Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n= 13) or portal vein ligation (n=13). 2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group. 3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (−18%) in cirrhotic rats, but not in portal-vein-ligated rats. 4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.

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Magnetic Resonance Elastography and Portal Hypertension: Influence of the Portal Venous Flow on the Liver Stiffness

Stem Cells and Regenerative Medicine - Biomedical and Health Research ◽

10.3233/bhr210022 ◽

2021 ◽

Author(s):

Simon Chatelin ◽

Raoul Pop ◽

Céline Giraudeau ◽

Khalid Ambarki ◽

Ning Jin ◽

...

Keyword(s):

Portal Hypertension ◽

Magnetic Resonance ◽

Portal Vein ◽

Peak Flow ◽

Peak Velocity ◽

Liver Stiffness ◽

Portal Venous Flow ◽

Venous Flow ◽

Velocity Magnitude ◽

Magnetic Resonance Imaging Mri

The invasive measurement of the hepatic venous pressure gradient is still considered as the reference method to assess the severity of portal hypertension. Even though previous studies have shown that the liver stiffness measured by elastography could predict portal hypertension in patients with chronic liver disease, the mechanisms behind remain today poorly understood. The main reason is that the liver stiffness is not specific to portal hypertension and is also influenced by concomitant pathologies, such as cirrhosis. Portal hypertension is also source of a vascular incidence, with a substantial diversion of portal venous blood to the systemic circulation, bypassing the liver. This study focuses on this vascular effect of portal hypertension. We propose to generate and control the portal venous flow (to isolate the modifications in the portal venous flow as single effect of portal hypertension) in an anesthetized pig and then to quantify its implications on liver stiffness by an original combination of MRE and 4D-Flow Magnetic Resonance Imaging (MRI). A catheter balloon is progressively inflated in the portal vein and the peak flow, peak velocity magnitude and liver stiffness are quantified in a 1.5T MRI scanner (AREA, Siemens Healthcare, Erlangen, Germany). A strong correlation is observed between the portal peak velocity magnitude, the portal peak flow or the liver stiffness and the portal vein intraluminal obstruction. Moreover, the comparison of mechanical and flow parameters highlights a correlation with the possibility of identifying linear relationships. These results give preliminary indications about how liver stiffness can be affected by portal venous flow and, by extension, by hypertension.

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Portal venous pressure and portasystemic shunting in experimental portal hypertension

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.257.1.g52 ◽

1989 ◽

Vol 257 (1) ◽

pp. G52-G57 ◽

Cited By ~ 2

Author(s):

J. G. Geraghty ◽

W. J. Angerson ◽

D. C. Carter

Keyword(s):

Portal Hypertension ◽

Portal Vein ◽

Venous Pressure ◽

Portal Pressure ◽

Rapid Change ◽

Quadratic Function ◽

Portal Venous Pressure ◽

Portal Vein Ligation ◽

Strong Positive Correlation ◽

The Relationship

The relationship between portal venous pressure and the degree of portasystemic shunting was studied in portal vein-ligated and cirrhotic rats anesthetized with halothane. One day after partial portal vein ligation there was a strong positive correlation (r = 0.80, n = 7) between portal pressure and shunting of mesenteric venous blood as measured by injection of radioactive microspheres. The relationship subsequently underwent rapid change but stabilized by 14 days postligation, when higher levels of shunting were again associated with higher portal pressures up to a limit of approximately 70% shunting, above which pressures did not increase further. This relationship was well described by a quadratic function (r = 0.75, n = 17). In cirrhotic rats there was no relationship between portal pressure and shunting (r = -0.01, n = 10). The results suggest that in the prehepatic model there is little inherent variability in capacity to develop shunts, which open to a degree directly related to portal pressure, but that this relationship may be altered in cirrhotic portal hypertension.

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Constriction rate variation produced by partial ligation of the portal vein at pre-hepatic portal hypertension induced in rats

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/s0102-67202014000400012 ◽

2014 ◽

Vol 27 (4) ◽

pp. 280-284 ◽

Cited By ~ 6

Author(s):

Daren Athiê Boy RODRIGUES ◽

Aline Riquena da SILVA ◽

Leonardo Carvalho SERIGIOLLE ◽

Ramiro de Sousa FIDALGO ◽

Sergio San Gregorio FAVERO ◽

...

