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.     

Acute effect of propranolol on splanchnic circulation in normal and portal hypertensive rats

Propranolol decreases portal venous pressure in patients with cirrhosis but no method is available in man to study the effect of this beta-blocker on splanchnic organ blood flow. Because in rats, the microsphere method allows evaluation of regional blood flow, the acute effect of propranolol on both splanchnic and systemic circulations was studied in normal rats and in rats with portal hypertension due to portal vein stenosis. Portal venous pressure significantly decreased during propranolol administration in normal (5.6 +/- 1.0-4.7 +/- 1.1 mm Hg; mean +/- SD) as well as in portal hypertensive rats (11.7 +/- 2.3-10.3 +/- 1.8 mm Hg). Propranolol slightly decreased cardiac output and arterial pressure in all rats. Portal tributary blood flow was significantly reduced by propranolol in normal rats (17.4 +/- 3.0-11.3 +/- 2.2 ml/min) and in portal hypertensive rats (23.7 +/- 5.0-16.6 +/- 3.3 ml/min). Accordingly vascular resistance of the different organs in the portal venous territory increased in these rats receiving propranolol. The percentage of the decrease in portal tributary blood flow was significantly more marked than the percentage of reduction in cardiac output in portal hypertensive rats but, in normal rats, these percentages were parallel. Hepatic arterial blood flow did not change or slightly increased and, consequently, hepatic arterial vascular resistance decreased. These findings further clarify the marked effects of propranolol on splanchnic circulation.     

Hemodynamic changes in splenic blood flow during and after distal splenorenal shunt

The purpose of this study was to examine the hemodynamic changes of the spleen and the subsequent influence on the numbers of blood cells both during and 1 month after distal splenorenal shunt (DSRS) with splenopancreatic disconnection in 20 patients with portal hypertension. The intraoperative splenic blood flow, measured with an electromagnetic flowmeter, significantly increased after shunt insertion: the mean percentage increases within the splenic vein and artery were 60% (p less than 0.01) and 37% (p less than 0.05), respectively. The splenic venous blood flow, measured with a pulsed Doppler flowmeter, had not changed significantly 1 month postoperatively (676 +/- 501 to 540 +/- 306 ml/min). The WBC and platelet counts significantly (p less than 0.05 and p less than 0.01, respectively) increased 1 month postoperatively, whereas there was a small, but significant (p less than 0.05), decrease in RBC count. We concluded that splenic blood flow increases immediately after DSRS with splenopancreatic disconnection, but this increase may be only short term. The influence of the postoperative hemodynamic changes on blood cell count is uncertain.     

Measurement of azygos venous blood flow by a continuous thermal dilution technique: an index of blood flow through gastroesophageal collaterals in cirrhosis

A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive patients was developed. Since gastroesophageal collaterals drain into the azygos system, it is postulated that measurement of blood flow in the azygos vein should provide a quantitative measurement of gastroesophageal collateral blood flow changes in portal hypertensive patients. Azygos blood flow was measured using a double thermodilution catheter directed under fluoroscopy to the azygos vein. Ten patients with alcoholic cirrhosis were studied. Five of these patients had a history of repeated bleeding from gastroesophageal varices (Group I). The azygos blood flow in these patients was 596 +/- 78 ml per min. The other five patients all had decompressive surgery of the portal system (Group II). In these patients the azygos venous blood flow was 305 +/- 29 ml per min (p less than 0.01). The coefficient of variation of repeated baseline measurements was of 4.4 +/- 0.6%. The azygos venous blood flow measurement is a rapid, simple and sensitive method to evaluate blood flow changes in the vessels involved in gastroesophageal bleeding due to portal hypertension.     

