Increase In Portal Venous Pressure Research Articles

Imaging Approach to Portal Hypertension

Abstract Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices.

A new variant of Abernethy malformation treated by transhepatic interventional closure: a case report

BackgroundCongenital portosystemic shunts (CPSS) are rare vascular malformations and can be classified into extrahepatic and intrahepatic shunts. Extrahepatic CPSS, also termed Abernethy malformations are associated with severe long-term complications including portopulmonary hypertension, liver atrophy, hyperammoniemia and hepatic encephalopathy. We report a hitherto undescribed variant of Abernethy malformation requiring an innovative approach for interventional treatment.Case presentationWe describe a 31-year-old patient following surgical repair of atrioventricular septal defect at the age of 6 years. In the long-term follow-up he showed persistent pulmonary hypertension which deteriorated despite dual pulmonary vasodilative treatment. When he developed arterial desaturation and symptomatic hyperammoniemia detailed reassessment revealed as underlying cause a hitherto undescribed variant of Abernethy malformation connecting the portal vein with the right lower pulmonary vein. Following interdisciplinary discussions we opted for an interventional approach. Since the malformation was un-accessible to interventional closure via antegrade venous or retrograde arterial access, a transhepatic percutaneous puncture of the portal vein was performed. Temporary balloon occlusion of the malformation revealed only a slight increase in portal venous pressure. Interventional occlusion of the large vascular connection was achieved via this transhepatic approach by successive implantation of two large vascular occluding devices. The postinterventional course was unremarkable and both ammonia levels and arterial saturation normalized at follow-up of 12 months.ConclusionsPortal vein anomalies should be included in the differential diagnoses of pulmonary hypertension or pulmonary arterio-venous malformations. Based on careful assessment of the anatomy and testing of portal vein hemodynamics interventional therapy of complex Abernethy malformations can be performed successfully in specialized centers.

Hemodynamic effect through a novel endoscopic intervention in management of varices and hypersplenism (with video)

We previously reported a new and combined EUS-guided intervention in a patient with portal hypertension, consisting of obliteration of varices and partial splenic embolization (PSE). Performing PSE is known to diminish the increase in portal venous pressure after endoscopic intervention for varices. The aim of this study was to use multidetector CT portal venography to evaluate the anatomy of esophagogastric varices (EGV) and the impact on hemodynamics of portosystemic collaterals shortly after the concomitant procedures. From October 2019 to December 2020, 5 patients with cirrhosis and with clinically significant portal hypertension who had variceal bleeding history and hypersplenism were treated with combined endoscopic obliteration for varices and EUS-guided PSE. Multidetector CT portal venography was applied to assess the anatomic drainage patterns of the EGV, diameters of feeders and drainage vessels, and splenic embolization rate. Within 5 days after concomitant endoscopic interventions, we observed decreased mean diameters of the left gastric vein, short gastric vein, and azygos vein as .3mm, 1.0mm, and 5.2mm compared with 3.11mm, 7.1mm, and 5.4mm before the procedures, respectively. Patients showed increased white blood cells (mean count of 2.7× 109/L before vs 5.8× 109/L after) and platelets (mean count of 52.8× 109/L before vs 95.8× 109/L after). The mean splenic embolization rate was 64.5% (range, 28.8%-84.6%). Our experience may illustrate an alternative technique of combining EUS-guided PSE with endoscopic therapy of varices to treat patients with portal hypertension.

MASKED SEPSIS DUE TO ACUTE CHOLECYSTITIS IN A PATIENT WITH CARDIOPULMONARY DISEASE LEADING TO SEPTIC SHOCK: A CASE REPORT