Keyword(s):

Portal Hypertension ◽

Portal Vein ◽

Portal Pressure ◽

Functional Adaptation ◽

Rate Variation ◽

Portal Vein Ligation ◽

Initial Diameter ◽

Group 3 ◽

Group 2 ◽

Hepatic Portal

BACKGROUND: Partial portal vein ligation causes an increase in portal pressure that remains stable even after the appearance of collateral circulation, with functional adaptation to prolonged decrease in portal blood flow. AIM: To assess whether different constriction rates produced by partial ligation of the vein interfere with the results of this experimental model in rats. METHODS: Three groups of five rats each were used; in group 1 (sham-operated), dissection and measurement of portal vein diameters were performed. Portal hypertension was induced by partial portal vein ligation, reducing its size to 0.9 mm in the remaining 10 animals, regardless of the initial diameter of the veins. Five animals with portal hypertension (group 2) underwent reoperation after 15 days and the rats in group 3 after 30 days. The calculation of the constriction rate was performed using a specific mathematical formula (1 - π r 2 / π R2) x 100% and the statistical analysis with the Student t test. RESULTS: The initial diameter of the animal's portal vein was 2.06 mm, with an average constriction rate of the 55.88%; although the diameter of the veins and the constriction rate in group 2 were lower than in group 3 (2.06 mm - 55,25% and 2.08 mm - 56.51%, respectively), portal hypertension was induced in all rats and no significant macroscopic differences were found between the animals that were reoperated after 15 days and after 30 days respectively, being the shorter period considered enough for the evaluation. Comparing the initial diameter of the vein and the rate of constriction performed in groups 2 and 3, no statistic significance was found (p>0.05). CONCLUSION: Pre-hepatic portal hypertension in rat can be induced by the reduction of the portal vein diameter to 0.9 mm, regardless the initial diameter of the vein and the vessel constriction rate.

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Protection of estrogen in portal hypertension gastropathy: an experimental model

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032011000300011 ◽

2011 ◽

Vol 48 (3) ◽

pp. 211-216 ◽

Cited By ~ 4

Author(s):

Maria Isabel Morgan-Martins ◽

Simone Iahnig Jacques ◽

Renata Minuzzo Hartmann ◽

Camila Moraes Marques ◽

Cláudio Augusto Marroni ◽

...

Keyword(s):

Antioxidant Enzymes ◽

Portal Hypertension ◽

Portal Vein ◽

Experimental Model ◽

Portal Pressure ◽

The Other ◽

Portal System ◽

Sham Operation ◽

Portal Vein Ligation ◽

Significant Difference

CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

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Investigation of Clinical Safety of Human iPS Cell-Derived Liver Organoid Transplantation to Infantile Patients in Porcine Model

Cell Transplantation ◽

10.1177/0963689720964384 ◽

2020 ◽

Vol 29 ◽

pp. 096368972096438

Author(s):

Tomonori Tsuchida ◽

Soichiro Murata ◽

Shunsuke Hasegawa ◽

Satoshi Mikami ◽

Shin Enosawa ◽

...

Keyword(s):

Clinical Trials ◽

Portal Hypertension ◽

Portal Vein ◽

Fetal Liver ◽

Portal Pressure ◽

Ductus Venosus ◽

Portal Vein Ligation ◽

Ips Cell ◽

Liver Organoids ◽

Human Ipsc

Transplantation of liver organoids has been investigated as a treatment alternative to liver transplantation for chronic liver disease. Transportal approach can be considered as a method of delivering organoids to the liver. It is important to set the allowable organoid amount and verify translocation by intraportal transplantation. We first examined the transplantation tolerance and translocation of porcine fetal liver-derived allogeneic organoids using piglets. Fetal liver-derived organoids generated from the Kusabira Orange-transduced pig were transplanted to the 10-day-old piglet liver through the left branch of the portal vein. All recipients survived without any observable adverse events. In contrast, both local and main portal pressures increased transiently during transplantation. In necropsy samples, Kusabira Orange-positive donor cells were detected primarily in the target lobe of the liver and partly in other areas, including the lungs and brain. As we confirmed the transplantation allowance by porcine fetal liver-derived organoids, we performed intraportal transplantation of human-induced pluripotent stem cell (iPSC)-derived liver organoid, which we plan to use in clinical trials, and portal pressure and translocation were investigated. Human iPSC-derived liver organoids were transplanted into the same 10-day-old piglet. Portal hypertension and translocation of human iPSC-derived liver organoids to the lungs were observed in one of two transplanted animals. Translocation occurred in the piglet in which patent ductus venosus (PDV) was observed. Therefore, a 28-day-old piglet capable of surgically ligating PDV was used, and after the PDV was ligated, human iPSC-derived liver organoids with the amount of which is scheduled in clinical trials were transplanted. This procedure inhibited the translocation of human iPSC-derived liver organoids to extrahepatic sites without no portal hypertension. In conclusion, human iPSC-derived liver organoids can be safely transplanted through the portal vein. Ligation of the ductus venosus prior to transplantation was effective in inhibiting extrahepatic translocation in newborns and infants.

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Aminoguanidine ameliorates splanchnic hyposensitivity to glypressin in a haemorrhage-transfused rat model of portal hypertension

Clinical Science ◽

10.1042/cs0950629 ◽

1998 ◽

Vol 95 (5) ◽

pp. 629-636 ◽

Cited By ~ 8

Author(s):

Chi-Jen CHU ◽

Fa-Yauh LEE ◽

Sun-Sang WANG ◽

Full-Young CHANG ◽

Han-Chieh LIN ◽

...

