Serum concentration of adhesion molecules in postoperative biliary atresia patients: relationship to disease activity and cirrhosis

BACKGROUND/PURPOSE: Biliary atresia (BA) is associated with progressive liver fibrosis, which may be mediated by immunologic abnormalities involving adhesion molecules. This study investigates the relationship between serum intercellular adhesion molecule-1 (sICAM-1), serum vascular cell adhesion molecule-1 (sVCAM-1), and the clinical and histologic severity of BA. METHODS: Serum ICAM-1 and VCAM-1 levels were measured by enzyme-linked immunosorbent assay in 35 patients with BA and 20 healthy controls. Standard liver function tests (LFTs), and frozen section liver biopsy specimens were used to determine liver status. On the basis of LFT results, the BA patients were classified into group I (n = 10; normal LFTs), group II (n = 15; elevated LFTs, anicteric), and group III (n = 10; elevated LFTs, icteric). Eight subjects in group II, and all subjects in group III had portal hypertension (PH). RESULTS: sICAM-1 levels were significantly elevated in group III (1760.0 +/- 717.5 ng/mL) compared with group II (555.1 +/- 199.4 ng/mL), group I (272.1 +/- 59.9 ng/mL) and controls (256.3 +/- 71.6 ng/mL). Although sVCAM-1 levels were significantly elevated in group III (1932.9 +/- 282.6 ng/mL) compared with group II (1054.3 +/- 297.0 ng/mL), group I (605.4 +/- 112.4 ng/mL), and controls (616.0 +/- 112.0 ng/mL; P <.001), there was no statistically significant difference between groups I, II, or controls. sVCAM-1 levels were elevated significantly in BA subjects in group II with PH (1253.0 +/- 245.1 ng/mL) compared with those who did not have PH (827.3 +/- 151.7 ng/mL; P <.01). PH did not affect sICAM-1 levels. There was strong expression of ICAM-1 and VCAM-1 in proliferating bile ductules, endothelial cells, and liver cells in group III compared with group II and controls. CONCLUSIONS: In BA, sICAM-1 and sVCAM-1 levels could be useful as markers of end-stage liver disease, with sVCAM-1 being more specific for PH. Induction of ICAM-1 and VCAM-1 may be an important factor in the development of cirrhosis.     

Hyaluronic acid: a specific prognostic indicator of hepatic damage in biliary atresia

BACKGROUND/PURPOSE: Hepatic fibrosis can progress in biliary atresia (BA) and is associated with capillarization of hepatic sinusoids. The significance of serum hyaluronic acid (HA) as a noninvasive indicator of histological sinusoidal endothelial cell (SEC) damage and hepatic fibrosis in BA, is investigated. METHODS: A total of 28 postoperative BA patients (mean age, 11.0+/-3.7 years) and 20 normal controls (mean age, 10.5+/-2.8 years) were studied. BA patients were divided into group I, good liver function (n = 8); group II, moderate liver dysfunction (n = 10); and group III, severe liver dysfunction (n = 10). Serum HA was determined using a one-step sandwich enzyme immunoassay, and liver histological damage was confirmed immunohistochemically using an antibody against factor VIII-related antigen (FVIIIRAg), which is specific for detecting damaged SEC. RESULTS: Serum HA was significantly higher (P < .0001) in group III (84.6+/-36.5 ng/mL) than in group I (15.9+/-6.9 ng/mL) or group 11 (28.7+/-10.7 ng/mL). Although immunoreactive products of FVIIIRAg were abundant in group III, they were not detected in SEC from group II. CONCLUSION: Serum HA may be of value for monitoring postoperative BA patients as a noninvasive indicator of SEC damage and progressive hepatic fibrosis.     

