Postprandial splanchnic haemodynamic changes in patients with liver cirrhosis and patent paraumbilical vein

OBJECTIVE: The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). METHODS: We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. RESULTS: We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. CONCLUSIONS: PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.     

Postprandial middle cerebral arterial vasoconstriction in cirrhotic patients. A placebo, controlled evaluation

BACKGROUND/AIMS: The objective of this study was to determine whether cerebral arterial vasoconstriction occurs in relation to postprandial splanchnic blood pooling in cirrhotic patients. METHODS: The pulsatility and the resistive indexes and blood flow in the middle cerebral artery were measured by magnetic resonance imaging in 21 cirrhotics and 14 controls. These measurements were repeated 30 min after ingestion of a 400 kcal liquid meal or placebo. Seven controls and 14 patients received the meal, and seven controls and seven patients received placebo. RESULTS: In the fasting conditions, cirrhotics had a greater pulsatility index (0.81 +/- 0.10 vs. 0.67 +/- 0.05, P < 0.001) and a greater resistive index (0.61 +/- 0.04 vs. 0.53 +/- 0.04, P < 0.001) and a lower blood flow (127 +/- 42 ml/min vs. 167 +/- 37 ml/min, P < 0.03) in the middle cerebral artery compared with controls. Meal ingestion significantly increased the pulsatility index (P < 0.03) and the resistive index (P < 0.01) and decreased blood flow (P < 0.03) in the middle cerebral artery in cirrhotics but not in controls. In contrast, placebo ingestion had no effect on the hemodynamic parameters in the middle cerebral artery in the two groups. CONCLUSIONS: Results support the hypothesis that middle cerebral arterial vasoconstriction seen in cirrhotic patients is one of the cerebral artery's homeostatic responses to underfilling of the splanchnic arterial circulation.     

Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: an operator-blind echo-Doppler study

In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity.     

Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: A double-blind randomized echo-doppler study

The effect of octreotide, a long-acting synthetic analog of somatostatin, on fasting and postprandial splanchnic hemodynamics was investigated in cirrhotic patients. Splanchnic hemodynamics were assessed using an echo-Doppler duplex system in a prospective, double-blind, placebo-controlled, crossover study performed on 2 separate days, 1 week apart, in 30 cirrhotic patients. Measurements of portal vein (PV) cross-sectional area (PVA) and mean velocity (PV-V), and of superior mesenteric artery (SMA) mean velocity (SMA-V) and pulsatility index (SMA-PI) (an index of vascular resistance) were performed at baseline, 30 minutes after octreotide (200 μg subcutaneously) or placebo administration, and 30 and 60 minutes after the ingestion of a liquid meal. In the fasted state, octreotide induced a significant decrease in PV-V (−7%) and in SMA-V (−10%) and an increase in PI (+16%). On the day of placebo administration, meal ingestion induced a significant increase in PV-V (+21%) and in SMA-V (+43%) and a decrease in PI (−21%). In contrast, meal ingestion on octreotide day induced significantly smaller increases in PV-V (+10%) and in SMAV (+18%) and a significantly smaller decrease in PI (−10%). Octreotide, although producing a mild reduction in PV-V and SMA-V in the fasted state, markedly blunts postprandial splanchnic hyperemia in cirrhotic patients.     

Influence of esophageal varices and spontaneous portal-systemic shunts on postprandial splanchnic hemodynamics

OBJECTIVE: The aim of the study was to assess postprandial splanchnic hemodynamic changes in cirrhosis in relation to variceal status. METHODS: In 9 healthy controls and 56 patients with liver cirrhosis, stratified according to variceal status and presence of spontaneous portal-systemic shunts, the portal vein diameter and flow velocity, the congestion index of the portal vein, and the resistive index of the superior mesenteric artery (SMA-RI) were studied by Doppler ultrasound before and 30, 60, and 120 min after the intake of a standard meal. Comparison of postprandial parameters with basal ones was done within each group by paired t test and among groups by ANOVA and Duncan test. RESULTS: Healthy controls and cirrhotic patients without varices showed similar significant splanchnic hemodynamic changes, namely a reduction of SMA-RI (-13% at 30 min) and a consequent increase in portal vein diameter (respectively, +32% and +17% in the two groups) and velocity (+66% and +51%). A significant reduction of SMA-RI was also found in patients with varices, irrespective of the variceal size (range, -7 to -11%), but the expected portal vein dilation and velocity increase were progressively blunted with the increase of variceal size (range, 0-5% for diameter and 5-19% for velocity). Patients with spontaneous portal-systemic shunts showed a response similar to that of patients with large varices. Significant modification of the congestion index of the portal vein did not occur in any group. CONCLUSIONS: Our results show that the hemodynamic response to meal in patients with liver cirrhosis is influenced by the presence and size of esophageal varices and the presence of spontaneous portal-systemic shunts.     

