pituitrin and Hypertension--Portal

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.

Topics: Acute Kidney Injury; Acute-On-Chronic Liver Failure; Albumins; Antidiuretic Hormone Receptor Antagonists; Ascites; Fluid Therapy; Hepatic Encephalopathy; Hepatorenal Syndrome; Humans; Hypertension, Portal; Hyponatremia; Liver Cirrhosis; Liver Transplantation; Renin-Angiotensin System; Saline Solution, Hypertonic; Splanchnic Circulation; Tolvaptan; Vasodilation; Vasopressins

Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions.

Topics: Acute Kidney Injury; Adrenal Insufficiency; Ascites; Creatinine; Evidence-Based Medicine; Hepatorenal Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Transplantation; Lypressin; Midodrine; Norepinephrine; Octreotide; Plasma Substitutes; Portasystemic Shunt, Transjugular Intrahepatic; Serum Albumin; Terlipressin; Vasodilator Agents; Vasopressins

Kidney dysfunction is a common complication of patients with advanced cirrhosis and is associated with poor prognosis. Patients with advanced cirrhosis show circulatory dysfunction characterized by reduced systemic vascular resistance due to splanchnic arterial vasodilation, which is caused by portal hypertension. The progressive reduction in systemic vascular resistance leads to effective arterial hypovolemia. In order to maintain arterial pressure within normal limits in this setting, there is activation of systemic vasoconstrictor systems, including the renin-angiotensin-aldosterone system, sympathetic nervous system and, in late stages, nonosmotic hypersecretion of vasopressin. Although these systems have positive effects in maintaining arterial pressure, they have a negative influence on kidney function, leading to the retention of sodium and solute-free water, and in late stages of the disease an intense kidney vasoconstriction develops, leading to decrease of the glomerular filtration rate and the development of hepatorenal syndrome (HRS). Moreover, bacterial translocation and the existence of a systemic inflammatory state in patients with advanced cirrhosis may play a role in the impairment of circulatory function. HRS is a unique cause of kidney failure of functional origin that develops in patients with cirrhosis. However, besides HRS, patients with cirrhosis may develop kidney failure due to other causes, including bacterial infections, prerenal kidney failure, shock, use of nephrotoxic drugs or intrinsic kidney diseases. Considering the existence of circulatory dysfunction and some degree of kidney vasoconstriction, patients with advanced cirrhosis have fragile kidney function and are susceptible to easily developing kidney failure associated with other complications of the disease, particularly bacterial infections and gastrointestinal bleeding.

Topics: Hemodynamics; Hepatorenal Syndrome; Humans; Hypertension, Portal; Hypovolemia; Inflammation; Kidney; Liver; Liver Circulation; Liver Cirrhosis; Vascular Resistance; Vasopressins

Acute variceal bleeding is a potentially life-threatening complication of portal hypertension. Management consists of emergent hemostasis, therapy directed at hemodynamic resuscitation, protection of the airway, and prevention and treatment of complications including prophylactic use of antibiotics. Endoscopic treatment remains the mainstay in the management of acute variceal bleeding in combination with pharmacotherapy aimed at reducing portal pressure. This article intends to highlight only the current nonendoscopic treatment approaches for control of acute variceal bleeding.

Topics: Acute Disease; Acute Kidney Injury; Anti-Bacterial Agents; Balloon Occlusion; Blood Transfusion; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hormones; Humans; Hypertension, Portal; Intubation, Intratracheal; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Somatostatin; Vasoconstrictor Agents; Vasopressins

Portal hypertension is an increase in pressure in the portal vein and its tributaries. It is defined as a portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) greater than 5 mm Hg. Although this gradient defines portal hypertension, a gradient of 10 mm Hg or greater defines clinically significant portal hypertension, because this pressure gradient predicts the development of varices, decompensation of cirrhosis, and hepatocellular carcinoma. The most direct consequence of portal hypertension is the development of gastroesophageal varices that may rupture and lead to the development of variceal hemorrhage. This article reviews the pathophysiologic bases of the different pharmacologic treatments for portal hypertension in patients with cirrhosis and places them in the context of the natural history of varices and variceal hemorrhage.

Topics: Adrenergic beta-Antagonists; Fibrosis; Hemorrhage; Humans; Hypertension, Portal; Liver; Randomized Controlled Trials as Topic; Somatostatin; Varicose Veins; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Portal hypertension is a progressively debilitating complication of cirrhosis and a principal cause of mortality in patients who have hepatic decompensation. This article describes the classification system and pathophysiology of portal hypertension. It also discusses a practical approach to prevention of first variceal hemorrhage, general management of the acute bleeding episode, and secondary prophylaxis to prevent rebleeding. Pharmacologic, endoscopic, radiologic, and surgical modalities are all described in detail.

Topics: Algorithms; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Octreotide; Portal System; Primary Prevention; Secondary Prevention; Vasoconstrictor Agents; Vasopressins

Type 1 hepatorenal syndrome (HRS) is prerenal failure specific to decompensated cirrhosis. In patients with HRS, there is marked splanchnic/systemic vasodilation resulting in arterial hypotension, arterial baroreceptor unloading, overstimulation of the sympathetic nervous and renin-angiotensin systems. This reflex neurohumoral hyperactivity via endogenous vasoconstrictors/vasopressors such as angiotensin II and noradrenaline induces arterial vasoconstriction in different extrasplanchnic vascular beds (including preglomerular arteries in the kidneys). Decreased arterial pressure (i.e. low renal perfusion pressure) and preglomerular vasoconstriction are thought to play a major role in the decline of the glomerular filtration rate (GFR). Nonrandomized studies in patients with HRS have shown that the administration of a splanchnic vasoconstrictor (vasopressin analogue or alpha(1)-adrenoceptor agonist), usually combined with intravenous albumin, causes increases in arterial pressure, arterial baroreceptor uploading, decreased neurohumoral activity, decreased renal vascular resistance, and increased GFR. Randomized clinical trials have shown that treatment with a combination of the vasopressin analogue terlipressin and intravenous albumin improves renal function in patients with type 1 HRS. Vasopressor therapy with terlipressin plus intravenous albumin is the medical treatment of choice for type 1 HRS.

Topics: Acute Kidney Injury; Antihypertensive Agents; Humans; Hypertension, Portal; Lypressin; Terlipressin; Treatment Outcome; Vasopressins

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.

Topics: Acute Disease; Adrenergic beta-Antagonists; Antibiotic Prophylaxis; Drug Therapy, Combination; Esophageal and Gastric Varices; Humans; Hypertension, Portal; Liver Cirrhosis; Lypressin; Octreotide; Somatostatin; Terlipressin; Vasoconstrictor Agents; Vasopressins

Portal hypertension, a major hallmark of cirrhosis, is defined as a portal pressure gradient exceeding 5 mm Hg. In portal hypertension, porto-systemic collaterals decompress the portal circulation and give rise to varices. Successful management of portal hypertension and its complications requires knowledge of the underlying pathophysiology, the pertinent anatomy, and the natural history of the collateral circulation, particularly the gastroesophageal varices.

Topics: Collateral Circulation; Dilatation, Pathologic; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostatics; Humans; Hypertension, Portal; Ligation; Portasystemic Shunt, Transjugular Intrahepatic; Pyloric Antrum; Risk Factors; Sclerotherapy; Vasopressins

Cirrhosis results in portal hypertension in many patients. The major complications of portal hypertension include development of ascites and esophageal or gastric varices. Varices lead to hemorrhage and death in a significant proportion of patients. This review focuses on the pharmacologic approach to management of portal hypertension in patients at risk of variceal hemorrhage, or those who have already had variceal bleeding. Pharmacologic therapy is used for 1) primary prevention of bleeding, 2) management of acute bleeding, and 3) prevention of recurrent bleeding (secondary prophylaxis). For acute esophageal variceal hemorrhage, a variety of pharmacologic agents are used, including somatostatin, octreotide, vapreotide, lanreotide, terlipressin, and vasopressin (with nitrates). For primary and secondary prevention of esophageal variceal hemorrhage, beta-blockers remain the mainstay therapy.

Topics: Adrenergic beta-Antagonists; Algorithms; Antihypertensive Agents; Cardiovascular Agents; Esophageal and Gastric Varices; Esophagoscopy; Gastrointestinal Hemorrhage; Hemostatics; Humans; Hypertension, Portal; Ligation; Liver Cirrhosis; Nitrates; Portasystemic Shunt, Transjugular Intrahepatic; Recurrence; Sclerotherapy; Somatostatin; Vasoconstrictor Agents; Vasopressins

Portal hypertension is one of the main consequences of cirrhosis. It results from a combination of increased intrahepatic vascular resistance and increased blood flow through the portal venous system. The condition leads to the formation of portosystemic collateral veins. Esophagogastric varices have the greatest clinical impact, with a risk of bleeding as high as 30% within 2 years of medium or large varices developing. Ascites, another important complication of advanced cirrhosis and severe portal hypertension, is sometimes refractory to treatment and is complicated by spontaneous bacterial peritonitis and hepatorenal syndrome. We describe the pathophysiology of portal hypertension and the current management of its complications, with emphasis on the prophylaxis and treatment of variceal bleeding and ascites.

Topics: Algorithms; Anti-Bacterial Agents; Ascites; Collateral Circulation; Diuretics; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatorenal Syndrome; Hormones; Hypertension, Portal; Liver Cirrhosis; Lypressin; Peritonitis; Portasystemic Shunt, Transjugular Intrahepatic; Sclerotherapy; Secondary Prevention; Somatostatin; Spironolactone; Terlipressin; Vascular Resistance; Vasoconstrictor Agents; Vasodilation; Vasopressins

Vasopressin, synthesized in the hypothalamus, is released by increased plasma osmolality, decreased arterial pressure, and reductions in cardiac volume. Three subtypes of vasopressin receptors, V1, V2, and V3, have been identified, mediating vasoconstriction, water reabsorption, and central nervous system effects, respectively. Vasopressin and its analogs have been studied intensively for the treatment of states of "relative vasopressin deficiency," such as sepsis, vasodilatory shock, intraoperative hypotension, and cardiopulmonary resuscitation. Infusion of vasopressin (0.01-0.04 U/min) decreases catecholamine requirements in patients with sepsis and other types of vasodilatory shock. Bolus application of 1 mg terlipressin, the V1 agonist, reverses refractory hypotension in anesthetized patients and has been studied in patients with septic shock and chronic liver failure. During cardiopulmonary resuscitation, a 40-U bolus dose of vasopressin may be considered to replace the first or second bolus of epinephrine regardless of the initial rhythm. The side effects of vasopressin and its analogs must be further characterized.

Topics: Adrenocorticotropic Hormone; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Cardiopulmonary Resuscitation; Hemostasis; Humans; Hypertension; Hypertension, Portal; Neuroendocrine Tumors; Shock, Septic; Vasopressins; Water-Electrolyte Balance

Portal hypertension is a progressively debilitating complication of cirrhosis and a principal cause of mortality in patients who have hepatic decompensation. During the last few decades, significant clinical advances in the prevention of initial variceal hemorrhage, the management of acute variceal hemorrhage, and the prevention of recurrent variceal hemorrhage have reduced the morbidity and mortality of this lethal complication of cirrhosis. This article discusses the pharmacologic treatment of portal hypertension, including preprimary prophylaxis, prevention of a first variceal hemorrhage, treatment of acute variceal hemorrhage, and secondary prophylaxis of a variceal hemorrhage.

Topics: Adrenergic beta-Antagonists; Humans; Hypertension, Portal; Nitrates; Somatostatin; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

A POTENTIALLY SEVERE EVENT: Upper gastrointestinal haemorrhage in a cirrhotic patient is always extremely serious, particularly in the case of rupture of the oesophageal varices, which is the most frequent cause. THE TWO POLES OF TREATMENT: Early vasoactive treatment permits elastic ligature in optimal conditions using an endoscope. The prevention of other complications of cirrhosis is an essential element in the management of these patients.

Topics: Acute Disease; Emergencies; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatics; Hepatic Encephalopathy; Hormones; Humans; Hypertension, Portal; Ligation; Liver Cirrhosis; Octreotide; Recurrence; Risk Factors; Rupture; Sclerotherapy; Shock, Hemorrhagic; Somatostatin; Vasopressins

Portal hypertension (PHT) is common in children and a majority of cases in India are constituted by extrahepatic portal venous obstruction or cirrhosis of liver. Morbidity and mortality in this condition is related to variceal bleeding, most commonly from esophageal varices. Acute variceal bleeding is best controlled by endoscopic therapy. Somatostatin and octreotide are useful in acute variceal bleeding as a supplementary therapy. Acute variceal bleeding uncontrolled by medical therapy merits preferably a shunt surgery or devascularization depending upon etiology of PHT and expertise of the surgeon. Acute variceal bleeding originating from gastric varices can be effectively controlled by endoscopic injection of tissue adhesive agent (n-butyl 2 cyanoacrylate). Eradication of esophageal varices by endoscopic measures (sclerotherapy or band ligation) is successful in prevention of recurrence of bleeding. Surgical portosystemic shunts especially in non-cirrhotic PHT are successful in achieving portal decompression and significant reduction in recurrence of variceal bleeding. Role of beta-blockers in primary prophylaxis of variceal bleeding in children still remains to be substantiated.