Intrahepatic mast cell population correlates with clinical outcome in biliary atresia

PURPOSE: To determine if mast cells influence the clinical outcome in biliary atresia (BA), the authors examined the intrahepatic mast cell population in BA. METHODS: Mast cells were identified histochemically using Toludin Blue and immunohistochemically using antimast cell tryptase antibody in formalin-fixed paraffin-embedded sections from 21 cases of BA. Patients were divided into 3 groups; group I (n = 8) with good liver function, group II (n = 8) with moderate liver dysfunction, and group III (n = 5) with severe liver dysfunction. Liver biopsies from patients with choledochal cysts (CDC, n = 5), and normal liver (NL, n = 4) served as controls. The results were compared among the groups. RESULTS: Both histochemical and immunohistochemical methods showed similar data. Mast cells were seen mostly in the portal tracts. Mast cell numbers per medium power field (20 x magnification) were higher in BA than in the controls (15. 03 +/- 2.25 v 3.85 +/-.65, [mean +/- SEM], P <.05, BA v CDC; 15.03 +/- 2.25 v 1.73 +/-.06, [mean +/- SEM], P <.05, BA v NL, immunohistochemical data). Clinical correlation showed an association between higher mast cell number and liver dysfunction (32.62 +/-.80 v 8.52 +/-.87 [mean +/- SEM], group III v group I; P <. 05, immunohistochemical data). CONCLUSION: Increased mast cell population in BA adversely affects liver function and raises the possibility that type I allergic reaction may play role in the pathology of BA.     

Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens

BACKGROUND AND OBJECTIVE: An alteration in production of both interleukin-10 (IL-10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL-10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL-10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL-10 circulating concentrations. METHODS: Thirty-two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme-linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively. RESULTS: In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51 mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38 +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/- 1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1 and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1) at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL-10 and NO. CONCLUSIONS: During the postoperative period, IL-10 overproduction does not correlate with the decrease in systemic NO concentration.     

Effect of restrictive fluid management and acute normovolemic intraoperative hemodilution on transfusion requirements during living donor hepatectomy

The aim of this study was to evaluate the safety and effectiveness of a restrictive fluid management strategy and acute normovolemic intraoperative hemodilution (ANIH) to decrease transfusion requirements among living-donors for liver transplantation (LDLT). We retrospectively reviewed the data of 114 consecutive LDLT donors. The patients were divided into 2 groups based on whether (Group I; n = 73) or not (Group II; n = 41) a restrictive fluid management strategy with ANIH was used during the procedure. For each group we recorded demographic features, intraoperative and postoperative transfusions, amount of administered intraoperative crystalloid and colloids, intraoperative hemodynamics, preoperative and postoperative laboratory values (renal and liver functions), intraoperative and postoperative urine output, and length of hospital stay. Demographic features and preoperative laboratory values were similar for the 2 groups, except for age (Group I, 36 +/- 9 vs Group II, 33 +/- 8; P = .04). Intraoperatively, 7 patients (10%) in Group 1 and 9 (22%) in Group II required blood transfusions (P = .06). The respective amount of heterologous blood transfusion for Groups I and II was 96 +/- 321 mL vs 295 +/- 678 mL (P = .06). Postoperative renal and liver functions were not different between the 2 groups (P > .05). Patients in Group I had a shorter hospital stay than those in Group II (8.2 +/- 4.6 days vs 10.1 +/- 4.9 days; P = .03). In conclusion, a restrictive fluid management strategy with ANIH was a safe blood-salvage technique for LDLT. This approach was also associated with decreased length of hospital stay and a trend toward decreased transfusion requirements.     

A hybrid artificial liver system composed of primary cultured canine hepatocytes

The usefulness of newly device hybrid artificial liver system was evaluated in anhepatic dogs. The artificial liver module was composed of 60 to 80gm. primary cultured canine (Beagle) hepatocytes which were attached to 200 borocillicate glass plates. Total hepatectomy were done through cavo-caval and porto-caval shunt method using Anthron catheter to 14 dogs. Dogs were divided into following three groups. Group I; no treatment (n = 6) Group II; plasma perfusion (n = 4) Group III; treated with the artificial liver systems (n = 4) The survival times were 21.3 +/- 5.6, 27.8 +/- 4.0, and 55.0 +/- 11.3 hours in group I, II, and III, respectively. The longest survival time was 65 hours in one of group III dogs. APTT levels in group I and II increased more than 100 sec. within 24 hours. On the other hand it was maintained within 50 sec. during 54 hours treatment in group III. Ammonia levels in group I and II extremely increased over 2000ng/dl. In group III, it was less than 400ng/dl for 54 hours. Plasma amino acid levels in group I and II (Glutamine, Arginine, AAA) revealed significantly higher than in group III at 18 hours after operation. It is concluded that the newly device hybrid artificial liver system was useful for in vivo liver support.     

