Effect of Peroral Administration of Isosorbide Dinitrate on Portal Pressure and Blood Flow in Patients with Cirrhosis of the Liver

1989 ◽  
Vol 17 (6) ◽  
pp. 560-564 ◽  
Author(s):  
J. Cervinka ◽  
V. Kordac ◽  
M. Kalab
Keyword(s):  
Blood Flow ◽  
Hepatic Vein ◽  
Isosorbide Dinitrate ◽  
Slow Release ◽  
Portal Pressure ◽  
Blood Flow Rate ◽  
Portal Blood Flow ◽  
Peroral Administration ◽  
Oesophageal Varices ◽  
Wedged Hepatic Vein Pressure

The effect of slow-release isosorbide dinitrate, given orally four times daily for 14 days, on the portal circulation was studied in 10 patients with liver cirrhosis and oesophageal varices. Mean arterial pressure and heart rate were not influenced significantly by isosorbide dinitrate. Statistically significant dilation of the portal vein by 11.9% and an increase in blood flow velocity by 35.4% and in portal blood flow rate by 54.3% were observed at the end of therapy. The average wedged hepatic vein pressure was 32.9 mmHg before therapy and after therapy it was decreased to 60.5%. The slight decrease observed in free hepatic vein pressure was not statistically significant. Before treatment the portohepatic gradient was four times above normal and after therapy it fell to 9.5 mmHg. The results indicate that, in patients with portal hypertension, an improvement in haemodynamics can be achieved by the use of isosorbide dinitrate. This improvement may lead to the prevention of bleeding from oesophageal varices.

Splanchnic blood flow in the monkey during hemorrhagic shock

1965 ◽  
Vol 208 (2) ◽  
pp. 265-269 ◽  
Author(s):  
Francis L. Abel ◽  
John A. Waldhausen ◽  
Ewald E. Selkurt
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Portal Vein ◽  
Hemorrhagic Shock ◽  
Hepatic Vein ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Mesenteric Arteries ◽  
Splanchnic Blood Flow

Blood flow in the celiac and superior mesenteric arteries was measured in nine Macaca monkeys during a standardized hemorrhagic shock procedure. Simultaneous pressures were obtained from the hepatic vein, portal vein, and aorta. Each animal was bled rapidly to an arterial pressure of 40 mm Hg and maintained at this level until 30% of the bled volume had spontaneously reinfused. The remaining blood was then rapidly reinfused and the animal observed until death. The results show a lack of overshoot of venous pressure on reinfusion, grossly pale intestines with some microscopic congestive changes, and a decrease in splanchnic conductance throughout the postinfusion period. Hepatic venous pressure exceeded portal pressure in six of the nine animals during the period of hemorrhage. The results are interpreted as indicative of insignificant splanchnic pooling during hemorrhagic shock in this animal.

scholarly journals A Hemodynamic Study to Evaluate the Buffer Response in Cirrhotic Patients Undergoing Liver Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Margarita Anders ◽  
Daniel Alvarez ◽  
Emilio Quiñonez ◽  
Federico Orozco ◽  
Nicolas Goldaracena ◽  
...  
Keyword(s):  
Blood Flow ◽  
Isosorbide Dinitrate ◽  
Liver Blood Flow ◽  
Resistance Index ◽  
Portal Blood Flow ◽  
Human Model ◽  
Physiological Regulation ◽  
Meal Ingestion ◽  
Artery Flow ◽  
Liver Transplant Recipients

The physiological regulation of the liver blood flow is a result of a reciprocal portal vein and hepatic artery flow relationship. This mechanism is defined as the hepatic arterial buffer response (HABR). This study was addressed to investigate whether HABR is maintained in denervated grafts in liver transplant recipients. Portal blood flow (PBF) and hepatic arterial resistance index (PI) were measured 6 months after transplantation using Doppler. In each patient we consecutively measured the vasodilator (Ensure Plus PO versus placebo) and vasoconstrictor (isosorbide dinitrate 5 mg SL versus placebo) stimuli. The meal ingestion caused a significant increase of both parameters, PBF (from 1495±260 to 2069±250 mL/min, P<0.05) and PI (from 0.7±0.2 to 0.8±0.2, P<0.05). By contrast, isosorbide dinitrate reduced PBF (from 1660±270 to 1397±250 mL/min, P<0.05) and PI (from 0.7±0.2 to 0.5±0.2, P<0.05). We show that PBF and PI are reciprocally modified with the administration of vasoconstrictor and vasodilator stimuli. These results suggest the persistence of the HABR in a denervated human model, suggesting that this mechanism is independent of the regulation from the autonomic nervous system.

