Liver transplantation using Chagas-infected donors in uninfected recipients: a single-center experience without prophylactic therapy.

Organ shortage is the first cause of death on liver transplant waiting lists. As a consequence, we recently decided to expand liver acceptance to those organs that could potentially transmit infectious diseases to their recipients. On January 2010, we initiated a prospective protocol using livers from Chagas-infected donors for transplanting uninfected recipients without using prophylactic therapy. During a 13-month period, 9 of 37 (24%) liver transplants were performed within this protocol. After transplant, each recipient was sequentially and strictly monitored for infection transmission using the Strout method and promptly treated with benznidazole if this occurs. During follow-up, two patients died without Chagas infection and only two (donor-derived T. cruzi transmission rate: 2/9; 22%) patients developed donor-derived Chagas transmission without clinical symptoms. The median follow-up time of the seven live patients was 15 months (range: 13-20). At present, all are symptoms-free with excellent allograft function and without evidence of Chagas disease. In conclusion, we consider that Chagas-infected donors are a promising source of liver grafts that could reduce the growing mortality on liver waiting lists in America. Relevant data from larger prospective studies are required to confirm these preliminary excellent results.

Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.

Chronic administration of propylthiouracil ameliorates hyperdynamic circulation in portal hypertensive rats.

OBJECTIVE: To evaluate the effect of a hypothyroid state, induced by chronic propylthiouracil administration, on splanchnic and systemic hemodynamic parameters in rats with portal hypertension due to portal vein ligation. METHODS: Portal hypertension was induced by surgical stenosis of the portal vein. Cardiac index and portal blood flow were measured using radioactive microspheres. Measurements were performed after treatment with propylthiouracil (1 mg/ml in drinking water) for 5 days. RESULTS: Propylthiouracil-treated portal hypertensive rats had a lower portal pressure (12.4 +/- 1.9 versus 16.3 +/- 0.7 mmHg; p < 0.05) and portal blood flow (11.6 +/- 0.7 versus 13.2 +/- 1.3 ml/min/100 g; p < 0.05) than non-treated animals. Splanchnic vasoconstriction in treated animals was associated with a higher peripheral vascular resistance (2.3 +/- 0.4 versus 1.8 +/- 0.3 mmHg/ml/min/100 g; p < 0.05) than controls. CONCLUSION: These results suggest that portal pressure can be lowered by inducing a hypothyroid state by chronic administration of propylthiouracil.

Pentoxifylline reduces nephrotoxicity associated with cyclosporine in the rat by its rheological properties.

BACKGROUND: The goals of this study were to evaluate whether administration of pentoxifylline (POF) reduces the nephrotoxicity associated with cyclosporine (CsA) in the rat, and whether the effect of POF is related to its rheological properties. METHODS: Mean arterial pressure was measured by an intraarterial catheter. Glomerular filtration rate and renal plasma flow were determined by measuring inulin and para-aminohippurate clearances, after double-blind coadministration for 10 days of CsA (25 mg/kg/day) with either vehicle or POF (45 mg/kg every 12 hr). These results were compared with those obtained in control rats. Blood viscosity and erythrocyte deformability were also evaluated after treatment using a cone plate viscometer and a filtration method, respectively. RESULTS: No changes were observed in mean arterial pressure in both groups compared with controls. Glomerular filtration rate was significantly lower in CsA-treated rats (0.3+/-0.1 ml/min/100 g) than in control animals (0.6+/-0.1 ml/min/100 g, P<0.02). The coadministration of CsA with POF normalized the glomerular filtration rate (0.6+/-0.1 ml/min/100 g). A parallel decrease in renal plasma flow was observed in CsA-treated rats compared with controls (CsA+vehicle: 1.5+/-0.2 vs. control: 2.2+/-0.1 ml/min/100 g, P<0.02), this effect completely reversed by cotreatment with POF (3.1+/-0.2 ml/min/100 g). Blood viscosity was significantly higher in CsA-treated rats than in the control group (CsA+vehicle: 5.6+/-0.7 vs. control: 5.0+/-0.4 m x Pa x s, P<0.05). This effect was associated with a lower erythrocyte deformability (CsA+vehicle: 1.2+/-0.2 vs. control: 1.5+/-0.3 ml/min, P<0.05). These rheological abnormalities were normalized by coadministration with POF (blood viscosity: 4.9+/-0.7 m x Pa x s and erythrocyte deformability: 1.9+/-0.4 ml/min, P<0.05). CONCLUSIONS: Our results show that administration of POF prevents the nephrotoxicity associated with CsA. This beneficial effect could be related to its rheological properties.

