Cirrhosis regression: extrahepatic angiogenesis and liver hyperarterialization persist

2018 ◽  
Vol 132 (12) ◽  
pp. 1341-1343
Author(s):  
Audrey Payancé ◽  
Pierre-Emmanuel Rautou
Keyword(s):  
Vascular Resistance ◽  
Antiviral Treatment ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Systemic Hemodynamics ◽  
Marginal Effect ◽  
Hemodynamic Changes ◽  
Systemic Hemodynamic ◽  
Duct Ligation ◽  
Intrahepatic Vascular Resistance

Data on the consequences of cirrhosis regression on portal hypertension and on splanchnic and systemic hemodynamic are scarce. Previous studies have reported a decrease in hepatic venous pressure gradient following antiviral treatment in patients with hepatitis B or C related cirrhosis. However, these studies did not investigate splanchnic and systemic hemodynamic changes associated with virus control. To fill this gap in knowledge, in a recent issue of Clinical Science, Hsu et al. (vol. 132, issue 6, 669-683) used rat models of cirrhosis induced by thioacetamide and by bile duct ligation and provided a comprehensive analysis of the effects of cirrhosis regression on splanchnic and systemic hemodynamics. They observed a significant reduction in portal pressure accompanied by a normalization of systemic hemodynamic (normal cardiac index and systemic vascular resistance) and a decrease in intrahepatic vascular resistance. No change in extrahepatic vascular structures were observed despite normalization of collateral shunting, meaning that portosystemic collaterals persist but are not perfused. One intriguing part of their results is the only marginal effect of cirrhosis regression on liver hyperarterialisation. This result suggests that changes in splanchnic hemodynamic features induced by cirrhosis remain when hepatic vascular resistance decreases, raising the hypothesis of an autonomous mechanism persisting despite regression of intrahepatic vascular resistance. Microbiota changes and bacterial translocation might account for this effect. In conclusion cirrhosis regression normalizes systemic hemodynamics, but some splanchnic hemodynamic changes persist including extrahepatic angiogenesis and liver hyperarterialization.

Discrepancy between portal pressure and systemic hemodynamic changes after incremental doses of propranolol in a wake portal hypertensive rats

Hepatology ◽  
1989 ◽  
Vol 9 (2) ◽  
pp. 269-273 ◽  
Author(s):  
Abraham Koshy ◽  
Catherine Girod ◽  
Samuel S. Lee ◽  
Antoine Hadengue ◽  
Raimondo Cerini ◽  
...  
Keyword(s):  
Portal Pressure ◽  
Hypertensive Rats ◽  
Hemodynamic Changes ◽  
Systemic Hemodynamic

Splanchnic and systemic haemodynamic response to volume changes in patients with cirrhosis and portal hypertension

1999 ◽  
Vol 96 (5) ◽  
pp. 475-481 ◽  
Author(s):  
Panagiotis VLAVIANOS ◽  
Padraik MAC MATHUNA ◽  
Roger WILLIAMS ◽  
David WESTABY
Keyword(s):  
Cardiac Output ◽  
Portal Hypertension ◽  
Systemic Vascular Resistance ◽  
Blood Volume ◽  
Vascular Resistance ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Haemodynamic Response ◽  
Volume Depletion ◽  
Compensated Cirrhosis

We investigated the haemodynamic response to volume depletion and subsequent repletion in patients with cirrhosis and portal hypertension. Twelve patients with compensated cirrhosis and portal hypertension were included in the study. The haemodynamic changes occurring after removal of approx. 15% of the blood volume, and subsequently after isovolume repletion with colloid, were assessed. Baseline haemodynamic measurements showed increased cardiac output and a systemic vascular resistance at the lower limit of normal. The hepatic venous pressure gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure, cardiac output and all right-heart-sided pressures decreased, and systemic vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes were statistically significant. After blood volume restitution, the haemodynamic values returned to baseline. In particular, an increase in HVPG was shown in four out of the twelve patients (two with ascites and two without), which was small in three of them. However, HVPG remained the same as or lower than the baseline in the other eight patients. Patients with cirrhosis and portal hypertension exhibit an abnormal haemodynamic response to blood volume depletion. After volume repletion, no increase in the portal pressure was noted in this group of patients as a whole, although four out of the twelve patients did show an increase, possibly due to extensive collateral circulation.

