Increase In Portal Venous Flow Research Articles

Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats.

Hydrogen sulfide (H2S) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of H2S production within the gut lumen; this source of H2S is primarily produced and detoxified in the colon under physiologic conditions. Nitric oxide (NO), a major endogenous vasodilator in the portal circulation, participates in H2S-induced vasodilation in some vascular beds. We hypothesize that jejunal but not colonic H2S increases portal vein flow in a NO-dependent fashion. To evaluate the effects of luminal H2S, venous blood flow, portal venous pressure, and systemic venous pressure were measured in rats after administration of either vehicle or an H2S donor (NaHS) into the jejunum or the colon. We found that portal venous pressure and systemic pressure did not change and were similar between the three study groups. However, portal venous blood flow significantly increased following jejunal administration of NaHS but not in response to colonic NaHS or vehicle administration. To test the contribution of NO production to this response, another group of animals was treated with either an NO synthase inhibitor (N-Ω-nitro-L-arginine, L-NNA) or saline prior to jejunal NaHS infusion. After L-NNA pretreatment, NaHS caused a significant fall rather than increase in portal venous flow compared to saline pretreatment. These data demonstrate that H2S within the small intestine significantly increases portal venous blood flow in a NO-dependent fashion.

Hypotension in Cirrhosis.

Circulatory and cardiac compromise in cirrhosis has been well studied. The primary pathophysiology stems from portal hypertension, which is induced from an increased resistance to flow secondary to distorted sinusoidal architecture and is further sustained from an increase in portal venous flow.1 Portal hypertension induces both progressive splanchnic and systemic vasodilation mediated via nitric oxide and other vasoactive molecules secondary to endothelial stretching and sheer stress.2 A hyperdynamic state then ensues with an increase in cardiac output, increase in heart rate, and a low systemic vascular resistance secondary to systemic vasodilatation. The decreased effective arterial blood volume activates neurohormonal systems such as the renin‐angiotensin‐aldosterone system (RAAS), leading to further volume expansion via sodium and water retention. However, because of portosystemic shunting and splanchnic vasodilatation, effective central blood volume remains low and the hyperdynamic state continues, eventually leading to high‐output heart failure (Fig. ​(Fig.1).1). A lower mean arterial pressure (MAP) of 60 to 65 mm Hg is often tolerated in compensated and stable patients through these compensatory mechanisms, which allow end‐organ perfusion to be maintained.1, 2 Any degree of insult to this system can result in significant hypotension and decompensation. Open in a separate window Figure 1 Pathophysiology of hypotension in cirrhosis.

Haematological splenomegaly does not directly relate to portal hypertension: From a clinical study to surgical choice

Background: Splenomegaly induces an increased inflow into the portal venous system; however, in the absence of pathology of the liver and of a portal vein system, secondary portal hypertension is unusual. We analyzed this problem through a clinical observational method. Methods: We selected 20 patients with splenomegaly secondary to B-cell chronic lymphocytic leukaemia; their imaging tests and clinical pathways were re-examined. Results: In the absence of diseases of the liver or of the portal venous system, an increased portal blood flow, secondary to the splenomegaly, could not be considered the sole cause of portal hypertension. Conclusions: The normal liver has a high venous capacity, and in the absence of other factors, the sole increase in portal venous flow cannot directly justify portal hypertension. This conclusion is still well founded, even if multiple humoral mediators, some of which are also released from the spleen in a number of pathological conditions, can differentially modulate the haemodynamics of hepatic sinusoids.

Impact of Portal Hemodynamic Changes in Partial Liver Grafts on Short-Term Graft Regeneration in Living Donor Liver Transplantation.

Regeneration of partial liver grafts is critical for successful living donor liver transplantation (LDLT), especially in adult recipients. The purpose of this study was to investigate the intraoperative hemodynamic changes in partial liver grafts and characterize their potential impact on post-transplant liver regeneration in LDLT. We examined the portal venous flow (PVF) and hepatic arterial flow (HAF) to partial liver grafts by means of ultrasonic transit time flowmeter of donors immediately before graft retrieval and of the corresponding recipients after vascular reconstruction in 48 LDLT cases. We evaluated post-transplant liver regeneration according to the changes in graft liver volume between the time of transplantation and the 7th post-transplant day. There was a significant increase in PVF to the partial liver grafts in recipients (rPVF) compared with that in donors. In contrast, graft HAF in recipients significantly decreased compared with that in donors. The rPVF inversely correlated with graft weight (GW)-recipient body weight ratio (GRWR), whereas HAF volume showed no significant correlation. The rPVF/GW positively correlated with the rate of liver regeneration (GRR), which inversely correlated with GRWR. The rPVF/GW was significantly higher, and GRR tended to be larger in the small graft group than in the non-small graft group. Intraoperative portal hemodynamic changes in partial liver grafts strongly affect their post-transplant regeneration. In particular, in small liver grafts, an immediate and remarkable increase in graft PVF may contribute to rapid liver regeneration after LDLT if the increased PVF remains within a safe range.

