Changes In Portal Venous Pressure Research Articles

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis

PurposeA meta-analysis aimed to systematically evaluate the safety and efficiency of I125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). Materials and methodsThe Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. ResultsTotally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I125 irradiation stent improved the cumulative stent patency rates in 6months [OR=1.65, 95% CI (1.32–2.05), P<0.001] and 12months [OR=2.55, 95% CI (1.90–3.42), P<0.001] and the survival rates in 6months [OR=1.77, 95% CI (1.41–2.22), P<0.001], 12months [OR=3.14, 95% CI (2.24–4.40), P<0.001] and 24months [OR=7.39, 95% CI (3.55–15.41), P<0.001]. However, there was no difference in the objective response rate of PVTT [OR=1.13, 95% CI (0.87–1.48), P=0.365], main portal venous pressure and the occurrence adverse event [OR=0.88, CI=0.72–1.08, P=0.212] between two groups. ConclusionI125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.

Patterns of splenic arterial enhancement on computed tomography scan are related to portal venous hypertension.

We have previously shown that patterns of splenic arterial enhancement on computed tomography scan change following liver transplantation. We suggested that this is related to changes in portal venous pressure. The aim of this study was to see if similar patterns occur in patients with and without portal hypertension and in patients before and after portal systemic shunts (transjugular portosystemic shunts). We evaluated contrast enhanced computed tomography scans in patients being evaluated for liver disease and compared those from patients with and without portal hypertension. In addition we evaluated patients who had computed tomography scans before and after transjugular portosystemic shunts shunts. Splenic arterial enhancement was evaluated using Hounsfield units (pixel counts). Twenty-four patients with clinically significant portal hypertension were compared to 91 without. Mean splenic pixel count was significantly lower in patients with clinically significant portal hypertension (88.2 ± 17.7 vs. 115.2 ± 21.0; m ± SD, P < 0.01). Computed tomography scans were available in 18 patients pre- and post-transjugular portosystemic shunts. Pixel counts were significantly higher in the post-transjugular portosystemic shunts scans (99.7 ± 20.9 vs. 88.9 ± 26.3; P < 0.05). This study supports the hypothesis that changes in portal venous pressure are related to changes in splenic arterial enhancement. We suggest that this reflects changes in the splenic micro-circulation. This mechanism may be part of the innate immune response and may also be important in the pathogenesis of hypersplenism.

Effects of terlipressin infusion during hepatobiliary surgery on systemic and splanchnic haemodynamics, renal function and blood loss: a double-blind, randomized clinical trial

BackgroundTerlipressin, in general, is a vasopressor which acts via V1 receptors. Its infusion elevates mean blood pressure and can reduce bleeding which has a splanchnic origin. The primary outcome was to assess the impact of intraoperative terlipressin infusion on portal venous pressure during hepatobiliary surgery; the 2ry outcomes included effects upon systemic hemodynamics, estimated blood loss, and postoperative renal functions.MethodsThis prospective randomized study involved 50 patients undergoing hepatobiliary surgery who were randomly and equally allocated into terlipressin group, or a control group. The terlipressin group received an initial bolus dose of (1 mg over 30 min) followed by a continuous infusion of 2 μg/kg/h throughout the procedure and gradually weaned over the first four postoperative hours, whereas the control group received the same volumes of normal saline. The portal venous pressure changes were measured directly through a portal vein angiocatheter.ResultsPortal pressure was significantly reduced over time in the terlipressin group only (from 17.88 ± 7.32 to 15.96 ± 6.55 mmHg, p < .001). Mean arterial blood pressure was significantly higher in the terlipressin group. Estimated blood loss was significantly higher in the control group than the terlipressin group (1065.7 ± 202 versus 842 ± 145.5 ml; p = 0.004), and the units of packed RBCs transfused were significantly higher in the control group ((0–2) versus (0–4) p = 0.003). There was no significant difference between groups as regards the incidence of acute kidney injury.ConclusionIntraoperative infusion of terlipressin during hepatobiliary surgery was shown to improve intraoperative portal hemodynamics with subsequent reduction in blood loss.Trial registrationClinical trial number and registry URL: Trial registration number: NCT02718599. Name of registry: ClinicalTrials.gov. URL of registry: https://clinicaltrials.gov/ct2/show/NCT02718599. Date of registration: March 2016. Date of enrolment of the first participant to the trial: April 2016.

