Effects of octreotide on central hemodynamics and systemic oxygen use in patients with viral cirrhosis

OBJECTIVE: Octreotide has potentially beneficial effects in patients with cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen use have not been established. The present study was undertaken to evaluate the effect of octreotide on central hemodynamics and oxygen use in patients with viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in the study. They were randomly assigned to receive either placebo (n = 10) or a continuous infusion of 100 microg/h of octreotide after an initial 100-microg bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained before and 60 min after octreotide or placebo administration. RESULTS: Placebo administration did not have any effect on hemodynamic and oxygenation values. In patients who received octreotide, systemic hemodynamic values including cardiac index, mean arterial pressure, and systemic vascular resistance were not affected. The mean pulmonary arterial pressure tended to increase after octreotide administration but was statistically insignificant. There was a significant increase in pulmonary arterial vascular resistance, whereas the pulmonary capillary wedge pressure and right atrial pressure were significantly decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction ratio were significantly decreased after octreotide administration, whereas oxygen transport as well as arterial and mixed venous oxygen contents remained unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide administration exerted a significant effect on pulmonary circulation. It also resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio. These results suggested that octreotide may impair tissue oxygenation in patients with viral cirrhosis.     

Effect of terlipressin on blood volume distribution in patients with cirrhosis

BACKGROUND: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of terlipressin to patients with cirrhosis. METHODS: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual-head gamma-camera technique and systemic haemodynamics was measured before and after intravenous administration of terlipressin (2 mg). RESULTS: Terlipressin increased the blood volume in the thorax region (+6.0%, P < 0.002) and the liver region (+12.2%, P < 0.002), whereas blood volume in the splanchnic region remained unchanged. Systemic vascular resistance (SVR) and mean arterial blood pressure increased after terlipressin (+34 and +21%, P < 0.001). The increase in liver blood volume correlated directly with the increase in SVR (r = 0.88. P < 0.001). CONCLUSIONS: Terlipressin ameliorates the hyperdynamic circulation, increases thorax and liver blood volumes, but produces no effect on the splanchnic blood volume. Besides decreasing the splanchnic inflow, terlipressin may affect portal pressure by causing vasodilatation of intrahepatic vessels.     

Importance of maintaining systemic blood pressure during nitroglycerin administration for reducing ischemic injury in patients with coronary disease. Effects on coronary blood flow, myocardial energetics and left ventricular function.

Because of the controversy concerning the effects on myocardial ischemia of maintaining systemic pressure concomitant with administration of nitroglycerin, this study was undertaken of the actions of nitroglycerin, with and without simultaneous phenylephrine infusion, on coronary blood flow, myocardial energetics and left ventricular function in 17 patients with multivessel coronary artery disease. Five minutes after sublingual administration of 0.4 mg of nitroglycerin, mean arterial pressure, left ventricular filling pressure, cardiac index and coronary sinus blood flow were reduced (P < 0.05) from control values. With mean arterial pressure raised to control level with phenylephrine in 10 patients (Group I), values for coronary sinus blood flow, myocardial perfusion gradient, cardiac efficiency index and ratio of coronary sinus flow/cardiac output all increased (P < 0.05) compared with values in 7 patients receiving only nitroglycerin (Group II) and in patients receiving nitroglycerin before phenylephrine in Group I and with the values in 7 patients who received no phenylephrine. Left ventricular function and coronary vascular resistance were unchanged (P > 0.05) from control values by the addition of phenylephrine to nitroglycerin. Because myocardial oxygen extraction decreased while coronary sinus flow increased, the phenylephrine-induced increase in coronary flow was not due to augmented cardiac oxygen demands. Thus, preservation of systemic pressure concomitant with nitroglycerin enhances myocardial perfusion. From these findings, with greater nitroglycerininduced decreases in mean arterial pressure and coronary flow in patients with acute ischemia, it appears that phenylephrine with nitroglycerin may particularly improve myocardial energetics.     

Hemodynamic changes of systemic,hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20–40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.This work was supported in part by a grant from the Italian Ministry of Education (National Project Liver Cirrhosis).     

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.     