Mesenteric blood flow is related to disease activity and risk of relapse in Crohn''s disease: a prospective follow-up study

OBJECTIVE: The diagnostic significance of increased splanchnic blood flow in Crohn's disease is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. METHODS: Splanchnic flowmetry was performed in 59 patients with Crohn's disease and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Twenty-one patients measured during the active state and in clinical remission were followed-up for 6 months. Hemodynamic parameters of the superior and inferior mesenteric arteries and the portal vein were related to clinical (Crohn's disease activity index [CDAI]), laboratory (C-reactive protein), and endoscopic (Crohn's Disease Endoscopic Index of Severity) parameters of disease activity. RESULTS: The postprandial mean velocity of the superior mesenteric artery correlated closest with clinical activity (CDAI, p < 0.005) and C-reactive protein (p < 0.01), but was unrelated to endoscopic activity. All patients in remission after 6 months (9/9) showed an increase in postprandial pulsatility index of the superior mesenteric artery, compared with an initial measurement during active disease (+28%). In contrast, the majority of patients with later relapse or surgery (11/12) had decreased pulsatility index during initial remission (-20%). The positive predictive value of this index for maintenance of remission was 0.82. CONCLUSIONS: Postprandial flow measurements in the superior mesenteric artery are closely related to clinical but not endoscopic disease activity in patients with Crohn's disease. The repeated measurement of the postprandial pulsatility index allows estimation of the risk of recurrence.     

Superior mesenteric artery impedance in chronic liver diseases: relationship with disease severity and portal circulation

Objective: The increase of splanchnic blood flow volume in liver cirrhosis is attributed to decreased arterial resistance. The aim of this study was to noninvasively investigate superior mesenteric artery impedance in patients with chronic liver diseases and to assess its relationship with portal hemodynamics and with clinical parameters.
Methods: Superior mesenteric artery (SMA) pulsatility (SMA-PI) and resistance (SMA-RI) indices and portal vein flow parameters (velocity, volume, and congestion index) were measured by duplex-Doppler ultrasound in 14 patients with chronic hepatitis, in 73 cirrhotics, in 30 liver transplant recipients, and in 31 control subjects.
Results: SMA-PI significantly differed among the five groups (   p < 0.0001  ), being lower in cirrhotics (2.55 ± 0.70) and transplanted patients (2.77 ± 0.69) than in chronic hepatitis (3.28 ± 0.57) and control subjects (3.42 ± 0.92). SMA-PI was lower in ascitic cirrhosis (2.40 ± 0.71) than in compensated cirrhosis (2.71 ± 0.70) (   p < 0.01  ) and in cirrhotics with large varices (2.30 ± 0.67) than in those without varices (2.75 ± 0.65) (   p < 0.05  ). Moreover SMA-PI correlated with numeric Child-Pugh score (  r =−0.28  ) and portal vein congestion index (  r =−0.36  ).
Conclusion: Hyperdynamic splanchnic circulation, noninvasively assessed by a decrease of mesenteric artery impedance, occurs in cirrhosis since the early stage of the disease and tends to worsen in relation to liver failure and the severity of portal hypertension. Furthermore, the persistent SMA-PI decrease in transplant recipients suggests a consistent contribution to this circulatory alteration from a patent portosystemic collateral circulation.     