Pentoxifylline, a drug with rheological effects, decreases portal pressure in an experimental model of cirrhosis.

OBJECTIVE: To evaluate the influences of blood viscosity changes, mediated by a haemorheological agent, on splanchnic and systemic haemodynamic parameters in rats with cirrhosis due to chronic bile duct ligation. METHODS: Blood viscosity was measured using a cone-plate viscometer and whole blood filterability was determined by a filtration method. Cardiac index and portal venous inflow were measured using radioactive microspheres. Measurements were performed 30 min after double-blind administration of placebo or pentoxifylline (25 mg/kg, intravenously). RESULTS: As compared with placebo, pentoxifylline-treated cirrhotic rats had a lower portal pressure (13.8 +/- 1.4 vs. 12.1 +/- 1.6 mmHg, P < 0.05) and blood viscosity at shear rates of 115/s (6.6 +/- 0.8 vs. 5.8 +/- 0.3 mPas, P < 0.05), associated with an improvement of whole blood filterability (45.0 +/- 12.9 vs. 20.0 = 3.9 s/ml, P < 0.01). Similar values of mean arterial pressure, cardiac index and portal venous inflow were observed in both groups. A significant correlation was found between portal pressure and blood viscosity at a shear rate of 115/s (r = 0.71, P < 0.01). CONCLUSION: These results suggest that portal pressure can be modified by pentoxifylline in an experimental model of cirrhosis. These haemodynamic changes are associated with a lower blood viscosity and whole blood filterability. Pentoxifylline may be a new approach in the treatment of portal hypertension.

[Dexamethasone, an inhibitor of the expression of inducible nitric oxide synthase, does not modify the hyperdynamic state in cirrhotic rats]. / La dexametasona, un inhibidor de la expresion de la óxido nítrico sintasa inducible, no modifica el estado hiperdinámico en ratas cirróticas.

Increased nitric oxide formation has been shown to be involved in the hyperdynamic circulation of portal hypertension. It has been proposed that it could be related to stimulation of the inducible nitric oxide synthase by endotoxin. Therefore, the aim of the present study was to evaluate whether dexamethasone treatment, an inhibitor of the expression of the inducible enzyme, ameliorates the hyperdynamic circulation observed in cirrhotic rats due to chronic bile duct ligation. Systemic and splanchnic hemodynamic parameters were measured after administration of dexamethasone (3 mg/kg/day during 3 days, i.p.) or its vehicle. In cirrhotic rats dexamethasone treatment caused a mild but not significantly higher mean arterial pressure in comparison with vehicle while similar values of cardiac output, peripheral vascular resistance, portal blood flow and portal pressure were observed in both group of animals. A significant body weight loss over the three days of treatment was observed in rats receiving dexamethasone. In sham-operated rats, dexamethasone administration caused similar changes as observed in cirrhotic animals. Endotoxemia was observed in five of six cirrhotic rats while it was not detected in the control group. Our results show that dexamethasone administration does not modify systemic and splanchnic hemodynamic parameters in endotoxemic cirrhotic rats. This finding suggests that stimulation of the inducible nitric oxide synthase may not play a role in the increased nitric oxide production in portal hypertension.

[Role of nitric oxide in alterations of the systemic and splanchnic hemodynamics in a experimental model of portal hypertension]. / Papel del óxido nítrico en las alteraciones de la hemodinámica sistémica y esplácnica en un modelo experimental de hipertensión portal.

