Chronic Administration of Octreotide Ameliorates Portal Hypertension and Portal Hypertensive Gastropathy in Rats with Cirrhosis

1998 ◽  
Vol 94 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Che-Chang Chan ◽  
Fa-Yauh Lee ◽  
Sun-Sang Wang ◽  
Full-Young Chang ◽  
Han-Chieh Lin ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Carbon Tetrachloride ◽  
Portal Pressure ◽  
Chronic Administration ◽  
Portal Hypertensive Gastropathy ◽  
Cross Sectional ◽  
Hyperdynamic Circulation ◽  
Morphometric Analyses ◽  
Octreotide Treatment ◽  
To Receive

1. Portal hypertension and hyperdynamic circulation have been postulated to play a role in the pathogenesis of portal hypertensive gastropathy. Administration of octreotide to portal hypertensive rats has been shown to reduce portal pressure and ameliorate hyperdynamic circulation. 2. This study investigated the effects of chronic administration of octreotide on systemic and portal haemodynamics and the development of portal hypertensive gastropathy in carbon tetrachloride-induced cirrhotic rats. 3. After 12 weeks of carbon tetrachloride induction, cirrhotic rats were randomly assigned to receive either placebo (5% dextrose in water) or octreotide (65 μg/kg in 5% dextrose in water) subcutaneously twice daily for 10 days. Haemodynamic studies with a thermodilution technique and gastric morphometric analyses were performed at 10 days after treatment. 4. In cirrhotic rats, octreotide treatment induced a significant increase in systemic vascular resistance (2.7 ± 0.2 versus 3.4 ± 0.2 mmHg/ml · min−1 · 100 g−1, P < 0.05) and decrease in portal pressure (12.5 ± 1.2 versus 9.9 · 0.5 mmHg, P < 0.05) compared with placebo-treated rats. In addition, octreotide treatment significantly reduced the mean cross-sectional area of gastric mucosal vessels (2290 ± 145 versus 1810 ± 101 μm2, P < 0.05). 5. This study shows that chronic octreotide treatment ameliorates the development of portal hypertensive gastropathy in cirrhotic rats. The effect of octreotide on portal hypertensive gastropathy may, at least partly, be due to the alleviation of portal hypertension and hyperdynamic circulation.

Chronic Administration of Octreotide Increases Vascular Responsiveness in Rats with Portal Hypertension

1996 ◽  
Vol 91 (5) ◽  
pp. 601-606 ◽  
Author(s):  
Yi-Tsau Huang ◽  
Ju-Fen Tsai ◽  
Tsun-Bin Liu ◽  
Chuang-Ye Hong ◽  
May C.-M. Yang ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Mesenteric Artery ◽  
Portal Pressure ◽  
Chronic Administration ◽  
Treated Group ◽  
Contractile Responses ◽  
Vascular Responsiveness ◽  
Octreotide Treatment ◽  
Vehicle Treated Group

1. It has been reported that octreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 μg/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries from sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation

2021 ◽  
pp. 096452842110392
Author(s):  
Yu-Sheng Chen ◽  
Chorng-Kai Wen ◽  
Geng-Hao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Portal Hypertension ◽  
Growth Factor ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Portal Pressure ◽  
Contractile Responses ◽  
Hyperdynamic Circulation ◽  
Duct Ligation ◽  
Tnf Α ◽  
Cox 1

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

Adaptive vasodilatory response after octreotide treatment

2001 ◽  
Vol 281 (1) ◽  
pp. G117-G123 ◽  
Author(s):  
Ying-Ying Yang ◽  
Han-Chieh Lin ◽  
Yi-Tsau Huang ◽  
Tzung-Yan Lee ◽  
Wui-Chiang Lee ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Endothelial Nitric Oxide Synthase ◽  
Pressor Response ◽  
Plasma Glucagon ◽  
Enos Expression ◽  
Vasodilatory Activity ◽  
Octreotide Treatment ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
To Receive