Long-term postsurgical outcome of biliary atresia

BACKGROUND/PURPOSE: A successful Kasai procedure is effective in creating biliary drainage and radically altering the natural history of infants with biliary atresia (BA). Since its introduction in the 1950s, long-term follow-up would appear to show that only 30% to 50% of patients have a good long-term prognosis despite initially good surgical outcome. The authors reviewed their experience in treating BA from 1968 to 1997 to assess long-term outcome. MATERIALS AND METHODS: The records of 163 patients treated surgically for BA from 1968 to 1997 were reviewed. Forty-eight (29%) were alive at the end of 1997, of whom, 14 had received liver transplants (LT). Surviving patients who had not undergone transplantation were divided into two groups according to clinical condition: group A, normal liver function without cholangitis (CG) and portal hypertension (PH) and group B, liver dysfunction with CG or PH. The study period was divided arbitrarily into three periods, 1968 to 1975 (period I, n = 34); 1976 to 1985 (period II, n = 81); 1986 to 1997 (period III, n = 48). RESULTS: Thirty-four patients were alive without LT at the end of 1997. There were eight patients (mean age, 16.3+/-4.8 years) in group A, and 26 patients (mean age, 14.3+/-7.6 years) in group B. Recently, four group A patients (mean age, 19.3+/-1.9 years) shifted to group B because of sudden deterioration in condition involving severe CG with multiple bile lakes (n = 2), uncontrollable intestinal bleeding (n = 1), and liver atrophy (n = 1). Survival deteriorated with length of follow-up. There were three survivors from 34 patients treated in period I, 16 survivors from 81 patients treated in period II (three had LT), and 29 survivors from 48 patients treated in period III (11 had LT). CONCLUSIONS: Although satisfactory bile drainage can be obtained with portoenterostomy, our data suggest that liver function can deteriorate progressively, with a possible turning point in late adolescence, indicating that as the length of follow-up increases, clinical assessment should be regular and comprehensive. The timing of LT in postoperative BA patients with deteriorating liver function is a vital management issue.     

Evaluation of Pringle maneuver during liver resection in a rat model of surgical obstructive jaundice.

Temporary portal triad clamping (Pringle maneuver) during liver resection reduces intraoperative blood loss. A normal liver can safely tolerate normothermic ischemia for up to 60 min. However, its safety in patients with surgical obstructive jaundice (SOJ) is not known. Therefore, we investigated the effect of hepatic ischemia in an experimental rat model of SOJ created by ligating the bile duct. Four groups of rats were created: Group I (sham operation, 10 days later, liver resection); Group II (sham operation, 10 days later, liver resection with 5 min of hepatic ischemia); Group III (bile duct ligation, 10 days later, liver resection); and Group IV (bile duct ligation, 10 days later, liver resection with 5 min of hepatic ischemia). The ischemic injury was assessed by the survival of rats, liver tissue malondialdehyde and total glutathione (markers of free radical injury), serum alanine aminotransferase, aspartate aminotransferase, and liver histology. The results showed decreased survival (47.6% vs. 90% [p = .046]), increased liver tissue malondialdehyde (161 +/- 35 vs. 129 +/- 33 microg/gm liver tissue [p = .05]), and decreased liver tissue total glutathione (565 +/- 169 vs. 1075 +/- 276 nmol/gm liver tissue [p = .05]) in rats with SOJ subjected to hepatic ischemia when compared to nonjaundiced rats. The changes in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase showed an increasing trend in the SOJ group but were not statistically significant. Ischemic changes in liver histology were seen more often in the SOJ group but were not statistically significant. These data suggest that temporary portal triad clamping in an experimental model of SOJ is detrimental to the outcome of liver resection.     

