760 SORAFENIB DECREASES PORTAL PRESSURE, PORTOSYSTEMIC COLLATERAL BLOOD FLOW AND SPLANCHNIC BLOOD FLOW IN RATS WITH PREHEPATIC PORTAL HYPERTENSION

2009 ◽  
Vol 50 ◽  
pp. S279
Author(s):  
T. Reiberger ◽  
B. Angermayr ◽  
P. Schwabl ◽  
N. Rohr-Udilova ◽  
M. Peck-Radosavljevic
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Pressure ◽  
Splanchnic Blood Flow ◽  
Collateral Blood Flow ◽  
Portosystemic Collateral

scholarly journals The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 60
Author(s):  
Philipp Schwabl ◽  
Eva Hambruch ◽  
Grant R. Budas ◽  
Paul Supper ◽  
Michael Burnet ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Target Genes ◽  
Portal Pressure ◽  
Farnesoid X Receptor ◽  
Systemic Hemodynamics ◽  
Splanchnic Blood Flow ◽  
Hydroxyproline Content ◽  
Sirius Red

Background: The farnesoid X receptor (FXR) influences hepatic metabolism, inflammation and liver fibrosis as key components of non-alcoholic steatohepatitis (NASH). We studied the effects of the non-steroidal FXR agonist cilofexor (formerly GS-9674) on portal pressure and fibrosis in experimental NASH. Methods: NASH was induced in Wistar rats using a choline-deficient high-fat diet plus intraperitoneal sodium nitrite injections. First, a dose-finding study was performed with 10 mg/kg and 30 mg/kg of cilofexor, focusing on histological readouts. Liver fibrosis was assessed by Picro-Sirius-Red, desmin staining and hepatic hydroxyproline content. Gene expression was determined by RT-PCR. In a subsequent hemodynamic study, rats received 30 mg/kg cilofexor with or without propranolol (25 mg/kg). Portal pressure, systemic hemodynamics and splanchnic blood flow were measured. Results: Cilofexor dose-dependently induced FXR target genes shp, cyp7a1 and fgf15 in hepatic and ileal tissues, paralleled by a dose-dependent reduction in liver fibrosis area (Picro-Sirius-Red) of −41% (10 mg/kg) and −69% (30 mg/kg), respectively. The 30 mg/kg cilofexor dose significantly reduced hepatic hydroxyproline content (−41%), expression of col1a1 (−37%) and pdgfr-β (−36%), as well as desmin area (−42%) in NASH rats. Importantly, cilofexor decreased portal pressure (11.9 ± 2.1 vs. 8.9 ± 2.2 mmHg; p = 0.020) without affecting splanchnic blood-flow or systemic hemodynamics. The addition of propranolol to cilofexor additionally reduced splanchnic inflow (−28%) but also mean arterial pressure (−25%) and heart rate (−37%). Conclusion: The non-steroidal FXR agonist cilofexor decreased portal hypertension and reduced liver fibrosis in NASH rats. While cilofexor seems to primarily decrease sinusoidal resistance in cirrhotic portal hypertension, the combination with propranolol additionally reduced mesenteric hyperperfusion.

Splanchnic blood flow in the monkey during hemorrhagic shock

1965 ◽  
Vol 208 (2) ◽  
pp. 265-269 ◽  
Author(s):  
Francis L. Abel ◽  
John A. Waldhausen ◽  
Ewald E. Selkurt
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Portal Vein ◽  
Hemorrhagic Shock ◽  
Hepatic Vein ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Mesenteric Arteries ◽  
Splanchnic Blood Flow

Blood flow in the celiac and superior mesenteric arteries was measured in nine Macaca monkeys during a standardized hemorrhagic shock procedure. Simultaneous pressures were obtained from the hepatic vein, portal vein, and aorta. Each animal was bled rapidly to an arterial pressure of 40 mm Hg and maintained at this level until 30% of the bled volume had spontaneously reinfused. The remaining blood was then rapidly reinfused and the animal observed until death. The results show a lack of overshoot of venous pressure on reinfusion, grossly pale intestines with some microscopic congestive changes, and a decrease in splanchnic conductance throughout the postinfusion period. Hepatic venous pressure exceeded portal pressure in six of the nine animals during the period of hemorrhage. The results are interpreted as indicative of insignificant splanchnic pooling during hemorrhagic shock in this animal.

Vascular NE responsiveness in portal hypertension: role of portal pressure and portosystemic shunting

1994 ◽  
Vol 266 (3) ◽  
pp. H1162-H1168 ◽  
Author(s):  
Z. Y. Wu ◽  
J. N. Benoit
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Pressure ◽  
Portacaval Shunt ◽  
Effective Dosage ◽  
Sprague Dawley ◽  
Blood Flow Reduction ◽  
Portosystemic Shunting ◽  
Venous Collaterals ◽  
On Line

