Nicardipine Infusion Improved Hepatic Function But Failed to Reduce Hepatic Venous Pressure Gradient in Patients with Cirrhosis

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.     

Increased blood flow through the portal system in cirrhotic rats

Portal venous pressure is the result of the interplay between portal venous blood flow and the vascular resistance offered to that flow. Whether portal hypertension is maintained only by an increased portal venous resistance or also by an increased blood flow within the portal venous system is still open to speculation. To resolve these differences, splanchnic and systemic hemodynamics were evaluated in cirrhotic rats, induced by CCl4. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. All cirrhotic rats had portal hypertension (portal venous pressure 13.5 +/- 1.1 vs. 9.0 +/- 0.5 mmHg, in normal control rats; p less than 0.01), but portal-systemic shunting in cirrhosis (31% +/- 13% vs. 0.2% +/- 0.02%; p less than 0.05) was variable, ranging from 1% to 97%. Portal venous inflow, the total blood flow within the portal system, was increased in cirrhotic rats (5.75 +/- 0.04 vs. 4.52 +/- 0.36 ml/min per 100 g; p less than 0.05). Total splanchnic arterial resistance was reduced in cirrhotic rats (3.3 +/- 0.2 vs. 5.8 +/- 0.5 dyn X s X cm-5 X 10(5); p less than 0.01). Portal venous resistance, however, was not abnormally elevated in cirrhotic rats (4.6 +/- 0.5 vs. 4.7 +/- 0.5 dyn X s X cm-5 X 10(4), p = NS). Splanchnic hemodynamics in cirrhotic rats demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venous inflow. The hemodynamic data in cirrhotic rats provided evidence that supports the role of an increased portal blood flow in portal hypertension and gives a quantitative definition of splanchnic hemodynamics in intrahepatic portal hypertension.     

Systemic and splanchnic hemodynamic effects of intravenous hypertonic glucose in patients with cirrhosis

In animals, there may exist a hyperemic response in the portal circulation during intravenous administration of hypertonic glucose, but a hemodynamic response of this kind has never been described in man. This study was designed to evaluate if hyperglycemia itself could induce systemic or splanchnic hemodynamic changes in patients with cirrhosis. Sixteen patients with cirrhosis were studied before and during i.v. infusions of hypertonic (900 mOsmoles per liter) glucose (n = 8), mannitol (n = 4) or saline (n = 4) at 2 ml per min. In the group receiving glucose, there were significant increases in hepatic venous pressure gradient (+12%), azygos blood flow (+27%) and pulmonary capillary pressure (+32%), while calf blood flow decreased (-26%). No changes occurred in the mannitol or saline groups. Changes in plasma osmolality, plasma volume, splanchnic oxygen extraction and vasoactive hormones, including vasoactive intestinal polypeptide and glucagon, did not appear to be involved in the mechanism of these vasoactive phenomena. It is suggested that the possible deleterious effects of increase in portal pressure and azygos blood flow should be taken into consideration when administering hypertonic glucose to patients with portal hypertension.     

Reduced portosystemic hemodynamic responsiveness after orthostasis in patients with cirrhosis

We studied portosystemic hemodynamic responsiveness after 1 min orthostasis in nine patients with cirrhosis and nine age-matched normal subjects. Orthostasis increased diastolic arterial pressure, which is a close indicator of arterial tone, in normal subjects (+17%,P<0.01). In contrast, no significant change in diastolic arterial pressure was observed in patients with cirrhosis (–3%, NS). The increase in heart rate was less in patients with cirrhosis than in normal subjects (+15% vs +28%,P<0.05). Orthostasis also decreased portal blood flow, which was assessed by an echo-Doppler flowmetry, in normal subjects (–27%,P<0.01), but in patients with cirrhosis it was not modified (–3%, NS). Plasma noradrenaline concentration showed similar increase in both groups (normal vs cirrhosis; +61% vs +55%, NS). Although the change in plasma noradrenaline concentration was related with that in diastolic arterial pressure (r=0.71,P<0.05) and inversely with that in portal blood flow (r=–0.69,P<0.05) in normal subjects, no such significant correlation was found in patients with cirrhosis. We conclude that (1) a reduced hemodynamic responsiveness to sympathetic stimulation exists on both systemic and portohepatic vascular beds and (2) such a blunted baroreflex function is probably located at the receptor or effector level in patients with cirrhosis.     

Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin

The effects of somatostatin on hepatic and systemic hemodynamics were investigated in 17 patients with chronic liver disease and severe portal hypertension during the hemodynamic assessment before elective portal-systemic shunt surgery. The injection of somatostatin (1.0 microgram/kg) caused a decrease of the wedged hepatic venous pressure, from 19.5 +/- SE 1.3 mmHg to 14.0 +/- 1.0 mmHg (p < 0.001). Injections of 0.5 and 2.0 microgram/kg had similar effects. During somatostatin infusion at a constant rate (7.5 microgram/min) there was a reduction of the wedged hepatic venous pressure (-17.0%, p < 0.001) and estimated hepatic blood flow (-17.5%, p < 0.01) but no significant changes in hepatic vascular resistance, cardiac output, systemic blood pressure, peripheral resistance, or cardiopulmonary pressures. In marked contrast to the selective action of somatostatin on splanchnic hemodynamics, vasopressin infusion (0.3 U/min) in 6 patients caused not only significant falls in the wedged hepatic venous pressure and estimated hepatic blood flow (-28.6% and -31.8%, respectively), but also significant changes in the systemic circulation, including a reduction of the cardiac output (-19.7%, p < 0.01) and heart rate (-12.6%, p < 0.01) and an increase of the arterial pressure (+18.8%, p < 0.01) and peripheral resistance (+46.8%, p < 0.01). These results show that somatostatin effectively reduces hepatic blood flow and portal pressure in patients with cirrhosis and severe portal hypertension, without altering the systemic circulation.     

Correlation between hemodynamic parameters of the portal circulation in cirrhotic patients

The aim was to study the relationships between portal hemodynamic parameters in cirrhotic patients. Portal hemodynamics was assessed by scintisplenoportography and sonography, and the measurement of portohepatic gradient. Gradient between wedged and free hepatic venous pressures was 2.71 +/- 0.90 kPa (SD), and extrahepatic shunting was 49 +/- 31 p. 100 (SD) in 27 cirrhotic patients. Intrahepatic shunting was present in 17 p. 100 out of 23 cirrhotics. Portal blood flow was 0.582 +/- 0.196 l/min (SD) and hepatic resistance to portal blood flow was 4.84 +/- 2.62 kPa/l/min (SD). Portal blood flow correlated neither with the pressure gradient, nor with portosystemic shunting. The pressure gradient was significantly correlated with portal systemic shunting (r = 0.64, p less than 0.001). Hepatic resistance to portal blood flow was significantly (p less than 0.05) correlated with portal systemic shunting, however the value of the correlation coefficient was low (r = 0.433). The pressure gradient and portosystemic shunting were higher in patients with large esophageal varices than in those with small ones (respectively t = 2.665, p less than 0.02 and t = 3.00, p less than 0.01). Hemodynamic pattern was not correlated with the degree of hepatocellular failure, as assessed by the Child-Pugh index. In conclusion this study provides further evidence for the forward theory of portal hypertension in human liver cirrhosis.     

Echo-Doppler evaluation of acute flow changes in portal hypertensive patients: flow velocity as a reliable parameter

In order to evaluate the behavior of the portal vein cross-sectional area during changes in portal flow, two groups of subjects were analyzed in two blinded cross-over studies using echo-Doppler flowmetry. The first group (I) consisted of 21 patients with cirrhosis and 16 controls. They received a standardized meal which is known to increase portal flow. The second group (II) consisted of 31 patients with cirrhosis who received a dose of propranolol which is known to decrease portal flow. In Group I, 30 min after the meal, the portal vein blood velocity increased by 35 +/- 6% (p less than 0.01) in cirrhotic patients and by 55 +/- 5% (p less than 0.01), in normal subjects. The portal vein cross-sectional area increased significantly in normal subjects (22 +/- 2%, p less than 0.01) but not in cirrhotic patients (4 +/- 2%, n.s.). In Group II, 2 h after propranolol, there was a significant decrease in portal blood velocity (-14 +/- 2%), whereas the portal vein cross-sectional area did not show any significant changes. These data demonstrate that, in portal hypersensitive patients, the portal area measured by echo-Doppler flowmetry can be assumed to be constant and hence its calculation to estimate changes in portal blood flow can be omitted. Therefore, the use of blood velocity alone is suggested to monitor acute changes in flow in portal hypertension using Doppler flowmetry. The elimination of the portal vein cross-sectional area measurement simplifies the quantitative calculation of portal hemodynamics and increases the reliability of the technique by avoiding a source of error.     

