hr after hepatic artery ligation, or 2 hr after perfusing the liver through the portal vein alone save for some portal edema in the latter instance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of insulin antibodies on metabolic deterioration after interruption of continuous subcutaneous insulin infusion

To evaluate the influence of insulin antibodies (IA) on metabolic deterioration after interruption of continuous subcutaneous insulin infusion (CSII), we studied two groups of type I diabetic patients without residual insulin secretion: group 1 (5 patients) with insulin-binding antibodies below 10% and group 2 (8 patients) with insulin-binding antibodies above 10%. We investigated the changes in blood glucose, plasma non-esterified fatty acids (NEFA), bicarbonate and glucagon after stopping insulin infusion between 08.00 h. and 14.00 h. Insulin infusion cessation resulted in: 1) a similar increase in blood glucose in both groups after 2 hours of interruption (group 1: 9.45 +/- 1.28 mmol/L versus basal levels of 6.94 +/- 0.96 mmol/L, p less than 0.05; group 2: 8.11 +/- 2.87 mmol/L versus 5.75 +/- 2.17 mmol/L, p less than 0.02) and a greater increase in blood glucose in group 1 than group 2 after 4 hours (p less than 0.05) and after 6 hours (p less than 0.05); 2) a progressive increase in NEFA in group 1 throughout the study period (08.00 h.: 0.51 +/- 0.28 mmol/L; 14.00 h: 1.44 +/- 0.45 mmol/L, p less than 0.05) that was significant after 4 and 6 hours of CSII interruption; there were no changes in NEFA in group 2; 3) plasma level of IA correlated inversely with final glycemia (r = -0.67, p less than 0.01) and final NEFA (r = -0.56, p = 0.02). We conclude that IA may play a role in slowing metabolic deterioration after CSII interruption.     

Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10-20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 +/- 10 and 44 +/- 7 microU/ml, respectively) and glucagon (247 +/- 37 and 219 +/- 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 +/- 62 vs. 294 +/- 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious animals, the basal hepatic extractions of insulin (42 +/- 6 vs. 39 +/- 6%, respectively) and glucagon (12 +/- 7 vs. 7 +/- 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg X min) and glucagon (4 ng/kg X min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exogenous hormones was significantly greater in the anesthetized animals.     

Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats

BACKGROUND & AIMS: Vasoconstriction of the superior mesenteric artery (SMA) is the earliest hemodynamic event occurring after partial portal vein ligation (PVL). We tested the hypothesis that this early vasoconstriction of the SMA may initiate eNOS up-regulation in PVL. METHODS: Portal hypertension with or without mesenteric vasoconstriction was induced by differentially calibrated stenosis of the portal vein (PVL-20G and PVL-18G, respectively). In a separate group of rats, mesenteric vasoconstriction was achieved by renal artery ligation. Sham-operated rats were used as controls. Effects of vasoconstriction of the SMA in PVL and RAL rats were evaluated by measuring perfusion pressure changes in isolated SMA beds in response to methoxamine, nitric oxide synthase activity, and eNOS protein expression. Mean arterial pressure, portal pressure, and SMA blood flow were measured by catheterization and Doppler flowmetry. SMA vascular resistance was calculated from arterial pressure, portal pressure, and SMA flow. RESULTS: There was a significant increase in SMA vascular resistance in PVL-20G (2.33 +/- 0.13 vs. 1.22 +/- 0.03 mm Hg/% flow; P < 0.05) and RAL (2.32 +/- 0.18 vs. 1.18 +/- 0.02 mm Hg/% flow; P < 0.05) but not in PVL-18G, showing mesenteric vasoconstriction in both PVL-20G and RAL groups. The mesenteric vasculature of PVL-20G and RAL animals showed hyporeactivity to methoxamine (P < 0.01). Whereas both PVL groups were portal hypertensive (P < 0.01), RAL rats were not. The SMA hyporeactivity of PVL-20G and RAL rats was corrected by N(G)()-monomethyl-L-arginine, and nitric oxide synthase enzyme activity was significantly higher in PVL-20G and RAL rats (P < 0.05). CONCLUSIONS: Mesenteric arterial vasoconstriction plays a triggering role in up-regulation of eNOS catalytic activity in the SMA of portal hypertensive rats.     

The effect of liver denervation on hepatic hemodynamics during hypovolemic shock in swine.

