Increase In Portal Blood Flow Research Articles

Portal Vein Pulsatility Index as a Potential Risk of Venous Congestion Assessed by Magnetic Resonance Imaging: A Prospective Study on Healthy Volunteers.

High values of the portal vein pulsatility index (PI) have been associated with adverse outcomes in perioperative or critically ill patients. However, data on dynamic changes of PI related to fluid infusion are scarce. We aimed to determine if dynamic changes in PI are associated with the fluid challenge (FC). To address this challenge, we conducted a prospective single-center study. The population study included healthy subjects. FC consisted in the administration of 500 ml of Ringer lactate infusion over 5 min. The portal blood flow and PI were assessed by magnetic resonance imaging. The responsiveness to FC was defined as an increase in the cardiac stroke volume of at least 10% as assessed by echocardiography. We included 24 healthy volunteers. A total of fourteen (58%) subjects were responders, and 10 (42%) were non-responders. In the responder group, FC induced a significant increase in portal blood flow from 881 (762–1,001) at the baseline to 1,010 (778–1,106) ml min−1 (p = 0.005), whilst PI remained stable (from 31 [25–41] to 35 (25–42) %; p = 0.12). In the non-responder group, portal blood flow remained stable after FC (from 1,042 to 1,034 ml min−1; p = 0.084), whereas PI significantly increased from 32 (22–40) to 48% *(25–85) after FC (p = 0.027). PI was negatively correlated to portal blood flow (Rho coefficient = −0.611; p = 0.002). To conclude, PI might be a sensitive marker of early congestion in healthy subjects that did not respond to FC. This finding requires further validation in clinical settings with a larger sample size.

Celecoxib reduces hepatic vascular resistance in portal hypertension by amelioration of endothelial oxidative stress

The balance between endothelial nitric oxide (NO) synthase (eNOS) activation and production of reactive oxygen species (ROS) is very important for NO homeostasis in liver sinusoidal endothelial cells (LSECs). Overexpression of cyclooxygenase‐2 (COX‐2), a major intravascular source of ROS production, has been observed in LSECs of cirrhotic liver. However, the links between low NO bioavailability and COX‐2 overexpression in LSECs are unknown. This study has confirmed the link between low NO bioavailability and COX‐2 overexpression by COX‐2‐dependent PGE2‐EP2‐ERK1/2‐NOX1/NOX4 signalling pathway in LSECs in vivo and in vitro. In addition, the regulation of COX‐2‐independent LKB1‐AMPK‐NRF2‐HO‐1 signalling pathway on NO homeostasis in LSECs was also elucidated. The combinative effects of celecoxib on diminishment of ROS via COX‐2‐dependent and COX‐2‐independent signalling pathways greatly decreased NO scavenging. As a result, LSECs capillarisation was reduced, and endothelial dysfunction was corrected. Furthermore, portal hypertension of cirrhotic liver was ameliorated with substantial decreasing hepatic vascular resistance and great increase of portal blood flow. With the advance understanding of the mechanisms of LSECs protection, celecoxib may serve as a potential therapeutic candidate for patients with cirrhotic portal hypertension.

Contribution of Splenic Resistance Arteries to Splanchnic Blood Overflow in Cirrhosis.

In liver cirrhosis, a marked splanchnic vasodilation causes an increase in portal blood flow, contributing to the development of portal hypertension. To evaluate if, in experimental cirrhosis, a different vascular reactivity exists between splenic and mesenteric components of the splanchnic circulation. Liver cirrhosis was induced in Sprague Dawley rats by common bile duct ligation. In sections of splenic and superior mesenteric arteries, cumulative dose-response curves were obtained. mRNA expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and prostaglandin I2 synthase (PTGIS) was evaluated. In cirrhotic rats, mesenteric but not splenic arteries showed a significant increase in endothelium-dependent relaxation to acetylcholine. In control and cirrhotic rats, COX inhibition alone did not significantly change the response of mesenteric arteries to acetylcholine; after inhibiting also NOS, the relaxation was completely abolished in control but only partially decreased in cirrhotic rats. After the inhibition of COX and NOS, the relaxation to acetylcholine was similarly decreased in splenic arteries from control and cirrhotic animals. The contraction induced by phenylephrine of both mesenteric and splenic arteries was decreased in cirrhotic rats. PTGIS mRNA expression did not differ in splenic and mesenteric arteries from control and cirrhotic rats; in cirrhotic rats, eNOS and iNOS mRNA expression was increased in mesenteric but not in splenic vascular bed. In cirrhotic rats, a decreased splenic arterial response to vasoconstrictors, rather than an increased response to vasodilators, contributes to splanchnic vasodilation, while in mesenteric arteries also an increased response to vasodilators secondary to, but not only, eNOS and iNOS overexpression, plays a role.