Arterial Inflow Into the Mesenteric and Hepatic Vascular Circuits During Hemorrhagic Shock

1956 ◽  
Vol 185 (2) ◽  
pp. 365-371 ◽  
Author(s):  
Theodore E. Cull ◽  
Mario P. Scibetta ◽  
Ewald E. Selkurt
Keyword(s):  
Hemorrhagic Shock ◽  
Hepatic Artery ◽  
Vascular Resistance ◽  
Mesenteric Artery ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Outflow Resistance ◽  
Arterial Inflow ◽  
Flow Changes ◽  
Artery Flow

Mesenteric artery and hepatic artery flows were studied in dogs during a standardized hemorrhagic shock procedure. Both flows decreased in response to hemorrhage, with development of greater vascular resistance in the hepatic artery circulation. Toward the end of the hypotensive period vascular resistance in the mesenteric artery often entered a declining phase, correlated with an increase in portal venous pressure, but hepatic artery resistance increased somewhat further. On transfusion, mesenteric artery flow increased rapidly, often exceeding the control values. Portal pressure doubled, and mesenteric resistance decreased to values less than control for about 30 minutes. This may represent a phase of pooling and trapping of blood in the capillaries and venules of the mesenteric circulation favored by reduced inflow resistance, and increased outflow resistance. This was followed by a phase of increased mesenteric resistance which often persisted until the demise of the animal, although it decreased in some animals during the terminal stage. Following transfusion, hepatic artery flow increased more gradually than mesenteric artery flow and reached a peak about 1 1/2 hours post-transfusion, at a time when flow in the mesenteric artery was markedly reduced and its resistance was maximal. The mechanism of this reciprocity of flow and resistance is discussed and its relevance to the interpretation of the hepatic artery flow changes in shock is considered.

Passive autoregulation of portal venous pressure: distensible hepatic resistance

1992 ◽  
Vol 263 (5) ◽  
pp. G702-G708 ◽  
Author(s):  
W. W. Lautt ◽  
D. J. Legare
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Portal Blood Flow ◽  
Minor Effect ◽  
Basal Resistance ◽  
Resistance Vessels

Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined.

Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis

2013 ◽  
Vol 305 (7) ◽  
pp. G496-G502 ◽  
Author(s):  
María Gabriela Delgado ◽  
Jordi Gracia-Sancho ◽  
Giusi Marrone ◽  
Aina Rodríguez-Vilarrupla ◽  
Ramon Deulofeu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Vascular Resistance ◽  
Vascular Tone ◽  
Leptin Receptor ◽  
Portal Pressure ◽  
Systemic Hemodynamics ◽  
Receptor Blockade ◽  
Nitric Oxide Bioavailability

Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2− levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.

Effect of hepatic venous sphincter contraction on transmission of central venous pressure to lobar and portal pressure

1987 ◽  
Vol 65 (11) ◽  
pp. 2235-2243 ◽  
Author(s):  
W. Wayne Lautt ◽  
Dallas J. Legare ◽  
Clive V. Greenway
Keyword(s):  
Vascular Resistance ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Vena Cava ◽  
Pressure Rise ◽  
Portal Venous Pressure ◽  
Small Rise ◽  
Venous Resistance ◽  
Small Increments ◽  
Control State

In dogs anesthetized with pentobarbital, central vena caval pressure (CVP), portal venous pressure (PVP), and intrahepatic lobar venous pressure (proximal to the hepatic venous sphincters) were measured. The objective was to determine some characteristics of the intrahepatic vascular resistance sites (proximal and distal to the hepatic venous sphincters) including testing predictions made using a recent mathematical model of distensible hepatic venous resistance. The stimulus used was a brief rise in CVP produced by transient occlusion of the thoracic vena cava in control state and when vascular resistance was elevated by infusions of norepinephrine or histamine, or by nerve stimulation. The percent transmission of the downstream pressure rise to upstream sites past areas of vascular resistance was elevated. Even small increments in CVP are partially transmitted upstream. The data are incompatible with the vascular waterfall phenomenon which predicts that venous pressure increments are not transmitted upstream until a critical pressure is overcome and then further increments would be 100% transmitted. The hepatic sphincters show the following characteristics. First, small rises in CVP are transmitted less than large elevations; as the CVP rises, the sphincters passively distend and allow a greater percent transmission upstream, thus a large rise in CVP is more fully transmitted than a small rise in CVP. Second, the amount of pressure transmission upstream is determined by the vascular resistance across which the pressure is transmitted. As nerves, norepinephrine, or histamine cause the hepatic sphincters to contract, the percent transmission becomes less and the distensibility of the sphincters is reduced. Similar characteristics are shown for the "presinusoidal" vascular resistance and the hepatic venous sphincter resistance. Finally, a unit of pressure rise in downstream pressure will be more completely transmitted upstream as the basal starting downstream pressure is increased. These data fulfill the predictions of the distensible hepatic venous sphincter model developed for the cat liver and are incompatible with the Starling resistor – vascular waterfall theory. The distensible hepatic venous resistance allows the splanchnic blood volume to most efficiently buffer the largest changes in CVP by transmitting proportionately more pressure to the highly compliant splanchnic vessels. In addition the distensible sphincters serve to autoregulate portal venous pressure. As portal flow changes, the passively distensible sphincters minimize changes in PVP.