The role of monocyte chemoattractant protein-1 in biliary atresia

Background

The aim of this study was to explain the role of monocyte chemoattractant protein-1 (MCP-1) in biliary atresia (BA).

Methods

Concentrations of serum MCP-1 and collagen type IV were measured in 38 patients with BA by using commercially available kits. MCP-1 was also assessed in liver biopsy specimens by using immunohistochemistry. Subjects were classified into groups. Group 1 comprised BA patients with normal liver function (n = 13), group II comprised BA patients with moderate liver dysfunction (n = 18), group III comprised BA patients older than 20 years awaiting liver transplantation (n = 7), and the control group comprised age-matched patients without evidence of liver disease (n = 23).

Results

Serum MCP-1 levels were significantly increased in group II compared with group I (P < .0001) and the control group (P < .0001). Serum MCP-1 levels in group III were lower than in the control group (P < .0001). There was a significant linear correlation between serum MCP-1 levels and type IV collagen levels in group II. Group II subjects with portal hypertension (PH) had higher MCP-1 levels than those without PH (P = .0009). Biopsy specimens showed MCP-1 was expressed mainly on biliary epithelial cells, vascular endothelial cells, and hepatocytes in group II.

Conclusions

These findings suggest that MCP-1 probably plays a significant role in the development of progressive liver fibrosis in BA.     

Platelet Activating Factor and Thromboxane B2 Production After Cardiopulmonary Bypass

Platelet-activating factor (PAF) is believed to have a central role in the pathogenesis of ischemia-reperfision injury. The purpose of this study was to investigate the relationships among production of PAF, thromboxane B₂ (T_αB2), and cardiopulmonary sequelae in patients undergoing coronary artery bypass graft surgery (CABGS). Venous blood from nine patients (eight men, one woman) undergoing scheduled CABGS, was sampled from central venous catheters before anesthetic induction, pre-cardiopulmonary bypass (CPB), 10 and 30 minutes post-CPB, 10 and 30 minutes post-aortic declamping, and 120 minutes and 24 hours after the conclusion of CPB. Plasma levels of PAF and T_αB2 were determined by radioimmunoassay kits (Amersham Canada Ltd.). PAF and T_αB2 were significantly different between high-risk patients (group I; Canadian Cardiovascular Society class 3-4; n = 4) and low-risk patients (group II; Canadian Cardiovascular Society class 2; n = 5): group I PAF = 960 pg/mL, group II PAF = 159 pg/mL (P = 0.0029); group I T_αB2 = 320 pg/mL, group II T_αB2 = 229 pg/mL (P = 0.0262). Group I PAF was significantly greater than group II PAF: before CPB = 825 pg/mL (group I), 138 pg/mL (group II); during initiation of CPB = 1600-2015 pg/mL (group I), 158-200 pg/mL (group II) (P = 0.0143). Correlations between duration of CPB and peak PAF (r = 0.7049, P = 0.0339), peak PAF level, and time to extubation (r = 0.8863, P = 0.0079) were significant. PAF levels were different in patients requiring postoperative epinephrine (2124 ± 700 pg/mL) or dopamine (667 ± 266 pg/mL) (P = 0.0042). The production of PAF is determined by preoperative patient characteristics and duration of CPB. Increased levels of PAF in patients with unstable angina, left main coronary artery disease, or recent myocardial infarction are associated with the need for increased inotropy and prolonged ventilatory support following CABGS. The degree of PAF production during CPB may be a factor in postoperative instability in high-risk patients.     

