Free Hepatic Venous Pressure Research Articles

Relationship between degree of portal hypertension and liver histologic lesions in patients with alcoholic cirrhosis. Effect of acute alcoholic hepatitis on portal hypertension.

The relationship between the degree of portal hypertension and histologic liver lesions was studied in a group of 84 patients with histologically proven alcoholic cirrhosis. The degree of portal hypertension was evaluated by the gradient between wedged and free hepatic venous pressures. Five histologic lesions were quantified: liver cell necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis, and fatty infiltration. The gradient between wedged and free hepatic venous pressures was significantly correlated with the degree of liver cell necrosis and the degree of neutrophilic infiltrate. The stepwise regression analysis showed that only liver cell necrosis has a significant and independent correlation for the degree of portal hypertension. The value for the gradient between wedged and free hepatic venous pressures was significantly higher in patients with (N = 48) than in those without (N = 36) acute alcoholic hepatitis (19.4 +/- 0.8 and 16.5 +/- 0.7 mmHg, respectively). Thus, histologic liver lesions observed in acute alcoholic hepatitis may play a role in the risk of complications of portal hypertension in patients with alcoholic cirrhosis.

Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis.

The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05-0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic effect of verapamil on portal hypertension in patients with postnecrotic cirrhosis.

Wedged hepatic venous pressure, free hepatic venous pressure and cardiac index were measured before and 1 hr after i.v. administration as well as 1 month and 3 months after chronic oral administration of verapamil in 10 patients with HBsAg-positive cirrhosis. The gradient between wedged hepatic venous pressure and free hepatic venous pressure was decreased 14% at 1 hr after i.v. administration of 10 mg verapamil, and the sustained decrease in hepatic venous pressure gradient was also demonstrated in the patients after 1 month, and in six patients after 3 months of continuous oral administration of verapamil. The mean arterial pressure significantly decreased (p less than 0.01) 1 hr after the administration of verapamil. There was no significant change in other hemodynamic values. We conclude that chronic oral administration of verapamil can reduce the hepatic venous pressure gradient in patients with compensated HBsAg-positive cirrhosis and portal hypertension.

Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation.

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Under anesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension (portal venous pressure 15.3 +/- 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (-27%) and in cardiac index (-21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circulation.

Effect of isosorbide dinitrate, verapamil, and labetalol on portal pressure in cirrhosis.

The effects on portal pressure of the vasodilatory drugs isosorbide dinitrate and verapamil and of an alpha and beta blocking agent, labetalol, were assessed in 21 patients with cirrhosis and portal hypertension. The wedged hepatic venous pressure gradient (wedged minus free hepatic venous pressures) was used as an index of portal pressure and was not significantly changed by treatment with labetalol (n = 5) but was significantly decreased by verapamil (n = 6; p less than 0.05) and isosorbide dinitrate (n = 10; p less than 0.01). Long term administration of isosorbide dinitrate also had a significant effect (p less than 0.01).

Effects of captopril on hepatic venous pressure and blood flow in patients with liver cirrhosis

To examine the possible contribution of the renin-angiotensin-aldosterone system to portal hypertension in patients with cirrhosis of the liver, seven such patients were studied with the hepatic venous catheterization technique, in the basal state, and after the intake of 12.5 to 25 mg of captopril. Hepatic venous wedge pressure was 22 ±2 mm Hg in the basal state and fell to 19 to 20 mm Hg at 45 to 90 minutes after the administration of captopril (P < 0.05 to 0.01). Wedge to free hepatic venous pressure difference (basal 14 ± 2 mm Hg) remained unchanged after captopril, and estimated hepatic blood flow was unaltered. Small but significant reductions in arterial blood pressures were seen after the administration of captopril. Aldosterone concentrations decreased whereas renin activity tended to increase after captopril. It is concluded that captopril inhibits the renin-angiotensin system in patients with cirrhosis of the liver, but fails significantly to decrease portal venous pressure. Captopril is thus unlikely to favorably influence the incidence of bleeding in these patients.

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 signficantly 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.

The effect of ranitidine on the plasma clearance and hepatic extraction of indocyanine green in patients with chronic liver disease.

Since hepatic clearance of ICG is reduced by H2-receptor antagonists in normal subjects, it has been suggested that they reduce liver blood flow. We have studied the effect of intravenous ranitidine on ICG clearance in twelve patients with chronic liver disease. Wedged and free hepatic venous pressure were measured before and after intravenous ranitidine in nine of the patients, and the hepatic extraction of ICG was determined in six patients. ICG clearance fell by 22 +/- 11% (s.e. mean) 60 min after ranitidine. In patients in whom ICG clearance fell after intravenous ranitidine the hepatic extraction of ICG was also reduced. There was no significant change in the gradient between wedged and free hepatic venous pressure after ranitidine. It is therefore unlikely that ranitidine lowers liver blood flow.

Hemodynamic effects of dobutamine in patients with alcoholic cirrhosis.