Patterns of splenic arterial enhancement on computed tomography are related to changes in portal venous pressure.

One of the striking features of splenic imaging is variable heterogeneous gyriform arterial enhancement on dynamic computed tomography (CT). We speculated that these patterns of arterial enhancement may reflect changes in splenic micro-circulation related to changes in portal venous pressure. To test this hypothesis, we evaluated arterial phase CT scans performed before and after liver transplantation (n=91), as this is the most effective way of alleviating portal hypertension. We developed novel grading systems to assess heterogeneity. Two control groups were used: patients with cirrhosis undergoing transarterial chemoembolization (TACE) (n=28) and patients with cirrhosis on the liver transplant waiting list who had repeated CT scans (n=28). Splenic arterial heterogeneity increased in 55% of transplant patients compared with 14% in the TACE patients and 4% in the waiting list patients (P<0.0001). Mean Hounsfield units in areas of splenic enhancement were 71.7±2 before transplant and 90.1±2.5 after transplant (P<0.01). In contrast, there were no significant changes following TACE (86.3±4.2 vs. 83.5±4.5; P=NS) or in waiting list patients (80.9±4.6 vs. 73.8±3.7; P=NS). We have shown the heterogeneous gyriform enhancement patterns significantly increase following liver transplantation but not after TACE or in waiting list patients. We suggest that these changes are due to the reduction in portal venous pressure and likely reflect changes in splenic micro-circulation. These changes may be important in the pathophysiology of hypersplenism.

How Far Does Residual Liver Volume Affect Portal Pressure Gradient During Donor Hepatectomy in Living Donor Liver Transplantation

AbstractBackground: Living donor liver transplantation (LDLT) is now a solution for end stage liver disease, In living donors, up to 70% of the whole liver volume can be donated. Relative portal hypertension (increase of the portal pressure after donor hepatectomy as compared to the preoperative state was ob-served. Several factors affect portal pressure gradient in LDLT, we evaluate the effect of residual liver volume (RLV) on the portal pressure gradient.Aim of Study: In this study we aimed to studying the correlation between portal pressure gradient and residual liver volume after donor hepatectomy in living donor liver trans-plantation.Patients and Methods: This prospective study included 30 adult living donors who underwent right hepatectomy in Liver Transplantation Unit, Faculty of Medicine, Cairo Uni-versity during the period between June 2015 to October 2016. Inclusion criteria an age group from 21 to 50 years with a residual liver volume >_ 35%. Computed Tomography volum-etry was done to all donors to calculate the graft weight recipient ratio and the residual liver volume of the donor. PVP was measured intra-operatively using wide gauge cannula preclamping and postclamping of portal vein.Results: The mean portal pressure before and after clamp-ing of right portal vein was 9.9mmHg and 15.23mmHg re-spectively (p<0.001). The portal venous gradient is negatively correlated with RLV (p-value 0.029).Conclusion: The study has demonstrated a significant rise in PVP post clamping of right portal vein. Also, the lower the percentage of residual liver volume the higher the changes in portal venous pressure.

Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer.

An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144cm3 (95% CI 110-177cm3) to 209cm3 (95% CI 161-257cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655μm2/s to 543μm2/s, p = 0.11). No changes to portal vein diameter were seen. Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.