Effect of massive small bowel resection on gastric acid secretion in the rat

The phenomenon of a transitory gastric acid hypersecretory state after extensive bowel resection is well established. Its time of onset, however, is unknown. The purpose of this study was to determine the immediate effect of massive small bowel resection (MSBR) on gastric acid secretion (GAS). An anesthetized innervated rat model was prepared with gastric and jugular cannulae. Three groups of animals were studied: group I (n = 12), basal unstimulated state; group II (n = 12), pentagastrin (Pg) 16 micrograms/kg h-1 stimulated; and group III (n = 16), 5% liver extract meal (LEM) stimulated. Each group consisted of experimental animals that underwent 95% MSBR from proximal jejunum to terminal ileum and control animals that remained intact. Acid output was determined by extragastric titration with 0.1 M NaOH. Blood was taken for basal and postprandial serum gastrin levels. Basal acid output (mueq/10 min) significantly increased immediately after MSBR in all groups (p less than .01). Ninety minutes following MSBR, acid outputs were significantly elevated in basal and Pg-stimulated but not LEM-stimulated rats. Serum gastrin increased from 30 +/- 1 to 56 +/- 6 pg/mL (p less than .01) in group I rats and from 81 +/- 28 to 129 +/- 13 pg/mL in group III rats (p = NS). We conclude that GAS increases immediately after MSBR in group I and II rats. This increase in GAS may be mediated by gastrin release.     

Metabolic and hemodynamic changes during recovery and tracheal extubation in neurosurgical patients: immediate versus delayed recovery.

Delayed recovery has been advocated to limit the postoperative stress linked to awakening from anesthesia, but data on this subject are lacking. In this study, we measured oxygen consumption (V(O2)) and plasma catecholamine concentrations as markers of postoperative stress. We tested the hypothesis that delayed recovery and extubation would attenuate metabolic changes after intracranial surgery. Thirty patients were included in a prospective, open study and were randomized into two groups. In Group I, the patients were tracheally extubated as soon as possible after surgery. In Group II, the patients were sedated with propofol for 2 h after surgery. V(O2), catecholamine concentration, mean arterial pressure (MAP), and heart rate (HR) were measured during anesthesia, at extubation, and 30 min after extubation. V(O2) and noradrenaline on extubation and mean V(O2) during recovery were significantly higher in Group II than in Group I (V(O2) for Group I: preextubation 215 +/- 46 mL/min, recovery 198 +/- 38 mL/min; for Group II: preextubation 320 +/- 75 mL/min, recovery 268 +/- 49 mL/min; noradrenaline on extubation for Group I: 207 +/- 76 pg/mL, for Group II: 374 +/- 236 pg/ mL). Extubation induced a significant increase in MAP. MAP, HR, and adrenaline values were not statistically different between groups. In conclusion, delayed recovery after neurosurgery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence from general anesthesia. IMPLICATIONS: In this study, we tested the hypothesis that delayed recovery after neurosurgery would attenuate the consequences of recovery from general anesthesia. As markers of stress, oxygen consumption and noradrenaline blood levels were higher after delayed versus early recovery. Thus, delayed recovery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence after neurosurgery.     

Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin

BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.     

Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation.

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.     

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.     

The effect of intravenous pantoprazole and ranitidine for improving preoperative gastric fluid properties in adults undergoing elective surgery

We studied pantoprazole, a new potent and fast-acting proton pump inhibitor. Its effects on preoperative gastric fluid volume and pH have not yet been determined. In this randomized, controlled trial, we examined the effects of preoperative IV pantoprazole or ranitidine on gastric pH and volume. Ninety patients (ASA status I and II, scheduled for elective surgery) were studied. One hour before surgery, patients in Group I (n = 30) were given IV saline 5 mL, those in Group II (n = 30) were given 40 mg of pantoprazole IV, and those in Group III (n = 30) were given 50 mg of ranitidine IV. A nasogastric tube was inserted immediately after anesthesia induction. Gastric contents were aspirated, and volume and pH were recorded. The pH values determined in Group I were 3.73 +/- 0.82; in Group II, they were 5.30 +/- 1.84; and in Group III, they were 4.80 +/- 1.40. There was no statistical difference between Groups 2 and 3, but there was a significant difference between Group I and Groups 2 and 3 (P < 0.0005). The volume of the gastric contents was 28.67 +/- 10.98 mL in Group I, 15.20 +/- 15.52 mL in Group II, and 7.77 +/- 11.17 mL in Group III. There was no statistical difference between Groups 2 and 3, but there was a statistically significant difference between Group I and Groups 2 and 3 (P < 0.0005). The proportion of patients considered "at risk" of significant lung injury should aspiration occur was 20% of Group I, 10% of Group II, and 3.3% of Group III. When statistically evaluated, there was no difference among groups. We concluded that the administration of IV pantoprazole and ranitidine 1 h before surgery is effective in reducing gastric pH and volume. IMPLICATIONS: This randomized, controlled trial examined the effects of preoperative IV pantoprazole or ranitidine on gastric pH and volume. We concluded that IV pantoprazole and ranitidine, given 1 h before surgery, are effective in reducing gastric pH and volume.     