Significance of hepatic arterial responsiveness for adequate tissue oxygenation upon portal vein occlusion in cirrhotic livers

We investigated sinusoidal blood flow and hepatic tissue oxygenation during portal vein occlusion in cirrhotic rat livers to examine the effect of cirrhosis on the properties of hepatic microvascular blood flow regulation. After 8 weeks of CCl4/phenobarbital sodium treatment to induce cirrhosis Sprague-Dawley rats were prepared surgically to allow assessment of portal venous and hepatic arterial inflow using miniaturized flow probes with simultaneous analysis of hepatic microcirculation and tissue oxygenation by fluorescence microscopy and polarographic oxymetry. Age-matched noncirrhotic animals served as controls. Upon portal vein occlusion in cirrhotic livers (flow reduction to < 20%), hepatic arterial blood flow increased 1.5-fold (61 +/- 8 ml/min per 100 g liver) of baseline (40 +/- 7 ml/min per 100 g liver), reflecting an appropriate hepatic arterial buffer response (HABR), similarly as seen in control livers. The net result was a reduction in total liver inflow from 90 +/- 12 to 72 +/- 11 ml/min per 100 g liver, which was associated with a significant decrease in both sinusoidal red blood cell velocity and volumetric blood flow to approx. 71% and 76% of baseline values. However, portal vein occlusion did not cause a deterioration in hepatic tissue pO2 (11 +/- 3 vs. 10 +/- 3 mmHg at baseline). Sinusoidal diameters were found unchanged, disproving a major role of the sinusoidal tone in the regulation of HABR. Microvascular response of cirrhotic livers did not generally differ from that in noncirrhotic livers upon portal inflow restriction. We conclude that HABR in cirrhotic livers operates sufficiently to meet the liver tissue oxygen demand, most probably by an increased relative contribution of arterial perfusion of hepatic sinusoids.     

Short-term portal hemodynamic effects of partial splenic embolization for hypersplenism

BACKGROUND/AIMS: The purpose of this study was to investigate the short-term effects of partial splenic embolization (PSE) for hypersplenism on portal hemodynamics and liver function. METHODOLOGY: Thirty-seven patients with hypersplenism were included in this study. RESULTS: The wedged hepatic venous pressure before and after PSE were 39 +/- 10 and 33 +/- 8 cmH2O, respectively, showing significant change (p < 0.01). The flow volumes of the splenic vein before and after PSE were 477 +/- 200 and 319 +/-187 mL/min, respectively, also showing significant change (p < 0.05). However, the flow volumes of the portal vein before and after PSE were 713 +/- 284 and 684 +/- 152 mL/min, respectively, showing no significant change. The blood laboratory parameters showed no significant change after PSE. PSE damaged neither the portal blood flow volume nor the liver function, although it improved the local hyperdynamic state in the splenic area and thrombocytopenia. CONCLUSIONS: In conclusion, PSE is a safe and effective treatment for hypersplenism from the portal hemodynamic point of view.     

Measurement of splanchnic circulation in dogs: changes induced by prostaglandin E1

In seven anesthetized dogs the effects of intravenously administered prostaglandin E1 on mesenteric arterial and portal venous blood flows and pancreatic capillary blood flow were measured with a transit-time ultrasonic volume flowmeter and a laser Doppler flowmeter. Basal blood flow of the superior mesenteric artery and of the portal vein were 5.7 +/- 0.6 and 11.2 +/- 1.0 ml/min/kg, respectively. Prostaglandin E1 caused a dose-dependent increase in these blood flows. The maximal effect was observed at a dose of 1.0 microgram/kg, when the superior mesenteric arterial blood flow increased 117.9 +/- 3.2% and the portal venous blood flow increased 99.4 +/- 1.7%. Prostaglandin E1 produced an initial rapid increase, followed by a decrease in pancreatic capillary blood flow. The results indicate that the flowmeters used in the present study are widely available for the study of splanchnic circulation and may have a possibility for clinical application.     

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.     