Topics: Balloon Occlusion; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Hypertension, Portal; India; Male; Octreotide; Portasystemic Shunt, Surgical; Prognosis; Risk Assessment; Severity of Illness Index; Somatostatin; Survival Rate; Vasopressins

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Hypertension, Portal; Lypressin; Research; Somatostatin; Terlipressin; Vasopressins

The splanchnic pharmacodynamic effects of the drugs used for the treatment of hemorrhagic complications of portal hypertension were poorly clarified until some years ago. The introduction of Doppler ultrasound provided a powerful tool to investigate such hemodynamic effects and brought new insights in this field. The present article reviews the pharmacodynamics of the substances used in the treatment of portal hypertension, with particular regard to the effects assessable by duplex Doppler ultrasonography.

Topics: Adrenergic Agents; Adrenergic beta-Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Domperidone; Humans; Hypertension, Portal; Lypressin; Metoclopramide; Nitrates; Octreotide; Portal System; Somatostatin; Terlipressin; Ultrasonography, Doppler; Ultrasonography, Doppler, Duplex; Vasopressins

Topics: Animals; Disease Models, Animal; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Hemodynamics; Hormone Antagonists; Humans; Hypertension, Portal; Octreotide; Somatostatin; Vasoconstrictor Agents; Vasopressins

Topics: Adrenergic beta-Antagonists; Adult; Aged; Combined Modality Therapy; Diuretics; Female; Humans; Hypertension, Portal; Male; Middle Aged; Nitroglycerin; Portal Pressure; Propanolamines; Sclerotherapy; Somatostatin; Spironolactone; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Topics: Adrenergic beta-Antagonists; Animals; Dogs; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Lypressin; Nitroprusside; Pituitary Hormones, Posterior; Recurrence; Somatostatin; Terlipressin; Vasopressins

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Catheterization; Clinical Trials as Topic; Diuretics; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Lypressin; Metoclopramide; Molsidomine; Octreotide; Portasystemic Shunt, Surgical; Sclerotherapy; Somatostatin; Terlipressin; Vasodilator Agents; Vasopressins

Topics: Adrenergic beta-Antagonists; Ascites; Carcinoma, Hepatocellular; Catheterization; Diuretics; Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Neoplasms; Nitroglycerin; Peritonitis; Somatostatin; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Recurrence; Somatostatin; Vasoconstrictor Agents; Vasopressins

Topics: Drug Therapy, Combination; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Lypressin; Nitro Compounds; Sclerotherapy; Terlipressin; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Humans; Hypertension, Portal; Kidney; Nitrates; Somatostatin; Vasodilator Agents; Vasopressins

Once the bleeding patient has been resuscitated and the diagnosis of acute variceal hemorrhage established by endoscopy, emergency injection sclerotherapy should be employed as the therapeutic option of choice. Endoscopic band ligation is a promising new technique that may prove to be as effective as sclerotherapy, with fewer complications. Pharmacologic treatment (with vasopressin and nitroglycerin) and balloon tamponade remain important alternative treatments, both as empiric temporizing therapy before sclerotherapy can be arranged and in the approximately 30% of patients who continue to bleed after a single sclerotherapy session. Continued bleeding in many of these patients can be controlled with a second session of sclerotherapy. If active acute bleeding persists after two sclerotherapy treatments, treatment should be considered a failure. Some of these patients may be suitable for surgical treatment with either staple-gun transection of the esophagus or emergency portacaval shunting.

Topics: Acute Disease; Balloon Occlusion; Catheterization; Drug Administration Schedule; Emergencies; Endoscopy, Gastrointestinal; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Ligation; Nitroglycerin; Portacaval Shunt, Surgical; Sclerotherapy; Somatostatin; Vasopressins

Variceal formation and rupture are dreaded complications of chronic liver disease and portal hypertension. The pharmacologic treatment of portal hypertension should be able to stop as well as to prevent variceal hemorrhage. There are two principal types of vasoactive drugs in the treatment of portal hypertension: vasoconstrictors and vasodilators. Vasoconstrictors reduce the splanchnic blood flow, thereby decreasing the portal blood flow and portal pressure. Vasodilators act by different mechanisms, including by relaxation of myofibroblasts in the fibrous septa and presinusoidal areas of the liver and by direct vasodilation of the collateral circulation. In addition, paradoxically, they could decrease portal flow and pressure by inducing a baroreflex-mediated mesenteric arterial vasoconstriction. A miscellaneous group of drugs is also available. These drugs reduce the blood flow and pressure in the gastroesophageal variceal system by mechanisms other than vasoconstriction or vasodilation. The success of these pharmacologic agents is limited once the varices have ruptured. The use of beta-blockers in the prophylaxis of the first variceal bleeding has been proven of benefit in this respect. Future research should be aimed at elucidating the role that humoral and endothelial factors play in development of the hyperdynamic circulatory state that characterizes patients with portal hypertension. Once these etiologic factors have been identified and new knowledge is acquired about their role in the complications of chronic liver disease, the challenge will rest on developing novel pharmacologic therapies specifically targeting these factors.

Topics: Adrenergic beta-Antagonists; Animals; Calcium Channel Blockers; Clonidine; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Metoclopramide; Molsidomine; Nitrates; Nitroglycerin; Serotonin Antagonists; Somatostatin; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Successful pharmacological arrest of haemorrhage might avoid the risk of aspiration associated with tamponade and early studies have suggested that the vasoactive agent somatostatin may be as effective and perhaps safer than tamponade in controlling variceal haemorrhage. In our view, vasopressin has not established a role in management but we retain an open mind regarding the potential use of terlipressin in combination with nitroglycerin. It is unlikely that any of these agents can improve significantly our ability to control variceal haemorrhage when compared to balloon tamponade but they may reduce the incidence of pulmonary complications and thereby reduce subsequent mortality. Tamponade has proved successful in controlling acute haemorrhage from oesophageal varices in our hands. Late complications continue to give cause for concern but until effective safe alternatives to tamponade are developed, we continue to advocate its use for emergency control of acute variceal haemorrhage. Our own studies have shown that the high mortality seen in this patient population may reflect the severity of the underlying liver disease rather than failure of a management policy employing oesophageal tamponade for the initial control of acute variceal haemorrhage.

Topics: Antihypertensive Agents; Balloon Occlusion; Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Propranolol; Recurrence; Somatostatin; Splanchnic Circulation; Vasoconstrictor Agents; Vasopressins

The main aim of conservative treatment of upper gastrointestinal bleeding in portal hypertension is aim to treat and prevent esophageal variceal hemorrhage. Controlled trials show that the hemostasis rate following vaso-active therapy (vasopressin and analogues, somatostatin) is only slightly superior to the spontaneous hemostasis rate. Complications caused by vasopressin treatment can be avoided by concomitant application of nitroglycerin or by alternative treatment with somatostatin. Balloon tamponade is slightly superior to vasopressin for arresting variceal hemorrhage. Injection sclerotherapy influences acute bleeding most positively. Analysis of controlled trials favors sclerotherapy for prophylaxis of rebleeding, but beta-adrenoceptor blockers appear to be almost equally good.

Topics: Adrenergic beta-Antagonists; Balloon Occlusion; Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Sclerotherapy; Somatostatin; Vasodilator Agents; Vasopressins

Topics: Antihypertensive Agents; Drug Evaluation; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infusions, Intra-Arterial; Lypressin; Mesenteric Arteries; Propranolol; Terlipressin; Vasopressins

Portal hypertension may be caused by portal venous outflow obstruction, an increased portal venous inflow due to a hyperdynamic circulation or both. Portal venous collaterals usually develop above a threshold portal venous pressure of 10 to 12 mm Hg. Only about one third of patients with esophageal varices eventually bleed. However, the mortality in patients who do bleed is high (around 50%) mostly because patients frequently die prior to hospital admission. Immediate endoscopy for precise location of site of bleeding is essential. Bleeding then may be controlled by drugs which lower portal pressure, balloon-tube tamponade or emergency injection sclerotherapy. Of these therapeutic options sclerotherapy probably has the highest success rate for the acute control of variceal bleeding. It can in addition be combined with the initial endoscopic diagnostic procedure, and repeated injection sclerotherapy can reduce the incidence of recurrent variceal bleeding. Portasystemic shunts, transection and devascularisation operations are nowadays only used in patients in whom repeated sclerotherapy had failed. Beta-blocking agents may be an alternative for long-term management after variceal bleeding, although the results are controversial. The data regarding prophylaxis of first variceal hemorrhage are conflicting. Prophylactic regimens should only be carried out in the form of controlled trials.

Topics: Balloon Occlusion; Catheterization; Combined Modality Therapy; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Propranolol; Sclerotherapy; Vasopressins

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

Topics: Catheterization; Embolization, Therapeutic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Ligation; Lypressin; Portacaval Shunt, Surgical; Portasystemic Shunt, Surgical; Propranolol; Resuscitation; Sclerosing Solutions; Somatostatin; Splenorenal Shunt, Surgical; Terlipressin; Vasopressins

Topics: Adrenergic beta-Antagonists; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension, Portal; Portal System; Regional Blood Flow; Somatostatin; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Topics: Acute Disease; Adrenergic beta-Antagonists; Animals; Drug Therapy, Combination; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Lypressin; Nitroglycerin; Nitroprusside; Recurrence; Risk; Somatostatin; Terlipressin; Vasopressins

Drugs used to treat portal hypertension cause constriction of mesenteric arterioles, reducing inflow to the portal venous system, portal pressure, and flow through portasystemic collaterals (such as esophageal varices). Vasopressin and somatostatin are direct vasoconstrictors. Propranolol acts by blocking vasodilatory beta 1 receptors and reducing cardiac output. A major side effect of vasopressin therapy is impaired cardiac performance secondary to coronary vasoconstriction and increased work against high arterial pressure. Infusion of vasopressin together with a cardiac inotrope or a vasodilator, and administration of vasopressin as an inactive "hormonogen" which is slowly released in vivo, may lessen adverse effects. Somatostatin appears to act selectively in the mesenteric circulation. Controlled trials indicate that vasopressin may be useful for controlling hemorrhage from esophageal varices and that somatostatin works at least as well as vasopressin. Propranolol treatment has been used to prevent variceal bleeding; however, controlled trials of its effectiveness have produced conflicting results.

Topics: Animals; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Portal System; Propranolol; Somatostatin; Vasopressins

Topics: Acute Disease; Endoscopy; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hypertension, Portal; Nadolol; Propranolol; Somatostatin; Vasopressins

Topics: Acute Disease; Adult; Cholestasis; Cystic Fibrosis; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infant; Sclerosing Solutions; Splenomegaly; Vasopressins

Bleeding from esophageal varices remains a difficult clinical problem, carrying a high likelihood both of rebleeding and of mortality. The initial approach requires adequate but not overly vigorous volume replacement with blood and other fluids. Once the patient is resuscitated, upper gastrointestinal endoscopy should be performed to establish the source of bleeding. Both endoscopic variceal sclerotherapy and balloon tamponade appear to be effective in achieving temporary control of acute ongoing hemorrhage from esophageal varices. The value of intravenous vasopressin remains controversial. Rebleeding can be prevented in most patients by shunt surgery. However, surgery carries both considerable early morbidity and mortality (related mainly to the severity of the underlying liver disease) and substantial longer-term morbidity and mortality from hepatic encephalopathy and liver failure. The role of pharmacologic agents (eg, propranolol) intended to prevent variceal hemorrhage by reducing portal pressure remains to be established. At present, we recommend use of endoscopic variceal sclerotherapy for the control of active variceal bleeding, with employment of balloon tamponade and intravenous vasopressin if sclerotherapy is successful. Emergency shunt surgery should be reserved only for those patients whose bleeding cannot be controlled by these other means. For prevention of rebleeding in Child class C patients, we attempt to obliterate the varices by repeated endoscopic sclerotherapy. Patients who have two to three episodes of rebleeding despite this approach are considered for shunt surgery. For better-risk patients who do not have ascites, which is difficult to control, we are currently recommending a distal splenorenal shunt. Alternatively, repeated endoscopic variceal sclerotherapy is used for these better-risk patients (Child class A or B) in some centers, with shunt surgery reserved for patients who continue to rebleed. Which approach to preventing rebleeding in the better-risk patient is more effective, as well as the role of pharmacologic therapy with propranolol or other agents, remains to be settled by well-controlled randomized clinical trials.