This study tested the hypothesis that the denervated liver is more susceptible to hypovolemic shock than the normal liver. Fourteen swine, seven nondenervated and seven after liver denervation, were studied during hypovolemic shock to 50% of baseline blood pressure. Hepatic artery and portal vein flows were measured using transonic flow probes, and cardiac output and central venous pressure were measured using Swan-Ganz catheters. Hepatic artery flow fell equivalently in the two groups, from 132 +/- 71 to 94 +/- 17 ml/min in the nondenervated group compared with 149 +/- 56 to 91 +/- 55 ml/min in the denervated group. In contrast, portal flow in the denervated group (276 +/- 71 to 119 +/- 53 ml/min) fell significantly (p less than 0.001) more than in the nondenervated group (289 +/- 135 to 194 +/- 70 ml/min). The 58% reduction from baseline in portal flow in the denervated group compared with the 30% reduction in the nondenervated group suggests that the normal compensatory mechanism to maintain portal flow during hypovolemic shock is neurally mediated. It can be hypothesized that sensory afferent fibers might initiate a feedback to splanchnic vasodilatation in response to reduced portal flow. This study supports the hypothesis that the denervated liver is more susceptible to hypovolemic shock.     

双剂量奥曲肽对肝硬化门脉高压症断流术后患者血流动力学的影响

目的研究双剂量奥曲肽对肝硬化门脉高压症断流术后患者门脉压力、肝脏血流动力学影响。方法肝硬化门脉高压症断流术患者26例,随机分两组,术后24h开始用奥曲肽。A组12例,奥曲肽50μg／h;B组14例,奥曲肽25μg／h;胃网膜右静脉插管至门静脉主干,动态测定门脉压力;彩色超声多普勒测定门脉直径（PV）、门脉最大血流速度（PFVmax）、门脉平均血流速度（PFVmean）、肝动脉最大血流速度（HAVmax）、肝动脉最小血流速度（HAVmin）;计算门脉血流量参数（PFI）、肝动脉血流量参数（HAFI）。结果断流术后,两组患者门脉压力平均降幅15．4％,PFI降低（P〈0．05）;HAVmax、HAVmin、HAFI增加（P〈0．05）。用奥曲肽72h后,两组PFI、PFVmax、PFVmean降低（P〈0．05）;用药5min门脉压力降低,24h达高峰,门脉压力平均降幅20．6％。A组停药后48h内,门脉压力未见回升,平均降幅23．1％;B组停药后2h门脉压力有回升趋势,平均降幅11．6％;停药后24h、48h两组患者门脉压力比较差异有统计学意义（P〈0．01）。Logistic分析发现,PV、PFVmax、PFVmean、HAVmax、HAVmin与门脉压力无独立相关性。结论肝硬化门脉高压症患者行断流术后,门脉压力降低。双剂量奥曲肽均能明显降低门脉压力;停药后48h内,奥曲肽50μg／h组门脉压力未见回升。提示,临床用奥曲肽50μg/h对防止静脉曲张再出血更合理。     

Unilateral hepatic artery reconstruction is unnecessary in biliary tract carcinomas involving lobar hepatic artery: implications of interlobar hepatic artery and its preservation

BACKGROUND/AIMS: The interruption of hepatic arterial flow when performing a bilioenteric anastomosis has been reported to usually bring about serious postoperative complications, such as anastomotic leakage, hepatic abscess and infarction. We aimed to evaluate the surgical implications of the interlobar hepatic artery when patients with advanced biliary tract carcinomas undergo surgical resection with a bilioenteric anastomosis. METHODOLOGY: In 7 patients with advanced biliary tract carcinomas, the combined resection of the liver (greater than hemihepatectomy in 2 and less than hemihepatectomy in 5), extrahepatic bile duct, hepatic artery (right hepatic artery in 5, right and left hepatic artery in 1, left hepatic artery in 1), and the portal vein was performed in 4 patients. The portal vein was reconstructed in all 4 patients. The hepatic artery was reconstructed in only one patient, with combined resection of both right and left hepatic arteries, but was not reconstructed in 2 other patients, even though they underwent resection greater than hemihepatectomy. RESULTS: The interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence could be preserved in 5 patients, as shown by angiography, but could not be preserved in 2 patients who underwent greater than hemihepatectomy. Moderate and transient ischemic liver damage occurred, but no serious postoperative complications were induced in any of the 5 patients in the unilateral hepatic artery preserved group. However, both cases without preservation of the hepatic artery encountered liver failure, liver abscess and leakage of bilioenteric anastomosis, and one patient died of multiple organ failure. CONCLUSIONS: One major lobar branch of the hepatic artery involved by cancer invasion could be safely resected without reconstruction in patients with advanced biliary tract carcinomas when the interlobar hepatic artery running into the Glissonian sheath around the hepatic duct confluence is preserved.     