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Sepsis is a primary cause of death in nearly 23.5% of chronic heart failure patients. The relationship between acute cholecystitis and cardiovascular disease is vague but there have been few studies suggesting cholecystocardiac link. Here we describe a similar case that presented as pulmonary edema and myocardial ischemia. CASE PRESENTATION: 81-year-old male with past medical history of myocardial infarction, chronic obstructive pulmonary disease, hypothyroidism, hypertension, hyperlipidemia presented to the emergency department with worsening exertional dyspnea for the past 3 days. On physical examination he was afebrile, tachycardic, hypoxic requiring 4L oxygen. Chest auscultation revealed bibasilar rales. Electrocardiogram showed ST segment depression in lateral leads and troponins were elevated at 1.56. Labs showed mild leukocytosis, BNP 1658, Creatinine 1.8 and normal hepatic panel. Chest X-Ray suggested pulmonary edema for which he was diuresed. He was started on heparin drip. Echocardiogram showed reduced ejection fraction of 40%. Cardiac catheterization showed multivessel disease and moderate pulmonary hypertension. Coronary artery bypass surgery was recommended. Next day he developed mild periumbilical pain, which later moved to his right upper quadrant. CT abdomen showed cholelithiasis with pericholecystic inflammation. Cholescintigraphy confirmed acute cholecystitis. Patient started becoming more dyspneic and pulmonary edema worsened. He became hypotensive and febrile. Sepsis bundle was initiated including blood cultures, broad spectrum antibiotics and intravenous fluids. Patient was intubated and transferred to critical care unit. He required multiple pressors. Continuous hemodialysis was started for metabolic acidosis. Blood cultures revealed gram negative bacteremia. Unfortunately, the patient could not be saved. DISCUSSION: Gallbladder edema may be a response to the ischemia caused by cardiac instability. The exact mechanism linking acute cholecystitis to extracholecystic diseases is unknown, but it is likely due to an increase in portal venous pressure along with a decrease in plasma oncotic pressure. Chronic cardiopulmonary diseases and aging can cause immune-senescence that may increase the risk of sepsis which sometimes does not meet SIRS criteria. These patients, especially when on betablockers, cannot meet increased metabolic demands. Irritation and spasticity of the gallbladder can create reflex stimuli through the autonomic pathways, which leads to temporary alteration in coronary blood flow. CONCLUSIONS: Acute cholecystitis may coexist with or be misdiagnosed as a cardiovascular disorder. Looking for signs of end organ dysfunction or subtle vital sign irregularities may help identify older patients who are on their way to decompensation and allow us to intervene earlier with appropriate investigations and treatment which may lead to the prevention of fatal events. Reference #1: Ozeki M, Takeda Y, Morita H, et al. Acute cholecystitis mimicking or accompanying cardiovascular disease among Japanese patients hospitalized in a Cardiology Department. BMC Res Notes. 2015;8:805. Published 2015 Dec 19. doi:10.1186/s13104-015-1790-8 Reference #2: Walker AMN, Drozd M, Hall M, et al. Prevalence and Predictors of Sepsis Death in Patients With Chronic Heart Failure and Reduced Left Ventricular Ejection Fraction. J Am Heart Assoc. 2018;7(20):e009684. doi:10.1161/JAHA.118.009684 Reference #3: Meelu OA, Baber U, Theodoropoulos K, Mennuni MG, Kini AS, Sharma SK. Acute cholecystitis and myocardial infarction: a case study with coronary involvement. Clin Case Rep. 2016;4(8):793-796. Published 2016 Jul 13. doi:10.1002/ccr3.621 DISCLOSURES: No relevant relationships by Aditya Bansal, source=Web Response No relevant relationships by Hina Farrukh, source=Web Response No relevant relationships by sreeja sompalli, source=Web Response

Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells.

Portal hypertension is pathologically defined as increase of portal venous pressure, mainly due to chronic liver diseases such as fibrosis and cirrhosis. In fibrotic liver, activated hepatic stellate cells increase their contraction in response to endothelin-1 (ET-1) via autocrine and paracrine stimulation from liver sinusoidal endothelial cells and injured hepatocytes. Clinical studies are limited with ET receptor antagonists in cirrhotic patients with portal hypertension. Hence, studies are needed to find molecules that block ET-1 synthesis. Accumulation of extracellular matrix proteins in the perisinusoidal space, tissue contraction, and alteration in blood flow are prominent during portal hypertension. Therefore, novel matrix modulators should be tested experimentally as well as in clinical studies. Specifically, tumor necrosis factor-α, transforming growth factor-β1, Wnt, Notch, rho-associated protein kinase 1 signaling antagonists, and peroxisome proliferator-activated receptor α and γ, interferon-γ and sirtuin 1 agonists should be tested elaborately against cirrhosis patients with portal hypertension.