Correlation between diabetes mellitus and the clinical outcome of acute variceal bleeding in cirrhotic patients in Suez Canal University Hospital, Ismailia, Egypt

Variceal bleeding is one of the major complications of portal hypertension. Gastro-esophageal varices are present 40-60% of patients with cirrhosis; bleeding occurs in 25-35% of patients and account for 80-90% of bleeding episodes in these patients. Hepatic venous pressure gradient (HVPG) > 20 mmHg is associated with early re-bleed and failure to control bleeding (83%) with high mortality (64%) In the last two decades variceal re-bleeding has decreased from 47% to 13% with the use of pharmacological, endoscopic, and radiological intervention.DM co-existing with cirrhosis is considered to be one of the factors in the genesis of variceal bleeding. This may be due to an increase in portal blood flow. is to determine the correlation between DM as a risk factor and failure to control variceal bleeding and re-bleeding in cirrhotic patients. This study is a case-control study, sixty cirrhotic patients with variceal bleeding with or without DM were included in the study. The patients were divided into two groups: Group 1 (diabetic group): this group included 30 cirrhotic patients with variceal bleeding and had a history of DM. Group 2 (control group): this group included 30 cirrhotic patients with variceal bleeding and had no history of DM. All Patients were subjected to the following:-Complete clinical evaluation (history and physical examination) with Laboratory and imaging investigations. Tthere were significantly higher frequency of unstable course and mean times of previous admission in diabetic patients than control patients (73.3% and 1.6 times versus 36.6% and 1.3 times, respectively). Other variables showed insignificant differences between both groups (p>0.05). There were significantly higher mean numbers of attacks of hematemesis and melena and times of previous admission with these attacks in diabetic patients than control patients.

Modulation of splanchnic circulation: Role in perioperative management of liver transplant patients.

Splanchnic circulation is the primary mechanism that regulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods (e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models

IntroductionTo clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound.MethodsNormal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system.ResultsThe PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC.DiscussionDKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract.ConclusionWe suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction.

Liver stiffness and portal blood flow modifications induced by a liquid meal consumption: pathogenetic mechanisms and clinical relevance

Objective. The correlation between liver stiffness (LS) variations and portal blood flow (PBF) modifications induced by a standardized liquid meal consumption and the clinical relevance of this matter are two aspects not yet fully elucidated. Herein, we evaluated the variations of LS and PBF after a standardized liquid meal intake in patients with chronic liver disease. Material and methods. PBF and LS were determined after an overnight fasting period in 54 patients. They were divided in three groups according to baseline LS (absent, moderate, and severe). They consumed 200 ml of water and a standardized liquid meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after water and liquid meal consumption. Results. In all groups, LS and PBF values significantly increased only after meal consumption. A significant correlation between baseline LS values and post-meal increase of LS was observed. Moreover, higher basal stiffness values were associated to a larger increase of LS variation after meal consumption. The effect of the meal on LS remained statistically significant after multiple regression analysis. A significant correlation between increase of LS and PBF was found in patients with absent and moderate baseline LS. Nine patients (17%) switched from a lower to a higher level of LS after meal consumption. Conclusion. A low calories/low-volume meal is capable of significantly increasing LS regardless of the grade of stiffness, determining a reclassification rate of 17%. In presence of minimal or moderate stiffness, the increase of LS is significantly correlated with the augment of PBF.