scholarly journals The beneficial effects of curcumin in cirrhotic rats with portal hypertension

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Shao-Jung Hsu ◽  
Jing-Yi Lee ◽  
Te-Yueh Lin ◽  
Yu-Hsin Hsieh ◽  
Hui-Chun Huang ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Vascular Resistance ◽  
Portal Pressure ◽  
Acute Administration ◽  
Vegf Receptor ◽  
Variceal Hemorrhage ◽  
Common Bile Duct Ligation ◽  
Duct Ligation ◽  
Portosystemic Collaterals

In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague–Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral in situ perfusion was performed to evaluate vascular activity. Chronic curcumin treatment decreased portal pressure (PP), cardiac index (CI) and increased systemic vascular resistance (SVR) in cirrhotic rats. In splanchnic system, curcumin decreased superior mesenteric artery (SMA) flow and increased SMA resistance. Mesenteric angiogenesis was attenuated by curcumin. Acute administration of curcumin significantly induced splanchnic vasoconstriction. The mesenteric protein expressions of p-endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX) 2 (COX2), vascular endothelial growth factor (VEGF), p-VEGF receptor 2 (VEGFR2), and p-Erk were down-regulated. In collateral system, curcumin decreased portosystemic shunting and induced vasoconstriction. In conclusion, chronic curcumin administration in cirrhotic rats ameliorated portal hypertension related hemodynamic derangements and portosystemic collaterals. Curcumin also attenuated splanchnic hyperdynamic circulation by inducing vasoconstriction through inhibition of eNOS activation and by decreasing mesenteric angiogenesis via VEGF pathway blockade.

Gastrointestinal hemodynamics during compensation for hemorrhage and measurement of Pmcf

1994 ◽  
Vol 266 (3) ◽  
pp. H1242-H1250
Author(s):  
C. F. Rothe ◽  
R. Maass-Moreno
Keyword(s):  
Vascular Resistance ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Peripheral Resistance ◽  
Portal Flow ◽  
Total Blood ◽  
Flow Measurements ◽  
Control Value ◽  
Vascular Compliance ◽  
Autonomic Blockade

To quantify the degree of autonomic reflex control of the gastrointestinal vasculature, we studied the responses to a 10-ml/kg hemorrhage or transfusion and autonomic blockade in fentanyl- and pentobarbital-anesthetized dogs. The active total blood volume was estimated by indocyanine green dilution. Transfusion and hemorrhage did not significantly change gastrointestinal vascular compliance [1.82 +/- 0.68 (SD) ml/mmHg], but autonomic blockade with hexamethonium and atropine increased it by 0.57 +/- 0.37 ml/mmHg. Neither hemorrhage nor autonomic blockade significantly changed gastrointestinal vascular resistance from its control value of 10.8 +/- 4 mmHg.ml-1.min.kg body wt, but transfusion reduced it by 3.0 +/- 1.2 mmHg.ml-1.min.kg body wt. The ratio of gastrointestinal vascular resistance to total peripheral resistance was not significantly changed, however. We conclude that vascular compliance and resistance of the gastrointestinal bed are minimally influenced by the autonomic nervous system under the conditions studied. Portal pressure and flow measurements (transit-time ultrasound) during the above maneuvers were also combined with estimations of mean circulatory filling pressure (Pmcf) to test the hypothesis that, when the heart is stopped to measure Pmcf, portal pressure equals central venous pressure (Pcv) and hence that portal flow is zero. Seven seconds after the heart was stopped, portal venous pressure (Ppv) remained 0.83 +/- 0.78 mmHg higher than Pcv and portal flow decreased to only 25% of its control value. However, gastrointestinal compliance times (Ppv-Pcv), an estimate of the extra distending volume, was only 0.07 +/- 0.07 ml/kg body wt. Thus we conclude that the error in estimating Pmcf, given this (Ppv-Pcv) difference, is physiologically insignificant.

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