Oesophageal Variceal-Pulmonary Venous Fistula A Rare Cause of a Right-to-Left Shunt.

Oesophageal varices are a dilated submucosal venous plexus in the lower third of the oesophagus which result from increased pressure in the portal venous system. The portal system is connected to the systemic circulation in specific locations referred to as sites of portosystemic anastomosis. An increase in portal venous pressure is therefore reflected at these anastomotic sites, causing manifestations such as oesophageal varices, rectal varices, caput medusae and splenorenal shunts. Varices do not cause symptoms until they leak or rupture and this is the main complication which requires prompt treatment. Here, we present a post-liver transplant patient with metastatic hepatocellular carcinoma who had oesophageal varices that fistularized with a left pulmonary vein, thus creating a right-to-left shunt. Right-to-left shunts are usually intracardiac or intrapulmonary in location. The complications of a right-to-left shunt include predominantly hypoxia, cyanosis and, sometimes, paradoxical emboli in the case of intracardiac shunts. This patient had a very uncommon cause of such a shunt caused by a direct fistulous connection.LEARNING POINTSRight-to-left shunts create a ventilation-perfusion mismatch.Recognizing situations where there is a connection between the systemic circulation and pulmonary circulation without intermediate oxygenation is important because of possible clinical implications such as hypoxia.

Fatal reversal of the cholecystocardiac link

Abstract Patients presenting to the emergency department with right upper quadrant pain are usually placed on a list of critical, yet limited differential diagnoses. Of these diagnoses, cholecystitis is fairly common. Although most cases of cholecystitis are relatively straight-forward, there are numerous extracholecystic conditions which have been known to cause acute acalculous cholecystitis. Examples include systemic infections, acute and chronic renal failure, systemic lupus erythematosus, and congestive heart failure. These conditions lead may lead to diffuse gallbladder wall thickening through a number of hypothesized mechanisms, including an increase in portal venous pressure, and a decrease in plasma oncotic pressure. The right upper quadrant pain caused by this gallbladder wall thickening however, is usually a late complaint, after the primary etiology has made itself clear. We report the case of a 6 year old female who presented to the emergency department with acute right upper quadrant pain and vomiting. Apart from the gastrointestinal system, examination of all other systems (including cardiovascular) was negative. An ultrasound was done and the diagnosis of acute acalculous cholecystitis was made. The patient did not respond to treatment, and after additional investigations, evidence of congestive heart failure with bilateral pulmonary effusions was seen. It was concluded that the patient's heart failure, although not apparent on initial examinations, was the etiology behind her initial gallbladder thickening and abdominal pain. This case reports an important etiology to be aware of in patients presenting with right upper quadrant pain which is unresponsive to treatment methods. Multiple extracholecystic disease entities such as congestive heart failure, must be placed in the list of differential diagnoses by the caring physician.

Portal Hypertension: 2 years Experience in Department of Pediatric Gastroenterology and Nutrition, at a Tertiary Care Hospital, Bangladesh