Topics: Airway Obstruction; Catheterization; Esophageal and Gastric Varices; Fluid Therapy; Gastrointestinal Hemorrhage; Hemostatic Techniques; Humans; Hypertension, Portal; Liver Diseases, Alcoholic; Propranolol; Sclerosing Solutions; Vasopressins

Topics: Adrenergic beta-Antagonists; Blood Pressure; Endoscopy; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Recurrence; Sclerosing Solutions; Somatostatin; Vasopressins

Bleeding from esophageal varices is a feared complication of liver cirrhosis with high mortality. Pharmacotherapy of the acute bleeding episode with vasopressin has been shown to be effective in controlled studies, but side effects of this therapy are high and therefore replacement of vasopressin with somatostatin is under investigation. Another potential lead is the combination of vasopressin with vasodilators such as nitroglycerin. While acute pharmacotherapy of the patient with esophageal varices is well accepted, chronic or prophylactic pharmacotherapy is still in the investigative stage. Prophylactic therapy with beta-blockers, e.g. propranolol, has been shown to be effective in compensated patients with alcoholic cirrhosis. In patients with more advanced stages of the disease, or with cirrhosis of other etiology, the effectiveness of propranolol has not been proven. The mechanism of propranolol is similar to that of vasopressin, i.e. it lowers portal pressure by reducing portal flow. To maintain function of the affected organ, an alternative approach--namely lowering of portal pressure through reduction of the pathologically elevated resistance--should be actively investigated.

Topics: Acute Disease; Adrenergic beta-Antagonists; Chronic Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Propranolol; Random Allocation; Somatostatin; Vasopressins

Topics: Endoscopy; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Circulation; Portacaval Shunt, Surgical; Pressure; Sclerosing Solutions; Splenorenal Shunt, Surgical; Vasopressins

Topics: Blood Transfusion; Central Venous Pressure; Cimetidine; Emergencies; Esophageal and Gastric Varices; Esophagoscopy; Esophagus; Fluid Therapy; Gastrointestinal Hemorrhage; Hemostasis, Surgical; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Prognosis; Sclerosing Solutions; Vasopressins; Vitamin K

Topics: Blood Flow Velocity; Embolization, Therapeutic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Portasystemic Shunt, Surgical; Propranolol; Receptors, Adrenergic, alpha; Sclerosing Solutions; Somatostatin; Vasopressins

Topics: Acute Disease; Embolization, Therapeutic; Esophageal and Gastric Varices; Esophagus; Gastrointestinal Hemorrhage; Hemostatic Techniques; Humans; Hypertension, Portal; Intubation; Intubation, Gastrointestinal; Liver Cirrhosis; Sclerosing Solutions; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Laser Therapy; Portacaval Shunt, Surgical; Sclerosing Solutions; Tampons, Surgical; Vasopressins

During the last 25 years, there have been important developments in visualising the portal vein, in examining its contents, and in measuring the pressure of blood flowing within it. Radiologists have set the scene and now is the time of the scanner. These technical advances have been applied to the diagnosis and treatment of patients with portal hypertension, and many ingenious surgical techniques have been proposed. The problem of successful treatment of the patient with bleeding oesophageal varices and cirrhosis of the liver, however, has not yet been solved. This report discusses the portal vein in terms of pressure, flow, and regeneration factors. Portal hypertension is classified and methods of relief are discussed.

Topics: Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Regeneration; Portal Vein; Radiography; Regional Blood Flow; Ultrasonography; Vasopressins; Venous Pressure

Topics: Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Veins; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Portacaval Shunt, Surgical; Portal Vein; Prospective Studies; Radiography; Regional Blood Flow; Vasopressins; Venous Pressure

Topics: Anti-Bacterial Agents; Blood Transfusion; Cryotherapy; Drainage; Esophageal and Gastric Varices; Esophageal Perforation; Gastrointestinal Hemorrhage; Hemostasis; Hepatic Encephalopathy; Humans; Hypertension, Portal; Intubation, Gastrointestinal; Liver Cirrhosis; Myocardial Infarction; Peptic Ulcer; Pneumonia, Aspiration; Portacaval Shunt, Surgical; Sclerosing Solutions; Therapeutic Irrigation; Ulcer; Vasopressins; Vitamin K

Topics: Diverticulum, Esophageal; Hemorrhage; Humans; Hypertension, Portal; Ligation; Liver Cirrhosis; Portacaval Shunt, Surgical; Tampons, Surgical; Vasopressins

Topics: Budd-Chiari Syndrome; Chemical and Drug Induced Liver Injury; Collateral Circulation; Epinephrine; Hepatic Artery; Humans; Hypertension, Portal; Hypoxia; Liver Circulation; Liver Cirrhosis; Liver Diseases; Norepinephrine; Portal System; Vasopressins; Venous Pressure

Portal hypertensive gastropathy is an important complication of liver cirrhosis and it contributes to acute gastric bleeding. Effective management of this condition remains a clinical challenge. We assessed and compared the efficacy of octreotide, vasopressin, and omeprazole in the treatment of acute bleeding in patients with portal hypertensive gastropathy.. Sixty-eight patients with portal hypertensive gastropathy were randomized into Octreotide, Vasopressin, and Omeprazole groups. Bleeding was monitored by observing the contents of the nasogastric tube. Blood transfusion requirements and side-effects of drugs were recorded. Repeat endoscopies were scheduled 2 weeks after treatment.. Complete bleeding control after 48 h of drug infusion was achieved in all patients receiving octreotide (100%), 14/22 patients receiving vasopressin (64%), and 13/22 patients receiving Omeprazole (59%). Octreotide required much less time and significantly fewer blood transfusions to control bleeding. Patients receiving vasopressin experienced more side-effects than those receiving octreotide and omeprazole. In the 17 patients whose bleeding was not controlled within 48 h by either vasopressin or omeprazole, complete bleeding control was achieved by combined use of these two agents. Follow-up endoscopy showed dramatic improvement in gastric mucosal erosions, superficial ulceration and erythema.. Octreotide appeared to be more effective in controlling acute bleeding in patients with hypertensive gastropathy, with significantly rapid action, smaller transfusion requirements, and minor side-effects. Simultaneous administration of vasopressin and omeprazole appeared to have additive effects.

Topics: Adult; Aged; Drug Evaluation; Enzyme Inhibitors; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Gastroscopy; Hemostatics; Humans; Hypertension, Portal; Male; Middle Aged; Octreotide; Omeprazole; Prospective Studies; Treatment Outcome; Vasopressins

The effects of vasopressin plus oxygen and vasopressin alone on gastric mucosal perfusion and oxygenation were studied using reflectance spectrophotometry and laser Doppler velocimetry in 23 cirrhotic patients with portal-hypertensive gastropathy. The measurements were performed under basal conditions and after double-blinded administration of placebo (n = 7), vasopressin (0.3 U/min; n = 8) or vasopressin (0.3 U/min) plus nasal oxygen (4 L/min; n = 8). No significant effects on gastric mucosal haemodynamics and oxygenation were observed after placebo. In contrast, vasopressin and vasopressin plus oxygen induced a similar reduction in haemoglobin content (-26 +/- 2 and -21 +/- 4%, respectively P < 0.01), and laser Doppler signal (-23 +/- 2 and -22 +/- 2%, respectively, P < 0.01). Although each treatment induced a significant reduction in oxygen saturation (-21 +/- 2 and -7 +/- 1%, respectively P < 0.01), the effect was less pronounced in patients receiving the combination than in those receiving vasopressin alone (P < 0.01). These data suggest that vasopressin and vasopressin plus oxygen reduce gastric mucosal hyperaemia and that the oxygen supplement partially protects against gastric mucosal hypoxia during vasopressin infusion in cirrhotic patients with portal-hypertensive gastropathy.

Topics: Aged; Analysis of Variance; Combined Modality Therapy; Double-Blind Method; Female; Gastric Mucosa; Hemodynamics; Humans; Hypertension, Portal; Laser-Doppler Flowmetry; Liver Cirrhosis; Male; Middle Aged; Oxygen; Oxygen Inhalation Therapy; Spectrophotometry; Stomach Diseases; Vasopressins

Topics: Acute Disease; Double-Blind Method; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Lypressin; Perfusion; Stomach Diseases; Terlipressin; Vasoconstrictor Agents; Vasopressins

Gastric mucosal perfusion is increased in portal-hypertensive gastropathy, and this may contribute to gastric bleeding from these lesions. Therefore drugs reducing gastric mucosal perfusion may be beneficial in the treatment of overt bleeding from portal-hypertensive gastropathy. In this study gastric mucosal perfusion was assessed in 28 cirrhotic patients with portal-hypertensive gastropathy under basal conditions and after double-blind intravenous administration of vasopressin (0.4 U/min), glypressin (2-mg injection) or placebo, with laser-Doppler flowmetry and reflectance spectrophotometry. Vasopressin and glypressin induced a significant increase in blood pressure and a decrease in heart rate. These effects were more pronounced in the vasopressin group. Both vasopressin and glypressin induced a sustained and similar reduction in gastric mucosal perfusion as assessed by laser-Doppler flowmetry (-36% +/- 8% and -34% +/- 6%, respectively; p < 0.05 with respect to basal values and with respect to the control group), whereas placebo had no effect. Both drugs significantly reduced the oxygen content of the gastric mucosa; however, the impairment in mucosal oxygenation was greater (p < 0.05) in the vasopressin group (-17% +/- 3%) than in the glypressin group (-6% +/- 0.1%). We conclude that the increased gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy may be reduced by either vasopressin or glypressin. These findings support the use of these drugs in clinical trials treating bleeding portal-hypertensive gastropathy. The lower reduction in gastric mucosal oxygen content observed with glypressin could decrease the incidence of ischemic adverse events associated with the use of vasopressin.

Topics: Double-Blind Method; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Hyperemia; Hypertension, Portal; Laser-Doppler Flowmetry; Liver Cirrhosis; Lypressin; Male; Middle Aged; Oxygen; Regional Blood Flow; Spectrophotometry; Stomach Diseases; Terlipressin; Vasopressins

The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.

Topics: Aged; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Male; Middle Aged; Nicardipine; Splanchnic Circulation; Vasopressins

This randomized controlled trial was conducted to compare the efficacy of intravenous infusion of octreotide (a synthetic long-acting somatostatin analogue) with vasopressin in 48 cirrhotic patients with endoscopically proven bleeding esophageal varices. Twenty-four patients received a continuous infusion of octreotide 25 micrograms/h for 24 h after an initial bolus of 100 micrograms and another 24 patients received a continuous infusion of vasopressin 0.4 U/min for 24 h. Bleeding was initially controlled after 6 h of drug infusion in 88% (21/24) and 54% (13/24) of the patients treated with octreotide and vasopressin respectively (p = 0.03). Complete control of bleeding after 24 h of drug infusion was achieved in 15 (63%) patients receiving octreotide and in 11 (46%) patients receiving vasopressin (p > 0.05). Side effects during drug infusion such as headache, chest pain and abdominal pain were significantly lower in the octreotide group (3/24) than in the vasopressin group (11/24). Serum gastrin and insulin levels fell significantly following octreotide infusion, but plasma glucose levels remained unchanged. Mortality related to bleeding esophageal varices was no different between the two groups. This report showed that octreotide infusion was more effective and had fewer side effects than vasopressin in initial controlling of acute esophageal variceal bleeding until an elective endoscopic sclerotherapy could be performed.

Topics: Aged; Blood Glucose; Esophageal and Gastric Varices; Female; Gastrins; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Injections, Intravenous; Insulin; Liver Cirrhosis; Male; Middle Aged; Octreotide; Vasopressins

The management of both acute and recurrent variceal bleeding continues to be a significant challenge to the clinician. The cause and pathogenesis of portal hypertension has been described. Alcoholic cirrhosis is the most common cause of intrahepatic sinusoidal and postsinusoidal obstruction in the United States. Long term survival depends on rapid institution of an established protocol of surgical management for variceal hemorrhage. A patient who presents with variceal bleeding must be rapidly stabilized with fluid resuscitation, and specific measures, such as the use of vasopressin and balloon tamponade, must be instituted to control hemorrhage so that endoscopy can be used to establish the diagnosis. Sclerotherapy achieves a high rate of success in the acute situation, but if hemorrhage cannot be controlled, percutaneous transhepatic embolization or emergent shunting must be performed, depending on the condition of the patient. Angiography, prior to surgical treatment, is necessary to define venous anatomy and determine portal hemodynamics, both of which provide information vital in choosing the type of shunt. If bleeding is massive and the patient is unstable, H-grafts are most appropriate, for they are technically easier and give excellent short term results. In a stable Child's A or B patient with minor ascites as well as suitable anatomy and hepatopedal flow, DSRS is the procedure of choice because it produces the smallest degree of HE postoperatively and increases the survival rate for nonalcoholics. If this is not feasible or if the surgeon lacks the technical expertise to perform DSRS, PCS is the logical alternative. In view of the data from the series observed in the United States, ablative procedures cannot be recommended at the present for the treatment of variceal bleeding. In the Child's C poor-risk patient, the operative mortality rate is prohibitive, and only nonsurgical means should be used to establish control of bleeding. In the elective situation, the surgical options change. The efficacy of ES as a definitive procedure to control recurrent variceal bleeding is unproved, and rebleeding can be significant; therefore, it cannot be recommended. H-grafts have a prohibitively high rate of long term thrombosis and are also not recommended, and the Linton or proximal splenorenal shunt offers no advantages over conventional portacaval shunting. Moreover, arterialization of the hepatic stumps of the portal vein does not prevent hepatic encephal

Topics: Acute Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Portacaval Shunt, Surgical; Radiography; Recurrence; Sclerosing Solutions; Vasopressins

We have evaluated the haemodynamic effects of intravenous (iv) nitroglycerin (NG) and vasopressin (VP) alone and in combination, in 12 patients with cirrhosis and recent variceal haemorrhage (two to seven days). Nitroglycerin infusion alone (200 micrograms/min) produced a significant fall in portal pressure (WHVP-FHVP) (from 16.4 (0.6) to 13.3 (1.2) mmHg; p less than .001) associated with hypotension (mean arterial pressure from 95 (7) to 78 (9) mmHg; p less than 0.005). Vasopressin alone (0.4 IU/min) reduced portal pressure (20.7 (1.3) to 14.0 (1.3) mmHg; p less than 0.001), but there was considerable variation in the systemic haemodynamic changes with increased cardiac output in four of six patients. The combination of vasopressin and nitroglycerin corrected all systemic haemodynamic disturbances produced by either agent alone. This combination led, however, to a further reduction in portal pressure (from 13.7 (0.9) to 11.7 (0.7) mmHg p less than 0.01). These results show that: (1) intravenous nitroglycerin reduces portal pressure, and (2) the combination of nitroglycerin and vasopressin reverses systemic haemodynamic disturbances produced by either agent alone and leads to a further decrease in portal pressure.