Regarding “liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution”

We congratulate Arena et al.1 for their interesting article regarding the confounding effect of a meal on the accuracy of liver stiffness (LS) measurements for the prediction of fibrosis stage in patients with chronic hepatitis C virus (HCV) hepatitis. In that study the most prominent postprandial increase in LS was observed in patients with cirrhosis. Hemodynamic parameters were not measured, but it is suggested that the postprandial changes in LS are likely consequent to the adaptation of the hepatic microcirculation to increased portal blood flow (PBF) and to the postprandial increase in portal pressure. We recently published a study2 involving 19 patients with cirrhosis and portal hypertension in whom LS and hepatic hemodynamics were measured by Doppler-ultrasonography at baseline and 30 minutes after the ingestion of a standardized meal similar to that used by Arena et al. In a subgroup of 10 patients, the baseline and postprandial hepatic venous pressure gradient (HVPG) were also measured. In agreement to what was described by Arena et al.,1 showing that most patients irrespective of the stage of fibrosis had a peak increase of LS 30 minutes after the meal, in our series postprandial hyperemia (confirmed by a marked increase in PBF, +33 ± 31%, P < 0.0001 versus baseline) was accompanied by a marked increase in LS (+27 ± 33%; P < 0.0001). However, we observed that postprandial changes in LS did not correlate with the changes in PBF. Similarly, in patients in whom HVPG was measured, LS changes did not mirror the HVPG increase after the standardized meal. In contrast, postprandial changes in LS were directly correlated with changes in hepatic artery blood flow (r = 0.658; P = 0.002), so that in patients showing the expected postprandial decrease in hepatic artery blood flow (reflecting the “buffer response” to increased PBF after a meal) the LS increase was significantly attenuated as compared with patients lacking this adaptive mechanism (+12 ± 21% versus +62 ± 29%, P < 0.0001). Altogether, our results suggest that the postprandial increase in LS in cirrhosis cannot be explained by the increase in PBF and portal pressure, while it seems at least in part dependent on changes in the arterial component of hepatic blood flow. Since extensive formation of collaterals in advanced portal hypertension leads to increased dependence of the hepatic blood flow on its arterial component, and since hepatic artery buffer response is reduced in cirrhosis,3 a greater postprandial increase in LS should be anticipated in overt cirrhosis. Annalisa Berzigotti, M.D. Juan G. Abraldes, M.D. Jaume Bosch, M.D. Hepatic Hemodynamic Laboratory, Liver Unit, IDIBAPS and CIBERehd, Hospital Clinic, Barcelona, Spain

Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis

The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 10(9) /L before OLT to 162.4 ± 86 × 10(9) /L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena.

Liver metastases, a rare cause of portal hypertension and stoma bleeding. Brief review of literature

INTRODUCTIONPortal hypertension is an unusual complication of liver metastases, which is frequently occurring in malignant disease. Portal hypertension may cause oesophageal varices and also stoma varices (colostomy and ileostomy). Oesophageal varices and bleeding from these varices have been frequently reported in literature. Stomal varices have also been reported in literature mostly associated with liver cirrhosis. These stomal varices lead to the massive bleeding causing morbidity and mortality.Portal hypertension is a pathological increase in portal pressure gradient (the difference between pressure in the portal and inferior vena cava veins). It is either due to an increase in portal blood flow or an increase in vascular resistance or combination of both. In liver cirrhosis, the primary factor leading to portal hypertension is increase in portal blood flow resistance and later on development of increased portal blood flow. It has been postulated that in liver metastasis the increase in portal flow resistance occurs at any site within portal venous system as a consequence of mechanical architectural disturbance. PRESENTATION OF CASEWe report a case of a 64 year old gentleman who developed portal hypertension due to secondary metastases from colorectal cancer. He subsequently developed bleeding varices in his end colostomy. DISCUSSIONWe believe that the combination of extensive metastases and chemotherapy induced portal hypertension in our patient. CONCLUSIONOur case and other literature review highlight that the recurrent bleeding stoma associated with colorectal cancer should be investigated for portal hypertension.