Background: Portal hypertension is a clinical syndrome defined by a pathologic increase of portal venous pressure. The objectives of this study were to evaluate etiological and clinical presentation of portal hypertension admitted in a tertiary care centre of Bangladesh.Materials and Methods: This cross sectional study was done at the Department of Paediatric Gastroenterology & Nutrition, BSMMU on 100 consecutive cases admitted during the period from July 2013 through June 2015. Confirmation of the presence of portal hypertension was done by demonstration of oesophageal varices during upper GI endoscopic examination. The diagnosis of chronic liver disease was based on a combination of clinical, biochemical (abnormal liver function tests) and ultrasonographic (coarse echotexture of liver) features. Extrahepatic portal hypertension was diagnosed on the basis of clinical, normal liver function test and ultrasonographic evidence of portal or splenic vein thrombosis, with or without cavernous transformation. Doppler ultrasound showed increase portal venous pressure.Results: Patient's age group was 2 to 15 years. 69 cases were extra hepatic portal hypertension. Haematemesis and/or melaena were found in 42(60.9%) and splenomegaly was found in 68(98.6%) cases. Of extra hepatic 69 cases 10% had history of umbilical sepsis. Of the 31cases of CLD with portal hypertension, haematemesis and/or melaena was found in 20(64.5%) cases, splenomegaly in 30(96.8%), ascites 8(25.8%).Most (50%) of CLD cases were cryptogenic followed by Wilson’s disease 29%. Of the 100 cases, endoscopy revealed grade 3 esophageal varices in 45% cases. All the patients were treated with propranolol. EVL was done in 70% cases.Conclusion: In this study, most of the cases were extra hepatic portal hypertension. Gastrointestinal bleeding & splenomegaly were found in most of the cases. No risk factor was found in most of extra hepatic cases. Portal vein thrombosis & cryptogenic were the most common cause in extra-hepatic and intra-hepatic cases respectively.J Shaheed Suhrawardy Med Coll, June 2016, Vol.8(1); 26-29

Abstract P4-21-36: Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer

Abstract Introduction Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate used for treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. An association between T-DM1 and splenic enlargement was noted anecdotally on sequential whole-body MRI (WB-MRI) examinations. A retrospective analysis of WB-MRI examinations of patients on T-DM1 was undertaken to investigate the hypothesis that an increase in splenic volume is due to either a generalised hyperplasia of the bone marrow and reticulo-endothelial system and/or an increase in portal venous pressure. Methods 12 patients underwent 29 serial WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow muscle-normalised signal intensity (nSI), water diffusivity (apparent diffusion coefficient, ADC) and fat fraction were measured. Changes in splenic volume were analysed, and correlations between the measured variables were obtained. Results An increase in splenic volume was 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). Increase in splenic volume correlated with treatment duration (r2=0.71). Increase in normal bone marrow signal was seen (nSI 3.5 to 4.8, p=0.12), along with a decrease in fat fraction (64.3% to 57.3%, p=0.12), and reduced ADC (655µm2/s to 543µm2/s, p=0.11). No consistent changes to portal vein diameter were seen. Discussion An increase in splenic volume was consistently observed in patients on T-DM1 therapy. This was unrelated to portal vein changes but correlated with bone marrow hyperplasia. Caution should be applied when assessing metastatic disease in bone to avoid incorrectly attributing T-DM1-related changes in normal bone marrow to disease progression. Citation Format: Kosmin M, Makris A, Jawad N, Miles D, Padhani AR. Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-36.

Percutaneous transhepatic obliteration and percutaneous transhepatic sclerotherapy for intractable hepatic encephalopathy and gastric varices improves the hepatic function reserve.

Percutaneous transhepatic obliteration (PTO) and percutaneous transhepatic sclerotherapy (PTS) are widely performed as an emergency measure in cases of variceal hemorrhage and intractable hepatic encephalopathy. The PTO/PTS technique is capable of directly blocking the blood supply in cases in which balloon-occluded retrograde transvenous obliteration (B-RTO) is not effective, or in cases with complicated collateral flow. Although PTO/PTS is not currently the first choice due to the invasiveness of transhepatic puncture, this procedure can modify the blood flow in an antegrade manner. The present study examined the changes in hepatic function reserve following PTO/PTS for intractable hepatic encephalopathy and/or gastric varices. In total, the study included 37 patients (mean age, 61.75±12.77 years; age range, 32-88 years; male to female ratio, 23:14) with a variety of gastrorenal shunts, or B-RTO-intractable hepatic encephalopathy and gastric varices without gastrorenal shunts. The patients underwent PTO/PTS by embolizing a microcoil or injection of a sclerosing agent (5% ethanolamine oleate iopamidol). Alterations in hepatic function reserve prior to and following the procedure were compared. The patients were treated for hepatic encephalopathy in 11 patients, gastric varices in 19 patients, and both conditions in 7 patients. The results indicated that the blood ammonia level improved from 135.76±75.23 mg/dl to 88.00±42.16 and 61.81±33.75 mg/dl at 3 and 6 months after therapy, respectively. In addition, the Child-Pugh score improved from 8.48±2.01 prior to therapy to 7.70±1.84 and 7.22±2.01 at 3 and 6 months after the procedure, respectively. Although there was a concern that PTO/PTS may cause complications due to an increase in portal venous pressure (PVP) arising from shunt occlusion, no severe complications were observed. In conclusion, for patients with various gastrorenal shunts or those with B-RTO-intractable hepatic encephalopathy and gastric varices without gastrorenal shunts, PTO/PTS can improve the antegrade blood flow to the liver, as demonstrated by improvement in the hepatic function reserve.