Recent experimental studies have suggested that an increase in the synthesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to portal hypertension. The present study was addressed to investigate the effects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by partial portal vein ligation. Intravenous infusion of L-NNA (50 ug/kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increase in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (300 mg/Kg, i.v.) prevented the hemodynamic changes induced by L-NNA. Similar values of endotoxin levels were detected in both groups of animals. In the control group, L-NNA caused a mild but significant increase of mean arterial pressure; no significant changes on the other hemodynamic parameters were observed. These results suggest that an increase in endogenous synthesis of nitric oxide may play an important role in hemodynamic disturbances associated with chronic portal hypertension.

[Renal failure in patients with liver transplant: incidence and predisposing factors]. / Insuficiencia renal en pacientes con trasplante hepático: incidencia y factores predisponentes.

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Hemostatic and hemodynamic effects of vasopressin analogue DDAVP in patients with cirrhosis.

Desmopressin (DDAVP), a synthetic analogue of vasopressin, has been shown to improve the bleeding time in patients with cirrhosis. The duration of this effect and the hemodynamic changes associated with DDAVP have not been studied so far. To evaluate these issues, 14 cirrhotics with portal hypertension were studied in basal conditions and after DDAVP (0.3 uk/kg). In 8 patients, hemostatic tests were done at basal conditions and 1, 3, 6 and 24 hs after drug administration. In the remaining 6 patients, mean arterial pressure, cardiac output, portal and femoral blood flows were evaluated. Hemodynamic parameters were measured by Doppler ultrasound. DDVP caused a marked decrease in bleeding time at 1, 3, 6 and 24 hs (14 +/- 9 vs 8 +/- 3, 7 +/- 4, 6 +/- 4 and 8 +/- 4 min, respectively); the decrease was maximal and statistically significant at 6 hs (55 +/- 15%, p < 0.02) after DDAVP infusion. Bleeding time reduction was observed in every patient studied. In the hemodynamic study, DDAVP caused a mild but significant decrease in mean arterial pressure (12 +/- 8%, p < 0.05); no significant changes were observed in the rest of hemodynamic parameters studied. These findings show that DDAVP can be used to shorten the bleeding time for a period of at least 24 hs in patients with cirrhosis, without deleterious hemodynamic effects. This beneficial effect may be of potential relevance in the medical management of patients with chronic liver diseases.

Extremely marginal liver grafts from deceased donors have outcome similar to ideal grafts.

BACKGROUND: Although there is a worldwide need to expand the donor pool, many cadaveric marginal livers are usually discarded for transplantation. Herein, we report the outcome of a series of patients receiving marginal grafts. METHODS: We analyzed all patients who underwent liver transplantation in our unit from August 2006 to March 2011 (n = 125) with the use of a prospectively collected database. Patients with ≥3 of donor (prolonged hypotensive episodes, donor age >55 years, high vasopressor drug requirement, hypernatremia, prolonged intensive care unit stay, elevated transaminases) and graft-related (cold ischemia >12 hours, warm ischemia time >40 minutes and steatosis >30%) extended criteria were defined as extremely marginal liver grafts (EMLG). The outcomes of patients receiving EMLG were compared with the recipients of grafts without any marginal criteria (ideal grafts). RESULTS: The EMLG group (n = 36) showed higher operative transfusion requirement (66.6% vs 55.6%) as well as 30-day (11.1% vs 55%) and 1-year (22.2% vs 5.5%) mortality rates, compared with the ideal grafts group (n = 18) but without a significant difference. Other variables, such as major complications, postoperative hemodialysis, ICU and hospital stay, and 1-year survival also were not significantly different. CONCLUSIONS: The liver pool can be safely expanded using EMLG from deceased donors for liver transplantation. These usually discarded liver grafts showed similar early and long-term outcomes compared with ideal organs.

Serotonin blockade in conscious, unrestrained cirrhotic dogs with portal hypertension.