Increased splanchnic arterial vascular resistance in oldest old patients

OBJECTIVES: The aim of this study was to evaluate possible age-related changes in mesenteric artery and portal venous blood flow dynamics in relation to systemic haemodynamics in order to delineate putative haemodynamic changes relevant for postprandial hypotension in the elderly. Studies were performed over a wide age-range and for the first time in over 85-year-old patients. DESIGN: Superior mesenteric artery (SMA) parameters (diameter, peak systolic velocity, end diastolic velocity, pulsatility index, volume flow) and portal vein (PV) parameters (diameter, portal vein velocity, volume flow) were measured by duplex ultrasound (General Electrics, Vivid 3) in 98 fasting subjects aged from 21 to 96 years. Systemic vascular parameters such as blood pressure, heart rate and cardiac output (echocardiography) were also determined. Excluded were patients with severe heart failure, liver cirrhosis, sepsis and those with mesenteric artery stenosis. RESULTS: Pulsatility index (PI) was positively correlated with age (r=0.33, p=0.015). In patients over 85 years, PI was significantly increased (p=0.002) as compared to younger controls. Cardiac output was negatively correlated with age (r=-0.247, p=0.005). The other haemodynamic parameters did not show age-dependent alterations. CONCLUSION: The increase of PI in the SMA in patients over 85 years represents an increase of vascular resistance in the splanchnic area, because PI is sensitive to resistance changes of small arterial vessels. The pulsatility index in the splanchnic area seems to rise steeply in oldest old patients, probably as an attempt to compensate diminutions in cardiac output seen in this age group. These findings indicate that the splanchnic vascular bed is already used in the fasting state to guarantee systemic haemodynamics. Vasodilatation of this vascular bed as physiologically seen postprandially may therefore easily induce postprandial hypotension in the oldest old.     

Acute administration of carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of portal pressure in patients with viral cirrhosis

OBJECTIVE: Propranolol is known to decrease portal pressure in cirrhotic patients with portal hypertension; however, a substantial number of patients do not respond to propranolol administration. The addition of isosorbide-5-mononitrate may enhance portal pressure reduction in patients receiving propranolol. Carvedilol is a nonselective beta-blocker with alpha(1)-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. Additionally, carvedilol has a greater portal hypotensive effect than propranolol alone in patients with cirrhosis. The current study is aimed at comparing the acute hemodynamic effects of carvedilol with the effects of propranolol plus isosorbide-5-mononitrate in patients with viral cirrhosis. METHODS: Patients with viral cirrhosis were randomly assigned to receive an oral administration of carvedilol of 25 mg (n = 11) or an oral administration of propranolol 40 mg plus isosorbide-5-mononitrate 20 mg (n = 11). Hemodynamic values were measured at basal and 90 min after drugs administration. RESULTS: Both carvedilol and propranolol plus isosorbide-5-mononitrate significantly decreased cardiac index, heart rate, and HVPG. The magnitude of changes in HVPG observed between the basal and after drugs administration was greater in patients receiving carvedilol than in those receiving propranolol plus isosorbide-5-mononitrate (-18.6 +/- 3.6%vs-10.1 +/- 3.6%, p < 0.05). Hepatic blood flow increased following carvedilol administration but remained unchanged in patients receiving propranolol plus isosorbide-5-mononitrate. The magnitude of decrease in mean arterial pressure (MAP) did not differ between the two groups of patients. CONCLUSION: In our patients with viral cirrhosis, carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of HVPG. Carvedilol administration causes an increase in hepatic blood flow, but its systemic effects were similar to those of propranolol plus isosorbide-5-mononitrate.     

Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis

BACKGROUND: Lanreotide, a new long-acting somatostatin analogue, has been shown to inhibit the meal-stimulated increase of splanchnic blood flow in healthy volunteers. To date, similar data in patients with liver cirrhosis have not been available. We have examined the effect of lanreotide compared with placebo on meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler ultrasound. METHODS: 20 cirrhotic patients (placebo n = 12, lanreotide n = 8) with proven portal hypertension were studied after an overnight fast. Lanreotide, at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min, Doppler technique) were determined at regular intervals. RESULTS: Baseline PVF amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507 (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in heart rate for the first 2 h of meal perfusion. CONCLUSIONS: Because of potent inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis, lanreotide may be useful in the treatment of complications of portal hypertension.     