Splanchnic Hemodynamics in Idiopathic Portal Hypertension: Comparison with Chronic Persistent Hepatitis

A comparative study of splanchnic hemodynamics was made in 12 patients with idiopathic portal hypertension and in eight patients with chronic persistent hepatitis, but without portal hypertension, who served as the control. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, and organ volume by computed tomography. Splenic artery blood flow was 788 +/- 242 ml/min in idiopathic portal hypertension and about four times that in chronic persistent hepatitis (215 +/- 42 ml/min), whereas there was no difference in superior mesenteric artery blood flow between the former and the latter (408 +/- 142 vs. 389 +/- 32 ml/min). Spleen volume in idiopathic portal hypertension was six times that in chronic persistent hepatitis, and splenic artery blood flow showed a significant linear correlation with spleen volume in idiopathic portal hypertension (r = 0.71, p less than 0.02). The sum of splenic artery blood flow and superior mesenteric artery blood flow in idiopathic portal hypertension was 1195 +/- 294 ml/min, twice that in chronic persistent hepatitis (603 +/- 109 ml/min). Portal vascular resistance and intrahepatic portal vascular resistance were three times and four times those in chronic persistent hepatitis, respectively. These results indicate that both increased intrahepatic portal vascular resistance and increased splenic artery blood flow may play roles in the development of portal hypertension in idiopathic portal hypertension.     

Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in portal hypertensive rats

Serotonergic mechanisms have recently been implicated in the pathogenesis of portal hypertension; this suggests that blockade of serotonin S2 receptors may be a new approach for the pharmacological therapy of portal hypertension. This study was aimed at investigating the effects of ritanserin, a selective S2-serotonergic antagonist, in portal-hypertensive rats whose condition was due to partial portal vein ligation. The animals were randomized under double-blind conditions into two groups: the first received ritanserin (0.7 mg/kg body wt, intravenously), and the second received the same volume of placebo (isotonic saline solution). The hemodynamic studies were performed using radiolabeled microspheres 60 min after drug administration. Ritanserin administration significantly reduced portal pressure (from 11.8 +/- 0.8 mm Hg to 9.4 +/- 0.6 mm Hg; p less than 0.05). This was associated with lower portocollateral resistance (1.8 +/- 0.2 mm Hg/ml/min 100 gm in the ritanserin group vs. 2.3 +/- 0.2 mm Hg/ml/min 100 gm in rats receiving placebo; not significant), but we saw no changes in portal-vein inflow (5.5 +/- 0.7 ml/min 100 gm vs. 5.4 +/- 0.5 ml/min 100 gm), mean arterial pressure (95.9 +/- 3.5 mm Hg vs. 94.0 +/- 4.0 mm Hg) and cardiac index (31.9 +/- 3.5 ml/min 100 gm vs. 28.5 +/- 2.6 ml/min 100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. In summary, our results demonstrate that ritanserin infusion decreases portal pressure without causing systemic hemodynamic changes. This effect is probably due to a decrease in portocollateral resistance in portal-hypertensive rats. These results provide further for a role of serotonin in the pathogenesis of portal hypertension.     

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.     

Changes of Splanchnic Circulation with Progression of Chronic Liver Disease Studied by Echo-Doppler Flowmetry

Changes that occurred in splanchnic circulation with the progression of chronic liver disease were investigated using an ultrasonic Doppler flowmeter in healthy adults and in patients with chronic active hepatitis and liver cirrhosis in the supine position after an overnight fast. Superior mesenteric venous flow, splenic venous flow, and portal venous flow were significantly increased in patients with liver cirrhosis but not in patients with chronic active hepatitis compared with normal subjects. Portal venous flow (control value 10.5 +/- 2.3 ml/min/kg body weight) minus the sum of superior mesenteric venous flow and splenic venous flow was 0.8 +/- 2.1 ml/min/kg body weight in the control, (0.1 +/- 1.9) in chronic active hepatitis, and (-2.2 +/- 4.3) in liver cirrhosis; the difference was significant between the control and cirrhosis groups. These results indicate that in patients with liver cirrhosis a hyperdynamic state occurs in the splanchnic circulation of the intestine and spleen and that some portion of splanchnic blood flow bypasses the liver into the systemic circulation.     