Role of portal venous pressure changes in the liver dysfunction caused by hepatic congestion after extended liver resection

Objective To explore the role of portal venous pressure changes in the liver dysfunction caused by hepatic congestion after extended liver resection. Methods The experimental study was adopted. According to the random number table, 90 Sprague-Dawley rats were divided into 3 groups, 30 in each group: 30 rats in the non-congestion group received 70% of liver resection (median lobe+ left lobe), 30 rats in the congestion group received 70% of liver resection (median lobe+ left lobe) with whole caudal lobe congestion by ligation of veins and 30 rats in the congestion+ splenectomy group received 70% of liver resection (median lobe+ left lobe) with whole caudal lobe congestion by ligation of veins and splenectomy. (1) Twenty rats in each group were used to make postoperative survival analysis.Ten rats in each group were used for related experiments. The portal venous pressures (PVPs) of 5 rats in each group were detected at postoperative 12 hours and 24 hours, and then blood and liver specimens were collected. (2) PVP changes were detected at postoperative 12 hours and 24 hours. (3) Clinical and biochemical test: level of total bilirubin (TBil) was tested at postoperative 12 hours and 24 hours. (4) Pathological examination: liver pathological damage was detected by HE staining. (5) The expression of CD68 macrophagocyte was detected by immunohistochemical staining. (6) The relative expressions of Cleaved Casepase-3 and hypoxia inducible factor-1α (HIF-1α) proteins at postoperative 24 hours were detected by Western blot. (7) The relative expressions of mRNA of vascular regulation related genes (ET-1/eNOS) and inflammatory factors (TNF-α and IL-6) were detected by real-time polymerase chain reaction (RT-PCR). (8) The hyaluronic acid (HA) was measured by enzyme-linked immuno-sorbent assay (ELISA). Measurement data with normal distribution were represented as ±s. Comparison among 3 groups was done using the ANOVA, and pairwise comparison was done by the LSD test. The postoperative 5-day survival curve was drawn by the Kaplan-Meier method, and the survival was compared using the Log-rank test. Results (1) Survival analysis: 5-day survival rate in the non-congestion group, congestion group and congestion+ splenectomy group were respectively 75%, 10% and 55%, with a statistically significant difference among the 3 groups (χ2=18.21, P<0.05). (2) Changes of PVPs and TBil: levels of PVP and TBil in the non-congestion group, congestion group and congestion+ splenectomy group were respectively (15.77±0.67)cmH2O, (18.33±0.28)cmH2O, (14.87±0.58)cmH2O, (1.48±0.10)μmol/L, (1.76±0.15)μmol/L, (1.62±0.11)μmol/L at postoperative 12 hours and (13.49±0.45)cmH2O, (16.96±0.82)cmH2O, (15.69±0.85)cmH2O, (1.47±0.11)μmol/L, (1.94±0.07)μmol/L, (1.67±0.11)μmol/L at postoperative 24 hours, showing statistically significant differences among 3 groups (F=56.53, 29.01, 6.81, 27.85, P<0.05). (3) Results of pathological examination: compared with non-congestion group, there were a lot of vacuolar cells with degeneration appearing in non-congestion liver tissues, severe liver cell swelling and hepatic sinus congestion in the congestion group at postoperative 24 hours. Compared with congestion group, vacuolar degeneration appearing in non-congestion liver tissues have some improvement in the congestion+ splenectomy group. (4) Immunohistochemical staining: compared with non-congestion group and congestion+ splenectomy group, the positive CD68 marked macrophages in the congestion group were increased at postoperative 24 hours. (5) Western blot assay: the relative expressions of Cleaved Casepase-3 and HIF-1α proteins in the non-congestion group, congestion group and congestion+ splenectomy group were 0.63±0.05, 1.17±0.18, 0.95±0.17 and 0.63±0.14, 1.48±0.08, 1.13±0.17, respectively, showing statistically significant differences among 3 groups (F=17.42, 50.58, P<0.05). (6) Results of RT-PCR: the relative expression of mRNA of ET-1/eNOS in the non-congestion group, congestion group and congestion+ splenectomy group was respectively 1.01±0.63, 2.09±0.27, 0.82±0.12 at postoperative 12 hours and 0.73±0.17, 2.16±0.94, 0.80±0.24 at postoperative 24 hours, showing statistically significant differences among 3 groups (F=62.91, 10.65, P<0.05). The relative expression of mRNA of TNF-α in the non-congestion group, congestion group and congestion+ splenectomy group was respectively 0.99±0.08, 127.80±13.15, 7.34±1.56 at postoperative 12 hours and 0.99±0.06, 116.62±13.32, 58.62±12.12 at postoperative 24 hours, showing statistically significant differences among 3 groups (F=436.77, 154.54, P<0.05). The relative expression of mRNA of IL-6 in the non-congestion group, congestion group and congestion+ splenectomy group was respectively 0.98±0.06, 1.87±0.34, 1.54±0.15 at postoperative 12 hours and 0.99±0.05, 2.02±0.27, 1.51±0.11 at postoperative 24 hours, with statistically significant differences among 3 groups (F=22.08, 46.71, P<0.05). (7) Results of ELISA: the level of HA in the non-congestion group, congestion group and congestion+ splenectomy group was respectively (149±9)ng/L, (200±19)ng/L, (174±9)ng/L at postoperative 12 hours and (136±16)ng/L, (202±13)ng/L, (91±11)ng/L at postoperative 24 hours, with statistically significant differences among 3 groups (F=19.23, 34.68, P<0.05). Conclusions On the basis of extended liver resection, a wide range of liver congestion through increasing PVP causes hepatic microcirculation disorders, hypoxia, inflammation, vacuoles degeneration cells, increased cells apoptosis, aggravated damage of liver function and increased mortality of rats. Splenectomy could reduce PVP and then improve the liver tissues damage caused by liver congestion, meanwhile, increase the survival rate of rats. Key words: Hepatic congestion; Hepatectomy; Portal venous pressure; Liver function