Role of echo Doppler ultrasonography in the evaluation of postprandial hyperemia in cirrhotic patients

AIM： TO assess the role of echo-Doppler ultrasonography in postprandial hyperemia in cirrhotic patients by comparing the results with the hepatic vein catheterization technique.
METHODS： Patients with cirrhosis, admitted to the portal hemodynamic laboratory were included into the study. After an overnight fast, echo-Doppler ultrasonography （basal and 30 min after a standard meal） and hemodynamic studies by hepatic vein catheterization （basal, 15 min and 30 min after a standard meal） were performed. Ensure Plus （Abbot Laboratories, North Chicago, IL） was used as the standard liquid meal. Correlation analysis of the echo- Doppler and hepatic vein catheterization measurements were done for the basal and postprandial periods.
RESULTS： Eleven patients with cirrhosis （5 Child A, 4 Child B, 2 Child C） were enrolled into the study. After the standard meal, 8 of the 11 patients showed postprandial hyperemia with increase in portal blood flow, portal blood velocity and hepatic venous pressure gradient. Hepatic venous pressure gradient in the postprandial period correlated positively with postprandial portal blood velocity （r = 0.8, P 〈 0.05） and correlated inversely with postprandial superior mesenteric artery pulsatility index （r = -1, P 〈 0.01）.
CONCLUSION： Postprandial hyperemia can be efficiently measured by echo-Doppler ultrasonography and the results are comparable to those obtained with the hemodynamic studies.     

Splanchnic haemodynamics in patients with coeliac disease: effects of a gluten-free diet

BACKGROUND: Coeliac disease is characterized by structural and functional changes in the small bowel which may also result in haemodynamic changes. AIMS: To establish whether splanchnic haemodynamics can be modified by a gluten-free diet. PATIENTS: Ten coeliac patients and 10 paired healthy subjects. METHODS: Echo-Doppler measurements were made of splanchnic vessels both fasting and after a standard meal before and after 9 months of a gluten-free diet. RESULTS: In comparison to controls, coeliac patients had higher superior mesenteric artery blood velocity and flow, with lower resistance indexes and higher portal vein velocity and flow, particularly 3 h after a meal. Postprandial hyperaemia was reduced and delayed in time. Intrasplenic resistance indexes were also significantly lower both fasting and after a meal. After 9 months of a gluten-free diet, no significant differences were observed between coeliac patients and controls, both fasting and after a meal. CONCLUSIONS: Splanchnic haemodynamics is significantly changed in coeliac patients, mainly after a meal. On treatment with a gluten-free diet, both fasting and postprandial haemodynamics became normal.     

Lack of effects of isosorbide-5-mononitrate on hepatic hemodynamics in HBsAg-positive cirrhosis

We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 +/- 13 (mean +/- S.D.) to 82 +/- 14 mmHg, from 12.9 +/- 4.5 to 9.3 +/- 2.4 mmHg and from 6.9 +/- 3.4 to 4.3 +/- 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 +/- 3.6 to 17.5 +/- 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 +/- 5.2 to 16.6 +/- 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (less than mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.     

Effect of meal induced splanchnic arterial vasodilatation on renal arterial haemodynamics in normal subjects and patients with cirrhosis

Aims—To investigate the relation between changesin splanchnic arterial haemodynamics and renal arterial haemodynamicsin controls and patients with cirrhosis.
Methods—Superior mesenteric artery pulsatilityindex (SMA-PI) and renal artery pulsatility index (R-PI) were measuredusing Doppler ultrasonography in 24 controls and 36 patients withcirrhosis. These measurements were repeated 30 minutes after ingestionof a liquid meal or placebo. Sixteen controls and 24 patients received the meal, and eight controls and 12 patients received placebo.
Results—In the fasting condition, patients withcirrhosis had a lower SMA-PI (p<0.01) and a greater R-PI (p<0.01)compared with controls. Placebo ingestion had no effect on splanchnicand renal haemodynamics. In contrast, ingestion of the meal caused anotable reduction in SMA-PI (p<0.01, p<0.01) and an increase in R-PI(p<0.01, p<0.01) in controls and patients with cirrhosis. The mealinduced haemodynamic change in SMA-PI was inversely correlated withthat in R-PI in controls (t=−0.42, p<0.05) and inpatients with cirrhosis (t=−0.29, p<0.05).
Conclusions—Results support the hypothesis thatrenal arterial vasoconstriction seen in patients with cirrhosis is oneof the kidney's homoeostatic responses to underfilling of thesplanchnic arterial circulation.

