Interaction of flow and resistance in maintenance of portal hypertension in a rat model

1986 ◽  
Vol 250 (2) ◽  
pp. G205-G212 ◽  
Author(s):  
E. Sikuler ◽  
R. J. Groszmann
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Rat Model ◽  
Portal Pressure ◽  
Flow Theory ◽  
Sham Operation ◽  
Portal Flow ◽  
Hemodynamic Changes ◽  
Forward Flow ◽  
Arteriolar Resistance

To clarify the roles that portocollateral resistance ("backward-flow" theory) and portal flow ("forward-flow" theory) play in maintaining chronic portal hypertension, we studied, in a rat model with prehepatic portal hypertension, the hemodynamic changes that occur when portocollateral resistance is reduced and high portal venous inflow is maintained. In 30 portal-hypertensive rats the constriction around the portal vein was removed 4 days after induction of portal hypertension, 30 rats were used as portal vein-constricted controls, and 30 additional rats were subjected to a sham operation. The removal of the ligature constricting the portal vein was followed by an immediate decrease in portal pressure (from 16.3 +/- 0.8 to 9.6 +/- 0.8 mmHg, P less than 0.001). Two days after the ligature removal, hyperdynamic circulation was still evident and was characterized by a decreased splanchnic arteriolar resistance and an increased portal venous inflow. The coexistence of high portal venous inflow and normal portal pressure indicates that high portal venous inflow per se is not sufficient to produce an increase in portal pressure when it faces a low-resistance vascular bed. We conclude that portal hypertension is induced by the interaction of an abnormally high portal venous inflow and high resistance offered to the flow by the portocollateral vessels. Neither the forward-flow theory nor the backward-flow theory can be applied solely to explain the increased portal pressure.

Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

1985 ◽  
Vol 248 (6) ◽  
pp. G618-G625 ◽  
Author(s):  
E. Sikuler ◽  
D. Kravetz ◽  
R. J. Groszmann
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Rat Model ◽  
Portal Pressure ◽  
Portal System ◽  
Hypertensive Rats ◽  
Hemodynamic Changes ◽  
Sequence Of Events ◽  
Radioactive Microsphere

In rats with portal hypertension induced by partial ligation of the portal vein, we have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. We evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 +/- 0.89 vs. 4.18 +/- 0.71 dyn X s X cm-5 X 10(4), mean +/- SE, P less than 0.01), increased portal pressure (17.7 +/- 0.9 vs. 9.5 +/- 0.6 mmHg, P less than 0.001), and decreased portal venous inflow (3.93 +/- 0.26 vs. 6.82 +/- 0.49 ml X min-1 X 100 g body wt-1, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension

1983 ◽  
Vol 244 (1) ◽  
pp. G52-G57 ◽  
Author(s):  
J. Vorobioff ◽  
J. E. Bredfeldt ◽  
R. J. Groszmann
Keyword(s):  
Animal Model ◽  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Peripheral Resistance ◽  
Flow Theory ◽  
Portal Blood Flow ◽  
High Grade ◽  
Forward Flow ◽  
Arteriolar Resistance

Two dissimilar hemodynamic hypotheses, the “backward flow” theory and the “forward flow” theory, have been advanced to define splanchnic hemodynamics in portal hypertension. An animal model with portal hypertension and high-grade portal-systemic shunting, the portal vein-stenotic rat, was studied to determine whether a hemodynamic picture compatible with either theory would develop. Splanchnic and systemic hemodynamics and portal-systemic shunting were measured by radioactive microsphere techniques. The portal-hypertensive rats (portal pressure, 12.8 +/- 0.5 vs. 8.3 +/- 0.4 mmHg) with greater than 95% portal-systemic shunting had a 60% increase in portal venous inflow (23.46 +/- 2.54 vs. 14.97 +/- 1.61 ml/min; P less than 0.01) with a concomitant 50% decrease in splanchnic arteriolar resistance (3.86 +/- 0.43 vs. 7.60 +/- 0.80 dyn . s . cm-5 . 10(5); P less than 0.001) compared with control rats. Cardiac index (391 +/- 17 vs. 250 +/- 20 ml . min-1 . kg-1) was elevated 50% (P less than 0.001), and total peripheral resistance (7.1 +/- 0.4 vs. 11.7 +/- 0.8 dyn . s . cm-5 . 10(4)) was decreased 60% (P less than 0.001). The resistance to portal blood flow in portal vein-stenotic rats (4.77 +/- 0.57 dyn . s . cm-5 . 10(4)) was similar to the resistance to portal blood flow in control rats (4.82 +/- 0.43 dyn . s . cm-5 . 10(4)), indicating that the hyperdynamic portal venous inflow, not resistance, provided the main impetus for maintaining the elevated portal venous pressure. The splanchnic hemodynamic observations directly support the forward flow theory of portal hypertension. The relation between splanchnic arteriolar resistance and total peripheral resistance (r = 0.67; P less than 0.01) indicated that the systemic hemodynamic parameters were secondarily altered by the splanchnic hemodynamic changes. This animal model of chronic portal hypertension gave evidence for a generalized splanchnic arteriolar vasodilation occurring in the presence of high-grade portal-systemic shunting.

scholarly journals Protection of estrogen in portal hypertension gastropathy: an experimental model

2011 ◽  
Vol 48 (3) ◽  
pp. 211-216 ◽  
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.

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

1998 ◽  
Vol 95 (5) ◽  
pp. 629-636 ◽  
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.