Keyword(s):

Nitric Oxide ◽

Portal Hypertension ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Portal Vein ◽

Rat Model ◽

Portal Pressure ◽

Hypotensive Effect ◽

Portal Vein Ligation ◽

Nitric Oxide Synthase Inhibitor

1.Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding. 2.Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 ;mg/kg) or aminoguanidine (70 ;mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ;ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine. 3.Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P< 0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P> 0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P< 0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P> 0.05). 4.Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.

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Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.6.g984 ◽

1994 ◽

Vol 267 (6) ◽

pp. G984-G990 ◽

Cited By ~ 3

Author(s):

J. C. Garcia-Pagan ◽

M. Fernandez ◽

C. Bernadich ◽

P. Pizcueta ◽

J. M. Pique ◽

...

Keyword(s):

Cardiac Output ◽

Portal Vein ◽

Portal Pressure ◽

Continuous Treatment ◽

Portal Vein Ligation ◽

Sprague Dawley ◽

Portal Vein Stenosis ◽

No Inhibition ◽

Arteriolar Resistance ◽

Lower Cardiac Output

The present study investigated whether chronic nitric oxide (NO) inhibition prevents the hyperdynamic circulatory syndrome that appears in rats after partial portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30 micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17) was infused continuously from PPVL through subcutaneously osmotic pumps. Studies were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days, PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric-systemic shunting were lower, although nonsignificantly, in PPVL rats treated with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change portal pressure at either 4 or 8 days. After 4 days of continuous treatment with L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats treated with vehicle. Contrary to PPVL rats, these effects were maintained after 8 days of treatment. The present study shows that NO contributes to the systemic disturbances of portal hypertension. However, NO inhibition delayed but did not prevent the splanchnic vasodilation that appears after PPVL, suggesting that other factors could also be involved.

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A Novel Method of Determining Portal Systemic Shunting using Biodegradable 99TCm Labelled Albumin Microspheres

HPB Surgery ◽

10.1155/1995/31761 ◽

1995 ◽

Vol 8 (4) ◽

pp. 223-229 ◽

Cited By ~ 2

Author(s):

J. Yates ◽

D. M. Nott ◽

P. J. Maltby ◽

D. Billington ◽

J. N. Baxter ◽

...

Keyword(s):

Portal Hypertension ◽

Portal Vein ◽

Portal Pressure ◽

Repeated Measurements ◽

Control Group ◽

Portal Vein Ligation ◽

Hypertensive Rats ◽

Albumin Microspheres ◽

Novel Method

Portal systemic shunting (PSS) and portal pressure were measured in control rats and in animals with portal hypertension induced by partial portal vein ligation (PPVL). The portal pressure in rats with partial portal vein ligation (13.4 ± 0.5 mm.Hg.) was significantly higher (p < 0.005) than in the control group (9.6 ± 0.6 mm.Hg.). Portal systemic shunting measured by consecutive injections of radiolabelled methylene diphosphonate (MDP), a non-diffusable marker and albumin microspheres directly into the splenic pulp was significantly increased (P < 0.005) in the portal hypertensive animals (30.8 ± 2.5%) compared to sham operated rats (2.6 ± 1.5%). Similarly, in portal hypertensive rats portal systemic shunting measured by intrasplenic injections of radiolabelled cobalt microspheres (37.1 ± 3.9%) was significantly greater (p < 0.005) than in control animals. There was a good correlation and agreement (r = 00.97) between the two methods of measuring portal systemic shunting. However because the 99Tcm-albumin microspheres are biodegradable the method allows portal systemic shunting to be measured in man. Furthermore since the computer adjusts the baseline to zero after each determination of portal systemic shunting the methodology allows repeated measurements to be made.

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Percutaneous Thrombin Injection for Treatment of a Hepatic Arterial Pseudoaneurysm after the Placement of a Transjugular Intrahepatic Portosystemic Shunt

Journal of Clinical Imaging Science ◽

10.25259/jcis_87_18 ◽

2019 ◽

Vol 9 ◽

pp. 20 ◽

Cited By ~ 1

Author(s):

Daniel C. Oppenheimer ◽

Luann Jones ◽

Ashwani Sharma

Keyword(s):

Portal Hypertension ◽

Transjugular Intrahepatic Portosystemic Shunt ◽

Portosystemic Shunt ◽

Thrombin Injection ◽

Portal Venous Flow ◽

Venous Flow ◽

Artery Pseudoaneurysm ◽

Imaging Guidance ◽

Intrahepatic Portosystemic Shunt ◽

Percutaneous Thrombin Injection

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely accepted option for treating the complications of portal hypertension. The procedure involves creating a communication between the portal and hepatic venous systems using imaging guidance, thereby diverting the portal venous flow and reducing the portosystemic gradient. However, as with any procedure, TIPS insertion is not without potential complications. We present a case of a 37-year-old female who developed a hepatic artery pseudoaneurysm following the placement of a TIPS which was successfully treated with percutaneous thrombin injection.

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