Etiology of Portal Hypertension in Children-An Experience in a Tertiary Centre of Bangladesh

Background: Portal hypertension is defined by a pathological increase in portal venous pressure. Any condition that interfere with blood flow at any level within the portal system can lead to portal hypertension. For better management, it is important to determine the underlying cause.Objective: To evaluate the etiology of portal hypertension in children admitted in a tertiary care centre of Bangladesh.Materials & Methods: This cross sectional study was done in the Department of Pediatric Gastroenterology, Hepatology & Nutrition, Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh on 40 consecutive cases of portal hypertension enrolled from April 2014 to March 2015. Results: Age of the children was 2-12 years with mean age of 7.2±4.3 years and male:female ratio was 1.5:1. Out of 40 children, 32 (80%) developed portal hypertension due to pre-hepatic causes and 8 (20%) hepatic causes. In pre-hepatic causes of portal hypertension, out of 32 children, portal vein thrombosis was found in 20 (62.5%) cases, splenic vein thrombosis in 4 (12.5%) & 8 (25%) were idiopathic. On the other hand hepatic causes of portal hypertension, out of 8 children, cryptogenic was found in 4 (50%) cases, wilson’s disease, chronic hepatitis B virus infection, biliary cirrhosis & autoimmune hepatitis each was found in 1 (12.5%) case. In pre-hepatic cases first variceal bleed much earlier than hepatic cases (4.4±3.6 Vs 7.6±4.6 years).Conclusion: Extra-hepatic diseases were the most common etiology of portal hypertension in studied children. Portal venous thrombosis in extra-hepatic cases & cryptogenic liver disease in intra-hepatic cases were the most common causesBangladesh J Child Health 2015; VOL 39 (1) :14-17

Simultaneous combined balloon-occluded retrograde transvenous obliteration and partial splenic embolization for gastric fundal varices.

We previously reported the techniques and usefulness of simultaneous combined balloon-occluded retrograde transvenous obliteration (B-RTO) and partial splenic embolization (PSE), based on the hypothesis that concomitant PSE can diminish the increase in portal venous pressure after B-RTO. After experiencing more cases and performing longer-term follow-up, we re-evaluated the efficacy of simultaneous combined B-RTO and PSE for gastric fundal varices (GVs). We performed B-RTO in 36 consecutive patients treated for GVs from 2005 to 2013. Twenty-three patients underwent simultaneous combined B-RTO and PSE (Group 1) and 13 underwent B-RTO monotherapy (Group 2). The outcomes were retrospectively evaluated. There were no significant differences in baseline characteristics between the two groups except that the splenic volumes were larger in Group 1 than 2. B-RTO was technically successful in 21 of 23 patients (91.3%) in Group 1 and in 12 of 13 patients (92.3%) in Group 2. In all patients with ruptured GVs (six in Group 1 and five in Group 2), complete hemostasis was obtained by B-RTO. Exacerbation of esophageal varices was significantly less frequent in Group 1 than 2 (p = 0.0017). Concomitant PSE with B-RTO may contribute to prevention of the exacerbation of esophageal varices after B-RTO.