Enhancement of portal pressure reduction by the association of isosorbide-5-mononitrate to propranolol administration in patients with cirrhosis

This study investigated whether oral doses of isosorbide-5-mononitrate, a preferential venous dilator that decreases portal pressure, could enhance the effects of propranolol on portal hypertension. Taking part in the study were 28 patients with cirrhosis and portal hypertension. Twenty patients (group 1) had hemodynamic measurements in baseline conditions after beta-blockade by intravenous administration of propranolol and after receiving oral doses of isosorbide-5-mononitrate. The remaining eight patients (group 2) were given oral isosorbide-5-mononitrate while receiving chronic propranolol therapy. In group 1, propranolol significantly reduced portal pressure (estimated as the gradient between wedged and free hepatic venous pressures) from 21.5 +/- 3.9 to 18.6 +/- 4.2 mm Hg (-13.7%, p less than 0.001), azygos blood flow (-38%, p less than 0.001), hepatic blood flow (-12.8%, p less than 0.05), cardiac output (-24.5%, p less than 0.001) and heart rate (-18.4%, p less than 0.001) without significant changes in mean arterial pressure. Addition of oral isosorbide-5-mononitrate caused a further and marked fall in portal pressure (to 15.7 +/- 3.1 mm Hg, p less than 0.001), without additional changes in azygos blood flow but with significant additional reductions in hepatic blood flow (-15.5%, p less than 0.05), cardiac output (-11.5%, p less than 0.001) and mean arterial pressure (-22%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of verapamil on hepatic and systemic hemodynamics and liver function in patients with cirrhosis and portal hypertension

The effects of verapamil on hepatic and systemic hemodynamics and on liver function were investigated in 10 patients with portal hypertension due to advanced micronodular cirrhosis to verify whether, as it has been suggested, this calcium channel blocker may improve liver function and reduce portal pressure in these patients. The oral administration of 100 mg of verapamil caused systemic vasodilation, evidenced by a significant reduction in mean arterial pressure (-8.1 +/- 7.6%, p less than 0.025) and systemic vascular resistance (-12.5 +/- 9.5%, p less than 0.001), and increased heart rate (+13.9 +/- 10.4%, p less than 0.01). However, no beneficial effect was noted on portal pressure evaluated by hepatic vein catheterization (baseline 19.8 +/- 4.0, verapamil 20.2 +/- 3.6 mmHg, NS), hepatic blood flow (1.45 +/- 0.64 vs. 1.47 +/- 0.62 liters per min, NS) and hepatic vascular resistance (1.314 +/- 611 vs. 1,266 +/- 513 dyn per sec per cm-5, NS). Similarly, no change was observed in portal blood flow, measured in six patients by pulsed Doppler flowmeter (0.94 +/- 0.30 vs. 0.89 +/- 0.35 liter per min, NS). In addition, verapamil did not increase the hepatic intrinsic clearance of these patients (0.20 +/- 0.07 vs. 0.19 +/- 0.06 liter per min, NS). This study suggests that verapamil is of no beneficial effect in patients with advanced cirrhosis of the liver.     

Effects of molsidomine, a long acting venous dilator, on portal hypertension. A hemodynamic study in patients with cirrhosis.

The present study investigated the effects of molsidomine, a predominant venous dilator which, contrary to organic nitrates, does not produce pharmacological tolerance on splanchnic and systemic hemodynamics in patients with cirrhosis. Twenty-seven cirrhotic portal hypertensive patients were studied prior to and up to 2 h after the oral administration of 2 mg of molsidomine (n = 11), 4 mg of molsidomine (n = 8) or placebo (n = 8). Molsidomine caused a significant reduction in the hepatic venous pressure gradient. The mean decrease at 60 min was -6.8 +/- 9% after 2 mg (p less than 0.05) and -15.4 +/- 12% after 4 mg (p less than 0.01). The decrease in the hepatic venous pressure gradient was maintained at 120 min: -11% after 2 mg (p less than 0.05) and -19% with 4 mg (p less than 0.01). This was associated with mild changes in azygos blood flow and with a significant decrease in hepatic blood flow (-17%, p less than 0.05). There was a moderate reduction in mean arterial pressure (-12.6% after 2 mg and -13.2% after 4 mg, p less than 0.01), which was due to a reduction in cardiac output, without any significant fall in systemic vascular resistance. Placebo administration did not change systemic or hepatic hemodynamics. This study shows that molsidomine causes a significant and sustained reduction in portal pressure in patients with cirrhosis, suggesting the potential role of this agent in the treatment of portal hypertension.     

Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.     

Portohepatic Pressures, Hepatic Function, and Blood Gases in the Combination of Nitroglycerin and Vasopressin: Search for Additive Effects in Cirrhotic Portal Hypertension

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.     

Effects of different octreotide dosages on splanchnic hemodynamics and glucagon in patients with TIPS

OBJECTIVE: The aim of this study was to evaluate the hemodynamic effects of octreotide in patients treated with transjugular intrahepatic portosystemic stent shunt in relation to plasma levels of octreotide and glucagon and the correlation between portal pressure and noninvasive Doppler parameters. METHODS: In 15 fasting patients, we i.v. administered isotonic sodium chloride followed by octreotide 25 microg/h and 100 microg/h, each over 1 h. We measured portal pressure (PP) directly and portal vein blood flow velocity by Doppler ultrasound simultaneously and calculated portal vascular resistance (PVR) and portal venous flow (PVF). Blood samples were taken for glucagon and octreotide (mean +/- SE). RESULTS: Octreotide reduced PP (120': -7.7+/-2.2%, p < 0.01 vs baseline; 180': - 11.4+/-2.1%, p < 0.01 vs baseline) and PVF (120': -21.7+/-31.7%, p < 0.01 vs baseline; 180': -11.6+/-18.1%, p < 0.05 vs baseline). Glucagon decreased with the increase in octreotide levels and showed a correlation with the decrease in PP and with PVF. In patients with a high PVR, we found a close inverse correlation between PP and portal vein blood flow velocity (r = -0.83, p = 0.03) as well as Cl (r = 0.81, p = 0.05), whereas poor correlation was found in patients with low PVR. CONCLUSIONS: Octreotide caused a dose-related, moderate but sustained reduction in PP in patients with transjugular intrahepatic portosystemic stent shunt. PVR seems to be an important parameter that influences the efficacy of octreotide and the relation between PP and noninvasive Doppler parameters.     

Portal hemodynamics during nitroglycerin administration in cirrhotic patients

Nitroglycerin is a potent venous dilator and a mild arterial vasodilator that has been shown to improve the hemodynamic response to vasopressin in portal hypertensive patients and to decrease portal pressure in experimental animals. In order to determine the effect of nitroglycerin on portal venous hemodynamics, we studied 11 patients with alcoholic cirrhosis before and during the administration of sublingual nitroglycerin (0.4 and 0.6 mg). The hepatic venous pressure gradient (which was obtained by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure) decreased from 17.9 +/- 6.5 mm Hg (mean +/- S.D.) to 15.1 +/- 5.1 mm Hg (p less than 0.02) at the peak of the effect, which occurred from 2 to 12 min after nitroglycerin administration. The mean arterial pressure was reduced from 96 +/- 10 mm Hg to a peak decrease of 76 +/- 18 mmHg (p less than 0.001). The peak change in the hepatic venous pressure gradient induced by nitroglycerin correlated directly with the peak change in mean arterial pressure (r = 0.79, p less than 0.01). There was a moderate increase in heart rate in response to the decrease in blood pressure (73 +/- 15 to 83 +/- 15 beats per min, p less than 0.001). Two of the 11 patients did not reduce their hepatic venous pressure gradient after 0.6 mg nitroglycerin. Reductions in portal pressure were observed with both increases and moderate decreases in azygos blood flow, suggesting that, as observed in experimental animals, the portal-pressure-reducing effect of nitroglycerin could be due to two different and independent mechanisms, a reduction in portal blood flow or portal-collateral vasodilatation.     

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.     

Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats

Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4-induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol-treated rats had significantly lower cardiac output (-31%) and heart rate (-26%) than controls (p less than 0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 +/- 0.4 vs. 6.3 +/- 0.5 ml per min.100 gm in controls, p less than 0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 +/- 0.2 vs. 2.0 +/- 0.1 mmHg per ml per min.100 gm body weight (not significant)]. Hence, the fall in portal pressure (-19%) was expected from the decrease in portal inflow (-24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral vessels, since beta-blockade does not modify portal vascular resistance in cirrhosis.     