Effects of the combined administration of propranolol plus sorafenib on portal hypertension in cirrhotic rats

2012 ◽  
Vol 302 (10) ◽  
pp. G1191-G1198 ◽  
Author(s):  
M. D'Amico ◽  
M. Mejías ◽  
E. García-Pras ◽  
J. G. Abraldes ◽  
J. C. García-Pagán ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Beta Blockers ◽  
Combined Therapy ◽  
Portal Pressure ◽  
Additive Effect ◽  
Sham Operation ◽  
Portal Flow ◽  
Similar Reduction ◽  
Sorafenib Treatment

Low doses of sorafenib have been shown to decrease portal pressure (PP), portal-systemic shunts, and liver fibrosis in cirrhotic rats. Nonselective beta blockers (NSBB) are the only drugs recommended for the treatment of portal hypertension. The aim of our study was to explore whether the combination of propranolol and sorafenib might show an additive effect reducing PP in cirrhotic rats. Groups of common bile duct-ligated cirrhotic rats (CBDL) and sham-operated control rats were treated by gavage with vehicle, propranolol (30 mg·kg−1·day−1), sorafenib (1 mg·kg−1·day−1), or propranolol+sorafenib. Treatment began 2 wk after the CBDL or sham operation. Hemodynamic evaluation was performed after 2 wk of treatment. In cirrhotic rats, propranolol and sorafenib produced a significant ( P < 0.001) and similar reduction in PP (−19 and −15%, respectively). This was achieved through different mechanisms: whereas propranolol decreased PP by reducing portal blood flow (−35%; P = 0.03), sorafenib decreased PP without decreasing portal flow indicating decreased hepatic resistance. After propranolol+sorafenib, the fall in PP was significantly greater (−30%; P < 0.001) than with either drug alone, demonstrating an additive effect. However, the reduction in portal flow (−39%) under combined therapy was not significantly greater than after propranolol alone. Sorafenib, alone or in combination with propranolol, produced significant reduction in portal-systemic shunting (−25 and −33%, respectively), splanchnic vascularization (−37 and −41%, respectively), liver fibrosis (38%), and hepatic neovascularization (−42 and −51%, respectively). These effects were not observed after propranolol alone. In conclusion, the combination of propranolol+sorafenib causes a greater reduction in PP than either drug alone and decreases markedly the extent of portal-systemic shunting, splanchnic and hepatic neovascularization, and liver fibrosis, suggesting that this drug combination is a potentially useful strategy in the treatment of portal hypertension.

Stability of a rat model of prehepatic portal hypertension caused by partial ligation of the portal vein

2009 ◽  
Vol 15 (32) ◽  
pp. 3449
Author(s):  
Zhe Wen ◽  
Jin-Zhe Zhang ◽  
Hui-Min Xia ◽  
Chun-Xiao Yang ◽  
Ya-Jun Chen
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Rat Model

scholarly journals Failure of Splenectomy to Ameliorate Portal Hypertension in Myeloproliferative Disorders

1994 ◽  
Vol 8 (2) ◽  
pp. 97-100
Author(s):  
Samuel S Lee ◽  
Guido Van Rosendaal ◽  
Thomas E Lay ◽  
James K Kelly ◽  
Graham F Pineo
Keyword(s):  
Portal Hypertension ◽  
Portal Pressure ◽  
Myeloproliferative Disorders ◽  
Myeloproliferative Disorder ◽  
Correct Treatment ◽  
Forward Flow ◽  
Optimum Treatment ◽  
Flow Component ◽  
Significant Amelioration

The correct treatment of portal hypertension associated with myeloproliferative disorders remains uncertain. Splenectomy has been advocated by some to eliminate the forward flow component of the portal hypertension and thus reduce portal pressure. The authors describe three recent cases of myeloproliferative disorder in whom splenectomy failed to achieve any significant amelioration of portal hypertension, with in-depth hemodynamic studies in one patient. Based on these experiences, the authors suggest that splenectomy is not the optimum treatment of the portal hypertension associated with myeloproliferative disorders.

scholarly journals The Surgical Treatment for Portal Hypertension: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lanning Yin ◽  
Haipeng Liu ◽  
Youcheng Zhang ◽  
Wen Rong
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Variceal Bleeding ◽  
Meta Analysis ◽  
Portal Pressure ◽  
Combined Treatment ◽  
Cochrane Library ◽  
Quality Of Reporting ◽  
Portal Vein Pressure ◽  
Shunt Procedure

Aim. To compare the effectiveness of surgical procedures (selective or nonselective shunt, devascularization, and combined shunt and devascularization) in preventing recurrent variceal bleeding and other complications in patients with portal hypertension. Methods. A systematic literature search of the Medline and Cochrane Library databases was carried out, and a meta-analysis was conducted according to the guidelines of the Quality of Reporting Meta-Analyses (QUOROM) statement. Results. There were a significantly higher reduction in rebleeding, yet a significantly more common encephalopathy () in patients who underwent the shunt procedure compared with patients who had only a devascularization procedure. Further, there were no significant differences in rebleeding, late mortality, and encephalopathy between selective versus non-selective shunt. Next, the decrease of portal vein pressure, portal vein diameter, and free portal pressure in patients who underwent combined treatment with shunt and devascularization was more pronounced compared with patients who were treated with devascularization alone (). Conclusions. This meta-analysis shows clinical advantages of combined shunt and devascularization over devascularization in the prevention of recurrent variceal bleeding and other complications in patients with portal hypertension.

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

1992 ◽  
Vol 83 (1) ◽  
pp. 41-45 ◽  
Author(s):  
M. Dagenais ◽  
G. Pomier-Layrargues ◽  
B. Rocheleau ◽  
L. Giroux ◽  
P.-M. Huet
Keyword(s):  
Cardiac Output ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Portal Pressure ◽  
Reference Sample ◽  
Peripheral Resistance ◽  
Haemodynamic Effects ◽  
Portal Vein Ligation ◽  
Portal Venous Flow ◽  
Venous Flow

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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