The effects of dobutamine infusion on cardiac output, hepatic blood flow, and the gradient between wedged and free hepatic venous pressures were studied in 14 patients with alcoholic cirrhosis. Cardiac output rose from 5.8 +/- 1.2 l/min (mean +/- SD) to 7.1 +/- 1.5 l/min. Hepatic blood flow and the gradient between wedged and free hepatic venous pressures did not change significantly during the dobutamine infusion (1.360 +/- 0.510 l/min to 1.446 +/- 0.502 l/min and 17.7 +/- 4.9 mm Hg to 17.9 +/- 3.7 mm Hg). We conclude that in alcoholic cirrhotic patients, dobutamine increased cardiac output as a result of increased heart rate and that there were no significant changes in percentage of cardiac output distributed to the liver.

Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension.

This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.

Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis

We studied the relationship between the degree of portal hypertension measured by the gradient between wedged and free hepatic venous pressures, the size of esophageal varices, and the risk of gastrointestinal bleeding in a series of 100 unselected patients with alcoholic cirrhosis. The degree of portal hypertension was not different in patients with no visible, in those with small-sized, and in those with large-sized, esophageal varices. The degree of portal hypertension was not different in patients without and with gastrointestinal bleeding, whether the source of hemorrhage was ruptured varices or acute gastric erosions. The risk of gastrointestinal bleeding, whether due to ruptured varices or acute gastric erosions, was significantly higher in patients with large-sized, than in those with no visible or small-sized, esophageal varices. It is concluded that, in patients with alcoholic cirrhosis, (a) the degree of portal hypertension has no predictive value for the risk of gastrointestinal bleeding and (b) large-sized esophageal varices are associated with a high risk of occurrence or recurrence of gastrointestinal bleeding and could be taken into account for a better selection of patients for portacaval shunt.

Portal hypertension in fulminant viral hepatitis.

The gradient between wedged and free hepatic venous pressures were measured in 10 unselected adult patients suffering from fulminant viral hepatitis. The gradient was increased in all the studied patients, ranging from 0.9 to 2.1 kPa; this finding indicates that portal hypertension was present in all these cases. Ascites was present in all the five patients having a gradient about 1.5 kPa and affected only two of the five patients having a gradient below 1.5 kPa; this observation suggests that portal hypertension plays a role in the mechanism of ascites in fulminant viral hepatitis. Portal hypertension in fulminant viral hepatitis is likely to be the consequence of an intrahepatic block due to massive necrosis of the liver cells.

Wedged and free hepatic venous pressure measured with a balloon catheter

The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (WHVP) were evaluated in 82 simultaneous determinations using the balloon catheter technique and the direct measurement of portal venous pressure. These measurements showed a close positive correlation (r = 0.97) over a wide range of pressures in 32 normal and 4 cirrhotic dogs. Studies were then performed in 13 cirrhotic patients in whom the balloon catheter was introduced using the Seldinger technique. Free hepatic venous pressure (FHVP) was measured with the balloon undistended. By distending the balloon to occlude the hepatic vein, the WHVP was recorded. Comparison of FHVP and WHVP with the conventional and balloon techniques revealed a close positive correlation (r = 0.89 and 0.93, respectively). The correlation was virtually perfect for the hepatic venous pressure gradient (WHVP-FHVP, r = 0.98). The balloon technique offers many advantages over the conventional approach, including the ease of achieving and demonstrating the wedged position from the femoral approach, the ability to measure the free and wedged pressure repeatedly without manipulating the catheter, and the measurement of pressure in a larger, more representative segment of the liver.

Wedged and free hepatic venous pressure measured with a balloon catheter

Wedged and free hepatic venous pressure measured with a balloon catheter

Hepatic circulation during and after infectious hepatitis.

Hepatic circulation was studied at rest and during and after supine bicycle exercise by hepatic venous catheterization and i.v. constant infusion of indocyanine green dye in 3 males with infectious hepatitis, both during the acute stage and 5–6 weeks later during convalescence. In 2 of them injections of a solution of 85Kr and 133Xe in saline were also given at rest into an occluded hepatic vein, and the disappearance rates of the isotopes were measured with an external scintillator over the liver. Hepatic fat content was estimated from the actual hematocrit and the quotient between the half-time for krypton and for xenon. During the acute stage the patients had larger total hepatic blood flow, higher splanchnic oxygen uptake, greater difference between wedged and free hepatic venous pressure, and higher hepatic fat content than a previously studied group of controls. At re-examination, all values had decreased markedly as compared with those from the first study, hepatic blood flow and splanchnic oxygen uptake by 20–25%, and all values equalled those of the control group. It is concluded that the observed changes in the acute stage were attributable to the disease and that they were reversible.

The extrahepatic uptake of radioactive colloidal gold in cirrhotic patients as an index of liver function and portal hypertension.