Current principles and practice in autologous intraportal islet transplantation: a meta-analysis of the technical considerations.

Autologous islet transplantation (IAT) following pancreatectomy is now a recognized, albeit highly specialized procedure carried out in a small number of centers worldwide. Current clinical principles and best practice with emphasis on examining the technical aspects of surgery in centers with significant IAT experience are reviewed. Literature search for studies discussing any technical aspect of pancreatectomy with intraportal IAT was included. Thirty-five papers were included; all were single-center case series. The indications, surgical approach to pancreatectomy with IAT, islet yield, static pancreas preservation prior to islet digestion, portal vein access, absolute islet infusion volumes, and portal venous pressure changes during transfusion evaluated. IAT is considered a "last resort" when alternative approaches have been exhausted. Pre-morbid histology and prior surgical drainage adversely influence islet yields and may influence the clinical decision to perform pancreatectomy and IAT. Following pancreas digestion, absolute numbers of islets recovered and smaller islet size predict rates of insulin independence following IAT. Islet volumes and portal venous pressure changes are important factors for the development of complications. Surgical access for IAT includes intra-operative, immediate or delayed infusion via an "exteriorized" vein, and radiological percutaneous approaches. Delayed infusion can be combined with pancreas preservation techniques prior to islet isolation.

Activated Protein C Restores Hepatic Microcirculation During Sepsis by Modulating Vasoregulator Expression