Topics: Drug Therapy, Combination; Female; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Injections, Intravenous; Liver Circulation; Liver Cirrhosis; Male; Nitroglycerin; Vasopressins

Topics: Adrenergic beta-Antagonists; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension, Portal; Portal System; Regional Blood Flow; Somatostatin; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Drugs used to treat portal hypertension cause constriction of mesenteric arterioles, reducing inflow to the portal venous system, portal pressure, and flow through portasystemic collaterals (such as esophageal varices). Vasopressin and somatostatin are direct vasoconstrictors. Propranolol acts by blocking vasodilatory beta 1 receptors and reducing cardiac output. A major side effect of vasopressin therapy is impaired cardiac performance secondary to coronary vasoconstriction and increased work against high arterial pressure. Infusion of vasopressin together with a cardiac inotrope or a vasodilator, and administration of vasopressin as an inactive "hormonogen" which is slowly released in vivo, may lessen adverse effects. Somatostatin appears to act selectively in the mesenteric circulation. Controlled trials indicate that vasopressin may be useful for controlling hemorrhage from esophageal varices and that somatostatin works at least as well as vasopressin. Propranolol treatment has been used to prevent variceal bleeding; however, controlled trials of its effectiveness have produced conflicting results.

Topics: Animals; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Portal System; Propranolol; Somatostatin; Vasopressins

Bleeding from esophageal varices is a feared complication of liver cirrhosis with high mortality. Pharmacotherapy of the acute bleeding episode with vasopressin has been shown to be effective in controlled studies, but side effects of this therapy are high and therefore replacement of vasopressin with somatostatin is under investigation. Another potential lead is the combination of vasopressin with vasodilators such as nitroglycerin. While acute pharmacotherapy of the patient with esophageal varices is well accepted, chronic or prophylactic pharmacotherapy is still in the investigative stage. Prophylactic therapy with beta-blockers, e.g. propranolol, has been shown to be effective in compensated patients with alcoholic cirrhosis. In patients with more advanced stages of the disease, or with cirrhosis of other etiology, the effectiveness of propranolol has not been proven. The mechanism of propranolol is similar to that of vasopressin, i.e. it lowers portal pressure by reducing portal flow. To maintain function of the affected organ, an alternative approach--namely lowering of portal pressure through reduction of the pathologically elevated resistance--should be actively investigated.

Topics: Acute Disease; Adrenergic beta-Antagonists; Chronic Disease; Clinical Trials as Topic; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Propranolol; Random Allocation; Somatostatin; Vasopressins

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration-response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205's lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

Topics: Animals; Ascites; Diuretics; Hyperaldosteronism; Hypertension, Portal; Liver Cirrhosis; Natriuretic Agents; Rats; Receptors, Vasopressin; Sodium; Vasopressins

The role of renal aquaporin-2 (AQP2) water channel turnover in patients with liver cirrhosis, portal hypertension and water retention remains unclear. Transjugular intrahepatic portosystemic shunt (TIPS) insertion reduces portal hypertension, improves water excretion and lowers plasma vasopressin. The aim of this study was to establish whether TIPS insertion decreases urinary AQP2 excretion (uAQP2) in parallel with improved water excretion.. Fourteen cirrhosis patients with refractory ascites were studied before TIPS insertion and 4 and 12 weeks after insertion. A 24-h urine collection was followed by an oral water load (20 ml/kg body weight) with a 4-h blood and urine sampling.. TIPS reduced the portal pressure gradient from a median 18(4) (25-75% InterQuartile-range) to 7(2) mmHg, p < 0.05 and the need for diuretics (p < 0.05). TIPS increased plasma sodium from 136(6) mmol/l to 139(4), (p < 0.05) and diuresis from 1650(1043) ml/24 h to 2230(560) (p < 0.05), although the 24-h urinary sodium excretion did not change. There was no change in the baseline uAQP2 before 274(249) ng/(mmol creatinine/24 h) and 12 weeks after TIPS 242(201). There were no systematic changes in uAQP2, plasma vasopressin or other vasoactive substances during the water loads, before or after TIPS.. The effective amelioration of portal hypertension improved the patient's water excretion and plasma sodium, but there was no change in renal AQP2 trafficking or vasopressin. These findings do not support a primary role for renal AQP2 water channels in portal hypertensive water retention.

Topics: Aquaporin 2; Ascites; Diuresis; Female; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Pressure; Portasystemic Shunt, Transjugular Intrahepatic; Sodium; Vasopressins

Portal hypertension is associated with splanchnic vasodilation which is claimed responsible for the maintenance of chronically elevated portal pressure. Vasopressin analogues are used in the treatment of acute variceal bleeding, since they effectively reduce splanchnic blood flow and portal pressure. Dehydration stimulates the release of endogenous vasopressin release. Here we compared the effects of deprivation of drinking water for 18 h with those of vasopressin infusion on mesenteric hemodynamics in portal vein-ligated (PVL) and sham-operated (SHAM) rats. Blood flow in the superior mesenteric artery was measured with the ultrasonic transit time shift technique. Deprivation of drinking water had no hemodynamic effects in SHAM rats, but completely reversed the mesenteric hyperemia and portal hypertension in PVL rats to figures measured in SHAM rats, without altering blood pressure. Similarly, intravenous infusion of low doses of arginine vasopressin (1-10 pmol/min) selectively reduced mesenteric blood flow in PVL rats but had little effect in SHAM rats. These data suggest that control of water balance or aquaretic drugs might have beneficial effects on splanchnic hemodynamics and portal pressure in advanced liver disease, possibly by stimulating endogenous vasopressin release.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Disease Models, Animal; Hyperemia; Hypertension, Portal; Ligation; Liver Diseases; Male; Mesenteric Artery, Superior; Portal Vein; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilation; Vasopressins; Water Deprivation

Topics: Animals; Hypertension, Portal; Nitric Oxide Synthase; Vasopressins

Topics: Esophageal and Gastric Varices; Evidence-Based Medicine; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hemostatics; Humans; Hypertension, Portal; Liver Cirrhosis; Meta-Analysis as Topic; Sclerotherapy; Somatostatin; Vasopressins

F-180 is a new, long-acting analog of vasopressin with a selective agonist effect on the vascular V1a receptors, with the advantage of having no effect on renal V2 receptors. F-180 is approximately 20 times more powerful than terlipressin in reducing portal pressure and has less marked systemic effects. The present study investigated the effects of F-180 on the outcome of portal hypertension-related bleeding in hypovolemic rats. Partial portal vein-ligated rats were subjected to portal hypertension-related bleeding by sectioning a first-order branch of the ileocolic vein. After hemodynamic stabilization, a second sectioning of the first-order branch of the ileocolic vein section was performed in the already hypovolemic animals, and either F-180 or placebo was administered. Blood transfusion was adjusted to maintain mean arterial pressure (MAP) gamma > 80 mm Hg. The first section of a first-order branch of the ileocolic vein induced a hemorrhage of similar severity in both groups of rats. After a 2nd sectioning of a first-order branch of the ileocolic vein section, F-180 was more effective than placebo in recovering shock (MAP, 21% +/- 23% vs. 0% +/- 13% in placebo; P <.05), preventing portal pressure (PP) increase during blood transfusion (PP: -1% +/- 19% vs. 47% +/- 65% in placebo; P =.07), reducing transfusion requirements (2.9 +/- 3.3 mL vs. 11.2 +/- 6.0 mL in placebo; P <.01), diminishing the magnitude of collected blood losses (5.1 +/- 2.2 g vs. 12.7 +/-7.7 g in placebo; P <.05), and decreasing the mortality from the portal hypertension-related bleeding (10% vs. 60% in placebo; P <.05). In conclusion, in hypovolemic portal-hypertensive rats during a portal hypertension-related bleeding, F-180 rapidly recovers arterial pressure and decreases transfusion requirements, blood losses, and mortality.

Topics: Animals; Blood Pressure; Blood Transfusion; Gastrointestinal Hemorrhage; Hypertension, Portal; Male; Portal Pressure; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasopressins

Chronic portal hypertension is associated with the development of portal-systemic collaterals. Long-term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats.. Partially portal vein-ligated rats were divided into two groups to receive subcutaneous injection of either placebo (5% dextrose in water) or octreotide (30 microg kg(-1)) twice daily for 7 days. Two series of experiments were performed to measure: (a) the systemic and portal hemodynamics and cumulative concentration-response curves of collateral vessels to vasopressin (10(-10) to 10(-7 )M) and (b) the slopes of the flow-pressure curves of collaterals (an index of portal-systemic shunting). The cumulative concentration-response curves and flow pressure curves were determined by the in situ collateral perfusion.. Long-term octreotide treatment significantly lowered the portal pressure without changes in the mean arterial pressure. Vasopressin significantly and similarly increased the perfusion pressure of collateral vessels in both the placebo- and octreotide-treated groups. In addition, long-term octreotide treatment exerted no effect on the EC(50) of vasopressin (-8.25 +/- 0.19 vs. -8.20 +/- 0.10, P > 0.05) and the slopes of flow-pressure curves (0.97 +/- 0.02 vs. 0.94 +/- 0.04, P > 0.05) in the collaterals.. Despite lowering the portal pressure, long-term octreotide treatment did not enhance the vasoconstrictive effect of vasopressin in the collateral vessels of portal hypertensive rats and ameliorate the degree of portal-systemic shunting.

Topics: Animals; Collateral Circulation; Disease Models, Animal; Drug Synergism; Hypertension, Portal; Linear Models; Male; Octreotide; Portal System; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

F-180 has been proposed as a new vasopressin analogue for the treatment of portal hypertension. This study investigates the contractile profile of F-180 compared to vasopressin and its analogue terlipressin on isolated systemic and splanchnic vessels from sham-operated and partial portal vein ligated (PPVL) rats. F-180 (10(-9)-10(-6) M), vasopressin (10(-11)-10(-8) M) and terlipressin (10(-9)-10(-4) M) induced contraction of the mesenteric vein, aorta, iliac, tail and mesenteric arteries. The order of potency in these vessels was vasopressin (pD2 approximately 9) > F-180 (pD2 approximately 8) > terlipressin (pD2 approximately 6). Significant (P<0.01) differences between sham-operated and PPVL rats were noticed exclusively in the mesenteric vein, being the maximal effect of the three agonists at least twice greater in PPVL rats than in sham-operated rats. The order of sensitivity to the vasoconstrictors in vessels from PPVL rats was aorta < mesenteric artery << iliac artery approximately equal tail artery approximately equal mesenteric vein. The contractile profile of these peptides in each vessel from PPVL animals was quite similar, except in the mesenteric vein and the aorta. F-180 showed higher efficacy (P<0.01) than terlipressin in the mesenteric vein and lower (P<0.05) efficacy than vasopressin in the aorta. These findings suggest the existence of a vasoconstrictor territorial selectivity for vasopressin and its analogues, which could justify the efficacy of these drugs in portal hypertension therapy. In particular, F-180 appears to be a viable alternative to the classic vasopressin analogues.

Topics: Animals; Hypertension, Portal; Lypressin; Male; Mesenteric Arteries; Mesenteric Veins; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Terlipressin; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B(2) receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.