Effects of exogenous endothelin-1 application on liver perfusion in native and transplanted porcine livers

PURPOSE: This study was designed to assess and differentiate the impact of progressivly increasing portal venous endothelin-1 (ET) plasma concentrations on hepatic micro- and macroperfusion of native porcine livers (Group A) and liver grafts after experimental transplantation (Group B). METHODS: A standardized gradual increment in systemic ET plasma concentration (0-58 pg/ml) was induced by continuous ET-1 infusion into the portal vein in both groups (A: n = 10, B: n = 10). Control animals received only saline (n = 5, each group). Hepatic microcirculation (HMC) was quantified by thermodiffusion electrodes, hepatic artery flow (HAF), and portal venous flow (PVF) by Doppler flowmetry. RESULTS: No changes in ET or perfusion parameters were observed in controls. The mean ET level after orthotopic liver transplantation (OLT) in Group B was elevated (baseline: 3.8 +/- 2.4 pg/ml) compared with Group A (2.8 +/- 1.9 pg/ml). With rising ET levels HAF decreased progressively in Group A from 205 +/- 97 (baseline) to 160 +/- 72 ml/min, and in Group B from 161 +/- 87 to 146 +/- 68 ml/min. PVF decreased in Group A from 722 +/- 253 to 370 +/- 198 ml/min, and in Group B from 846 +/- 263 to 417 +/- 203 ml/min. Baseline HMC in Group A was 86 +/- 15 and decreased significantly to 29 +/- 9 ml/100 g/min, and baseline MC in Group B was 90 +/- 22 and decreased to 44 +/- 32 ml/100 g/min. No significant alteration in systemic circulation was noted at the ET concentrations investigated. CONCLUSIONS: Significant impairment of hepatic micro- and macrocirculation was detected after induction of systemic ET levels above 9.4 pg/ml both in native and in transplanted livers. Disturbance of HMC was caused predominantly by reduction of portal venous flow, while the effect of ET on HAF was less pronounced. Characteristics of flow impairment in transplanted and native livers were analogous after short cold ischemic graft storage (6 h).     

Portal vein reconstruction in pediatric liver transplantation from living donors.

OBJECTIVE: The authors analyze the surgical pattern and the underlying rationale for the use of different types of portal vein reconstruction in 110 pediatric patients who underwent partial liver transplantation from living parental donors. SUMMARY BACKGROUND DATA: In partial liver transplantation, standard end-to-end portal vein anastomosis is often difficult because of either size mismatch between the graft and the recipient portal vein or impaired vein quality of the recipient. Alternative surgical anastomosis techniques are necessary. METHODS: In 110 patients age 3 months to 17 years, four different types of portal vein reconstruction were performed. The portal vein of the liver graft was anastomosed end to end (type I); to the branch patch of the left and right portal vein of the recipient (type II); to the confluence of the recipient superior mesenteric vein and the splenic vein (type III); and to a vein graft interposed between the confluence and the liver graft (type IV). Reconstruction patterns were evaluated by their frequency of use among different age groups of recipients, postoperative portal vein blood flow, and postoperative complication rate. RESULTS: The portal vein of the liver graft was anastomosed by reconstruction type I in 32%, II in 24%, III in 14%, and IV 29% of the cases. In children <1 year of age, type I could be performed in only 17% of the cases, whereas 37% received type IV reconstruction. Postoperative Doppler ultrasound (mL/min/100 g liver) showed significantly (p < 0.05) lower portal blood flow after type II (76.6 +/- 8.4) versus type I (110 +/- 14.3), type III (88 +/- 18), and type IV (105 +/- 19.5). Portal vein thrombosis occurred in two cases after type II and in one case after type IV anastomosis. Portal stenosis was encountered in one case after type I reconstruction. Pathologic changes of the recipient native portal vein were found in 27 of 35 investigated cases. CONCLUSION: In living related partial liver transplantation, portal vein anastomosis to the confluence with or without the use of vein grafts is the optimal alternative to end-to-end reconstruction, especially in small children.     