Despite the suppression of glucagon release, an adaptive response aimed at maintaining vasodilatation after octreotide treatment may exist in portal hypertension. The present study was undertaken to evaluate the possible interaction between endothelium and non-endothelium-derived vasodilators after 1-wk octreotide administration in cirrhotic rats. Rats were allocated to receive either vehicle or octreotide (30 or 100 μg/kg every 12 h subcutaneously). Hemodynamic values, plasma glucagon levels, endothelium-related vasodilatory activities, and aortic endothelial nitric oxide synthase (eNOS) expression were determined after treatment. Octreotide administration decreased plasma glucagon and increased serum 6-keto-PGF1α and NOx levels without affecting the hemodynamic values. In cirrhotic rats receiving octreotide, there was a blunt response to either l-NAME or indomethacin administration alone, but this blunt pressor response disappeared after simultaneous administration of the two drugs. Additionally, an increased aortic eNOS expression was observed in cirrhotic rats receiving 1-wk octreotide. It is concluded that 1-wk octreotide treatment did not correct the hemodynamic derangement in cirrhotic rats. The enhanced endothelium-related vasodilatory activity was noted after octreotide treatment that overcame the octreotide-induced hemodynamic effects in portal hypertension.

Effect of Long-Term Octreotide and Isosorbide Dinitrate on Haemodynamics in Rats with Portal Vein Stenosis

1998 ◽  
Vol 94 (6) ◽  
pp. 645-650 ◽  
Author(s):  
Han-Chieh Lin ◽  
Yi-Tsau Huang ◽  
Yuh-Ren Cheng ◽  
Ming-Chih Hou ◽  
Fa-Yauh Lee ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Isosorbide Dinitrate ◽  
Portal Pressure ◽  
Vehicle Group ◽  
Hyperdynamic Circulation ◽  
Portal Vein Stenosis ◽  
Term Administration ◽  
Vein Stenosis

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 μg/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

scholarly journals Thromboelastometry in patients with advanced chronic liver disease stratified by severity of portal hypertension

2020 ◽  
Author(s):  
Pierre Raeven ◽  
Joanna Baron-Stefaniak ◽  
Benedikt Simbrunner ◽  
Alexander Stadlmann ◽  
Philipp Schwabl ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Cross Sectional Study ◽  
Chronic Liver ◽  
Cross Sectional ◽  
Reactive Protein ◽  
The Impact

Abstract Background Rotational thromboelastometry (ROTEM) has been studied in patients with advanced chronic liver disease (ACLD) without considering the impact of portal hypertension. We evaluated the influence of the hepatic venous pressure gradient (HVPG) on ROTEM results in patients with ACLD. Methods Cross-sectional study; ACLD patients undergoing HVPG measurement within the prospective Vienna Cirrhosis Study (NCT03267615) underwent concomitant ROTEM testing. Results Among 159 patients (68% male; Child–Pugh-A: 53%, Child–Pugh-B: 34%, Child–Pugh-C: 13%), 21 patients (13%) had a HVPG between 6 and 10 mmHg, 84 patients (53%) between 10 and 19 mmHg, and 54 patients (34%) ≥ 20 mmHg. Child–Pugh-C patients (vs. Child–Pugh-A and vs. Child–Pugh-B patients, respectively) showed longer clot formation time (CFT: median 187 s vs. 122 s vs. 122 s, p = 0.007) and lower maximum clot firmness (MCF: median: 45 mm vs. 56 mm vs. 56 mm, p = 0.002) in extrinsic thromboelastometry (EXTEM), while platelet counts were similar across Child–Pugh stages. In the overall cohort, ROTEM parameters did not differ by severity of portal hypertension. However, among compensated Child–Pugh-A patients, MCF decreased with increasing portal pressure, i.e. in higher HVPG strata (HVPG 9–10 mmHg: median MCF: 59 mm vs. HVPG 10–19 mmHg: 56 mm vs HVPG ≥ 20 mmHg: 54 mm, p = 0.023). Furthermore, patients with short CFT and high MCF in EXTEM had higher levels of lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin, as well as higher leukocyte counts (all p < 0.05). Conclusions Portal hypertension seems to impact ROTEM results only in compensated Child–Pugh-A patients. Bacterial translocation and systemic inflammation may trigger a procoagulant state in patients with ACLD.

Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state

2006 ◽  
Vol 290 (5) ◽  
pp. G980-G987 ◽  
Author(s):  
Juan G. Abraldes ◽  
Yasuko Iwakiri ◽  
Mauricio Loureiro-Silva ◽  
Omar Haq ◽  
William C. Sessa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Portal Hypertension ◽  
Portal Pressure ◽  
No Production ◽  
Portal Vein Ligation ◽  
Vegf Expression ◽  
Enos Expression ◽  
Hyperdynamic Circulation ◽  
Intestinal Microcirculation ◽  
Hypertension Portal

Increased nitric oxide (NO) is the main factor leading to the hyperdynamic circulation associated with advanced portal hypertension (PHT), but the initial mechanisms and the magnitude of increase in portal pressure required to trigger NO production are not known. We addressed these issues by studying systemic and splanchnic hemodynamics and endothelial NO synthase (eNOS) and VEGF expression in rats with different degrees of portal hypertension. Portal vein ligation (PVL) performed over needles of three different calibers (16-, 18-, and 20-gauge) yielded different degrees of PHT and portosystemic shunting. Compared with sham rats, all three groups of PVL rats exhibited features of hyperdynamic circulation. Rats with minimal portal hypertension (PVL with a 16-gauge needle) showed an early increase in VEGF and eNOS expression selectively at the jejunum. Immunofluorescence showed that VEGF expression was located in highly vascularized areas of the mucosa. Inhibition of VEGF signaling markedly attenuated the increase in eNOS expression. In conclusion, mild increases in portal pressure are enough to upregulate eNOS at the intestinal microcirculation, and this occurs, at least in part, through VEGF upregulation.

scholarly journals CIRRHOTIC PATIENTS;

2017 ◽  
Vol 24 (01) ◽  
pp. 132-138
Author(s):  
Ammarah Saeed ◽  
Tehzeeb Zehra ◽  
Ayaz Ahmad ◽  
Umbreen Idrees ◽  
Sajjad Sabir
Keyword(s):  
Portal Hypertension ◽  
Esophageal Varices ◽  
Gastric Varices ◽  
Common Type ◽  
Type I ◽  
Portal Hypertensive Gastropathy ◽  
Vascular Changes ◽  
Cross Sectional ◽  
Study Results ◽  
Child Class

At present time portal hypertension is perceived as one of the complications ofadvanced liver disease. It results in various vascular changes in gastrointestinal tract (GI),including esophageal varices, gastric varices and portal hypertensive gastropathy (PHG). PHGand gastric varices are a common cause of acute as well as chronic bleeding from GI tractwhich resulted in significant mortality among patients. Objectives: To determine the frequencyof gastric vascular changes in various causes of cirrhosis. Study Design: Cross sectional study.Setting: Department of Gastroenterology, Pakistan Institute of Medical Sciences, Islamabad.Period: 1st August 2007 to 31st July 2008. Materials and Methods: Patients of age ≥30 years,with clinical evidence of cirrhosis and without prior treatment of esophagiogastric varices wereincluded in the study. Results: A total of 100 patients were enrolled in the study out of which47 were male and 53 were females with mean age of 53.6 years. The most common type ofcirrhosis was turned out to be Hepatitis C affecting 50% of patients and most of the patientswere in Child class C. Portal hypertensive gastropathy was present in 74% of patients. Amongthem 24.3% have mild changes while severe changes were present in75.7% of patients. Gastricvarices were found in 40% of the patients and the most common type was IGV type I whichwas present in 29(72.5%) of the patients. Correlation of severity of PHG was seen with gradingof esophageal varices, grading of gastric varices and Child class. Conclusion: Frequency ofsevere gastropathy is higher than the mild gastropathy. It is also concluded that gastric vascularchanges are associated with cause of cirrhosis, child class and degree of portal hypertension.

scholarly journals Peptic Ulcer Diseases in Patients with Liver Cirrhosis and Portal Hypertension: Experience in a Tertiary Level Hospital in Bangladesh

2021 ◽  
Vol 16 (2) ◽  
pp. 68-71
Author(s):  
Ahmed Lutful Moben ◽  
Md Abdullahel Kafee ◽  
Md Jahangir Kabir ◽  
Arunanagshu Raha ◽  
Farjana Majid ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Peptic Ulcer ◽  
Portal Hypertension ◽  
Peptic Ulcer Disease ◽  
Oesophageal Varices ◽  
Portal Hypertensive Gastropathy ◽  
Class Iii ◽  
Cross Sectional ◽  
Ulcer Disease ◽  
Cirrhosis Of Liver