Previous studies have suggested that the development of portal venous collaterals and subsequent portosystemic shunting is the key event responsible for the reduced vasoconstrictor effectiveness in chronic portal hypertension. The purpose of the present study was to test this hypothesis. Thirty-nine male Sprague-Dawley rats were divided into four groups: end-to-side portacaval shunt (PCS, n = 11), chronic prehepatic portal hypertension (CPH, n = 10), acute prehepatic portal hypertension (APH, n = 8), and sham-operated controls (Sham, n = 10). The small intestine was prepared for microcirculatory studies. First-order arteriolar diameter and erythrocyte velocity were measured on-line, and blood flow was subsequently calculated. Once steady-state values were obtained the preparation was topically exposed to incremental doses of norepinephrine. The half-maximal effective dosage (ED50) for maximal vasoconstriction (diameter response) was significantly increased in PCS (4.5 microM) and CPH (1.5 microM) compared with Sham (0.8 microM). However, the ED50 was significantly lower in APH (0.17 microM) than in Sham. Similarly the ED50 for maximal blood flow reduction was higher in PCS (2.4 microM) and CPH (1.2 microM) compared with Sham (0.2 microM). The results demonstrate that vascular norepinephrine responsiveness is reduced in both portacaval shunted and chronic portal hypertensive rats, but not in acute portal hypertension. These data indicate that portosystemic shunting, not portal pressure elevation, is the key event leading to the reduced vascular norepinephrine responsiveness observed in CPH conditions.

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)

scholarly journals Splanchnic Haemodynamics and Vasoactive Agents in Experimental Cirrhosis

HPB Surgery ◽  
1994 ◽  
Vol 8 (2) ◽  
pp. 83-88 ◽  
Author(s):  
J. G. Geraghty ◽  
W. J. Angerson ◽  
D. C. Carter
Keyword(s):  
Blood Flow ◽  
Hepatic Cirrhosis ◽  
Portal Pressure ◽  
Splanchnic Blood Flow ◽  
Vasoactive Agents ◽  
Experimental Cirrhosis ◽  
Haemodynamic Changes ◽  
Experimental Rat Model ◽  
Circulating Levels ◽  
Cirrhotic Group

It is well known that portal hypertension is associated with a hyperdynamic systemic circulatory state. This study measures systemic and splanchnic haemodynamics in an experimental rat model of hepatic cirrhosis. It also investigates the association between haemodynamic changes in cirrhotic animals and circulating levels of the vasoactive hormones glucagon and vasoactive intestinal polypeptide (VIP). Splanchnic blood flow was significantly increased in the cirrhotic group (13.2 ± 1.3 vs. 9.2 ± 1.6 ml/min, P < 0.05). Circulating levels of glucagon and VIP were two and five fold increased respectively in cirrhotic animals compared to controls. There was a strong correlation between portal pressure and glucagon levels in the cirrhotic group (r = 0.85). Raised splanchnic blood flow is partly responsible for elevated portal pressure in this model and this rise may be humorally mediated.

Effect of portacaval surgical anastomosis on systemic and splanchnic hemodynamics in portal hypertensive, cirrhotic rats

1988 ◽  
Vol 66 (12) ◽  
pp. 1493-1498 ◽  
Author(s):  
José M. Romeo ◽  
Antonio López-Farré ◽  
Vicente Martín-Paredero ◽  
José M. López-Novoa
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Portal Pressure ◽  
Reference Sample ◽  
Arterial Blood Flow ◽  
Splanchnic Blood Flow ◽  
Portacaval Anastomosis ◽  
Systemic Hemodynamic ◽  
Hyperdynamic Circulation ◽  
Arterial Blood

The effect of surgical end-to-side portacaval anastomosis (PCSA) on systemic and splanchnic circulation has been studied in cirrhotic rats with portal hypertension (CCl4–Phenobarbital method) and in control animals. Hemodynamics have been measured using the microsphere technique, with a reference sample for the systemic hemodynamic measurements, and intrasplenic injection for portal systemic shunting rate measurements. Compared with controls, sham-operated (SO) cirrhotic rats showed a hyperdynamic circulation with increased cardiac output (CO) and decreased mean arterial pressure and peripheral resistances. PCSA in control rats induced only a small change in systemic hemodynamics, with parallel decreases in arterial pressure and peripheral resistances, and a small, nonsignificant increase in CO. In cirrhotic rats, PCSA induced a decrease of CO to values similar to those of control rats, with an increase in total peripheral resistances. PCSA induced an increase in hepatic arterial blood flow in control and in cirrhotic rats, portal pressure becoming in this latter group not different from that of control rats. Blood flow to splanchnic organs was higher in SO cirrhotic than in SO control animals. Thus portal venous inflow was also increased in SO cirrhotic rats. PCSA induced an increase in portal venous inflow in control rats, which was only significant in cirrhotic rats when expressed as a percentage of CO. In SO control animals, a significant correlation was observed between total peripheral resistances and splanchnic arteriolar resistances and between CO and splanchnic blood flow. These correlations were not observed in cirrhotic rats. These results do not support the hypothesis that hyperdynamic circulation shown by cirrhotic rats is based on increases in splanchnic blood flow and (or) massive portal systemic shunting.

600 NEBIVOLOL TREATMENT INCREASES SPLANCHNIC BLOOD FLOW AND PORTAL PRESSURE IN CIRRHOTIC RATS VIA MODULATION OF NO SIGNALING

2013 ◽  
Vol 58 ◽  
pp. S245
Author(s):  
T. Reiberger ◽  
B.A. Payer ◽  
P. Schwabl ◽  
H. Hayden ◽  
T. Horvatits ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Pressure ◽  
Splanchnic Blood Flow ◽  
No Signaling
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