Isosorbide dinitrate in experimental portal hypertension: a study of factors that modulate the hemodynamic response

Isosorbide dinitrate, a long-acting vasodilator, has been tested in human portal hypertension with conflicting results. In order to determine some of the factors that could affect the individual response to this drug, we infused isosorbide dinitrate at a low dose (10 to 25 micrograms per kg per min) and a high dose (100 micrograms per kg per min) to rats with portal vein stenosis. Under pentobarbital anesthesia, portal pressure was measured with an ileocolic vein catheter while cardiac output and regional blood flows were measured with the microsphere technique. At a dose that decreased arterial pressure by approximately 10%, cardiac output remained unchanged while portal vein inflow decreased significantly; portal pressure was not reduced (10.7 +/- 0.2 vs. 10.0 +/- 0.3 mm Hg), indicating a rise in portal vascular resistance. At a high dose of isosorbide dinitrate, arterial pressure and cardiac output fell markedly; portal pressure decreased only modestly (11.3 +/- 0.3 vs. 9.8 +/- 0.6 mm Hg, p less than 0.05), but portal flow was unchanged, indicating a reduction in portal vascular resistance. In addition, portal hypertensive rats received a constant i.v. infusion of N-acetyl-cysteine; the combination of the latter and isosorbide dinitrate markedly potentiated the effects on arterial pressure. Thus, the dose of the drug and the presence of cysteine-containing compounds appear to modulate the hemodynamic response to isosorbide dinitrate. Clinical testing with this drug should be undertaken with consideration of these factors.     

Chronic portal venous hypertension. The effect on liver blood flow and liver function and the development of esophageal varices

Portal venous hypertension was induced in G?ttingen minipigs by banding the portal vein. The pigs were checked repeatedly during the following 24 weeks. Portal pressure increased immediately on banding, from 8.4 +/- 0.7 mm Hg to 19.4 +/- 0.7 mm Hg, and remained constant throughout the observation period. Within 5 weeks all pigs developed esophageal varices, as demonstrated by portal angiography and endoscopy. The experimentally induced portal hypertension was accompanied by a 65% decrease in hepatic blood flow, most probably caused by almost complete shunting of portal venous blood. The hepatic arterial flow appeared to be within normal limits and sufficient to cover the oxygen demand of the liver; to judge from the splanchnic elimination rate of galactose, the hemodynamic changes did not affect the functional capacity of the liver.     

Effects of nitroglycerin and nifedipine on coronary and systemic hemodynamics during transient coronary artery occlusion

Nitroglycerin (NTG) and nifedipine (NIF) have the potential to augment coronary blood flow in addition to reducing peripheral determinants of myocardial oxygen demand as a synergistic protective mechanism during ischemia. To examine these effects, systemic and coronary hemodynamic responses were measured continuously before and during brief periods of myocardial ischemia induced by left anterior descending coronary balloon occlusion in 26 patients undergoing angioplasty (PTCA). Data were compared for two matched occlusion periods, one control and one "drug" occlusion. In 17 patients (NTG group), 200 micrograms of intracoronary NTG was given immediately before coronary occlusion. In nine patients (NIF group), 10 mg of sublingual NIF was given 15 minutes before the "drug" occlusion. NTG significantly but transiently reduced mean arterial pressure (91 +/- 11 to 82 +/- 15 mm Hg, p less than 0.05) and augmented basal coronary blood flow (95 +/- 38 to 127 +/- 54 ml/min, p less than 0.05) but did not alter great vein blood flow (59 +/- 29 vs 61 +/- 29 ml/min) or coronary occlusion pressure (25 +/- 7 to 24 +/- 7 mm Hg) during ischemia. NIF significantly reduced systolic, diastolic, and mean arterial pressure (119 +/- 21 to 95 +/- 8 mm Hg, p less than 0.001) and heart rate-pressure product from control. NIF maintained basal great vein blood flow (125 +/- 41 to 106 +/- 57 ml/min) during reduced myocardial oxygen demand, but did not affect great vein blood flow (73 +/- 29 to 79 +/- 37 ml/min) or coronary occlusion pressures during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of splanchnic blood flow and portal venous resistance to elevated portal pressure in the dog.