Introduction: Cirrhosis of liver and peptic ulcer disease (PUD) are very common in Bangladesh. PUD may coexist with cirrhosis and portal hypertension. Haematemesis and melaena in cirrhosis of liver are not always from ruptured oesophageal varices; rather it may be due to bleeding peptic ulcer disease. Objective: To find the prevalence of PUD among patients with liver cirrhosis and portal hypertension. Materials and Methods: This cross sectional, descriptive study was conducted on 96 patients of cirrhosis of liver diagnosed with oesophageal varices at endoscopy unit of Kurmitola general hospital, during endoscopic evaluations in 4 months period from september 2017 to december 2017. Results: Total cirrhotic patients enrolled were 96 (M=61, F=35), mean age was 51.8 ± 14.2 yrs (18-86years). Hepatitis B virus (HBV) was the leading cause of cirrhosis in 54.1%, Hepatitis C virus (HCV) 5.2 %, proven non-alcoholic steatohepatitis (NASH) were 11.5% and rest were from unknown aetiology. Their average Child-Turcotte-Pugh (CTP) score were 8.6 (12-5), 37.6% associated with portal hypertensive gastropathy. Grade-III oesophageal varices found in 52 patients, whereas grade-II in 25 patients. Among this 96 patients 39 (40.6%) revealed peptic ulcer disease more in the form of gastric ulcer (n=23) than duodenal ulcer (n=10) and both (n=6). Most of the ulcers belonged to Forrest class III (76.9%). Conclusions: Variceal bleeding and portal hypertensive gastropathy are the common causes of bleeding and anaemia in patients with cirrhosis of liver. Peptic ulcer disease has been found to be one of the potential causes of haematemesis, melaena, and anaemia among these patients in Bangladesh. Large multicenter controlled studies are needed to confirm the reports. JAFMC Bangladesh. Vol 16, No 2 (December) 2020: 68-71

scholarly journals Clinical Profile and Upper Gastrointestinal Endoscopic Findings of Patients Presenting with Liver Cirrhosis with Portal Hypertension

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Shatdal Chaudhary ◽  
Niraj Kumar Jaiswal ◽  
Aakash Shahi ◽  
Pradip Chhetri
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Esophageal Varices ◽  
Clinical Profile ◽  
Upper Gastrointestinal Endoscopy ◽  
Portal Hypertensive Gastropathy ◽  
Cross Sectional ◽  
Female Ratio ◽  
Endoscopic Findings ◽  
Upper Gastrointestinal

Introduction: Liver cirrhosis is a common problem faced by physicians worldwide and is also responsible for 11th most common cause of death globally. Data regarding prevalence of esophageal varices and other upper gastrointestinal changes in patients with liver cirrhosis is scare in Nepal. So this study was carried out to find clinical profile and upper gastrointestinal endoscopic findings of patients presenting with liver cirrhosis with portal hypertension. Methods: This was a cross-sectional observational hospital based study conducted in the department of internal medicine and endoscopy unit of the Universal College of Medical Sciences, Bhairahawa, Nepal. The study was done from 21 February 2019 to 20 November 2019 in the patients presented with liver cirrhosis with portal hypertension. Sample size of 80±10 was calculated based on the statistics of previous data. The upper gastrointestinal endoscopy was done in all the patients. The data was collected using the predesigned pro-forma. Results: Total 89 patients with liver cirrhosis were enrolled with mean age of 51.84±12.26 years and male: female ratio of 3.68:1. As per Child Pugh classification (CTP) 45 patients (51%) were in Class C, 33 patients (37%) were in Class B and 11 patients (12%) were in Class A. Esophageal varices were present in 51 (57.3%) patients. According to Westaby classification grade I esophageal varices were seen in 17 (19.1%), grade II esophageal varices were seen in 26 (29.2%), grade III esophageal varices were seen in 8 (8.9%) patients. Portal hypertensive gastropathy (PHG) was seen in 64 (71%) patients. The association between esophageal varices and PHG grade was found statistically significant (P= <0.001). Conclusions: Liver cirrhosis was more commonly seen in middle age males. Esophageal varices and portal hypertensive gastropathy were common endoscopic findings present in patients with liver cirrhosis. There was statistically significant association between esophageal varices and PHG.

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