Effect of TIPS placement on portal and splanchnic arterial blood flow in 4-dimensional flow MRI.

To assess changes in portal and splanchnic arterial haemodynamics in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) using four-dimensional (4D) flow MRI, a non-invasive, non-contrast imaging technique. Eleven patients undergoing TIPS implantation were enrolled. K-t GRAPPA accelerated non-contrast 4D flow MRI of the liver vasculature was applied with acceleration factor R = 5 at 3Tesla. Flow analysis included three-dimensional (3D) blood flow visualization using time-resolved 3D particle traces and semi-quantitative flow pattern grading. Quantitative evaluation entailed peak velocities and net flows throughout the arterial and portal venous (PV) systems. MRI measurements were taken within 24h before and 4weeks after TIPS placement. Three-dimensional flow visualization with 4D flow MRI revealed good image quality with minor limitations in PV flow. Quantitative analysis revealed a significant increase in PV flow (562 ± 373ml/min before vs. 1831 ± 965ml/min after TIPS), in the hepatic artery (176 ± 132ml/min vs. 354 ± 140ml/min) and combined flow in splenic and superior mesenteric arteries (770ml/min vs. 1064ml/min). Shunt-flow assessment demonstrated stenoses in two patients confirmed and treated at TIPS revision. Four-dimensional flow MRI might have the potential to give new information about the effect of TIPS placement on hepatic perfusion. It may explain some unexpected findings in clinical observation studies. • 4D flow MRI, a non-invasive, non-contrast imaging technique, is feasible after TIPS. • Provides visualization and quantification of hepatic arterial, portal venous, collateral and TIPS haemodynamics. • Better understanding of liver blood flow changes after TIPS and patient management.

Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension

Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon-occluded retrograde transvenous obliteration (B-RTO) can affect glucose and insulin metabolism in patients with LC. Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh's class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure. Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of β-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure. Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.

Effect of propofol on hepatic blood flow and oxygen balance in rabbits

Propofol has been reported to alter hepatic blood flow and to increase hepatic oxygen consumption. This study was designed to determine the effect of propofol on hepatic blood flow and oxygenation in rabbits, in order to establish its net effect on hepatic oxygen balance. Twenty, adult male, New Zealand white rabbits were randomly divided into two groups: Group P (propofol, 0.6 mg.kg(-1).min(-1)) or Group C (10% intralipid, 0.6 mg.kg(-1).min(-1)). An electromagnetic flowmeter was used to measure hepatic blood flow, and blood, from the carotid artery, the portal vein, and the hepatic vein, was used to determine hepatic oxygenation. After we obtained baseline values, we repeated measurements ten, 30, and 60 min after initiating the infusion. Intralipid did not affect systemic hemodynamics, hepatic blood flow, or oxygenation during the 60 min infusion; however, propofol caused a time-dependent decrease in mean arterial blood pressures and an increase in portal venous flow and total hepatic blood flow. In contrast, hepatic arterial blood flow remained unchanged during the propofol infusion. Hepatic oxygen delivery and consumption increased in a time-dependent manner to maximums of 25% and 21.4% (both, P < 0.05) above baseline, respectively. Hepatic venous oxygen saturation and extraction was unchanged throughout the study period. Propofol increases total hepatic blood flow, primarily by increasing hepatic portal venous flow. The increase in liver oxygen consumption was fully compensated by an increase in oxygen supply to the liver, resulting in a preserved, hepatic oxygen balance.

Measurement of portal venous flow velocity with an implantable miniature Doppler probe in pig liver transplantation.