In the present study, 21 cirrhotic patients underwent hepatic scintigraphy with radioactive colloidal gold. The extrahepatic uptake of this colloidal material was evaluated, using anterior and posterior scintigrams, by grading the spleen (0 to +++) and the vertebral bone marrow uptake (0 to ++). The summation of these two gradations was used as an index of extrahepatic uptake (198Au-EHU). The relative clearance of indocyanine green (K-ICG) was calculated in 19 cases. Combined portal and hepatic vein catheterization was performed, and free portal venous pressure (FPVP), free hepatic venous pressure (FHVP), and wedged hepatic venous pressure (WHVP) were recorded. The portohepatic gradient (FPVP-FHVP) was used to measure portal hypertension. A significant positive correlation was found between portohepatic gradient and198Au-EHU. A highly significant negative correlation was found between K-ICG and198Au-EHU and between the portohepatic gradient and K-ICG. The present study suggests that198Au-EHU cannot be useful as a single indirect evaluation of portal hypertension in individual cirrhotic patients. However, when both are recorded,198Au-EHU and K-ICG can be helpful in identifying cirrhotic patients with a significant degree of portal hypertension (a portohepatic gradient of 10 mmHg or more).

Hepatic circulation in young males with infectious hepatitis, studied at rest, during and after exercise.

AbstractHepatic vein catheterization was performed in 6 young males with infectious hepatitis and 11 healthy male volunteers. At rest in the supine position the total hepatic blood flow estimated by the Bradley technique using indocyanine green dye was significantly higher in the patients than in the controls (2.37 and 1.37 l/min, respectively). During supine bicycle exercise the absolute reduction of the hepatic blood flow was similar in patients and controls, with the patients on a significantly higher flow level. The difference between the wedged and free hepatic venous pressure was higher in the patients than in the controls both before and after exercise. The increased hepatic blood flow in the patients with hepatitis seemed to be caused by an increased hepatic artery blood flow, most likely of metabolic origin.

The effect of physical exercise on the wedged and free hepatic venous pressure in normal men.

Abstract. Hepatic vein catheterization has been performed in 10 healthy male volunteers, 20–27 years old. Wedged and free hepatic venous pressures were repeatedly measured in supine position, at rest and up to 35 min after heavy bicycle exercise that reduced the hepatic blood flow to about one third. The mean pressure difference between the wedged and free catheter positions was in all subjects higher after exercise than before. The average value of 0.76 mmHg at rest increased to 1.92 mmHg after exercise. If the wedged hepatic venous pressure still measured the portal venous pressure after exercise, the increased pressure gradient indicated a 2.5–3 times higher resistance to the portal blood flow over the hepatic sinusoids. This finding can be explained by increased water content and osmolarity of the hepatocytes, causing a mechanical obstruction of the sinusoids. The pathogenesis might be metabolic or hypoxic changes induced by the exercise.

Reduction of portal venous pressure in cirrhotic patients with bleeding from oesophageal varices, by administration of a vasopressin derivative, phenylalanine 2-lysine 8-vasopressin

PLV 2 (phenylalanine 2-lysine 8-vasopressin, Octapressin ®) is a new synthetic vasopressin derivative which, in comparison with natural vasopressins, has a more selective pressor effect and no appreciable antidiuretic action. The effect of PLV 2 on the hepatic circulation was studied experimentally by means of hepatic vein catheters in ten patients in whom the liver was normal and in twelve patients with hepatic cirrhosis and portal hypertension. PLV 2 (10 units in 200 ml. 5 per cent glucose solution) was infused intravenously within ten minutes. The normal “effective” portal venous pressure (difference between wedged hepatic venous pressure and free hepatic venous pressure) is affected only slightly. In portal hypertension it fell on the average by 46 per cent and the more so the higher the initial pressure. In normal persons the mean decline in hepatic blood flow was 43 per cent,in those with portal hypertension 35.8 per cent. The oxygen saturation of the hepatic vein blood decreased, and the oxygen consumption in the splanchnic region remained unchanged in both groups. Corresponding results in human subjects and animals given natural vasopressins are summarised from the literature. Clinically, PLV 2 was used for the treatment of acute oesophageal haemorrhage in doses of 20 units delivered within twenty minutes in nine patients with hepatic cirrhosis. Ten of fifteen haemorrhages could thereby be stopped. The corresponding experience with forty-seven patients treated with natural vasopressins is summarised from the literature. The side effects of PLV 2 consist of marked pallor of the skin, also occasionally nausea, abdominal cramps, urgent micturition and tenesmus, none troublesome. Angina pectoris, ischemic electrocardiographic changes, anti-diuresis and pulmonary edema were not observed. Infusion of PLV 2 is suggested in the initial treatment of bleeding oesophageal varices. Infusions can be repeated every two hours. If these fail, the Sengstaken-Blakemore tube, which involves a higher morbidity, can then be used. For bleeding gastric varices, treatment with vasopressins is superior to use of the oesophageal tube. Vasopressins lower the portal pressure both in cases of postsinusoidal portal hypertension (hepatic cirrhosis) and in prehepatic portal hypertension (portal vein thrombosis). PLV 2 has the advantage over natural vasopressins in the treatment of bleeding oesophageal varices in respect to its selective pressor effect, the absence of any measurable diminution in cardiac output, its negligible anti-diuretic effect and possible increase in renal blood flow.