Systemic and splanchnic hemodynamic effects of molsidomine in rats with carbon tetrachloride-induced cirrhosis

Molsidomine, a long-acting vasodilator mainly used as an antianginal agent, was reported to decrease the portohepatic venous pressure gradient in patients with alcoholic cirrhosis. This study investigated the effects of linsidomine, the active metabolite of molsidomine, on systemic and splanchnic hemodynamics in rats with CCl4-induced cirrhosis using the microsphere technique. Compared with placebo-treated rats, linsidomine-treated animals were found to have a significant decrease in portal venous pressure (-18%, p less than 0.01) and in mean arterial pressure (-16%, p less than 0.01), smaller peripheral resistances (p less than 0.01), greater portal venous inflow (p less than 0.05), smaller splanchnic arteriolar resistances (p less than 0.01) and smaller protocol-lateral resistances (p less than 0.05). Cardiac output, hepatic arterial blood flow, portal blood flow and estimated hepatic blood flow were not significantly different between the two groups of animals. Linsidomine-treated rats exhibited a trend toward greater collateral blood flow compared with controls, but this difference was not significant. We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow. These effects should be beneficial for patients with cirrhosis and portal hypertension.     

Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis

In patients with cirrhosis and portal hypertension, propranolol administration reduces heart rate and cardiac output and diminishes portal pressure and collateral blood flow. However, there is little information on the possible effects of propranolol on hepatic artery blood flow. The present study addressed this question in 12 cirrhotic patients with end-to-side portacaval shunt, in whom all of the liver blood flow represents the hepatic artery blood flow. Hepatic artery blood flow (continuous infusion of indocyanine green), cardiac output (thermal dilution), heart rate and mean arterial pressure were measured before and 20 min after the intravenous infusion of 10 to 15 mg of propranolol. beta-Adrenergic blockade caused a significant reduction of cardiac output (from 9.1 +/- 2.1 to 7.1 +/- 1.4 liters per min, p less than 0.001) (mean +/- S.D.) and heart rate (from 85 +/- 10 to 71 +/- 7 beats per min, p less than 0.001), and a significant increase of systemic vascular resistance (from 9.0 +/- 2.1 to 11.7 +/- 2.7 mmHg per liter per min, p less than 0.001), whereas mean arterial pressure did not change (77 vs. 78 mmHg). Propranolol significantly reduced hepatic artery blood flow (from 0.65 +/- 0.20 to 0.55 +/- 0.14 liters per min, p less than 0.01). However, reduction of hepatic artery blood flow (-12.9 +/- 7.3%) was significantly less than reduction of cardiac output (-21.1 +/- 5.2%, p less than 0.01). As a result, the fraction of the cardiac output delivered to the liver was significantly greater after propranolol (8.0 +/- 1.7%) than before (7.3 +/- 1.7%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Presinusoidal portal hypertension in non-alcoholic cirrhosis

The simultaneous measurement of wedged hepatic vein pressure (WHVP) and portal vein pressure (PVP) was performed in 156 cirrhotic patients. In the 110 alcoholic cirrhotic patients (97 micronodular and 13 macronodular cirrhosis), WHVP and PVP were closely related (25.8 +/- 6.3 vs. 25.9 +/- 6.3 mm Hg; p = not statistically significant). The difference between the two parameters was greater than 4 mm Hg in only six patients. In the 46 patients with nonalcoholic cirrhosis (41 macronodular and 1 micronodular cirrhosis; 4 primary biliary cirrhosis), PVP was significantly higher than was WHVP (25.8 +/- 6.2 vs. 21.7 +/- 6.8 mm Hg; p less than 0.001); in 20 patients, PVP exceeded WHVP by more than 4 mm Hg, and the mean difference was 7.5 mm Hg. There was no correlation between the porto-hepatic gradient and total hepatic blood flow measured by the indocyanine green single injection method or the portal fraction of total hepatic blood flow measured by indicator dilution curves. It is concluded that: (i) measurement of WHVP in alcoholic cirrhosis provides a reliable estimate of the severity of the portal hypertension, and (ii) hemodynamic evaluation of nonalcoholic cirrhosis should include PVP measurement in order to avoid underestimation of the porto-hepatic gradient.     

Different hemodynamic patterns of alcoholic and viral endstage cirrhosis: analysis of explanted liver weight, degree of fibrosis and splanchnic Doppler parameters

OBJECTIVE: In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis. MATERIAL AND METHODS: Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study. RESULTS: In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246+/-295 g versus 1070+/-254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49+/-0.36 ml g(-1) min(-1) versus 0.85+/-0.56 ml g(-1) min(-1), p=0.004) and hepatic pulsatility indices were higher (1.45+/-0.31 versus 1.26+/-0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7+/-5.5% versus 11.0+/-4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p<0.001) but not in alcoholic disease. CONCLUSIONS: A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.