The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery

1985 ◽  
Vol 63 (6) ◽  
pp. 717-722 ◽  
Author(s):  
W. Wayne Lautt ◽  
Dallas J. Legare
Keyword(s):  
Blood Flow ◽  
Hepatic Artery ◽  
Portal Pressure ◽  
Portal Blood Flow ◽  
Portal Blood ◽  
Maximal Response ◽  
Local Concentration ◽  
Portal Flow ◽  
Response Curves ◽  
Adenosine Concentration

Reduction of portal blood flow results in compensatory vasodilation of the hepatic artery, the hepatic arterial buffer response. The hypothesis tested is that the regulation of the buffer response is mediated by adenosine, where the local concentration of adenosine in the region of the hepatic arterial resistance vessels is regulated by washout of adenosine into portal venules that are in intimate contact with hepatic arterioles. In anesthetized cats, portal flow was reduced to zero by complete occlusion of all arterial supply to the guts. The resultant dilation of the hepatic artery compensated for 23.9 ± 4.9% of the decrease in portal flow. Dose–response curves were obtained for the effect of intraportal adenosine infusion on hepatic arterial conductance in doses that did not lead to recirculation and secondary effects on the hepatic artery via altered portal blood flow. The dose to produce one-half maximal response for adenosine is 0.19 mg∙kg−1∙min−1 (intraportal) and the estimated maximal dilation is equivalent to an increase in hepatic arterial conductance to 245% of the basal (100%)) level. The adenosine antagonist, 8-phenyltheophylline, produced dose-related competitive antagonism of the dilator response to infused adenosine (but not to isoproterenol) and a similar, parallel antagonism of the hepatic arterial buffer response. If supramaximal blocking doses were used, the hepatic artery showed massive and prolonged constriction with blood flow decreasing to zero. The data strongly support the hypothesis that intrinsic hepatic arterial buffer response is mediated entirely by local adenosine concentration. This hypothesis is contrary to the popular views that the hepatic artery is controlled either by myogenic responses to change in portal pressure or by metabolic feedback from the parenchymal cells.

scholarly journals Absorption kinetics of some carbohydrates in conscious pigs

1984 ◽  
Vol 51 (3) ◽  
pp. 517-529 ◽  
Author(s):  
A. A. Rerat ◽  
P. Vaissade ◽  
P. Vaugelade
Keyword(s):  
Blood Flow ◽  
Lactic Acid ◽  
Test Meal ◽  
Reducing Sugars ◽  
Blood Flow Rate ◽  
Portal Blood Flow ◽  
Portal Blood ◽  
Maize Starch ◽  
Hydrolysis Products ◽  
Electromagnetic Flow Probe

1. Concentrations of reducing sugars, glucose, fructose and lactic acid in blood obtained from arterial and portal catheters were measured together with the portal hepatic blood flow-rate for periods of 8–24 h in twenty-six unanaesthetized pigs (mean body-weight 51 kg). The animals received experimental meals containing different amounts (100–1600 g) of different sugars (glucose fifteen meals, sucrose twenty-four meals, lactose fourteen meals, maize starch nineteen meals) together with a protein–mineral–vitamin mixture (150 g) 6–8 d after implantation of the catheters and an electromagnetic flow probe.2. Because the portal blood flow pattern did not differ between test meals, net absorption followed the same trends as for porto-arterial concentration differences (Rérat et al. 1984). Apart from lactose, the amounts of reducing sugars appearing in the portal vein correlated with the intake of the test meal, but the absorption pattern was different for each sugar. The appearance of reducing sugars was faster and earlier after intake of glucose than after sucrose and the same was the case for sucrose relative to maize starch. The differences between the three carbohydrates tended to increase with the level of intake.3. With a test meal containing 1 kg carbohydrate, i.e. a normal meal in a 50 kg pig, digestion of sucrose and maize starch was not finished 8 h after the meal since only 60 and 52% respectively of their hydrolysis products were recovered in the portal blood. In the case of lactose, the amounts of reducing sugars appearing in the portal blood were always very small and constant (113–118 g within 8 h) whatever the level of intake, i.e. 30 and 15% of their hydrolysis products for intakes of 400 and 800 g respectively.4. Depending on the carbohydrate ingested, the uptake of glucose by the gut cell wall ranged from 14 to 21 g/h and the production of lactic acid from 2.5 to 3.5 g/h.

Spleen Blood Flow and Splanchnic Haemodynamics in Blood Dyscrasia and other Splenomegalies

1970 ◽  
Vol 38 (1) ◽  
pp. 73-84 ◽  
Author(s):  
L. M. Blendis ◽  
D. C. Banks ◽  
C. Ramboer ◽  
R. Williams
Keyword(s):  
Blood Flow ◽  
Liver Blood Flow ◽  
Portal Tract ◽  
Reticuloendothelial System ◽  
Blood Dyscrasia ◽  
Oesophageal Varices ◽  
Spleen Size ◽  
Blood Flows ◽  
Hepatic Histology ◽  
Wedged Hepatic Vein Pressure