Splanchnic and hepatic metabolism of somatostatin: a study in cirrhotic patients with a portacaval shunt

Experimental data suggest that somatostatin is metabolized by both liver and kidneys. Results in humans are conflicting. By studying a group of cirrhotic patients with surgically induced end-to-side portacaval shunts, basally and during a somatostatin infusion, we have been able to analyze separately the hepatic and splanchnic metabolism of this peptide. After catheterization, samples were obtained from the pulmonary artery, portal and hepatic veins. Basal pulmonary artery immunoreactive somatostatin (IRS) was significantly higher (p less than 0.001) in the cirrhotic patients (96 +/- 11 pg per ml) than in a sex- and age-matched control group (31.4 +/- 5.8 pg per ml). During the infusion of exogenous somatostatin, IRS values were higher in arterial (12,269 +/- 1,198 pg per ml) than in hepatic venous blood (7,648 +/- 1,234 pg per ml), indicating hepatic extraction of the peptide; but there was also a substantial splanchnic extraction demonstrated by higher arterial (12,269 +/- 1,532 pg per ml) than portal values (6,754 +/- 1,040 pg per ml) of IRS. During the somatostatin infusion, at very high circulation IRS levels, the liver was able to extract 38% of the peptide. This suggests that the high basal IRS levels found in liver cirrhosis are not likely to be due to hepatic failure. Possible mechanisms may involve increased somatostatin secretion, predominance of high molecular weight moieties of IRS which may not be as effectively removed by the liver, and/or portal-systemic shunting.     

Hemodynamics during liver transplantation: the interactions between cardiac output and portal venous and hepatic arterial flows.

Liver blood flow and systemic hemodynamics were measured intraoperatively in 34 patients after liver transplantation. Ultrasound transit-time flow probes measured hepatic arterial and portal venous flow over 10 to 75 min 1 to 3 hr after reperfusion. Cardiac output was measured by thermodilution. Mean cardiac output was 9.5 +/- 2.8 L/min; the mean total liver blood flow of 2,091 +/- 932 ml/min was 23% +/- 11% of cardiac output. Mean portal flow of 1,808 +/- 929 ml/min was disproportionately high at 85% +/- 10% of total liver blood flow. Correlation analysis showed a significant (p less than 0.01; r = 0.42) correlation between cardiac output and portal venous flow and a trend toward negative correlation (p = 0.087) between cardiac output and hepatic arterial flow. These data show that increased flow in the newly transplanted liver is predominantly portal venous flow and is associated with high cardiac output and reduced hepatic arterial flow. In the last 13 patients studied, portal flow was reduced by 50% and the hepatic artery response was measured. We saw a significant (p less than 0.05) increase in hepatic artery flow from 322 +/- 228 to 419 +/- 271 ml/min, indicating an intact hepatic arterial buffer response. The hepatic artery response also showed that it is a reversible rather than a fixed resistance that contributes to the low hepatic artery flow in these patients.     

Impact of intraportal N(omega)-nitro-L-arginine infusion on hepatic glucose metabolism in total parenteral nutrition-adapted dogs: interaction with infection

During chronic total parenteral nutrition (TPN), liver glucose uptake and lactate release are markedly elevated. However, in the presence of an infection, hepatic glucose uptake and lactate release are reduced. Glucose delivery (the product of liver blood flow and inflowing glucose concentration) is a major determinant of liver glucose uptake. Hepatic blood flow is increased during infection, and increased nitric oxide (NO) biosynthesis is thought to contribute to the increase. Our aim was to determine if the increase in liver blood flow served to limit the infection-induced decrease in hepatic glucose uptake and metabolism. Chronically catheterized conscious dogs received TPN for 5 days at a rate designed to match daily basal energy requirements. On the third day of TPN administration, a sterile (SHAM) or Escherichia coli (E. coli)-containing (INF) fibrin clot was implanted in the peritoneal cavity. Forty-two hours later, somatostatin was infused with intraportal replacement of insulin (10 +/- 2 v 23 +/- 2 microU/mL, SHAM v INF, respectively) and glucagon (22 +/- 4 v 90 +/- 8 pg/mL) to match concentrations observed in sham and infected animals. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism. Following a 120-minute basal sampling period, sham and infected animals received either intraportal saline or N(omega)-nitro-L-arginine (L-NNA; 37 microg x kg(-1) x min(-1)) infusion for 180 minutes. Isoglycemia (120 mg/dL) was maintained with a variable glucose infusion. In the infected group L-NNA infusion decreased hepatic arterial blood flow (23.3 +/- 0.7 to 8.6 +/- 0.5 mL x kg(-1) x min(-1)), but not portal vein blood flow. Neither portal vein nor hepatic artery blood flow were altered by L-NNA infusion in the sham group. Hepatic glucose uptake and lactate metabolism were not altered by L-NNA infusion in either group. In summary, during infection, an increase in NO biosynthesis contributes to the increase in hepatic arterial blood flow, while it exerts no effect on hepatic glucose metabolism.