Portal venous flow (PVF) was serially monitored after pig liver transplantation (LTX) with the use of an implantable, miniature Doppler probe developed in our laboratory. Throughout the study period, the mean PVF in pigs that underwent LTX was significantly greater than that in pigs that were sham operated. For three animals with early graft failure secondary to primary nonfunction and for six that survived longer than 7 days, the mean PVF on postoperative day (POD) 1 was 18.7 +/- 3.8 cm/s and 41.7 +/- 11.2 cm/s, respectively (P < 0.05). For animals with acute cellular rejection (ACR), the mean PVF was 61.3 +/- 9.9 cm/s on POD 7 and 54.3 +/- 6.38 cm/s on POD 14. These values were significantly higher than those for animals without ACR (P < 0.05). Moreover, the increase in PVF correlated well with the degree of ACR. The actual PVF volume was measured by ex vivo perfusion, which showed a clear correlation with the PVF velocity obtained with the implanted, miniature Doppler probe. We feel that the liver graft requires increased PVF volume after transplantation to facilitate functional recovery from damage to hepatocytes due to preservation-reperfusion injury, and that ACR is also associated with an increased PVF. We conclude that monitoring the PVF in the early postoperative period after LTX is useful in the evaluation of graft function, particularly for predicting primary nonfunction and severity of ACR.

Systemic and hepatic hemodynamic changes in acute liver injury.

Systemic and hepatic circulatory changes were studied in rats over the course of acute liver injury. Hepatic injury was induced by intraperitoneal injection of D-galactosamine (1.1 g/kg), and systemic and hepatic hemodynamics were measured over a 72-h period using a radioactive microsphere technique with direct measurement of arterial, portal venous, and hepatic venous blood oxygen content. Cardiac output increased to a maximum at 48 h, producing a marked increase (450%) in hepatic arterial blood flow so that it became the dominant supply of oxygen at the time of maximal hepatic injury. A subsequent increase in portal venous flow resulted in an overall increase in total hepatic blood flow of 500%. At this point the oxygen delivery by the hepatic arterial and portal venous systems was equal. These circulatory changes returned to control values by 72 h with recovery of liver function. These results demonstrate the development of a hyperdynamic circulation and a marked change in the normal relationship between portal venous and hepatic arterial blood flows that occur during hepatic injury.

Recovery of portal blood flow after percutaneous transhepatic biliary drainage in patients with obstructive jaundice.

Using an ultrasonic Doppler system, we prospectively studied the changes in portal venous flow (PVF) following percutaneous transhepatic biliary drainage (PTBD) and evaluated the correlation between PVF and liver function in 10 patients with obstructive jaundice. The patients were divided into two groups according to their rate of decrease in serum bilirubin ("b"). Group A comprised 5 patients with a "b" of less than -0.1, while group B consisted of 5 patients who did not meet this criterion. The mean PVF increased following PTBD (P < 0.01). The increase in PVF was due to an increase in the maximum velocity of the portal vein (Vmax). The rate of increase in the Vmax in group A was significantly higher than that in group B on both the 7th and 14th postdrainage days (P < 0.05). The rate of increase in the Vmax correlated significantly with the rate of decrease in the serum bilirubin concentration (P < 0.01). Based on the above findings, we conclude that measuring the Vmax by Doppler ultrasonography is useful in evaluating the liver function in patients with obstructive jaundice.

Effectiveness of combined anticoagulant therapy for extending portal vein thrombosis in Crohn's disease

Portal vein thrombosis is a rare complication of Crohn's disease, and its precise cause and appropriate treatment are not known. We describe a patient with extending portal vein thrombosis in Crohn's disease who was successfully treated with combined anticoagulant therapy. Urokinase and tissue plasminogen activator were administered from a catheter inserted into the superior mesenteric artery, and heparin and a serine protease inhibitor also were given intravenously. On admission, thromboembolic occlusion was observed throughout the entire portal venous system in association with massive ascites and remarkable intestinal edema. After administration of combined anticoagulant therapy, thrombus rapidly decreased in size, and color Doppler ultrasonography showed a gradual increase in portal venous flow. The patient had no recurrence of symptoms while receiving warfarin after resolution of thrombus. This case report suggests that combined anticoagulant therapy is effective for patients with severe portal vein thrombosis in Crohn's disease and that color Doppler ultrasonography is useful for evaluation of portal venous flow.

Enhancement of portal blood flow by ursodesoxycholic acid in partially hepatectomized rats.

Portal venous flow (PVF) was examined after portal injection of ursodesoxycholic acid (URSO) in rats that were partially hepatectomized by either 40% or 66%. URSO (10 mg/kg per minute) was injected into the portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal venous pressure (PVP) in control animals. The increase in PVF in response to URSO was dose-dependent. In hepatectomized rats, the PVF response was augmented when the same dose of URSO was portally injected, and the magnitude of response was enhanced in proportion to the volume of liver resected. These results suggest that URSO increases PVF through vasodilation of the portal vessels, and therefore URSO is considered to increase PVF potently in a partially hepatectomized condition.