1. Splenic blood flow and splanchnic haemodynamics have been studied in twenty patients with splenomegaly due to blood dyscrasia or diseases involving the reticuloendothelial system. Thirteen of these patients had portal hypertension, three had abdominal collaterals on arteriovenography and one oesophageal varices. 2. Total spleen blood flow was increased in all with values up to 1550 ml/min, and associated with this liver blood flows increased up to 2·61 1 min−1 m−2. In four patients the cardiac output was raised. 3. In five patients a raised wedged hepatic vein pressure was found which was solely related to the increase in liver blood flow, but in two others, in whom hepatic histology was abnormal, there was also an increase in postsinusoidal resistance. Nine patients had a raised hepatic pre-sinusoidal resistance. This was related to a greatly increased liver blood flow with portal tract fibrosis and cellular infiltration as possible additional factors. 4. The haemodynamic findings in these patients were similar to those found previously in patients with tropical splenomegaly. In both groups spleen blood flow in ml 100 g−1 min−1 was inversely proportional to spleen size. There were similar increases in total spleen and liver blood flows and in the percentage of patients with an increased pre-sinusoidal resistance. In contrast, in cirrhosis there was no inverse relationship between flow in 1 100 g−1 min−1, and of spleen size, and for the degree of splenomegaly total spleen blood flow was relatively greater.

Pathophysiology and a Rational Basis of Therapy

2015 ◽  
Vol 33 (4) ◽  
pp. 508-514 ◽  
Author(s):  
Jordi Gracia-Sancho ◽  
Raquel Maeso-Díaz ◽  
Jaime Bosch
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Liver Disease ◽  
Endothelial Dysfunction ◽  
Vascular Tone ◽  
Portal Pressure ◽  
Portal Blood Flow ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Flow Through

Portal hypertension is a common complication of chronic liver disease. Its relevance comes from the fact that it determines most complications leading to death or liver transplantation in patients with cirrhosis of the liver: bleeding from esophageal or gastric varices, ascites and renal dysfunction, sepsis and hepatic encephalopathy. Portal hypertension results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two mechanisms: (1) distortion of the liver vascular architecture due to the liver disease causing structural abnormalities (nodule formation, remodeling of liver sinusoids, fibrosis, angiogenesis and vascular occlusion), and (2) increased hepatic vascular tone due to sinusoidal endothelial dysfunction, which results in a defective production of endogenous vasodilators, mainly nitric oxide (NO), and increased production of vasoconstrictors (thromboxane A2, cysteinyl leukotrienes, angiotensin II, endothelins and an activated adrenergic system). Hepatic endothelial dysfunction occurs early in the course of chronic liver disease as a consequence of inflammation and oxidative stress, and determines loss of the normal phenotype of liver sinusoidal endothelial cells (LSECs) that become proliferative, prothrombotic, proinflammatory and vasoconstrictor. The cross-talk between LSECs and hepatic stellate cells (HSCs) induces activation of the latter, which in turn proliferate, migrate and increase collagen deposition around the sinusoids, contributing to fibrogenesis, architectural disruption and angiogenesis, which further increase the hepatic vascular resistance and worsen liver failure by interfering with the blood perfusion of the liver parenchyma. An additional factor further worsening portal hypertension is an increased blood flow through the portal system due to splanchnic vasodilatation. This is an adaptive response to decreased effective hepatocyte perfusion, and is maximal once portal pressure has increased sufficiently to promote the development of intrahepatic shunts and portal-systemic collaterals, including varices, through which portal blood flow bypasses the liver. In human portal hypertension collateralization and hyperdynamic circulation start at a portal pressure gradient >10 mm Hg. Rational therapy for portal hypertension aims at correcting these pathophysiological abnormalities: liver injury, fibrogenesis, increased hepatic vascular tone and splanchnic vasodilatation. Continuing liver injury may be counteracted specifically by etiological treatments (the best example being the direct-acting antivirals for hepatitis C viral infection), while architectural disruption and fibrosis can be ameliorated by a variety of antifibrotic drugs and antiangiogenic strategies. Several drugs in this category are currently under investigation in phase II-III randomized controlled trials. Sinusoidal endothelial dysfunction is ameliorated by statins as well as by other drugs increasing NO availability. It is of note that simvastatin has already been proven to be clinically effective in two randomized controlled trials. Splanchnic hyperemia can be counteracted by nonselective β-blockers (NSBBs), vasopressin analogs and somatostatin analogs, drugs that until recently were the only available treatments for portal hypertension, but that are not very effective in the initial stages of cirrhosis. There is experimental and clinical evidence indicating that a more effective reduction of portal pressure is obtained by combining agents acting on these different pathways. It is likely that the treatment of portal hypertension will evolve to use etiological treatments together with antifibrotic agents and/or drugs improving sinusoidal endothelial function in the initial stages of cirrhosis (preprimary prophylaxis), while NSBBs will be added in advanced stages of the disease.

Passive autoregulation of portal venous pressure: distensible hepatic resistance

1992 ◽  
Vol 263 (5) ◽  
pp. G702-G708 ◽  
Author(s):  
W. W. Lautt ◽  
D. J. Legare
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Portal Blood Flow ◽  
Minor Effect ◽  
Basal Resistance ◽  
Resistance Vessels

Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined.

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