Combination of acute preoperative plateletpheresis, cell salvage, and aprotinin minimizes blood loss and requirement during cardiac surgery

Acute preoperative plateletpheresis (APP), cell salvage (CS) technique, and the use of aprotinin have been individually reported to be effective in reducing blood loss and blood component transfusion while improving hematological profiles in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this prospective randomized clinical study, the efficacy of these combined approaches on reducing blood loss and transfusion requirements was evaluated. Seventy patients undergoing primary coronary artery bypass grafting (CABG) were randomly divided into four groups: a control group (group I, n = 10) did not receive any of the previously mentioned approaches. An APP and CS group (group II, n = 20) experienced APP in which preoperative platelet-rich plasma was collected and reinfused after reversal of heparin, along with the cell salvage technique throughout surgery. The third group (group III, n = 22) received aprotinin in which 5,000,000 KIU Trasylol was applied during surgery, and a combination group (group IV, n = 18) was treated with all three approaches, i.e., APP, CS, and aprotinin. Compared with group I (896+/-278 mL), the postoperative total blood loss was significantly reduced in groups II, III, and IV (468+/-136, 388+/-122, 202+/-81 mL, respectively, p < 0.05). The requirements of packed red blood cells in the three approached groups (153+/-63, 105+/-178, 0+/-0 mL, respectively) also were reduced when compared with group I (343+/-118 mL, p < 0.05). In group I, six patients (6/10) received fresh-frozen plasma and three patients (3/10) received platelet transfusion, whereas no patients in the other three groups required fresh-frozen plasma and platelet. In conclusion, both plateletpheresis concomitant with cell salvage and aprotinin contribute to the improvement of postoperative hemostasis, and the combination of these two approaches could minimize postoperative blood loss and requirement.     

Comparison of the effects of on-pump versus off-pump coronary artery bypass surgery on serum prostate-specific antigen levels

AIM: To compare the effects of coronary artery bypass operation with or without extracorporeal circulation on serum total prostate-specific antigen levels. METHODS: Seventy-six men with a mean age of 57.04+/-9.27 years (range 44-77 years), who underwent coronary artery bypass surgery were enrolled to the study. In 50 patients (Group I), coronary revascularization was performed using extracorporeal circulation, and in 26 patients (Group II) coronary bypass grafting was performed on the beating heart without using extracorporeal circulation. All the patients had serum total prostate-specific antigen levels measured preoperatively and twice postoperatively in the first and fifth postoperative days. Differences in mean total prostate-specific antigen levels between the two groups in the postoperative period were analysed. RESULTS: The mean preoperative total prostate-specific antigen levels in Group I and Group II were 1.28+/-1.13 ng/mL and 1.11+/-0.93 ng/mL, respectively, and there was no significant difference in the preoperative total prostate-specific antigen values between the two groups (P=0.519). In Group I, postoperative means were 4.96+/-6.29 ng/mL and 5.86+/-9.09 ng/mL in the first and fifth days, respectively (P=0.0001, P=0.0001). Total prostate-specific antigen means in the same postoperative period for Group II were 2.13+/-2.72 ng/mL and 2.00+/-2.20 ng/mL, respectively (P=0.014, P=0.024). The comparison of total postoperative prostate-specific antigen levels between the groups showed significantly higher elevation in Group I (postoperative day 1: P=0.013; day 5: P=0.05). CONCLUSIONS: Coronary revascularization can cause a statistically significant rise in serum total prostate-specific antigen levels. This rise is more marked in patients undergoing conventional coronary revascularization.