Keywords:cirrhosis; Doppler ultrasonography; pulsatilityindex; renal artery; superior mesenteric artery

     

Effect and mechanism of action of isosorbide-5-mononitrate.

Nitrates have been shown to decrease portal pressure in cirrhotic patients with portal hypertension and this has been attributed to decreased portal venous resistance. We studied the effect and mechanism of action of oral administration of isosorbide-5-mononitrate (Is-5-Mn) (20 mg), which, unlike the dinitrate, does not require hepatic biotransformation to a vasoactive metabolite on portal and systemic haemodynamics in 11 patients with portal hypertension complicating cirrhosis. A significant reduction in portal pressure gradient (WHVP-FHVP) (from 23.9 (3.4) to 21.8 (3.4) mmHg: p less than 0.005) occurred 60 minutes after Is-5-Mn due entirely to a fall in WHVP, associated with decreased estimated liver blood flow (from 1940 (159) to 1639 (179) ml/min: p less than 0.05). Right atrial and pulmonary artery pressures and cardiac index fell significantly whilst mean arterial pressure remained unaffected. Heart rate and the calculated systemic vascular resistance index increased significantly. Significant correlations existed between the reduction in portal pressure gradient and fall in cardiac index (r = 0.65, p less than 0.05) and increase in systemic vascular resistance index (r = 0.72, p less than 0.02). The observed decrease in estimated liver blood flow, in association with an increase in systemic vascular resistance index, suggests that baroreceptor mediated splanchnic vasoconstriction may be one of the factors responsible for the fall in portal pressure, rather than portal venous dilatation.     

Change in portal flow after liver transplantation: effect on hepatic arterial resistance indices and role of spleen size

Information on changes in splanchnic hemodynamics after liver transplantation is incomplete. In particular, data on long-term changes are lacking, and the relationship between changes in arterial and portal parameters is still under debate. The effect of liver transplantation on splanchnic hemodynamics was analyzed with echo-Doppler in 41 patients with cirrhosis who were followed for up to 4 years. Doppler parameters were also evaluated in 7 patients transplanted for acute liver failure and in 35 controls. In cirrhotics, portal blood velocity and flow increased immediately after transplantation (from 9.1 plus minus 3.7 cm/sec to 38.3 plus minus 14.6 and from 808 plus minus 479 mL/min to 2,817 plus minus 1,153, respectively, P <.001). Hepatic arterial resistance index (pulsatility index) also augmented (from 1.36 plus minus 0.32 to 2.34 plus minus 1.29, P <.001) and was correlated with portal blood velocity and flow. The early changes in these parameters were related, in agreement with the hepatic buffer response theory. Portal flow returned to normal values after 2 years. Superior mesenteric artery flow normalized after 3 to 6 months. Splenomegaly persisted after 4 years, when spleen size was related to portal blood flow. In 7 patients transplanted for acute liver failure, portal flow, and hepatic arterial resistance index were normal after transplantation. In conclusion, a high portal flow was present in cirrhotics until 2 years after transplantation, probably because of maintenance of elevated splenic flow. An early increase in hepatic arterial resistance indices is a common finding, but it is transient and is related to the increase in portal blood flow. A normal time course of portal-hepatic hemodynamics was detected in patients transplanted for acute liver failure.     

Role of gender upon basal and postprandial systemic and splanchnic haemodynamics in humans