Effects of glypressin on the splanchnic and systemic circulation in patients with cirrhosis

Although not demonstrated in patients with cirrhosis, it is generally claimed that administration of vasopressin in the form of triglycyl-lysine-vasopressin (glypressin) may prevent untoward systemic effects of this former hormone. The aim of this study was to assess the effects of intravenous administration of 2 mg of glypressin on splanchnic and systemic hemodynamics in 9 patients with cirrhosis under stable circulatory conditions. One hour after the injection, the following statistically significant changes were observed as compared to the baseline values (m +/- SEM): wedged hepatic venous pressure, -9 +/- 2 p. 100; hepatic venous pressure gradient, -16 +/- 3 p. 100; azygos blood flow, -24 +/- 6 p. 100; heart rate, -16 +/- 3 p. 100; cardiac index, -23 +/- 2 p. 100; systemic vascular resistances, +47 +/- 11 p. 100; wedged pulmonary arterial pressure, +44 +/- 15 p. 100. In conclusion, in patients with cirrhosis in a stable hemodynamic condition, intravenous administration of glypressin decreased portal venous pressure and blood flow into the superior portal systemic collateral circulation but did not prevent the untoward systemic hemodynamic effects of vasopressin.     

Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis

It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.     

Hemodynamic effects of a clonidine-induced decrease in sympathetic tone in patients with cirrhosis

A decrease in plasma noradrenaline--a reflection of sympathetic nervous system activity--by clonidine, a centrally acting alpha 2-agonist, could reduce the hyperdynamic circulation observed in cirrhosis and may thereby decrease portal hypertension. Plasma noradrenaline concentration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after administration of either 150 micrograms of clonidine or placebo. Plasma noradrenaline concentration significantly decreased in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (-17.4%), mean arterial pressure (-12.2%), hepatic venous pressure gradient (-19.7%) and azygos blood flow (-26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and changes in systemic or splanchnic hemodynamics. Hepatic blood flow was not changed by clonidine. Placebo administration had no effect on any laboratory or hemodynamic measurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation suggests that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.     

Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis

Abstract We investigated the effects of nifedipine on splanchnic haemodynamics in 13 patients with cirrhosis and portal hypertension, and in 10 control subjects using hepatic venous catheterization and pulsed Doppler ultrasound. There were no significant changes in systemic or splanchnic haemodynamics in control patients. In contrast, systemic vascodilatation, evidenced by significant decreases in mean arterial pressure and systemic vascular resistance, was observed in patients 20 min after sublingual application of 10 mg nifedipine. Moreover, hepatic venous pressure gradient and portal vein blood flow significantly increased after nifedipine administration. There was a significant correlation between the percentage increases in portal vein blood flow and in hepatic venous pressure gradient. However, no correlation was found between the percentage change in cardiac output and that in portal vein blood flow. Thus the increase in portal vein blood flow appears to be related to splanchnic arterial vasodilatation by nifedipine. Consequently, nifedipine has deleterious effects on portal haemodynamics in patients with cirrhosis. As nifedipine may potentially increase the risk of variceal haemorrhage in patients with less advanced varices, this drug should be used with caution in patients with chronic liver disease.     

Effect of terlipressin on blood volume distribution in patients with cirrhosis

Background: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of terlipressin to patients with cirrhosis. Methods: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual‐head gamma‐camera technique and systemic haemodynamics was measured before and after intravenous administration of terlipressin (2?mg). Results: Terlipressin increased the blood volume in the thorax region (+6.0%, P?P?P?r?=?0.88, P?Conclusions: Terlipressin ameliorates the hyperdynamic circulation, increases thorax and liver blood volumes, but produces no effect on the splanchnic blood volume. Besides decreasing the splanchnic inflow, terlipressin may affect portal pressure by causing vasodilatation of intrahepatic vessels.     

Effects of propranolol on renal blood flow and renal function in patients with cirrhosis

Systemic and splanchnic hemodynamics, renal blood flow, and renal function were studied in 13 patients with cirrhosis both before and 1 h after oral administration of 40 mg of propranolol (acute administration) and 1 mo after continuous administration of this substance at doses reducing the heart rate by 25% (chronic administration). Cardiac output and the gradient between wedged and free hepatic venous pressures significantly decreased after acute and chronic administration of propranolol; mean arterial pressure did not change significantly and systemic vascular resistance significantly increased. Renal blood flow and renal vascular resistance did not change significantly after acute administration of propranolol and renal function did not change significantly after acute or chronic administration of propranolol. We conclude that propranolol does not alter renal function in patients with cirrhosis who are in good physical condition.     

Hemodynamic Effects of a Combination of Octreotide and Terlipressin Patients with Viral Hepatitis Related Cirrhosis

Background: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. Methods: Patients were randomly assigned to receive either a placebo ( n = 11) or an intravenous infusion of octreotide 100 μg/h after an initial bolus of 100 μg ( n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. Results: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. Conclusion: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.     

Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis

BACKGROUND: Terlipressin or octreotide given alone has been used as the first-line pharmacological treatment for acute variceal bleeding. In portal hypertensive animals, pre-infusion of octreotide followed by the addition of terlipressin has an additive or complementary effect on splanchnic hemodynamics. The current study was aimed at evaluating such a combination treatment in patients with cirrhosis and portal hypertension. METHODS: Patients were randomly assigned to receive either a placebo (n = 11) or an intravenous infusion of octreotide 100 microg/h after an initial bolus of 100 microg (n = 13). Thereafter, each patient received an intravenous injection of terlipressin 2 mg. Hemodynamic values were measured basally, 30 min after octreotide or placebo, and 60 min after terlipressin. RESULTS: Placebo administration did not affect any of the hemodynamic values. Terlipressin administration resulted in expected changes in hepatic venous pressure gradient, hepatic blood flow and systemic hemodynamics. In contrast, octreotide administration significantly decreased hepatic blood flow but did not affect other hemodynamic values. After terlipressin administration, significant hemodynamic changes were observed that were similar to the hemodynamic changes with terlipressin alone. The magnitude of changes in hepatic venous pressure gradient, cardiac index and systemic vascular resistance were no different between the two groups of patients. The heart rate was significantly lower in patients receiving octreotide plus terlipressin than those receiving terlipressin alone. CONCLUSION: The current study showed that a combination of octreotide and terlipressin did not exert an additive effect in reducing hepatic venous pressure gradient in patients with cirrhosis. In addition, the systemic hemodynamic changes were comparable between the two groups.     

Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety-Schmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P = 0.016). Intracranial pressure increased significantly at 1 hour (P = 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics.     

Acute hemodynamic effects of pimobendan and captopril: a comparative study in the same patients with chronic heart failure]

In this study, the acute hemodynamic effects of pimobendan (2.5 mg), a new drug, was compared with that of captopril (12.5 mg) in the same 8 patients with chronic heart failure (NYHA class II-III); 3 with dilated cardiomyopathy and 5 with regurgitant valvular heart disease. The hemodynamics were serially assessed before and after drug administration for at most 6 hours. Pimobendan reduced mean blood pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, right atrial pressure, total systemic vascular resistance, and total pulmonary vascular resistance but it increased heart rate. By contrast, captopril reduced mean blood pressure and double product. No significant changes were noted in the cardiac index, stroke volume index, AV-O2 difference or the arterial oxygen pressure between the 2 drugs. In conclusion, pimobendan seems to function as a strong arterio-veno-dilator rather than as an inotropic agent in patients with chronic heart failure.     

Intravenous and oral prenalterol in congestive heart failure. Effects on systemic and coronary hemodynamics and myocardial catecholamine balance

Systemic and coronary hemodynamic effects of prenalterol, a beta-1 receptor agonist, were determined in patients with chronic congestive heart failure, initially after intravenous administration (10 patients) and then after oral administration (eight patients). Cardiac index increased by 33 percent and 30 percent after intravenous and oral prenalterol, respectively. The increase in stroke volume index and stroke work index and decrease in pulmonary capillary wedge pressure and systemic vascular resistance were not significant. Myocardial oxygen consumption and coronary sinus blood flow increased in the majority of patients, although these changes were not statistically significant. There were no significant changes in transmyocardial norepinephrine or epinephrine balance. The systemic and coronary hemodynamic effects of both intravenous and oral prenalterol were similar. Major side effects included sudden death (two patients) and hypotension and bradycardia (three patients) during oral prenalterol treatment. It is concluded that improved left ventricular function following both intravenous and oral prenalterol may be associated with increased myocardial oxygen consumption, and serious adverse effects may occur during prenalterol therapy.     