Short- and long-term hemodynamic effects of transjugular intrahepatic portosystemic shunts: a Doppler/manometric correlative study.

The purposes of this study were to evaluate the effect of a well-functioning transjugular intrahepatic portosystemic shunt (TIPS) on the splanchnic and intrahepatic circulation, to determine if sonographic measurements can predict shunt dysfunction before clinical manifestations of portal hypertension occur, and to compare Doppler sonographic findings with portocaval gradient measurements before and after shunt revision. Forty-four patients with cirrhosis (n = 43) and myelofibrosis (n = 1) who underwent successful TIPS insertion were included in this prospective study. Indications for TIPS placement were: refractory ascites (24 patients), bleeding esophageal varices (17 patients), portal hypertensive gastropathy (two patients), and bleeding colonic varices (one patient). The portal vein and the inferior vena cava were catheterized; and the portocaval gradient was recorded before TIPS placement, at 2 and 12 months after TIPS placement, and when clinical or Doppler findings suggested shunt dysfunction. Doppler studies were done within 1 week before TIPS placement, within 2 days after TIPS placement, every 2-3 months thereafter, and before and after a TIPS revision. The Doppler studies included flow volume measurements in the portal vein and in the stent, as well as determination of the direction of flow in the segmental branches of the portal vein, in the splanchnic veins, and in portosystemic collaterals. Changes in Doppler findings and in catheter pressure measurements were compared using Spearman's rank correlation test. Significance was set at the .05 level. A marked decrease (-51%) in portocaval gradient was observed after TIPS placement. At Doppler sonography, portal vein velocity and diameter were both higher after TIPS placement, resulting in a marked increase in portal venous flow (170%). Mean flow velocity in the shunt was 55.8 +/- 3.6 cm/sec, and flow volumes in the shunt and in the main portal vein were 1596 ml/min and 1731 ml/min, respectively (p = nonsignificant). Dysfunction of the stent occurred in 27% of the patients. Changes in stent blood flow volume were closely related to changes in the portocaval gradient (r = -0.67, p < .001). Reduction of blood flow volume in the stent or change of direction of flow in intrahepatic portal veins or in collateral veins signaled shunt dysfunction (84% sensitivity, 89% specificity). Marked hemodynamic changes in the portal venous system occur soon after a TIPS procedure. Monitoring of shunt function with periodic Doppler sonography, including calculation of shunt blood flow, is useful in detecting shunt dysfunction before clinical signs occur.

A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats.

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 micrograms/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 micrograms/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 micrograms/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 micrograms/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.

Prostaglandin E1 enhances hepatic portal venous flow by dilating the portal vascular bed in 70% hepatectomized dog.

The effects of portal, hepatic arterial and femoral venous administration of prostaglandin E1 (PGE) on portal venous flow (PVF) and hepatic arterial flow HAF were examined before and after 70% hepatectomy in anesthetized dogs. In the hepatectomized condition, portal venous administration of PGE (0.5 microgram/kg/min) caused an increase in PVF without any change in systemic arterial pressure (SAP). HAF was unchanged following the injection. The portal effect of PGE on PVF was dose-dependent, and a reduction in portal venous resistance was seen. However, the same dose of PGE failed to change PVF under intact liver conditions. Hepatic arterial administration of PGE (0.5 microgram/kg/min) brought no significant change in PVF or HAF, with or without hepatectomy. Femoral venous administration of PGE (0.5 micrograms/kg/min) produced an increase in PVF concomitant with a significant decrease in SAP. HAF showed no change after the injection. A decrease in PVR was seen only in the hepatectomized condition. It is concluded that PGE is potent in increasing PVF in the hepatectomized condition, and the portal vasculature is involved as the site of action.

Effect of secretin on portal venous flow.