Topics: Animals; Blood Pressure; Bradykinin; Canavanine; Enzyme Inhibitors; Hemodynamics; Hypertension, Portal; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Postoperative Hemorrhage; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vasopressins

This study investigated the effect of vasopressin on portal-systemic collaterals in portal hypertensive rats and the influence of nitric oxide (NO) and prostaglandin on the responsiveness of collateral vessels to vasopressin. The vascular responsiveness to graded concentrations of vasopressin was tested with or without the incubation of n(omega)-nitro-L-arginine (NNA) (100 micromol/L) and/or indomethacin (10 micromol/L) in perfused collateral vascular beds of rats with portal hypertension induced by partial portal vein ligation. In addition, concentration-response curves to vasopressin with incubation of a vasopressin V(1) receptor antagonist d(CH(2))(5)Tyr(Me) arginine vasopressin and concentration-response curves to a V(2) receptor agonist 1-desamino-8-D-arginine vasopressin were performed. Vasopressin significantly increased the perfusion pressure of collaterals, and this effect was suppressed by the addition of the V(1) receptor antagonist. Perfusion with the V(2) receptor agonist had no effect on the collaterals. Incubation with NNA, indomethacin, or both significantly potentiated the response of collaterals to vasopressin. In addition, the pressor response to vasopressin in the combination group was significantly higher than that in the NNA-alone group. The results show that vasopressin produces a direct vasoconstrictive effect on the portal-systemic collaterals of portal hypertensive rats. This effect is mediated by the vasopressin V(1,) but not V(2), receptors. The attenuation of the response to vasopressin by NO and prostaglandin suggest a function role of both mediators in the regulation of the portal-systemic collateral circulation in portal hypertensive rats.

Topics: Animals; Collateral Circulation; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Hypertension, Portal; Indomethacin; Male; Nitric Oxide; Nitroarginine; Portal System; Prostaglandins; Rats; Rats, Sprague-Dawley; Vasopressins

The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V1) receptor, both in normal rats and in portal-hypertensive animals. In preliminary vasopressor tests, F-180 was 18 times more potent than terlipressin (TP) (164 +/- 10 IU x mmol(-1) vs. 9.2 +/- 1.2 IU x mmol(-1)) and four times less potent than arginine VP (614 +/- 25 IU x mmol(-1)). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V1/V2) of 858 compared with 1.0 for VP and 2.2 for TP. In portal-hypertensive rats with partial portal vein ligation (PPVL), the vasopressor effect of F-180 was 19 times that of TP on a molar basis (ED50 F-180: 0.54 vs. TP: 10.02 nmol x kg(-1)). At low doses (0.405 nmol x kg(-1)), F-180 significantly reduced portal pressure (PP) (-13.8% +/- 6.7%) and superior mesenteric artery blood flow (SMABF) (-25.6% +/- 4.5%), whereas TP at 8.10 nmol x kg(-1) was required to achieve comparable splanchnic effects; however, this dose caused a significantly greater increase in mean arterial pressure (MAP) than F-180 at 0.405 nmol x kg(-1) (28.2% +/- 2.7% vs. 8.9% +/- 2.7% at 20 minutes; P < .05). F-180 at 0.405 nmol x kg(-1) had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU x kg(-1) in PPVL rats, but VP caused a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P < .05).

Topics: Animals; Antihypertensive Agents; Blood Pressure; Diuresis; Dose-Response Relationship, Drug; Female; Hemodynamics; Hypertension, Portal; Lypressin; Male; Mesenteric Artery, Superior; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Splanchnic Circulation; Terlipressin; Time Factors; Vasoconstrictor Agents; Vasopressins

We recently reported that vasopressin analogues correct the in vitro vascular hyporeactivity to adrenergic vasoconstrictors in portal hypertensive rats. The aim of the present study was to determine whether vasopressin reduces splanchnic blood flow in portal vein-ligated (PVL) rats by restoring vasoconstrictor responsiveness in vivo. The ultrasonic transit time-shift technique was used for blood flow measurements. At basal conditions, blood flow through the superior mesenteric artery was elevated 1.6-fold in PVL rats as compared with sham-operated (SHAM) control rats. PVL rats also exhibited blunted mesenteric constrictor responses to the adrenoceptor agonist, phenylephrine (0.03-1 micromol x min(-1) x kg(-1)). Terlipressin (2-20 microg x k(-1)) and arginine vasopressin (3-300 pmol x min(-1) x kg(-1)) dose-dependently reduced, and at the highest doses, even abolished, the difference in mesenteric blood flow (MBF) between PVL and SHAM rats. When expressed as percent changes relative to baseline, mesenteric arterial responses to terlipressin and arginine vasopressin were found to be enhanced in PVL rats as compared with SHAM rats. Moreover, pretreatment with terlipressin (20 microg x kg(-1)) reversed the mesenteric hyporesponsiveness to phenylephrine of PVL rats. These vasopressin effects were independent of the nitric oxide (NO) pathway, because they were not mimicked by inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) (0.1-10 mg x kg(-1)). These data indicate that pharmacological doses of vasopressin reverse the splanchnic hyperemia by restoring the responsiveness to adrenergic vasoconstrictors in portal hypertensive rats.

Topics: Anesthesia; Animals; Hemodynamics; Hyperemia; Hypertension, Portal; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; Splanchnic Circulation; Vasoconstriction; Vasopressins

The present study evaluates the effects of pre-hepatic portal hypertension, induced in rats by partial portal vein ligation, on the responsiveness of rostral (proximal) and caudal (distal) rings from the mesenteric vein. The anatomical origin of the sample influenced the response to vasoconstrictors in sham-operated animals, and this pattern of reactivity was specifically modified in portal-ligated rats. In veins from sham-operated rats, contraction induced by a submaximal concentration of KCl (60 mM) was greater in proximal than in distal rings. Vasopressin and 5-hydroxytryptamine contracted mainly distal rings, methoxamine showed a greater effect on proximal rings, and endothelin-1 and angiotensin-II contracted vein rings independently of their anatomical origin. In veins from portal hypertensive rats, response to KCl (60 mM) were increased in distal rings, and all rings exhibited enhanced reactivity to vasopressin and 5-hydroxyptyptamine as well as attenuation of the response to methoxamine. Responses to endothelin-1 were decreased in proximal vein rings from portal hypertensive rats whereas responses to angiotensin-II were not influenced by the anatomical origin. Incubation with atropine, propranolol or indomethacin, did not modify the responses to vasopressin and 5-hydroxytryptamine in tissues from either sham-operated or portal hypertensive animals. Likewise, the hyporeactivity to methoxamine and endothelin-1 in rings from portal hypertensive rats persisted in the presence of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester. These results suggest the physiological existence of anatomical differences in the responsiveness to vasoconstrictors throughout the mesenteric vein and that changes in the responsiveness of the mesenteric vein induced by portal hypertension are specific for each agonist and possibly result from individual variations at a receptor or post-receptor level.

Topics: Animals; Endothelin-1; Hypertension, Portal; Iliac Vein; In Vitro Techniques; Male; Mesenteric Veins; Muscle, Smooth, Vascular; Potassium Chloride; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasopressins

1. It has been reported that ortreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 micrograms/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries rom sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.

Topics: Animals; Aorta, Thoracic; Culture Techniques; Dose-Response Relationship, Drug; Drug Administration Schedule; Hypertension, Portal; Male; Mesenteric Arteries; Octreotide; Phenylephrine; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasopressins

The purpose of this study was to investigate the vascular contractile and inositol phosphate responses in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL) in Sprague-Dawley rats. Sham-operated rats served as controls. Pressures, vasoconstrictor responses, and inositol phosphate responses were determined at 14 days after surgery. The portal venous pressure was significantly higher, while systemic arterial pressure and heart rate were lower, in PVL rats. Dose-dependent contractile responses were observed for both norepinephrine (1 x 10(-8) - 3 x 10(-6) M) and vasopressin (3 x 10(-10) - 3 x 10(-8) M) in the tail artery of both groups. The contractile response to norepinephrine was significantly decreased in PVL rats compared with controls at all doses. The contractile response to vasopressin was significantly decreased in PVL rats at higher doses. After myo-[3H]inositol incorporation in tail artery, the levels of 3H-labelled phosphatidylinositols (cpm/mg) were similar between the two groups. Norepinephrine (10(-7) - 10(-5) M) and vasopressin (10(-10) - 10(-8) M) dose dependently stimulated the 3H-labelled inositol phosphate production in the tail artery of both PVL and sham-operated rats. However, the response was significantly lower in PVL rats. The results suggested that the attenuation of vascular contractile responses in portal hypertension was reflected in the phosphoinositide messenger system.

Topics: Animals; Blood Pressure; Hypertension, Portal; Inositol Phosphates; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Portal Vein; Rats; Rats, Sprague-Dawley; Vasopressins

A problem in pharmacotherapy for bleeding varices in portal hypertension is non-responders. The aim of this study was to elucidate the features of hemodynamic response to vasopressin in the gastroesophageal collateral vein in patients with esophageal varices.. Flow velocity in the portal and the collateral left gastric vein was measured with an echo-Doppler flowmeter before and during infusion of vasopressin, 0.2 U/min, in 41 patients with cirrhosis and esophageal varices.. The decrease in flow velocity in the left gastric vein with vasopressin (-29 +/- 25%) was significantly smaller than that in the portal vein (-56 +/- 20%). There was no or only minimal change in flow velocity in the left gastric vein in 39% of the patients, especially in those with large-size varices. In 28 patients examined by portal catheterization, changes in flow velocity in the left gastric vein were correlated with portal pressure, and portal pressure in non-responders was significantly higher than that in responders (non-responders: 363 +/- 49, responders: 312 +/- 41 mmH2O, p < 0.05).. It was concluded that hepatofugal blood flow in the gastroesophageal collateral is not readily reduced by vasopressin. However, as the study was performed in a stable condition without variceal bleeding, whether these hemodynamic features will apply during acute variceal bleeding in patients who are known to have a poor hemodynamic response to vasopressin remains to be elucidated.

Topics: Aged; Blood Flow Velocity; Collateral Circulation; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Hemodynamics; Hemostatics; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Retrospective Studies; Stomach; Ultrasonography, Doppler, Duplex; Ultrasonography, Doppler, Pulsed; Vasopressins; Veins

In 40 patients with esophageal varices, esophageal variceal pressure was assessed endoscopically using a pneumatic pressure sensor. The effects of vasopressin or nitroglycerin on variceal pressure and endoscopic findings were also assessed in two groups of seven patients. The results were as follows: (1) Variceal pressure was increased above 250 mmH2O in all patients who had bled, and the mean variceal pressure was significantly higher in patients who had bled than in those who had not (301 +/- 47 vs. 230 +/- 58 mmH2O respectively, p < 0.001). (2) Variceal pressure correlated with endoscopic findings, determined using the criteria of the Japanese Research Society for Portal Hypertension. It was significantly higher when varices with a feature of F2-F3 or RC(+2)-RC(+3) were compared to those with a feature of F1 or RC(-)-RC(+), respectively. (3) Both groups given vasopressin or nitroglycerin had significant reductions in variceal pressure; however, there was little improvement in endoscopic findings in those given nitroglycerin, compared to the improvement in those given vasopressin. Thus, use of a pneumatic pressure sensor proved to be a pertinent tool for assessing esophageal varices, along with endoscopic signs.

Topics: Aged; Blood Pressure; Blood Pressure Determination; Esophageal and Gastric Varices; Esophagoscopy; Esophagus; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Male; Middle Aged; Nitroglycerin; Vasopressins

The effects of clonidine, vasopressin or a combination of both substances on splanchnic and systemic haemodynamics were measured in conscious rats with portal vein stenosis. Clonidine alone significantly decreased portal pressure, portal tributary blood flow and cardiac index, but did not change arterial pressure. Vasopressin alone significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in portal tributary blood flow, arterial pressure and cardiac index were significantly higher with vasopressin than with clonidine alone. Vasopressin infusion in rats pretreated with clonidine significantly increased arterial pressure and significantly decreased portal pressure, portal tributary blood flow and cardiac index. Changes in arterial and portal pressures and portal tributary blood flow were significantly higher with combined therapy than with clonidine alone. Changes in arterial and portal pressures and portal tributary blood flow did not differ between combined therapy and vasopressin alone. Changes in cardiac index were significantly higher with combined therapy than with clonidine or vasopressin alone. Hepatic artery blood flow was not affected by either clonidine or vasopressin but significantly declined with combined therapy. In conclusion, this study suggests that a combination of vasopressin and clonidine accentuates the portal hypotensive action of clonidine but not the action of vasopressin. Moreover, this study suggests that a combination of vasopressin and clonidine may have deleterious effects on systemic and hepatic artery vascular beds.