BACKGROUND: Food intake, accompanied by systemic and splanchnic haemodynamic changes, has only been studied in males. The extent to which splanchnic postprandial hyperaemia shows gender differences is unknown. METHODS: We tested 1) the splanchnic hyperaemic response to food in females and 2) whether postprandial haemodynamic changes show gender differences. Twenty-four healthy women (aged 20-35 years) and 20 healthy men (aged 21-34 years) participated in the study. A liquid test meal (Ensure plus, 1.5 kcal/ml) was perfused intraduodenally for 75 min through an enteral feeding tube at a rate of 3 ml/min after a 45-min basal period. Blood flow parameters were measured using Echo-Doppler technology. RESULTS: Basal diastolic arterial blood pressure was significantly (P < 0.05) lower in females (66+/-2 versus 72+/-2 mmHg), whereas heart rate was the same (58+/-2 b/min, ns). Postprandially, diastolic blood pressure fell, but reached significance only in males (-10+/-3 mmHg; P < 0.05). Mean velocity in the superior mesenteric artery (SMA) was significantly (P < 0.05) higher in females compared to males at baseline (47+/-3 versus 39+/-2 cm/s), whereas maximal postprandial changes were similar (64+/-6 versus 56+/-6 cm/s, ns). Volume flow in the portal vein (PV) at baseline was 656+/-29 and 716+/-35 ml/min females and males, respectively (ns between gender). Maximal postprandial changes amounted to 808+/-86 and 884+/-107 ml/min, respectively (ns). CONCLUSIONS: 1) Perfusion of a liquid test meal induces significant increases in flow parameters in the SMA and PV in both genders. 2) These changes are partly paralleled by alterations in systemic haemodynamics. 3) Postprandial splanchnic flow parameters are qualitatively and quantitatively not different between genders.     

Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial

BACKGROUND: Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure. AIM: To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis. METHODS: A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 microg/hour) plus oral isosorbide 5-mononitrate (40 mg/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours. RESULTS: The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p<0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2) v 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p<0.05). CONCLUSION: In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.     

Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis. Pharmacokinetic-hemodynamic interactions

Isosorbide dinitrate, a long-acting organic nitrate, has been shown to decrease portal pressure in the experimental animal and humans. We conducted a double-blind randomized hemodynamic evaluation of the effects of placebo and 10 mg and 20 mg isosorbide dinitrate in stable individuals with alcoholic cirrhosis. Baseline values for all three groups were similar. Isosorbide dinitrate resulted in a peak reduction of the hepatic venous gradient of 24.7% +/- 3.0%, with significantly decreased values 4 h after the administration of the 20-mg dose. A reduction of arterial pressure and cardiac index (peak decrease of 25.7% +/- 1.5%) was well tolerated by 13 of 15 patients. Changes in mean arterial pressure were not predictive of modifications in the hepatic vein wedge pressure. There was no relation between the area under the plasma isosorbide dinitrate concentration curve and hemodynamic changes. Levels of isosorbide-5-mononitrate, a vasoactive metabolite, were detectable for an 8-h period. Isosorbide dinitrate significantly reduced portal pressure in stable cirrhotics, in association with systemic hemodynamic changes. Thus, titration of isosorbide dinitrate is required to maximize hemodynamic benefits in individual patients. As the decrease in portal pressure is more predictable than the effect of previously tested pharmacologic agents, isosorbide dinitrate should be evaluated for its efficacy in the management of portal hypertension.     

Octreotide ameliorates the increase in collateral blood flow during postprandial hyperemia in portal hypertensive rats

BACKGROUND/AIMS: The aims of this study were to examine, in a conscious rat model of portal hypertension, the effect of postprandial splanchnic hyperemia on collateral blood flow and to determine whether octreotide has an effect on postprandial collateral flow changes. METHODS: In rats with portal vein ligation, pulsed-Doppler flowmeters were implanted chronically around the splenorenal venous shunt (SRS), which is the main spontaneous collateral vessel in the portal hypertensive rat and around the superior mesenteric artery (SMA). Changes in flow after a standard liquid meal gavage and after the administration of octreotide were examined in the rat under unanesthetized and unrestricted conditions. RESULTS: SRS flow increased significantly after gavage with a standard liquid meal (10.6+/-2.9%) compared to orogastric intubation alone (-6.5+/-2.1%) (P<0.01). Similar flow changes were observed in the SMA after liquid meal gavage. The subcutaneous administration of octreotide at a dose of 400 g/kg reduces basal SRS flow (-19.5+/-2.3%) and significantly attenuated the change in SRS flow after liquid meal gavage (-8.1+/-2.9%) compared to animals that received placebo (3.6+/-4.1% and 27.8+/-7.6%, respectively) (P<0.05). CONCLUSION: These results demonstrate that, in an experimental model of prehepatic portal hypertension, postprandial splanchnic hyperemia results in an increase in collateral flow that can be ameliorated with the use of octreotide.