In this study we evaluated the effect of two different doses of secretin on portal haemodynamics (by pulsed Doppler associated with real time ultrasound) in 24 healthy humans. In 12 subjects (group A) we administered an intravenous dose of 75 clinical units of secretin and in the remaining 12 (group B) a dose of 20 CU. In all subjects the following parameters were studied before, during, and for 10 minutes after secretin administration: (a) calibre of the portal vein, (b) mean velocity of portal venous flow, and (c) volume of portal venous flow. In three subjects in each group we also evaluated the changes in flow in the superior mesenteric artery. Secretin injection induced a slight increase in both groups in comparison to basal values of portal vein calibre (mean of maximal per cent increase +25% in group A, not significant, and +16.7% in group B, not significant) and a noticeable increase of mean velocity (mean of maximal per cent increases +61.4% in group A, p less than 0.005, and +65.4% in group B, p less than 0.01) and flow volume (mean of maximal per cent increase +127% group A, p less than 0.005, and +114% group B, p less than 0.005). The magnitude of the haemodynamic changes did not differ significantly between the two groups. Doppler investigation of the superior mesenteric artery showed a marked increase of flow velocity (mean of maximal per cent increase +218% in group A and +246% in group B) and flow volume (mean of maximal per cent increase +276% in group A and +311% in group B). These data suggest that secretin has an appreciable vasoactive effect and induces a significant increase in portal venous flow even at doses much lower than those necessary for a maximal stimulation of exocrine pancreatic secretion.

Development of a chronic canine model for measurement of absorption by substrate appearance in portal venous blood.

Research in absorption physiology requires animal models which closely resemble the in vivo situation. The description of a new canine model satisfying these requirements is the objective of this report. Dogs were instrumented with indwelling portal vein and carotid artery catheters, a catheter jejunostomy and an electromagnetic flow measuring probe around the portal vein enabling continuous flow recordings. Following intrajejunal infusion of nutritive substrates in the conscious animal, absorption was measured as the product of porto-arterial substrate difference and portal venous flow. The model was validated in five mongrel dogs: (1) Catheters and flow measuring device function over several months. (2) The sensitivity of the method was evaluated following intrajejunal infusion of l-glycine-l-tyrosine and its constituent amino acids. A significant portoarterial concentration difference of both amino acids enabling quantitative measurement of absorption resulted when the peptide was infused at 4 mmoles/hour (20 mM solution, 200 ml/h). (3) Infusion of complete nutritive formulas caused a significant increase in portal venous flow whereas neither saline nor the amino acids or the peptides investigated had a comparable effect. (4) A validation experiment by implantation of a second flow probe distal to the chronically implanted device provided evidence that granulomatous tissue forming around the probe does not alter the accuracy of the flow recording. In summary, this method permits for the first time quantitative measurement of absorption by appearance rates in portal venous blood instead of by disappearance from the intestinal lumen.

Prostacyclin increases portal venous flow

Prostacyclin (PGI 2) is a potent vasolidator and is a potential therapeutic agent to increase blood flow during several disease states. PGI 2 is alos elevated in plasma during sepsis or pancreatitis. The hemodynamic effect of PGI 2 has not been investigated with regard to the portal venous system. In five anesthetized swine, cardiac output (CO), central venous pressure (CVP), femoral artery pressure (FAP), heart rate (HR), pulmonary artery pressure (PAP), portal venous flow (PoVF), and portal venous pressure (PoVP) were measured before and after increasing doses of PGI 2. The infusions were then repeated after atropine administration. The previously reported effects on the peripheral and pulmonary vascular systems were confirmed. after an injection of 0.5 to 5.0 ug/kg of PGI 2 into the left atrium, a significant decline in CO, FAP, and PAP occured. Atropinization further depressed CO. The most marked effecr of PGI 2, however, was an increase in PoVF without a change in PoVP. This effect was more pronounced when atropine was administered. In anethetized swine, PGI 2 is a potent vasodilator in all vascular beds, including the portal venous system. These hemodynamic changes should be realized when exogenous PGI 2 is considered as a therapeutic agent or when endogenous PGI 2 might increase in association with disease states like pancreatitis or sepsis.

The effect of environmental cooling on gastrointestinal thermogenesis in the anaesthetized dog

The effect of environment cooling on gastrointestinal thermogenesis in the anaesthetized warm-acclimatized dog was investigated. Changing ambient temperature from 29° ± 1.7° to 21.0° ± 0.8° C caused: 1. (1) increases in stomach-aorta, duodenum-aorta and portal vein-aorta temperature differences. 2. (2) significant increase in portal venous flow from 246.4 ± 21.5 − 331.62 ± 11.85 ml/min. 3. (3) an increase of 112.46% in the total gastrointestinal heat production (i.e. from 56.2 cal/min to 127.82 ± 4.88 cal/min. 4. (4) an increase of 46.8% in the gut oxygen consumption. The contribution of oxidative to total gut heat production in the warm environment was 77.0%. This reduced to 52.8% on environmental cooling. The result provides further support for the claim that gastrointestinal thermogenesis cannot be wholly explained on the basis of oxidative processes alone.