Diagnosis of portal hypertension by transabdominal ultrasound

Portal hypertension is pathologic increase in portal venous pressure, with diversion of portal blood to the systemic circulation. The study was directed to measure as well as to compare the diameters of splenic, superior mesenteric and portal veins with their variation with respiration in normal subjects and in patients with portal hypertension. An analytic type of cross-sectional study was conducted at Radiology and Imaging Department of BIRDEM, Shahbag, Dhaka for one year (2011-12) among purposively selected 59 study subjects with chronic liver disease and portal hypertension, and 45 individuals without liver disease. Transabdominal ultrasonograpy of hepatobiliary system was carried out using computed sonography system with multiple probes having multiple frequency depending on physical built of the subjects. The diameters of selected veins were measured in the course of expiration and deep inspiration. In all control subjects, diameter variations of splenic vein and superior mesenteric vein were noted in the phases of respiration, the diameters increased during deep inspiration and decreased during deep expiration mean diameter and standard deviation of splenic vein and superior mesenteric vein were 6.95 ± 1.75 mm and 8.77 ± 2.06 mm respectively and during expiration they were 4.45 ± 1.24 mm and 5.66 ± 1.41 mm respectively. The difference in deep inspiratory and expiratory diameters had high statistical significance (p<0.0001). Patients with portal hypertension diameter variation with breathing at the level of splenic and superior mesenteric veins was observed only in 5 (9.47%) cases. Diminished response of splenic and superior mesenteric veins with respiration in transabdominal ultrasonography is an indicator of portal hypertension. DOI: http://dx.doi.org/10.3329/bmjk.v47i1-2.22558 Bang Med J (Khulna) 2014; 47 : 21-24

Current concepts on the role of nitric oxide in portal hypertension

Portal hypertension (PHT) is defined as a pathological increase in portal venous pressure and frequently accompanies cirrhosis. Portal pressure can be increased by a rise in portal blood flow, an increase in vascular resistance, or the combination. In cirrhosis, the primary factor leading to PHT is an increase in intra-hepatic resistance to blood flow. Although much of this increase is a mechanical consequence of architectural disturbances, there is a dynamic and reversible component that represents up to a third of the increased vascular resistance in cirrhosis. Many vasoactive substances contribute to the development of PHT. Among these, nitric oxide (NO) is the key mediator that paradoxically regulates the sinusoidal (intra-hepatic) and systemic/splanchnic circulations. NO deficiency in the liver leads to increased intra-hepatic resistance while increased NO in the circulation contributes to the hyperdynamic systemic/splanchnic circulation. NO mediated-angiogenesis also plays a role in splanchnic vasodilation and collateral circulation formation. NO donors reduce PHT in animals models but the key clinical challenge is the development of an NO donor or drug delivery system that selectively targets the liver.

Simultaneous Combined Balloon-occluded Retrograde Transvenous Obliteration and Partial Splenic Embolization for Portosystemic Shunts

PurposeTo evaluate the efficacy and safety of simultaneous combined balloon-occluded retrograde transvenous obliteration (B-RTO) and partial splenic embolization (PSE) for gastric varices and/or hepatic encephalopathy. Materials and MethodsB-RTO was performed in 19 consecutive patients with gastric varices and/or hepatic encephalopathy, of whom 10 received simultaneous combined B-RTO and PSE (group 1) and nine received B-RTO monotherapy (group 2). To evaluate the safety of these techniques, we analyzed 20 patients who received PSE monotherapy during the same period as a control group (group 3). Outcomes were retrospectively assessed. ResultsNo significant differences were observed in baseline characteristics among the three groups except for significantly lower platelet counts and larger spleen volumes in group 3. In all cases in groups 1 and 2, gastric varices disappeared and hepatic encephalopathy improved after treatment. Procedure times were not significantly different between groups 1 and 2 (P = .7435). In group 1, the volume of sclerosing agent required for B-RTO was significantly lower (P = .0355) and exacerbation of esophageal varices was significantly less frequent (P = .0146) than in group 2. Few serious complications occurred in patients who received combined therapy. ConclusionsThis study indicates that concomitant PSE may help diminish the increase in portal venous pressure after B-RTO for portosystemic shunts, and may allow a reduction in the volume of hazardous sclerosing agent used. It is worth evaluating the efficacy of simultaneous B-RTO and PSE in a prospective study.