It has recently been reported that the administration of ketanserin, a serotonin antagonist, was associated with a significant reduction in portal pressure both in portal hypertensive rats and cirrhotic patients. However, this beneficial effect on splanchnic hemodynamics was accompanied by a significant reduction in arterial pressure. Using conscious dogs, we investigated the effect of the chronic oral administration of a new specific antiserotonergic drug, ritanserin (10 mg per day for 5 days), on portal pressure and systemic hemodynamics. Eleven dogs with secondary biliary cirrhosis and portal hypertension due to chronic bile duct ligation were evaluated. One week prior to study, heparinized catheters were placed in the portal vein and brought subcutaneously to the dorsal cervical area. Measurements were made under baseline conditions, following ritanserin administration and 72 hr after the last dose. Ritanserin administration caused a significant reduction in portal pressure (from 17.3 +/- 3.1 mmHg to 13.6 +/- 4.5 mmHg; mean decrease: 23.1%; p less than 0.001). Maximal effects on portal pressure were reached on the fourth day. During the recovery period, hemodynamic parameters returned to baseline values. In six of the 11 cirrhotic dogs with successful chronic catheterization of the inferior vena cava and aorta, ritanserin administration did not cause significant changes in the mean arterial pressure, heart rate, cardiac output and peripheral vascular resistance. These data indicate that chronic implantation of venous and arterial catheters in dogs with secondary biliary cirrhosis is a useful experimental model for pharmacological studies of portal hypertension in conscious animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The rat liver microcirculation in alcohol-induced hepatomegaly.

It has been suggested that hepatocyte enlargement can lead to compression of the extracellular space (sinusoidal and interstitial) and induce portal hypertension. However, this hypothesis has never been tested by measuring the vascular and extravascular spaces in the intact liver. The aim of the present study was to investigate the effects of chronic alcohol intake on the hepatic microcirculation using Goresky's multiple-indicator dilution technique in the isolated perfused rat liver. Female rat littermates were pair-fed either ethanol (n = 7) or an isocaloric carbohydrate diet (n = 7) for 21 days. As expected, chronic alcohol intake produced a significant increase in liver/body weight ratio (+32%, p less than 0.01) and hepatocyte size (+45%, p less than 0.001), which was accompanied by a marked increase in the cellular water space (control: 3.3 +/- 0.6 ml; ethanol-fed: 4.9 +/- 0.9 ml; p less than 0.001). When expressing data per total liver, the sinusoidal space was similar in the two groups (control: 1.87 +/- 0.2; ethanol-fed: 1.95 +/- 0.2 ml; not significant), whereas the interstitial space was increased in alcohol rats compared to controls (albumin space +58%, p less than 0.01; sucrose space +51%, p less than 0.01). In alcoholic rats, the sinusoidal space was probably stretched, with an overall reduced transversal diameter, as suggested by the reduced values found when data were expressed per gm of liver weight. However, despite this finding and the enlargement of the liver and hepatocytes observed in alcoholic rats, similar values were obtained between the two groups for the portal perfusion pressure and thus the intrahepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow measurements by the reference sample method with microsphere injection in to the aorta: an accurate and easy approach.

The validity of hemodynamic measurements by the reference sample method with microspheres injection into the aorta, via a carotid artery catheter, was evaluated in rats and compared with the results obtained after left ventricle injection. In the aorta injection group, a good mix of microspheres was observed in 83% of the animals. Moreover, a symmetrical distribution of microspheres was observed in 10 out of 12 rats (83%). An excellent correlation between right and left kidney-testes blood flows was observed (r = 0.93 and 0.96, respectively; P less than 0.01). Mean arterial pressure was not modified during microspheres injection into the aorta. Cardiac output (104 +/- 26 vs 101 +/- 23 ml/min, NS) and portal blood flow (14.2 +/- 3.3 vs 13.5 +/- 2.2 ml/min, NS) were similar after aorta and left ventricle injections series, respectively. Our results indicate that the injection of microspheres into the aorta is an adequate and easy approach to systemic and splanchnic hemodynamic measurements. This approach could be a good alternative to left ventricle injection of microspheres in experimental studies in rats.

Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats.

We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure (-17%) with minimal changes in portal venous inflow (+3%). Portal vascular resistance decreased significantly (-23%), whereas splanchnic arteriolar resistance was similar before and after ritanserin. A significant increase in mean arterial pressure (+5%) and cardiac output (+22%) was observed. Our results suggest that ritanserin lowers portal pressure through a mechanism separate from portal venous inflow. This effect could be due to changes in intrahepatic or on portocollateral resistances, or both. These findings support the potential use of this new agent in the treatment of portal hypertension.