Activated protein C (aPC) promotes fibrinolysis while inhibiting coagulation and inflammation. In septic patients, aPC levels are depleted, and aPC treatment has emerged as a therapeutic option. To better understand the mechanism(s) by which aPC improves survival in sepsis, we sought to determine the effect of aPC treatment on hepatic vasoactive gene and protein expression, leading to changes in hepatic vascular responsiveness in a septic animal model. Under anesthesia, rats underwent sham or cecal ligation and puncture followed by aPC treatment (1 mg/kg, twice daily, i.v.). Treatment with aPC significantly decreased hepatic endothelin 1 (ET-1)/ET A receptor mRNA and protein expression. To determine the effect of aPC on hepatic microvasculature, ET-1-induced changes in liver microcirculation were assessed by intravital microscopy. This approach demonstrated aPC significantly improved hepatic perfusion index in the animals that underwent cecal ligation and puncture in the absence of significant changes in portal venous pressure. Furthermore, although aPC did not affect ET-1-dependent sinusoidal vasoconstriction, aPC induced hepatoprotective effects via enhanced red blood cell velocity. Collectively, these data demonstrate aPC ameliorates ET-1-dependent changes in hepatic microcirculation and improves hepatic function in the setting of sepsis.

Human Islet Isolation for Autologous Transplantation: Comparison of Yield and Function Using SERVA/Nordmark Versus Roche Enzymes

Islet autotransplantation (IAT) is used to preserve as much insulin-secretory capacity as possible in patients undergoing total pancreatectomy for painful chronic pancreatitis. The enzyme used to dissociate the pancreas is a critical determinant of islet yield, which is correlated with posttransplant function. Here, we present our experience with IAT procedures to compare islet product data using the new enzyme SERVA/Nordmark (SN group; n = 46) with the standard enzyme Liberase-HI (LH group; n = 40). Total islet yields (mean +/- standard deviation; 216,417 +/- 79,278 islet equivalent [IEQ] in the LH group; 227,958 +/- 58,544 IEQ in the SN group; p = 0.67) were similar. However, the percentage of embedded islets is higher in the SN group compared to the LH group. Significant differences were found in pancreas digestion time, dilution time, and digested pancreas weight between the two groups. Multivariate linear regression analysis showed the two groups differed in portal venous pressure changes. The incidence of graft function and insulin independence was not different between the two groups. The SN and LH enzymes are associated with similar outcomes for IAT. Further optimization of the collagenase/neutral protease ratio is necessary to reduce the number of embedded islets obtained when using the SN enzyme.

Palliative Portal Vein Stent Placement in Malignant and Symptomatic Extrinsic Portal Vein Stenosis or Occlusion

This article evaluates the results of portal vein (PV) stent placement in patients with malignant extrinsic lesions stenosing or obstructing the PV and causing symptomatic PV hypertension (PVHT). Fourteen patients with bile duct cancer (n = 7), pancreatic adenocarcinoma (n = 4), or another cancer (n = 3) underwent percutaneous transhepatic portal venous stent placement because of gastroesophageal or jejunal varices (n = 9), ascites (n = 7), and/or thrombocytopenia (n = 2). Concurrent tumoral obstruction of the main bile duct was treated via the transhepatic route in the same session in four patients. Changes in portal venous pressure, complications, stent patency, and survival were evaluated. Mean +/- standard deviation (SD) gradient of portal venous pressure decreased significantly immediately after stent placement from 11.2 mmHg +/- 4.6 to 1.1 mmHg +/- 1.0 (P < 0.00001). Three patients had minor complications, and one developed a liver abscess. During a mean +/- SD follow-up of 134.4 +/- 123.3 days, portal stents remained patent in 11 patients (78.6%); stent occlusion occurred in 3 patients, 2 of whom had undergone previous major hepatectomy. After stent placement, PVHT symptoms were relieved in four (57.1%) of seven patients who died (mean survival, 97 +/- 71.2 days), and relieved in six (85.7%) of seven patients still alive at the end of follow-up (mean follow-up, 171.7 +/- 153.5 days). Stent placement in the PV is feasible and relatively safe. It helped to relieve PVHT symptoms in a single session.

Effect of portal hypertension on splenic blood flow, intrasplenic extravasation and systemic blood pressure.

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.

Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications.