To determine the relationship of splanchnic blood flow and portal venous resistance to elevated portal pressure, in situ perfusion of the splanchnic circuit was carried out in 12 freshly killed dogs at varying perfusion rates and degrees of acute and chronic portal vein constriction. In six normal dogs before being killed, portal pressure averaged 8-8 +/- 1-2 mmHg and portal flow 658 +/- 81 ml/min. In the absence of portal vein constriction, increasing splanchnic perfusion to 1800 ml/min, minimally raised portal pressure (12-8 +/- 1-5 mmHg). With progressive acute constriction of the portal vein, however, comparable perfusion rates lead to progressively higher portal pressure levels and with greater than 90% constriction, portal pressure was greater than 30 mmHg with minimal elevation in splanchnic flow rate. In six other dogs before being killed but live to nine weeks after placement of an ameroid constrictor on the portal vein, portal pressure averaged 13-6 +/- 1-4 mmHg or slightly higher than in normal dogs (P greater than 0-02). Mesenteric venography and necropsy findings uniformly demonstrated 90% occlusion of the portal vein with extensive portasystemic collateralization. With increased perfusion of the splanchnic bed, portal pressure rose rapidly to approximately 35 mmHg with a flow rate of 1 800 ml/min.. These data suggest that, in disorders where resistance to transhepatic portal flow is marked, a small increment in splanchnic blood flow, which normally exerts little or no influence on portal pressure, promotes profound portal hypertension and may account for spontaneous 'rupture' of oesophageal varices. On the other hand, where resistance to transhepatic portal flow is mild but splanchnic blood flow is markedly hyperdynamic, reducing inflow may be sufficient to ameliorate extreme portal hypertension and its sequelae.     

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.     

Hemodynamic effects of terbutaline, a beta 2-adrenoceptor agonist, in conscious rats with secondary biliary cirrhosis.

The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor agonist - were studied in conscious normal rats and in conscious rats with secondary biliary cirrhosis. Compared with those of normal rats, dose-response curves in cirrhotic rats indicated significantly decreased reactivity in arterial pressure and heart rate. Half-maximal effective dose was not significantly different between the two groups. Terbutaline induced significant, dose-dependent decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1 body wt) increased both cardiac output and portal tributary blood flow, thus mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to 22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The association of a decreased portal pressure and increased splanchnic blood flow suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal collateral vascular resistance.     

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.     

Glucagon hinders the effects of somatostatin on portal hypertension. A study in rats with partial portal vein ligation.

Whether the decrease of portal venous inflow and portal pressure induced by somatostatin is related to the effects of somatostatin in inhibiting the secretion of glucagon and other vasodilatory peptides that are increased in portal hypertension was investigated in the current study. Splanchnic vascular resistance and splanchnic blood flow were determined using radioactive microspheres in rats with portal hypertension caused by partial portal vein ligation. Somatostatin infusion significantly decreased portal pressure (from 13.1 +/- 1.9 to 12.1 +/- 2.2 mm Hg; P less than 0.05). This was associated with a significant decrease in portal venous inflow caused by splanchnic vasoconstriction, as evidenced by increased splanchnic vascular resistance, and with a marked suppression of glucagon secretion. The simultaneous infusion of somatostatin and glucagon (2.8 ng/min, a dose that prevented any decrease in circulating glucagon levels) abolished all the hemodynamic effects of somatostatin. This effect seems to be specific because no hemodynamic changes were noted in portal hypertensive rats receiving only the glucagon infusion.