Effects of somatostatin in patients with portal hypertension.

Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.

Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis.

The effects of beta-blockade with propranolol and of alpha-adrenergic stimulation with methoxamine, a powerful alpha-agonist, on azygos blood flow and on systemic and hepatic haemodynamics were investigated in 26 cirrhotic patients with portal hypertension. Beta-adrenergic blockade with propranolol (n = 12), evidenced by a significant reduction of heart rate (-17 +/- 1%, P less than 0.001) and cardiac index (-17 +/- 2%, P less than 0.001), caused a mild but significant decrease of hepatic venous pressure gradient (-10 +/- 2%, P less than 0.05) and a marked fall of azygos venous blood flow (-31 +/- 5%, P less than 0.05). Alpha-adrenergic stimulation with methoxamine (n = 14), manifested by a significant increase of mean arterial pressure (19 +/- 2%, P less than 0.001), mimicked the effects of propranolol on hepatic venous pressure gradient (-10 +/- 4%, P less than 0.05) and cardiac index (-11 +/- 2%, P less than 0.001). However, azygos blood flow was not significantly reduced by methoxamine (0.7 +/- 0.1 vs 0.6 +/- 0.1 l/min). On the contrary, hepatic blood flow was significantly reduced by methoxamine (-19 +/- 4%, P less than 0.01) but not by propranolol (-7 +/- 7%, ns). Similarly, in 8 patients who received methoxamine after being beta-blocked by propranolol, azygos blood flow, that was markedly reduced by beta-blockade, did not experience a further reduction but increased slightly by alpha-adrenergic stimulation, while hepatic blood flow, that was not reduced by propranolol, decreased significantly during the subsequent methoxamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Splanchnic hyperemia after liver transplantation in patients with end-stage liver disease.

Systemic and splanchnic hemodynamic parameters were evaluated in 12 patients with cirrhosis before and 3 and 6 months after liver transplantation. Results were compared with those obtained in 8 healthy subjects. Three months after liver transplantation recipients had an increase in mean arterial pressure (98 +/- 7 v 78 +/- 9 mmHg; P < .05), an insignificant decrease in cardiac index (3. 4 +/- 0.6 v 4.0 +/- 1.0 L . min-1 . m-2), and a marked increase in peripheral vascular resistance (1,563 +/- 308 v 800 +/- 205 dyne . s . cm-5; P < .05) compared with pretransplantation values. Portal blood flow was also significantly increased (1,494 +/- 200 v 829 +/- 130 mL/min; P < .05). These hemodynamic changes were more pronounced 6 months after transplantation (mean arterial pressure, 100 +/- 8 mmHg; cardiac index, 3.0 +/- 1.0 L . min-1 . m-2; P < .01; peripheral vascular resistance, 1,680 +/- 405 dyne . s . cm-5; portal blood flow, 1,520 +/- 180 mL/min). Systemic hemodynamics 6 months after liver transplantation were similar to those observed in the healthy control group (mean arterial pressure, 95 +/- 6 mmHg; cardiac index, 2.9 +/- 0.9 L . min-1 . m-2; peripheral vascular resistance, 1,480 +/- 380 dyne . s . cm-5). However, portal blood flow was still significantly higher than in healthy controls at 6 months (1,520 +/- 180 v 910 +/- 140 mL/min; P < .05). This study shows that systemic hemodynamics are normalized after liver transplantation. However, an increase in portal blood flow occurs and persists for at least 6 months after liver transplantation. Further studies are needed to clarify the cause of the abnormally high portal flows.

Noninvasive measurement of portal venous blood flow in patients with cirrhosis: effects of physiological and pharmacological stimuli.

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038 +/- 539 to 1572 +/- 759 ml/min, P less than 0.02); this effect was due to a significant rise in mean blood velocity (from 18.5 +/- 3.7 to 23.9 +/- 3.9 cm/sec, P less than 0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985 +/- 491 to 625 +/- 355 ml/min, P less than 0.05); a significant decline of mean blood velocity (from 18.8 +/- 4.5 to 14.5 +/- 2.5 cm/sec, P less than 0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.