Although living-donor liver transplantation (LDLT) has been accepted for adult populations, the occurrence and pathogenesis of small-for-size syndrome remain highly controversial. Portal venous pressure (PVP) was measured in 79 cases of LDLT from anhepatic phase to day 14. PVP was monitored through a catheter inserted via the inferior mesenteric vein. In a separate series of seven cases of adult LDLT, the splenic artery was ligated following arterial reperfusion. For days 2 to 4 and 9 to 11, recipients of small-for-size graft (<0.8% of body weight) displayed significantly higher PVP than recipients of larger grafts. The 13 patients with elevated mean PVP (>or=20 mm Hg) early in the first week (days 0-4) demonstrated significantly worse survival (84.5% vs. 38.5% at 6 months; P < 0.01), but this was not applicable to elevated mean PVP late in the first week (days 5-7). Elevated PVP early in the first week was also associated with higher incidence of bacteremia, cholestasis, prolonged prothrombin time, and ascites. Splenic artery ligation (SAL) immediately reduced PVP from 10 to 20 mm Hg (median, 16 mm Hg) to 9 to 13 mm Hg (median, 11 mm Hg; P = 0.02). Posttransplant PVP was significantly lower in SAL patients than in non-SAL patients from days 2 to 7 despite small graft size. Early PVP in SAL patients was consistently below 20 mm Hg, and survival was significantly better than in non-SAL patients with high early PVP (P < 0.01). Elevated PVP in the early phase is strongly associated with poor patient survival attributable, at least in part, to small-for-size graft. Further elucidation of the pathogenesis behind this phenomenon and efforts to modify PVP will be key to improving results.

Portal venous pressure changes after sequential clinical islet transplantation.

Sequential pancreatic islet transplantation via the portal vein has led to insulin independence in patients with type 1 diabetes. Complications associated with the injection of islets into the portal vein have been reported; therefore, in this study we sought to further characterize changes in portal venous pressure associated with islet infusion. Pre- and posttransplant portal venous pressures were recorded in 50 consecutive transplant procedures in 26 patients receiving highly purified, heparinized allogeneic islet preparations via a radiologically placed portal venous cannula. Doppler ultrasound scans of the portal vein were completed within 24 hr of transplantation. Posttransplant portal vein pressures rose significantly with sequential transplantation (12.4 mm Hg vs. 17.3 mm Hg, P <0.05). Portal pressure change correlated significantly with islet packed cell volume (r =0.66, P <0.001) and also with the number of islets transplanted ( r=0.49, P <0.001). Segmental portal vein thrombosis was radiologically detected after two procedures (4%). Multiple sequential islet transplants can be safely performed via the portal vein, provided that care is taken with islet purification and attention is paid to portal venous monitoring.

Total pancreatectomy with islet cell autotransplantation: anesthetic implications

Study Objective: To make recommendations for the perioperative management of patients undergoing total pancreatectomy with islet cell autotransplantation.Design: Retrospective review.Setting: University hospital.Patients: 41 patients undergoing total pancreatectomy with autologous islet cell transplantation for chronic pancreatitis from 1977 to 1996.Interventions: The charts and anesthetic records were reviewed, specifically investigating the changes in portal venous pressure, blood pressure (BP), and central venous pressure with islet cell injection. The records also were examined for blood glucose levels, type of fluids administered, blood loss, and postoperative complications.Measurements and Main Results: Injection of islet cells into the portal vein caused a significant increase in portal venous pressures (8.5 ± 4.8 to 27 ± 16 cm/H2O; p < 0.001), which remained elevated at the end of injection (23 ± 12 cm/H2O; p < 0.001). Central venous pressures also increased a small amount (9.3 ± 4.3 to 10.6 ± 5.8 mmHg; p < 0.05). In contrast, systolic blood pressures (SBPs) fell with administration of the islet cells (110 ± 15 to 103 ± 17 mmHg; p < 0.01), but SBP recovered in most patients at the end of injection (106 ± 16 mmHg; p = NS). However, 6 patients (14.6%) required vasopressors to maintain adequate BPs. Blood glucose levels were significantly higher immediately prior to islet cell infusion in patients who had received dextrose-containing solutions than those who did not (246 ± 80 vs. 176 ± 43 gm/dl; p = 0.002). Median blood loss was 2000 ml (range 350 to 12,000 ml), and most patients (95.1%) required blood transfusions.Conclusion: Although total pancreatectomy with islet cell autotransplantation is a difficult operation, with significant blood loss, most patients tolerate surgery and injection of islet cells into their portal system without hemodynamic instability. Glucose-containing solutions should not be administered to patients prior to islet cell infusion because hyperglycemia, which can damage islet cells, may result.