Topics: Animals; Clonidine; Drug Therapy, Combination; Hemodynamics; Hypertension, Portal; Male; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vasopressins

Topics: Animals; Disease Models, Animal; Hypertension, Portal; Indocyanine Green; Liver; Liver Circulation; Male; Octreotide; Rats; Rats, Wistar; Somatostatin; Vasopressins

Topics: Female; Humans; Hypertension, Portal; Injections, Intravenous; Middle Aged; Myocardial Infarction; Syndrome; Vasopressins

Topics: Arteriovenous Fistula; Blood Component Transfusion; Blood Transfusion; Carcinoma, Hepatocellular; Child; Endoscopy, Gastrointestinal; Epistaxis; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Hematemesis; Hepatic Artery; Humans; Hypertension, Portal; Liver Neoplasms; Portal Vein; Sclerotherapy; Tomography, X-Ray Computed; Ultrasonography; Vasopressins

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.

Topics: Aged; Catheterization, Peripheral; Child; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Nitroglycerin; Oxygen; Vasopressins

The experimental study was aimed at elucidating the effects of phentolamine and vasopressin used separately or in combination on hepatic and systemic hemodynamics in cirrhotic portal hypertensive dogs. The results showed that either of the two drugs used separately could lead to reduction in portal venous pressure and could also influence systemic hemodynamics or lower hepatic blood flow. When phentolamine in combination with vasopressin was administered, no side-effect could be found on hepatic and systemic hemodynamics, suggesting that the drugs used in combination could efficaciously decrease portal hypertension and counteract their respective side-effect. This combination therapy will be useful in treating bleeding from esophageal variceal rupture in cirrhotic patients with portal hypertension.

Topics: Animals; Dogs; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Hemodynamics; Hypertension, Portal; Liver Circulation; Liver Cirrhosis, Experimental; Male; Phentolamine; Vasopressins

In patients with portal hypertension, bleeding from the gastric mucosa is common, and is often treated with vasopressin (VP). VP reduces the portal pressure by contracting the arterioles of the abdominal organs. In normal rats, VP reduces the gastric mucosal blood flow (GMBF). However, it is not sure whether the reduction of the portal pressure by VP actually reduces the GMBF in patients with portal hypertension. Here, we studied the effects of VP on the GMBF of 24 patients with portal hypertension resulting from cirrhosis. The ICG15 test was done for 20 of the patients. We measured the GMBF of the antrum and body of the stomach using a laser Doppler flowmeter (Peliflux PF 2) connected with a gastrofiberscope without VP on one day and about 10 min after the start of administration of VP (0.4 U/min, i.v.) on another day. Unexpectedly, the GMBF was increased with VP in 14 of 22 patients at the antrum and in 19 of 24 patients at the body of the stomach. In the body of the stomach, there was correlation between the increase in the GMBF caused by VP and the results of the ICG15 test. A high ICG15 reflects high portal pressure, so this finding indicates that in high portal pressure, the GMBF is increased by VP, and in low portal pressure, the GMBF is decreased by VP.

Topics: Animals; Blood Flow Velocity; Gastric Mucosa; Humans; Hypertension, Portal; Liver Cirrhosis; Rats; Rats, Inbred Strains; Vasopressins

We measured the coronary, systemic, and splanchnic effects of vasopressin and vasopressin plus nitroglycerin in 8 stable patients with alcoholic cirrhosis. Vasopressin (0.1-0.8 U/min) increased pressure in the hepatic vein, pulmonary artery and pulmonary capillaries. Wedged hepatic (portal) vein pressure was unchanged; the hepatic venous pressure gradient (wedged-free hepatic vein pressure) fell. Insignificant declines occurred in cardiac output, gastroesophageal collateral (azygous) blood flow, hepatic blood flow and coronary sinus (cardiac) blood flow. The addition of nitroglycerin (40-70 micrograms/min) reduced pressure in the hepatic vein, pulmonary artery and pulmonary capillaries, while increasing the hepatic venous pressure gradient. Wedged hepatic vein pressure did not change. Gastroesophageal collateral (azygous) flow increased markedly; cardiac output rose to a lesser degree. Coronary sinus and hepatic blood flow did not change. Nitroglycerin ameliorated the increases in systemic and pulmonary artery pressure produced by vasopressin but also tended to reverse the decline in the hepatic venous pressure gradient and markedly increased gastroesophageal flow. Neither drug significantly affected coronary blood flow.

Topics: Adult; Coronary Circulation; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension, Portal; Indocyanine Green; Liver; Middle Aged; Nitroglycerin; Vasopressins

Topics: Animals; Atrial Natriuretic Factor; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Cirrhosis, Experimental; Natriuresis; Rats; Vasopressins

The effects of atrial natriuretic factor (ANF) on splanchnic hemodynamics and renal function in portal hypertensive models are described incompletely. Furthermore, ANF-induced vasodilatation and hypotension may limit the assessment of its own renal physiological effects. We infused ANF (human ANF 102-126) to anesthetized portal vein-ligated rats, a model with prehepatic portal hypertension. Arterial pressure was reduced by 17%, but portal pressure was unaffected. Diuresis and natriuresis were explained in part by an increase in glomerular filtration rate; in addition, renal vascular resistance was significantly decreased. The natriuretic response to ANF was slightly, but significantly, decreased in portal hypertensive rats as compared to controls (fractional excretion of sodium, 1.8 +/- 0.4 vs. 2.9 +/- 0.3; P less than .05). The addition of Phe-Ile-Orn-vasopressin, a V1 receptor agonist, normalized arterial pressure but induced a significant decrease in portal pressure (15 +/- 0.9 mm Hg base line vs. 12.8 +/- 0.7 combination group; P less than .01). Furthermore, the combination of both drugs markedly potentiated the natriuretic effects (0.4 +/- 0.1 microEq/min of control vs. 10.0 +/- 2.3 ANF vs. 32.2 +/- 3.3 combination group; P less than .001). The natriuretic potentiation resulted from increments in glomerular filtration rate and renal blood flow. Normalization of arterial pressure may enhance the renal physiological effects of ANF, in this portal hypertensive model.

Topics: Animals; Atrial Natriuretic Factor; Drug Synergism; Glomerular Filtration Rate; Hemodynamics; Hypertension, Portal; Kidney; Male; Natriuresis; Ornipressin; Rats; Rats, Inbred Strains; Splanchnic Circulation; Vasopressins

In view of the variability in the magnitude of the response of portal venous pressure to vasopressin in man, we investigated the effect of vasopressin on portal hemodynamics in seven patients with portal hypertension by simultaneous catheterization of the portal and the hepatic vein and the measurement of portal venous flow by an echo-Doppler flowmetry. Infusion of vasopressin (0.3 U/min) significantly decreased portal venous pressure (-36%), the gradient between portal venous pressure and free hepatic venous pressure (-50.6%), and portal venous flow (-54.3%) but did not reduce mean arterial pressure and pulse rate. Thus, vasopressin seems to decrease portal venous pressure by reducing portal venous flow.

Topics: Adult; Female; Hemodynamics; Humans; Hypertension, Portal; Male; Middle Aged; Rheology; Splanchnic Circulation; Ultrasonography; Vasopressins

This study was designed to evaluate the hemodynamic response to vasopressin infusion during hemorrhage and blood transfusion in a rat model of portal hypertension. Portal pressure, arterial pressure, and regional and systemic blood flows were measured in a rat model of portal hypertension receiving placebo or vasopressin infusion. Effects of the drugs were compared in control rats and rats subjected to hemorrhage and blood transfusion. In a stable portal hypertensive rat group (no hemorrhage or transfusion) a standard vasopressin dose, 2.5 mU X kg-1 X min-1, resulted in a significantly lower portal pressure (11.5 +/- 0.7 vs. 14.4 +/- 0.6 mmHg) with a concomitantly lower portal venous inflow (8.5 +/- 0.3 vs. 11.1 +/- 0.6 ml X min-1 X 100 g body wt-1) when compared with rats receiving placebo. These findings are in contrast to the effects obtained with the same dose of vasopressin given during blood transfusion to hemorrhaged portal hypertensive rats. The standard dose of vasopressin had no effect on any of the splanchnic or systemic circulatory parameters. Only when a dose of vasopressin 10 times larger was used in the hemorrhaged-transfused animals were hemodynamic effects noted. A significant decrease in portal flow and pressure was noted. These findings suggest that vasopressin given during hemorrhage may be less effective than when given during a stable state. Larger doses of vasopressin may be needed during hemorrhage to produce the same effect as seen during a controlled stable state. Caution should be used in extrapolating the results of pharmacologic studies in stable portal-hypertensive models to hypovolemic states in humans.

Topics: Animals; Blood Transfusion; Combined Modality Therapy; Disease Models, Animal; Drug Resistance; Hemodynamics; Hemorrhage; Hypertension, Portal; Male; Rats; Rats, Inbred Strains; Vasopressins

Topics: Ascites; Body Water; Hepatorenal Syndrome; Humans; Hypertension, Portal; Kidney; Liver Circulation; Liver Cirrhosis; Lymph; Sodium; Vasopressins

Topics: Catheterization; Esophageal and Gastric Varices; Humans; Hypertension, Portal; Sclerosing Solutions; Somatostatin; Vasopressins

Topics: Adrenergic beta-Antagonists; Emergencies; Esophageal and Gastric Varices; Esophagoscopes; Gastrointestinal Hemorrhage; Gastroscopes; Hemodynamics; Humans; Hypertension, Portal; Portasystemic Shunt, Surgical; Recurrence; Risk; Sclerosing Solutions; Somatostatin; Vasopressins

To assess the influence of vasopressin on splanchnic and renal circulatory changes induced by haemorrhage in portal hypertension, we studied 4 groups of 7 rats with chronic portal vein stenosis. Two groups received saline (C and H) and two groups vasopressin, 0.01 IU/kg/min (VP and VP-H). Ten minutes after starting drug infusion, group H and VP-H animals were allowed to bleed from the superior mesenteric vein. Both haemorrhage and vasopressin alone, decreased portal venous tributary blood flow and pressure but their association was not additive (as reflected by comparable bleeding rate in groups H and VP-H). By contrast, vasopressin increased renal perfusion in bleeding and non-bleeding animals whereas haemorrhage alone decreased renal perfusion. These results indicate that the effects of vasopressin on the splanchnic circulation in bleeding anaesthetized animals differ from the effects observed when blood volume is normal. Therefore, in patients with cirrhosis the effects of vasopressin during bleeding might also differ from those observed in patients in stable condition.

Topics: Anesthesia; Animals; Blood Pressure; Cardiac Output; Hemorrhage; Hypertension, Portal; Male; Rats; Rats, Inbred Strains; Renal Circulation; Splanchnic Circulation; Vascular Resistance; Vasopressins

Topics: Adrenergic beta-Antagonists; Blood Pressure; Collateral Circulation; Drug Therapy, Combination; Heart Rate; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Portal System; Somatostatin; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins; Venous Pressure

An ultrasonic sector scanner and pulsed Doppler flowmeter were combined to measure portal venous velocity in 19 patients with portal hypertension and compared with cineangiographic mapping of a droplet of oil released into the portal vein. In 12 patients, measurements were made before and after pitressin [7] or ranitidine [5]. With the Doppler method, maximum basal portal venous velocity was 17.0 +/- 3.9 cm/sec., while average cineangiographic velocity was 8.5 +/- 2.7 cm/sec., a significant difference (p less than 0.001). After pitressin, velocity decreased to 8.3 +/- 2.7 cm/sec. with the Doppler method and 3.6 +/- 1.0 cm/sec. with cineangiography. Ranitidine did not produce an appreciable change. Doppler and cineangiographic velocity measurements exhibited significant correlation over a wide range of values (r = 0.960). Thus the pulsed Doppler method may give accurate values of portal venous velocity if they are corrected to cineangiographic values. Flow can be calculated from velocity and the cross-sectional area of the portal vein as measured on the sonogram. The Doppler method is simple and noninvasive and is particularly useful in studying changes in portal hemodynamics.

Topics: Adult; Blood Flow Velocity; Cineangiography; Female; Humans; Hypertension, Portal; Iodized Oil; Male; Middle Aged; Portal Vein; Ranitidine; Ultrasonography; Vasopressins

Topics: Ascites; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Portal System; Propranolol; Sclerosing Solutions; Vasopressins

Blood flow in the azygos vein, an index of blood flow through gastro-oesophageal collaterals, was measured by continuous thermal dilution in 100 patients with cirrhosis. Azygos blood flow was directly related to portal pressure (r = 0.54, P less than 0.001). Patients with portal hypertension had very high azygos blood flow (692 +/- 32 ml/min) in comparison with controls (n = 11, 174 +/- 29 ml/min). Patients with previous oesophageal bleeding had similar azygos blood flow as those without, but azygos blood flow was significantly greater in patients with massive or recurrent bleeding than in those with less severe haemorrhage, suggesting that the magnitude of collateral flow may influence the course of variceal bleeding. Patients with grade III varices had higher azygos blood flow than those with grades II or I. In addition, both oesophageal tamponade and vasopressin infusion, procedures of known value in variceal bleeding, markedly reduced azygos blood flow (-40% and -25%, respectively). Measurement of azygos blood flow allows evaluation of haemodynamic changes in the oesophageal collaterals of patients with portal hypertension, and provides useful information on the effect of therapeutic procedures aimed at arresting or preventing variceal haemorrhage.