Effects of dobutamine on left ventricular performance and myocardial metabolic demands in patients with ischemic heart disease

Sixteen patients with coronary artery disease undergoing cardiac catheterization were studied. Eleven had previous infarcts and the patients were divided into two groups: In group I were 7 patients with no left ventricular dysfunction, no increase in ventricular size, or symptoms of congestive failure; group II included 9 patients with ventricular dysfunction, increased ventricular size, and 7 of the 9 had congestive failure. Each patient underwent a continuous infusion of dobutamine from 2.5 to 10 μUg/kg min^-1 with dosage increments of 2.5 μUg/kg at 15-minute intervals. Systemic and coronary hemodynamic measurements were obtained at the end of the 5 and 10 μUg/kg min^-1 infusion doses. Left ventricular performance improved (higher cardiac index, left ventricular stroke work index and mean systolic ejection rate, and lower left ventricular end-diastolic pressure), while heart rate, mean arterial pressure, and coronary sinus blood flow increased after dobutamine in the 16 patients. While patients in both groups had a rise in cardiac index, a reduction in left ventricular end-diastolic pressure, an unchanged mean arterial pressure and a rise in coronary blood flow, only patients in group I had a significant increase in heart rate, and only patients in group II had significant increases in left ventricular stroke work index and mean systolic ejection rate, and a significant reduction in systemic vascular resistance. Left ventricular oxygen consumption did not increase significantly in either group. However, 5 patients showed a decreased myocardial lactate extraction after 10 μUg/kg min^-1 of intravenous dobutamine, 3 from group I and 2 from group II. These 5 patients had less ventricular dysfunction than patients with a normal lactate response to intravenous dobutamine. We conclude that the improvement in left ventricular performance observed after dobutamine administration in patients with ischemic heart disease is not usually associated with a major increase in left ventricular oxygen consumption or with marked aggravation of myocardial ischemia. This appears to be particularly true in patients with relatively severe left ventricular dysfunction.     

Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis

Systemic and splanchnic haemodynamics were studied in patients with cirrhosis who had been classified in three groups (A, B, and C) according to the degree of liver failure (modified Pugh's classification). In patients of group A, cardiac index was significantly lower than that of group C and systemic vascular resistance was higher, but not significantly so, than that of patients with liver failure. Wedged hepatic venous pressure was significantly lower in the former group than in the latter. In patients in group B, corresponding values fell between those of groups A and C. Azygos blood flow averaged 0.477 +/- 0.242 l/min (mean +/- SD) in group A and it was significantly lower than in groups B and C (0.642 +/- 0.224 and 1.061 +/- 0.476 l/min, respectively). In the three groups, acute administration of propranolol induced statistically significant changes in systemic and splanchnic haemodynamics. In patients of group C but not of group B, the mean value of azygos blood flow after propranolol remained significantly higher than in group A. Moreover, the fraction of azygos blood flow to cardiac output decreased in groups A and B while slightly increased in group C. This study shows that in patients with cirrhosis, the degree of liver failure may be a determinant for the haemodynamic responses to drugs acting on portal hypertension.     

Chronic administration of losartan, an angiotensin II receptor antagonist, is not effective in reducing portal pressure in patients with preascitic cirrhosis

OBJECTIVES: Plasma angiotensin II (ANG II) concentrations are elevated in cirrhosis and have been implicated as a cause of portal hypertension. We aimed to study both the systemic and portal hemodynamics, and tolerability after chronic administration of losartan, an ANG II receptor antagonist. METHODS: Twelve patients with preascitic cirrhosis were studied: mean age of 53.8 +/- 3.3 yr; average Child-Pugh score of 5.8 +/- 0.3; alcohol etiology (5), hepatitis B/C (1/3), primary biliary cirrhosis (3). No patients were on diuretics or vasoactive medication. Hemodynamic measurements were performed at baseline and 4 weeks after daily administration of 25 mg losartan. RESULTS: There was no significant change in the hepatic venous pressure gradient (15.4 +/- 1.5 to 13.6 +/- 1.6 mmHg, -11.7%, p = NS), despite a significant reduction in the wedge hepatic venous pressure (20.3 +/- 1.8 to 17.3 +/- 1.8 mmHg, -14.8%, p < 0.05). Cardiac output, hepatic blood flow, systemic vascular resistance, creatinine clearance, and natriuresis were unaffected. The plasma renin activity increased significantly from 2.7 +/- 0.4 to 5.2 +/- 1.1 ng/ml/h (p < 0.05). There was a significant reduction in the mean arterial pressure from 96.9 +/- 3.3 to 89.3 +/- 3.5 mmHg, -7.8 +/- 3.0% (p = 0.02), with 1 patient experiencing symptomatic hypotension. CONCLUSIONS: Chronic administration of low-dose losartan does not lead to a significant reduction in the portal pressure gradient. Losartan is unlikely to be useful in the management of patients with early cirrhosis, who are at risk of variceal bleeding.     

Systemic and portal haemodynamic changes following triglycyllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.