Halothane-induced Intrahepatic Portovenous Shunting Reduces Hepatic Microvascular Sinusoidal Perfusion during Contrast Angiographic Procedures

Reduced intrahepatic perfusion that occurs during contrast angiography performed after administration of halothane anesthesia is thought to result from halothane-induced systemic hemodynamic alterations, such as reduced splanchnic blood flow, rather than intrahepatic microvascular alterations. The authors postulate that intrinsic hepatic effects caused by inhalational anesthetic agents rather than contrast materials, further reduce liver perfusion. With use of dynamic video microscopy, intrahepatic microvascular flow rates and patterns, hepatic cord/sinusoidal diameters, portal venous pressure changes, and quantitative and qualitative Kupffer cell phagocytic activity were continuously recorded in isolated perfused rat livers before and during exposure to 1.5% halothane in O2/CO2, with and without the addition of iothalamate meglumine. Exposure of livers to halothane resulted in intrahepatic portovenous shunting secondary to obstruction to sinusoidal outflow, diminished sinusoidal perfusion, and a mean elevation in terminal portal venous pressure of 12.8 mm Hg. Kupffer cell phagocytic activity was reduced even when normalized for flow within sinusoids. None of these changes were attributed to use of contrast material. Alterations in hepatic blood flow during exposure to halothane result, in part, from increased intrinsic hepatic vascular resistance, sinusoidal outflow obstruction, and portovenous shunting, and not only from systemic hemodynamic changes. Iothalamate meglumine produced no microvascular alterations.

‘Latent’ Portal Hypertension in Benign Biliary Obstruction

A prospective study was undertaken to evaluate the changes in portal venous pressure in patients with benign biliary obstruction (BBO) but without overt clinical, endoscopic or radiological evidence of portal hypertension. Portal venous pressure was measured at laparotomy in 20 patients (10 each with either benign biliary stricture or choledocholithiasis) before and after biliary decompression. Pressure was found to be on the high side in seven patients (>25 cm of saline in three patients and > 30 cm of saline in four). The mean fall of pressure was 3.4 cm of saline after biliary decompression. No correlation could, however, be found between portal venous pressure and duration of biliary obstruction, serum bilirubin or bile duct pressure. Liver histology showed mild to moderate cholestatic changes but maintained portal architecture in all. Benign biliary obstruction may therefore, lead to elevation of portal pressure, even though the patient may not necessarily have any clinical, endoscopic or radiological manifestations of portal hypertension. The pathogenesis of this ‘latent’ portal hypertension is probably multifactorial. If biliary obstruction is left untreated the development of overt portal hypertension may become a possibility in the future.

The effects of N omega-nitro-L-arginine methyl ester, sodium nitroprusside and noradrenaline on venous return in the anaesthetized cat.

