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)

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.

Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension

1984 ◽  
Vol 247 (5) ◽  
pp. G486-G493 ◽  
Author(s):  
J. N. Benoit ◽  
J. A. Barrowman ◽  
S. L. Harper ◽  
P. R. Kvietys ◽  
D. N. Granger
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Vascular Resistance ◽  
Portal Pressure ◽  
Systemic Arterial Pressure ◽  
Hypertensive Rats ◽  
Humoral Factors ◽  
Arterial Blood

The role of neural, metabolic, physical, and humoral factors in the intestinal hyperemia associated with chronic portal hypertension was examined by use of the rat portal vein stenosis model. Intestinal blood flow and splenic pulp pressure were increased, while systemic arterial pressure and total vascular resistance were reduced in portal vein-stenosed rats as compared with controls. The reduction in total vascular resistance was entirely due to a fall in precapillary resistance and was accompanied by an increase in intestinal capillary pressure, which exceeded that produced by acute portal pressure elevation to the same level. Arteriovenous shunting of 15-micron microspheres was four times higher in portal-hypertensive rats. Cross-perfusion of control intestinal preparations with arterial blood from portal-hypertensive rats produced a 30% increase in blood flow. Plasma glucagon levels in portal-hypertensive rats were three times higher than in controls. Intra-arterial infusion of glucagon (at a rate that achieved the concentration measured in portal-hypertensive animals) produced a 20% reduction in intestinal vascular resistance. The results of these studies indicate that humoral factors, including glucagon, are primarily responsible for the hyperemia associated with portal hypertension.

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.

Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats

1985 ◽  
Vol 249 (4) ◽  
pp. G528-G532 ◽  
Author(s):  
S. S. Lee ◽  
C. Girod ◽  
D. Valla ◽  
P. Geoffroy ◽  
D. Lebrec
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Regional Blood Flow ◽  
Hypertensive Rats ◽  
Pentobarbital Sodium ◽  
Portal Vein Stenosis ◽  
Pentobarbital Sodium Anesthesia ◽  
Vein Stenosis

To determine the effect of pentobarbital sodium anesthesia on the rat with portal hypertension due to portal vein stenosis, four groups of rats were studied. Cardiac output and regional blood flow were measured by radioactive microspheres in anesthetized and conscious sham-operated and portal-hypertensive rats. Anesthesia markedly decreased cardiac output in both sham-operated (109.7 +/- 4.6 vs. 77.8 +/- 1.4 ml/min, P less than 0.001) and portal-hypertensive rats (130.1 +/- 7.6 vs. 93.8 +/- 5.3 ml/min, P less than 0.01). In spite of this diminution in cardiac output, pentobarbital did not significantly change absolute blood flow values of splanchnic organs in either group. However, the fractions of cardiac output perfusing the splanchnic organs were significantly increased by pentobarbital in both groups because of the decrease in cardiac output: sham operated, anesthetized, 22.86 +/- 1.19% vs. conscious, 14.83 +/- 1.02%, P less than 0.001; and portal hypertensive, anesthetized, 26.67 +/- 0.71% vs. conscious, 19.07 +/- 1.44%, P less than 0.001. The hyperdynamic circulation of the portal vein-stenosed rat compared with the sham-operated rat continued to manifest itself with significantly increased portal pressure, cardiac output, and splanchnic blood flow, whether the animal was anesthetized or awake. We conclude that, despite marked hemodynamic changes induced by pentobarbital, the rat with portal vein stenosis remains a useful experimental model of portal hypertension.

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.

Hemodynamic effects of a combination of clonidine and propranolol in conscious cirrhotic rats

1989 ◽  
Vol 67 (10) ◽  
pp. 1369-1372 ◽  
Author(s):  
Dominique Roulot ◽  
Christophe Gaudin ◽  
Alain Braillon ◽  
Tatsuya Sekiyama ◽  
Yannick Bacq ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Pressure ◽  
Biliary Cirrhosis ◽  
Hemodynamic Effects ◽  
Hemodynamic Changes ◽  
Flow Measurements ◽  
Before And After ◽  
Radioactive Microsphere Method ◽  
Blood Flow Measurements

The hemodynamic effects of the combination of clonidine and propranolol were studied in conscious rats with portal hypertension owing to secondary biliary cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed in three groups of eight rats before and after drug administration. The combined effects of clonidine (2 μg/100 g body wt., i.v.) and propranolol (0.2 mg/min for 10 min) were compared with those observed after administration of either clonidine alone or propranolol alone. The association of clonidine and propranolol induced significant decreases in portal pressure (30%) and portal tributary blood flow (43%), the magnitude of these changes being significantly more marked than that after administration of either clonidine alone (12 and 20%, respectively) or propranolol alone (16 and 17%, respectively). After the combination, no significant change in arterial pressure was observed, but cardiac output significantly decreased and systemic vascular resistance significantly increased. Renal blood flow decreased to a similar extent (40%) in the three groups. These findings indicate that the combination of clonidine and propranolol is more effective for reversing splanchnic hemodynamic changes than clonidine alone or propranolol alone. The additive effects of this association are in agreement with the action of clonidine and propranolol at different levels (central and peripheral) and on different receptors (α and β). It suggests that an increase in sympathetic activity may play a major role in hemodynamic changes observed in experimental cirrhosis.Key words: portal hypertension, cirrhosis, splanchnic blood flow, α2-adrenergic agonist, β-blocker.

Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats

1990 ◽  
Vol 259 (1) ◽  
pp. G21-G25 ◽  
Author(s):  
P. Genecin ◽  
J. Polio ◽  
L. A. Colombato ◽  
G. Ferraioli ◽  
A. Reuben ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Mean Arterial Pressure ◽  
Bile Acids ◽  
Portal Pressure ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Hypertensive Rats ◽  
Hyperdynamic Circulation ◽  
Portosystemic Shunting

Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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

HPB Surgery ◽  
1995 ◽  
Vol 8 (4) ◽  
pp. 223-229 ◽  
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.

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
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