Topics: Azygos Vein; Blood Flow Velocity; Blood Pressure; Esophageal and Gastric Varices; Esophagoscopy; Female; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Portacaval Shunt, Surgical; Splenorenal Shunt, Surgical; Vasopressins

A number of recently introduced drugs have been applied to the treatment of acutely bleeding oesophageal varices. Another well established drug, propranolol, may have found a further useful therapeutic role in preventing bleeding from these vessels. However, before widespread use of these drugs can be endorsed further evidence of their efficacy and safety must be produced.

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Propranolol; Somatostatin; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Vasopressins

We have investigated the effects on systemic, pulmonary, hepatic, and renal hemodynamics, and on blood gases of vasopressin, 0.4 U/min I.V. first alone, then in combination with nitroprusside 1-5 micrograms/kg/min I.V., in 12 patients with liver cirrhosis and portal hypertension. Portal pressures were estimated by the gradient between occluded and free hepatic vein pressures, hepatic blood flow was measured by indocyanine green infusion, renal blood flow by an isotopic method, and cardiac output by thermodilution. Vasopressin alone reduced cardiac output (-23%) and O2 delivery to the tissues (-25%), increased mean arterial pressure (+20%) and filling pressures of the heart (+136%), reduced portal pressures (-36%) (from 19 +/- 1 to 12 +/- 1 mmHg, mean +/- SEM), hepatic blood flow (-35%) (1.33 +/- 0.2 to 0.87 +/- 0.1 l/min), and renal blood flow (-16%) (0.77 +/- 0.07 to 0.65 +/- 0.05 l/min). Adding nitroprusside restored cardiac output, preload and afterload, and renal blood flow to pretreatment values. Oxygen delivery remained depressed (-12%) because of a negative effect on pulmonary gas exchange (physiologic shunt increased from 16 +/- 2 to 28 +/- 4%). Portal pressures remained reduced by 31% and hepatic blood flow by 25%. These results suggest that small doses of I.V. nitroprusside minimize the deleterious hemodynamic effects of vasopressin while maintaining the therapeutic benefit of portal pressure reduction in cirrhotic patients.

Topics: Adult; Coronary Circulation; Drug Therapy, Combination; Female; Ferricyanides; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Male; Middle Aged; Nitroprusside; Pulmonary Circulation; Renal Circulation; Vasopressins

Ten patients with portal hypertension and esophageal varices had percutaneous transheptic portography with selective catheterization of the short gastric or left gastric vein. The effect was studied on variceal blood flow after injection of various drugs (vasopressin IV, pentagastrin IV, somatostatin IV, domperidone IV, and methylcholine SC). Vasopressin had no effect on variceal flow; pentagastrin gave a total occlusion of flow in five of nine patients; somatostatin interrupted the flow in one of four patients; domperidone obstructed flow completely in one patient, while another receiving the same dose was unaffected; methylcholine did not affect the flow in three patients examined.

Topics: Adult; Choline; Domperidone; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Male; Middle Aged; Pentagastrin; Pressure; Somatostatin; Vasopressins

Selective catheterization of the left gastric vein was performed after percutaneous transhepatic portography (PTP) in patients with portal hypertension and esophageal varices. Following the hypothesis that drugs increasing the lower esophageal sphincter (LES) pressure may obstruct the variceal blood flow through the lower esophagus, the effect of different drugs (i.e., intravenous injection of vasopressin, pentagastrin, domperidone and somatostatin and subcutaneous injection of metacholine) on the variceal blood flow was examined. Vasopressin did not change the variceal blood flow; pentagastrin, with its known effect of increasing the LES pressure produced a total interruption of the flow in four of eight patients; domperidone, also known to increase the LES pressure obstructed the variceal blood flow in the only patient examined with this drug; somatostatin has no reported action on the LES but blocked the flow in one of two patients; and metacholine, reported to increase the LES pressure did not produce any change in the flow in the three patients examined. LES pressure was recorded before and during vasopressin infusion in seven patients with portal hypertension and esophageal varices. No reaction on the pressure was found. The patient number in the study is small and the results are nonuniform but still they suggest that drugs increasing the LES tonus might be useful to control variceal blood flow.

Topics: Adult; Domperidone; Esophageal and Gastric Varices; Esophagogastric Junction; Humans; Hypertension, Portal; Male; Middle Aged; Pentagastrin; Radiography; Regional Blood Flow; Somatostatin; Vasopressins

Five patients given vasopressin by infusion to reduce portal hypertension developed signs of cutaneous gangrene 18-24 hours after the start of the infusion. Four patients were treated by application of local dressings; in three cases the lesions healed, but the fourth patient died from variceal haemorrhage. The remaining patient required split skin grafting but died 48 hours after operation. The mechanism of this effect of vasopressin is not clear, but if local blanching of the skin is noted during infusion the catheter should be flushed immediately with a vasodilator in an effort to counteract the drug's vasoconstrictor effect.

Topics: Adult; Aged; Constriction, Pathologic; Esophageal and Gastric Varices; Female; Gangrene; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infusions, Parenteral; Male; Skin; Vasopressins

Topics: Angiography; Catheters, Indwelling; Colonic Diseases; Endoscopy; Esophageal Diseases; Gastrointestinal Hemorrhage; Hemobilia; Humans; Hypertension, Portal; Intestinal Diseases; Peptic Ulcer Hemorrhage; Stomach Diseases; Vasoconstrictor Agents; Vasopressins

Experimental animal studies have suggested that certain vasodilators could minimize the adverse cardiovascular effects of vasopressin. We investigated the hemodynamic effects of isosorbide dinitrate, alone and in combination with vasopressin, in patients with liver cirrhosis. In 10 patients, isosorbide dinitrate, 5 mg sublingually, reduced portal pressure by 21% as assessed by the gradient between wedged and free hepatic venous pressure, but also decreased mean arterial pressure (MAP) by 20%, pulmonary artery wedge pressure (WP) by 50%, and oxygen delivery (DO2) by 13%. In 6 other patients, isosorbide dinitrate, 5 mg sublingually, combined with vasopressin, 0.4 U/min iv, reduced portal pressure by 37%, increased MAP by 13%, and mean pulmonary artery pressure (MPAP) by 70%, and decreased DO2 by 32%. Thus, isosorbide dinitrate reduces effectively portal hypertension in patients with liver cirrhosis, but also decreases DO2 to the tissues as a consequence of a fall in cardiac output due to decreased preload. At the dosage used in this study, isosorbide dinitrate does not prevent the adverse hemodynamic effects of vasopressin.

Topics: Adult; Aged; Blood Pressure; Cardiac Catheterization; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Portal; Isosorbide Dinitrate; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Oxygen; Pulmonary Wedge Pressure; Time Factors; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Propranolol; Somatostatin; Vasopressins

Topics: Angioplasty, Balloon; Diagnosis, Differential; Emergencies; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Intubation, Gastrointestinal; Liver Cirrhosis; Portacaval Shunt, Surgical; Prognosis; Sclerosing Solutions; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Vasopressins

The effects of 30-minute intravenous and superior mesenteric artery (SMA) infusions of vasopressin in dosages of 2.75 mU and 14 mU per min per kg were compared in five dogs that had cirrhosis and portal hypertension induced by fractionated intraportal polyvinyl alcohol injections. A reduction in portal pressure of approximately 35% was found with both SMA doses and the larger intravenous vasopressin dose, while the smaller intravenous dose reduced portal pressure only 18%. A significantly larger decrease in portal blood flow was found with SMA than intravenous vasopressin administration. Cardiovascular side effects were dose-dependent but independent of the administration mode. Liver enzymes were not affected. Portal vein thrombosis occurred in one dog after the larger SMA dose.

Topics: Animals; Dogs; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hypertension, Portal; Infusions, Intra-Arterial; Infusions, Parenteral; Liver Cirrhosis; Male; Mesenteric Arteries; Vasopressins

To analyze the relationship between the splanchnic and systemic effects of vasopressin and to measure its efficacy in lowering portal pressure relative to what can be accomplished by zero gradient shunting, intraoperative measurements of cardiac output and relevant pressures were made in 30 patients undergoing selective or total shunts. Vasopressin caused a significant increase in systemic vascular resistance and pulmonary capillary wedge pressure, but an insignificant overall reduction in cardiac index (CI). However, in ten patients the decrease in CI exceeded 20%, suggesting a subpopulation of especially susceptible individuals. High initial CI, age, pre-existent heart disease, and severity of cirrhosis did not predict greater vulnerability. Adding an infusion of nitroprusside regularly reverted CI to control levels, regardless of the extent of cardiac output depression. Vasopressin was 38% as effective as a subsequent shunt in reducing splanchnic venous pressure. The portal hypotensive action bore no relationship to CI, but the pressure decrease caused by vasopressin was predictive of the reduction that could be achieved by shunting. The effects of the two types of shunts on systemic hemodynamics were minor and remarkably similar.

Topics: Adult; Aged; Blood Pressure; Cardiac Output; Female; Heart; Hemorrhage; Humans; Hypertension, Portal; Male; Middle Aged; Nitroprusside; Portal System; Portasystemic Shunt, Surgical; Vasopressins

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.

Topics: Adult; Aged; Blood Pressure; Cardiac Output; Female; Heart Rate; Hemodynamics; Hepatic Veins; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Male; Middle Aged; Somatostatin; Vascular Resistance; Vasopressins; Venous Pressure

Vasopressin was infused intra-arterially or intravenously during 12 portal bypass operations. In comparison with a control group (without vasopressin), there was a very significant reduction in blood loss and portal pressure, and a moderate increase in arterial blood pressure.

Topics: Blood Pressure; Female; Hemostasis, Surgical; Humans; Hypertension, Portal; Infusions, Intra-Arterial; Infusions, Parenteral; Male; Middle Aged; Portacaval Shunt, Surgical; Portal Vein; Vasoconstriction; Vasopressins

Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis; Splenectomy; Splenomegaly; Vasopressins

Topics: Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Circulation; Vasopressins

Topics: Angiography; Barium Sulfate; Counseling; Esophageal and Gastric Varices; Esophagoscopy; Gastrointestinal Hemorrhage; Hemostatic Techniques; Hepatic Encephalopathy; Humans; Hypertension, Portal; Medical History Taking; Physical Examination; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Blood Pressure; Cardiac Output; Coronary Vessels; Dogs; Dopamine; Hemodynamics; Hypertension, Portal; Infusions, Parenteral; Liver Circulation; Myocardial Contraction; Portal Vein; Regional Blood Flow; Vasopressins

In four cirrhotic patients with portal hypertension we have measured some hemodynamic parameters over 60-120 min; portal venous pressure, hepatic venous pressure, mean arterial blood pressure, hepatic blood flow, transsinusoidal vascular resistance and splanchnic oxygen uptake under treatment with Vasopressin (1 IU/min for 10 min) and glypressin (50 mug/kg body weight). The effect on the parameters was less pronounced with glypressin but of longer duration.

Topics: Abdomen; Blood Flow Velocity; Blood Pressure; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Lypressin; Vascular Resistance; Vasopressins

Clinical states with portal venous hypertension are frequently associated with impairment in renal hemodynamics and water excretion, as well as increased renin secretion. In the present investigation, portal venous pressure (PVP) was increased in anesthetized dogs undergoing a water diuresis. Renal arterial pressure was maintained constant in all studies. As PVP was increased from 6 to 20 mm Hg, decreases in cardiac output (2.5-2.0 liter/min, P less than 0.05) and mean arterial pressure (140-131 mm Hg, P less than 0.05) were observed. Increases in PVP were also associated with decreases in glomerular filtration rate (GFR, 40-31 ml/min, P less than 0.001), renal blood flow (RBF, 276-193 ml/min, P less than 0.001), and increases in renin secretion (232-939 U/min, P less than 0.025) in innervated kidneys. No significant change in either GFR or RBF and a decrease in renin secretion occurred with increases in PVP in denervated kidneys. To dissociate the changes in cardiac output and mean arterial pressure induced by increase PVP from the observed decreases in GFR and RBF, studies were performed on animals undergoing constriction of the thoracic inferior vena cava. In these studies, similar decreases in cardiac output and mean arterial pressure were not associated with significant changes in GFR or RBF. Increases in PVP also were associated with an antidiuresis as urine osmolality increased from 101 to 446 mosmol/kg H2O (P less than 0.001). This antidiuresis was significantly blunted but not abolished by acute hypophysectomy. In hypophysectomized animals, changes in free water clearance and urine flow were linearly correlated as PVP was increased. These studies indicate that increases in PVP result in decreases in GFR and RBF and increases in renin secretion mediated by increased renal adrenergic tone. Increased PVP is also associated with antidiuresis; this antidiuresis is mediated both by vasopressin release and by diminished tubular fluid delivery to the distal nephron.