1. The vascular actions of N omega-nitro-L-arginine methyl ester (L-NAME), sodium nitroprusside and noradrenaline were investigated in cats under chloralose anaesthesia with controlled vascular tone and ventilation. Cardiac output, heart rate, vascular pressures and mean circulatory filling pressure (MCFP) were measured. Total peripheral resistance (TPR) and resistance to venous return (Rvr) were calculated from steady-state readings. 2. L-NAME (37 mumol kg-1, i.v.) administered to ten cats receiving noradrenaline (6 nmol kg-1 min-1, i.v.) increased aortic pressure by 47.5 +/- 7.1 mmHg from 106 mmHg, and MCFP by 1.56 +/- 0.36 mmHg from 10.0 mmHg (means +/- s.e. means). Mean changes in portal venous pressure, RAP and heart rate were not significant. Cardiac output fell by 29.7 +/- 3.3% from 130 ml min-1 kg-1. TPR rose by 108 +/- 7.2% from 796 mmHg l-1 min kg and Rvr by 58.4 +/- 4.5% from 64 mmHg l-1 min kg. 3. Infusion of sodium nitroprusside into cats receiving noradrenaline evoked dose-related falls in aortic pressure, MCFP, TPR and Rvr. Changes in portal venous pressure, RAP and heart rate were not significant and cardiac output fell slightly. After L-NAME, sensitivity to nitroprusside was increased by 139 +/- 34% for MCFP, 176 +/- 19% for TPR and 351 +/- 39% for Rvr, and cardiac output rose slightly. The nitroprusside infusion required to restore TPR after L-NAME was estimated to be 5.8 x 10(+/- 0.41) nmol kg-1 min-1, which was approximately three times more than that required to restore MCFP. 4. Infusion of noradrenaline evoked dose-related increases in aortic and portal venous pressures, heart rate, cardiac output, MCFP, TPR and Rvr. After L-NAME and nitroprusside (4.4 nmol kg-1 min-1, i.v.),TPR and Rvr were not significantly different, but MCFP was reduced by 1.76 +/- 0.24 mmHg, and cardiac output by 22 +/- 1.9%. After subsequent expansion of the circulating blood volume (5-7.5 ml kg-1 dextran-saline), mean values for all parameters were restored to their previous levels. Sensitivity to noradrenaline was not significantly altered for heart rate, TPR and Rvr but was reduced by 31.8 +/- 12%for MCFP and by 66.5 +/- 18% for cardiac output.5. The depression of cardiac output by L-NAME is attributed to the increase in Rvr, partly compensated by the rise in MCFP. For a given rise in MCFP, the increase in R, was seven times greater after L-NAME than after noradrenaline, and the difference in the relative actions of the two drugs on resistance and capacitance vessels largely accounts for their contrasting effects on venous return. A procedure is suggested for replacement of vascular nitric oxide by nitroprusside infusion and blood volume expansion.

High Rate of Portal Thrombosis After Splenectomy in Patients With Esophageal Varices and Idiopathic Portal Hypertension

Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough.

Zymosan-activated plasma-mediated thromboxane production by the perfused rabbit liver and isolated hepatocytes: Involvement of calcium

The present study investigates the mechanism of zymosan-activated plasma (ZAP)-mediated eicosanoid production by the isolated, perfused rabbit liver and describes ZAP-induced eicosanoid stimulation in cultured hepatocytes. Perfused livers receiving untreated plasma demonstrated no significant changes in portal venous pressure or the rates of release of lactic dehydrogenase or acid phosphatase activity (indicator of cellular injury). The control group livers demonstrated stable rates of release for 6-keto PGF1α and thromboxane B2 (TXB2). In contrast, the infusion of ZAP alone resulted in a rapid but transient releaes of TXB2 from the livers. No significant changes in perfusion pressure or enzyme release were observed following ZAP administration. Perfusion of livers with a calcium-free buffer decreased the basal rates of both 6-keto PGF1α and TXB2 production and significantly, but not completely, attenuated the ZAP-mediated increase in hepatic TXB2 production. Perfusion of livers with nifedipine (3 μM) had no effect on ZAP-mediated TXB2 production in this model. Isolated hepatocytes responded to ZAP-treatment with significant increases in TXB2 production. These data suggest that activated fluid phase complement components induce thromboxane production by specific cells within the liver and that this stimulation is partially dependent upon the release of intracellular calcium but independent of complement-mediated cellular injuiry.