Splenic neurohormonal modulation of mesenteric vascular tone

In portal hypertension, development of a hyperdynamic circulation is preceded by transient mesenteric vasoconstriction. Portal hypertension increases splenic venous outflow pressure. We hypothesized that this causes direct reflex activation of mesenteric vasoconstrictor nerves and splenorenal reflex-mediated activation of the renin-angiotensin system. In anaesthetized male rats, we measured mesenteric efferent nerve activity and mesenteric vascular conductance (MVC) after selectively elevating splenic venous pressure. Partial splenic vein occlusion raised splenic venous pressure (from 4.8 ± 0.4 to 24.1 ± 0.3 mmHg; n = 18) and induced a significant increase in mesenteric efferent nerve activity (from 23.2 ± 3.3 to 31.6 ± 3.5 spikes s(-1); n = 11); this response was abolished by prior splenic denervation (from 32.4 ± 2.4 to 31.2 ± 1.6 spikes s(-1); n = 7). Mesenteric vascular conductance, the ratio of superior mesenteric artery blood flow to mean arterial pressure, fell upon splenic vein occlusion (ΔMVC = -0.0120 ± 0.0014 ml min(-1)mmHg(-1); P < 0.05, n = 10). This was attenuated by splenic denervation (ΔMVC = -0.0044 ± 0.0018 ml min(-1)mmHg(-1); P < 0.05, n = 8), but unaffected by mesenteric denervation (ΔMVC = -0.0145 ± 0.0020 ml min(-1)mmHg(-1); n = 6) or bilateral renal denervation (ΔMVC = -0.0106 ± 0.0021 ml min(-1)mmHg(-1); n = 5). Localized blockade of mesenteric vascular angiotensin II type 1 (AT(1)) receptors significantly attenuated the response (ΔMVC = -0.0058 ± 0.0017 ml min(-1)mmHg(-1); P < 0.05, n = 5), whereas blockade of both AT(1) and α(1)-adrenergic receptors caused a significant increase in mesenteric conductance (ΔMVC = +0.0033 ± 0.0010 ml min(-1)mmHg(-1); P < 0.05, n = 6). Our evidence suggests that increased splenic venous outflow pressure reflexly activates adrenergic/angiotensinergic mesenteric nerves, vasodilator mesenteric nerves and the renin-angiotensin system. We propose that obstruction to splenic venous outflow, such as would normally accompany portal hypertension, induces reflex mesenteric vasoconstriction independently of the increase in portal venous pressure.

Hipertensión portal: desarrollo de una respuesta inflamatoria sistémica asociada a síndrome metabólico

Portal hypertension (PH) is characterised by increase in portal venous pressure by obstruction of portal flow. As a consequence of PH, a collateral circulation is developed, which shifts an important part of portal flow to the systemic circulation. Furthermore, hepatic steatosis is another feature of PH in the rat, which is also, associated which different risk factors such as, obesity, diabetes, hypercholesterolemia and hypertrygliceridemia. Several mechanisms such as insulin resistance, cytokine production and oxidative stress participate in the development of this clinical pathology. An experimental model of pre-hepatic portal hypertension by triple partial portal vein ligation enables complications produced both short-term or acute and long-term or chronic outcome to be studied. Most of the splanchnic and systemic alterations produced in this experimental model are of an inflammatory nature, and for this reason the study of the physiological mechanisms involved are of great interest to the research of new anti-inflammatory therapies.

Preoperative Portal Vein Embolization: An Approach to Improve the Safety of Major Hepatic Resection