Topics: Animals; Cardiac Output; Dogs; Female; Glomerular Filtration Rate; Hemodynamics; Hypertension, Portal; Hypophysectomy; Kidney; Male; Portal Vein; Regional Blood Flow; Renin; Vasopressins; Vena Cava, Inferior; Venous Pressure; Water

Vasopressin infusion initially controlled 80 per cent of patients bleeding from portal hypertension, and 53 per cent did not rebleed after removal of the catheter. This figure is significantly greater than the 28 per cent of patients totally controlled by esophageal tamponade (p less than 0.075). Similar rates of success were achieved by vasopressin infusion for gastric, duodenal, and colonic bleeding sites. These results suggest that visceral arterial infusion of vasopressin is the method of choice for the short-term therapeutic management of massive gastrointestinal bleeding from portal hypertension. Vasopressin infusion also appears to be a valuable means of treating patients with massive gastrointestinal bleeding secondary to shallow gastric ulcers, gastritis, Mallory-Weiss tears, colonic bleeding and "poor risk" patients with deep gastric, marginal, or duodenal ulcers when conventional medical therapy has failed. The presence of a coagulation abnormality in patients with portal hypertension significantly reduced the complete control of bleeding to only 27 per cent ( p less than 0.010) and survival rate to 14 per cent (p less than 0.050). Visceral arterial perfusion proved to be an effective means of arresting hemorrhage, but the overall improvement in hospital mortality in this group of poor risk patients remains unproved.

Topics: Abdomen; Angiography; Celiac Artery; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infusions, Parenteral; Mesenteric Arteries; Peptic Ulcer Hemorrhage; Vasopressins

Nine patients with cirrhosis and portal hypertension were given intraoperative vasopressin (40 U/hr) in a continuous peripheral infusion during establishment of a distal splenorenal shunt. In all patients a significant and sustained reduction in portal venous pressure was achieved. As a result, blood loss during dissection and the time required for operation were minimized. The expected vasopressin-induced reduction in cardiac output was limited to a transient decrease at 5 minutes. There were no significant cardiac arrhythmias. These results suggest that vasopressin given through a peripheral vein during shunt operations is safe and facilitates dissection by providing significant and sustained reductions in portal venous pressure.

Topics: Adult; Aged; Blood Pressure; Drug Evaluation; Female; Humans; Hypertension, Portal; Infusions, Parenteral; Male; Middle Aged; Renal Veins; Splenic Vein; Vasopressins

Topics: Furosemide; Humans; Hypertension, Portal; Lactulose; Liver Cirrhosis; Spironolactone; Vasopressins

The effects of superior mesenteric arterial and intravenous infusions of vasopressin and low and high dose intravenous infusions of vasopressin on splanchnic and systemic hemodynamics were compared in 20 anesthetized dogs. The following parameters were evaluated: flow in the superior mesenteric artery and portal vein, portal and systemic blood pressure, and cardiac output. In the comparison of selective arterial and intravenous infusions, no statistically significant difference was found between the degree of changes in portal flow, portal and systemic blood pressure, and cardiac output. Only the superior mesenteric artery flow showed a greater decrease with the selective arterial injection. In a comparison of intravenous high dose (corresponding to that used clinically) and low dose (one-fifth) infusions of vasopressin, a relatively high splanchnic and low systemic effectiveness of the low dose was found. It resulted in only a 15 to 20% smaller effect on flow in the superior mesenteric artery and portal vein and portal pressure; however, about 40% lesser systemic effect on arterial blood pressure and cardiac output than the high dose. The results of this experimental work warrant exploration in clinical practice, preferably by a controlled study. If clinical success in controlling hemorrhage confirms these hemodynamic results, an intravenous. low dose infusion of vasopressin would appear to be the method of choice in the vasoconstrictive therapy of gastrointestinal bleeding from varices.

Topics: Acute Disease; Animals; Blood Pressure; Cardiac Output; Dogs; Hemodynamics; Hypertension, Portal; Infusions, Parenteral; Liver; Liver Circulation; Mesenteric Arteries; Microspheres; Portal System; Portal Vein; Vasopressins

Selective infusion of vasopressin (0.2 U per min) was performed in 8 cirrhotic patients with portal hypertension who underwent umbilicoportal catheterization. There was a significantly decreased (9.6%) of the free portal venous pressure from 27.0 plus or minus 1.4 mm Hg to 24.4 plus or minus 1.4 mm Hg. In all patients, the portal PO2 significantly decreased with a mean fall of 18.8%. However, in all patients, significant systemic effects were noted: an increase in arterial blood pressure and a decrease in the arterial PO2. In 3 patients, a marked fall of the cardiac output (greater than 2.0 liters per min) was recorded during the selective infusion of vasopressin. It is concluded that if selective infusion of vasopressin into the superior mesenteric artery is efficacious in the control of bleeding varices, the therapeutic effect cannot be totally explained by the lowering of the portal venous pressure in cirrhotic patients with portal hypertension. The risk of vascular thrombosis, the decreased portal PO2, and the systemic effects have to be considered when this approach is used in cirrhotic patients with ruptured esophageal and/or gastric varices.

Topics: Blood Pressure; Cardiac Output; Catheterization; Humans; Hypertension, Portal; Infusions, Parenteral; Liver Cirrhosis; Male; Mesenteric Arteries; Oxygen; Portal System; Portal Vein; Umbilicus; Vasopressins; Venous Pressure

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Drug Synergism; Drug Therapy, Combination; Hepatectomy; Hypertension, Portal; Infusions, Parenteral; Isoproterenol; Liver Circulation; Portal Vein; Postoperative Care; Postoperative Complications; Preoperative Care; Vasopressins

Topics: Blood Transfusion; Blood Vessel Prosthesis; Catheterization; Collateral Circulation; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Injections, Intravenous; Mesenteric Arteries; Mesenteric Veins; Portacaval Shunt, Surgical; Radiography; Renal Veins; Splenic Vein; Vasopressins; Vena Cava, Inferior

Topics: Acute Disease; Adult; Aged; Angiography; Arteries; Celiac Artery; Duodenum; Endoscopy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Injections, Intra-Arterial; Male; Mesenteric Arteries; Middle Aged; Perfusion; Stomach; Vasopressins

Topics: Angiography; Contrast Media; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Artery; Humans; Hypertension, Portal; Injections, Intra-Arterial; Liver Cirrhosis; Mesenteric Arteries; Portacaval Shunt, Surgical; Splenic Artery; Vasopressins

Topics: Animals; Collateral Circulation; Disease Models, Animal; Dogs; Esophageal and Gastric Varices; Hemodynamics; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Nitrosamines; Portacaval Shunt, Surgical; Preoperative Care; Splenic Artery; Vasopressins; Venous Pressure

Topics: Animals; Cardiac Output; Dogs; Hepatectomy; Hypertension, Portal; Isoproterenol; Vasopressins

Topics: Alcoholism; Angiography; Autopsy; Esophageal and Gastric Varices; Fatty Liver; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infarction; Injections, Intra-Arterial; Intestine, Small; Liver Cirrhosis; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Mesenteric Veins; Thrombosis; Vasopressins

Topics: Adolescent; Adult; Aged; Angiography; Child; Child, Preschool; Epinephrine; Esophageal and Gastric Varices; Female; Gastritis; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Injections, Intra-Arterial; Male; Middle Aged; Peptic Ulcer Hemorrhage; Ulcer; Vasopressins

Topics: Acute Disease; Blood Transfusion; Emergencies; Esophageal and Gastric Varices; Esophagoscopy; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Methods; Middle Aged; Vasopressins

The effect of octapressin (2-phenylalanine-8-lysine vasopressin) on renal and intrarenal blood flow was studied in 11 normotensive cirrhotic patients with abnormal renal perfusion. Renal haemodynamic changes were assessed with the (133)Xenon washout technique. Of the six patients given suppressor doses of octapressin intravenously renal blood flow improved in one only. A further three patients responded to the drug in a dose which increased the mean arterial pressure by 5 or more mm Hg. The increase in mean renal blood flow was accompanied by an improvement in renal cortical perfusion. In two patients renal blood flow decreased after the administration of octapressin. These findings, in conjunction with previous reports, suggest that octapressin will only consistently improve renal perfusion in cirrhotic subjects who are hypotensive and in whom the mean arterial blood pressure is raised by the drug, but do not exclude the possibility that octapressin may have a direct renal circulatory effect in some patients.

Topics: Adult; Alkaline Phosphatase; Bilirubin; Blood Flow Velocity; Blood Pressure; Creatinine; Felypressin; Female; Humans; Hypertension, Portal; Hypotension; Kidney; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Serum Albumin; Vasopressins; Xenon

Topics: Blood Protein Disorders; Electrolytes; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Serum Albumin; Vasopressins

Topics: Adult; Child; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Laparotomy; Middle Aged; Vasopressins

Topics: Aminocaproates; Aprotinin; Bilirubin; Blood Proteins; Child; Esophageal and Gastric Varices; Esophagus; Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Methods; Portacaval Shunt, Surgical; Vasopressins

Topics: Blood Transfusion; Cardia; Esophageal and Gastric Varices; Gastrectomy; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Methods; Postoperative Complications; Stomach; Vasopressins

Topics: Acid-Base Equilibrium; Adult; Aged; Blood Pressure Determination; Catheterization; Electrocardiography; Esophageal Neoplasms; Female; Hematocrit; Hodgkin Disease; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Diseases; Lysine; Male; Methods; Middle Aged; Phenylalanine; Portal System; Respiratory Function Tests; Umbilical Veins; Valsalva Maneuver; Vasopressins; Venous Pressure

Topics: Adult; Anesthesia, General; Arteries; Blood Pressure; Felypressin; Female; Humans; Hypertension, Portal; Male; Middle Aged; Portal Vein; Vasopressins; Veins

Topics: Adolescent; Adult; Aged; Alcoholism; Child; Emergencies; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Portacaval Shunt, Surgical; Postoperative Complications; Vasopressins

Topics: Adult; Angiography; Animals; Blood Flow Velocity; Cardiac Output; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infusions, Parenteral; Liver Function Tests; Male; Mesenteric Arteries; Pituitary Hormones, Posterior; Vasopressins

Topics: Blood Pressure; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Manometry; Portal Vein; Pressure; Vasopressins

Topics: Blood Pressure Determination; Carbon Dioxide; Female; Hemodynamics; Humans; Hypertension, Portal; Isoproterenol; Lactates; Liver Neoplasms; Male; Manometry; Methods; Phenylephrine; Portal System; Radiography; Umbilical Veins; Valsalva Maneuver; Vasopressins

Topics: Animals; Azygos Vein; Blood; Blood Gas Analysis; Blood Pressure; Catecholamines; Dogs; Fluoresceins; Hypertension, Portal; Radioisotopes; Serotonin; Vasopressins; Xenon

Topics: Animals; Blood Pressure; Dogs; Hemorrhage; Hypertension, Portal; Portography; Vasopressins

Topics: Angiography; Animals; Aortography; Blood Circulation; Dogs; Esophageal and Gastric Varices; Hemorrhage; Hemostasis; Hypertension, Portal; Vasopressins

Topics: Blood Transfusion; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Mortality; Omentum; Splenectomy; Surgical Procedures, Operative; Vasopressins

Topics: Angiotensins; Drug Therapy; Humans; Hypertension; Hypertension, Portal; Liver Diseases, Parasitic; Methysergide; Schistosomiasis; Selective Serotonin Reuptake Inhibitors; Serotonin; Vasopressins

Topics: Alcoholism; Blood Pressure Determination; Blood Volume Determination; Heart Function Tests; Hepatic Veins; Humans; Hypertension; Hypertension, Portal; Iodine Isotopes; Liver Circulation; Liver Cirrhosis; Liver Function Tests; Oxytocin; Pharmacology; Pituitary Hormones, Posterior; Rose Bengal; Serum Albumin; Serum Albumin, Radio-Iodinated; Vasopressins

Topics: Adolescent; Biomedical Research; Blood Pressure; Cardiac Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Geriatrics; Humans; Hypertension; Hypertension, Portal; Infusions, Parenteral; Liver Circulation; Liver Cirrhosis; Lysine; Pharmacology; Phenylalanine; Portal Pressure; Portal Vein; Toxicology; Vasopressins

Topics: Angiotensins; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Pharmacology; Toxicology; Vasopressins

Topics: Blood Transfusion; Cryosurgery; Esophageal and Gastric Varices; Gastric Hypothermia; Hematemesis; Hypertension; Hypertension, Portal; Hypothermia, Induced; Liver Cirrhosis; Liver Diseases; Neomycin; Prognosis; Surgical Procedures, Operative; Vasopressins

Topics: Blood Transfusion; Esophageal and Gastric Varices; Esophagoscopy; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Pituitary Hormones, Posterior; Portography; Splenectomy; Surgical Procedures, Operative; Vasopressins; Vitamin K

Topics: Blood Circulation; Blood Pressure; Felypressin; Heart Function Tests; Hemodynamics; Hepatic Artery; Hepatic Veins; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Pharmacology; Vasopressins

Topics: Arginine Vasopressin; Humans; Hypertension; Hypertension, Portal; Liver; Vasopressins