Surgery has therefore become a mainstay in the treatment of both primary and metastatic liver lesions. Unfortunately, despite these advances, extended resections yielding small volume liver remnants continue to pose risks resulting from decreased functional liver capacity, both in patients with underlying hepatic disease and in those with otherwise-healthy livers. 3,4 Preoperative portal vein embolization (PVE) has thereby emerged as a significant adjunct to major hepatic resection (more than 3 Couinaud segments), allowing for an increased volume of the future liver remnant (FLR) and resultant improved outcomes in patients with small anticipated residual liver volume. 5-10 Embolization of the portal branches in the liver to be resected results in diversion of portal bloodflow to the nonembolized segments. This rerouted portal blood, rich in hepatotropic substances, stimulates hypertrophy of the liver parenchyma. 11 PVE thus increases the mass of FLR before surgery, and in the proper patient setting, may permit safe, potentially curative resection in patients who would otherwise not be surgical candidates because of their risk of postoperative liver failure.12 The benefits of preoperative PVE are not limited to increased size of the liver remnant; however, the greater number of hepatocytes does allow improved synthetic function and avert cholestasis. Embolization of the portal vein before hepatic resection also diminishes the otherwise-abrupt increase in portal venous pressure after resection that can lead to hepatocellular injury. In addition, PVE dissociates any damage caused by increased portal pressures from the direct trauma inflicted upon the FLR during resection. 13

Effects of β-adrenoceptor antagonists on anaphylactic hypotension in conscious rats

Anaphylactic shock is sometimes fatal or resistant to therapy in patients treated with propranolol, a nonselective β-adrenoceptor antagonist, against cardiovascular diseases. However, it remains unknown which subtype of β-adrenoceptors, β 1- or β 2-adrenoceptor, is primarily responsible for the detrimental effects of propranolol on anaphylactic hypotension. Effects of β 1- and β 2-adrenoceptor antagonists were therefore determined on the survival rate and systemic hypotension in conscious Sprague–Dawley rats that suffered from anaphylactic shock. Mean arterial pressure and portal venous pressure were simultaneously measured. The control rats showed a decrease in mean arterial pressure and an increase in portal venous pressure, but did not die within 48 h after an injection of ovalbumin antigen. The survival rate of the rats pretreated with propranolol (1 mg/kg; n = 7), the selective β 2-adrenoceptor antagonist ICI 118,551 (0.5 mg/kg; n = 7), or adrenalectomy ( n = 7) was significantly smaller than that with the selective β 1-adrenoceptor antagonist atenolol (2 mg/kg; n = 7). However, the changes in mean arterial pressure and portal venous pressure were similar for 10 min after antigen among any groups, although propranolol and atenolol attenuated the antigen-induced increase in heart rate. Furthermore, bolus injections of epinephrine (3 μg/kg) at 3 and 5 min after antigen prevented the death of the atenolol-pretreated rats, but only marginally prolonged the survival rates for the ICI 118,551- or propranolol-pretreated and adrenalectomized rats. In conclusion, in rat anaphylactic shock, inhibition of β 2-adrenoceptor causes more detrimental effects than that of the β 1-adrenoceptor. These β-adrenoceptor antagonists may exert detrimental effects on rat systemic anaphylaxis via inhibiting beneficial actions of catecholamines endogenously released from the adrenal gland.

Urotensin II modulates hepatic fibrosis and portal hemodynamic alterations in rats

The influence of circulating urotensin II (UII) on liver disease and portal hypertension is unknown. We aimed to evaluate whether UII executes a pathogenetic role in the development of hepatic fibrosis and portal hypertension. UII was administered by continuous infusion over 4 wk in 20 healthy rats divided into three treatment groups, controls (saline, n = 7), low dose (UII, 1 nmol x kg(-1) x h(-1), n = 8), and high dose (UII, 3 nmol x kg(-1) x h(-1), n = 5). Hemodynamic parameters and morphometric quantification of fibrosis were assessed, and profibrotic cytokines and fibrosis markers were assayed in hepatic tissue. UII induced a significant dose-dependent increase in portal venous pressure (5.8 +/- 0.4, 6.4 +/- 0.3, and 7.6 +/- 0.7, respectively, P = 0.03). High-dose UII infusion was associated with an increase in hepatic transcript for transforming growth factor-beta (P < 0.05) and platelet-derived growth factor-beta (P = 0.06). Liver tissue hydroxyproline was elevated in the high-dose group (P < 0.05). No systemic hemodynamic alterations were noted. We concluded that UII infusion elevates portal pressure and induces hepatic fibrosis in normal rats. This response may be mediated via induction of fibrogenic cytokines. These findings have pathophysiological implications in human liver disease where increased plasma UII levels have been observed.