Esophageal Varices: Pathophysiology, Approach, and Clinical Dilemmas

Esophageal Varices: Pathophysiology, Approach, and Clinical Dilemmas

Hemorrhage from varices in hepaticojejunostomy in the fifth and tenth year after surgery for hepatic hilar bile duct cancer: a case report

We report a case of a 64-year-old female patient who underwent a right lobectomy of the liver (including total resection of the caudate lobe), dissection of the group 2 lymph nodes, left hepaticojejunostomy (Roux-en-Y fashion), and reconstruction of the portal vein (end-to-end anastomosis between the main portal vein and the left portal branch) for treatment of hepatic hilar bile duct cancer in 1996. In 2001, the anastomotic site of the hepaticojejunostomy was dissected and re-anastomosed due to gastrointestinal bleeding caused by variceal rupture in the jejunal loop. In 2006, splenectomy was performed for recurrence of gastrointestinal bleeding due to another variceal rupture in the jejunal loop. Portal venography performed perioperatively showed a decrease in portal blood flow into the liver via the jejunal varices and an increase in portal blood flow into the liver via the left gastric vein. She had two jejunal variceal ruptures at five-year intervals after extrahepatic portal obstruction and underwent successful treatments.

Role of echo Doppler ultrasonography in the evaluation of postprandial hyperemia in cirrhotic patients

To assess the role of echo-Doppler ultrasonography in postprandial hyperemia in cirrhotic patients by comparing the results with the hepatic vein catheterization technique. Patients with cirrhosis, admitted to the portal hemodynamic laboratory were included into the study. After an overnight fast, echo-Doppler ultrasonography (basal and 30 min after a standard meal) and hemodynamic studies by hepatic vein catheterization (basal, 15 min and 30 min after a standard meal) were performed. Ensure Plus (Abbot Laboratories, North Chicago, IL) was used as the standard liquid meal. Correlation analysis of the echo-Doppler and hepatic vein catheterization measurements were done for the basal and postprandial periods. Eleven patients with cirrhosis (5 Child A, 4 Child B, 2 Child C) were enrolled into the study. After the standard meal, 8 of the 11 patients showed postprandial hyperemia with increase in portal blood flow, portal blood velocity and hepatic venous pressure gradient. Hepatic venous pressure gradient in the postprandial period correlated positively with postprandial portal blood velocity (r = 0.8, P < 0.05) and correlated inversely with postprandial superior mesenteric artery pulsatility index (r = -1, P < 0.01). Postprandial hyperemia can be efficiently measured by echo-Doppler ultrasonography and the results are comparable to those obtained with the hemodynamic studies.

Portal Hypertension

The initial factor leading to portal hypertension is an increase in hepatic resistance. Later, an increase in portal blood flow contributes to maintain and exacerbate portal hypertension despite the development of portosystemic collaterals. The critical step in the development and acceptance of these concepts, which proved crucial for the management of patients with portal hypertension, was the development of animal models. These allowed the full characterization of the profound hemodynamic abnormalities in the systemic and splanchnic circulation associated with portal hypertension, and the elucidation of the molecular mechanisms implicated in these disturbances. This review traces how seminal clinical observations in the 1950s raised meaningful questions that were subsequently answered at the bench, leading to our current understanding of the pathophysiology of portal hypertension and of the pathogenesis of severe complications of cirrhosis, such as variceal bleeding or ascites.

Effects of Portal Vein Arterialization on Regeneration and Morphology in Liver Transplantation: Investigations Using the Rat Model

Portal vein arterialization (PVA) has been proposed as a technical variant in liver transplantation in the case of non-recanalizable thrombosis. The present study investigates the effects of the arterialized portal vein on the function, morphology, and regenerative behavior of the liver. Different PVA techniques, including orthotopic liver transplantation, were used in a rat model. Portal blood flow was measured using a ultrasonic flowmeter. The regeneration capacity was determined on the basis of the increase of liver weight and the proliferating cell nuclear antigen index. The amount of hydroxyproline and the transcript levels of procollagen I were measured to determine the degree of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining. The measurements obtained with an ultrasonic probe revealed a significant increase in portal blood flow after PVA. The regeneration capacity in the groups after PVA with no flow reduction was comparable to that of the control. Liver transplantation and PVA with no flow reduction was followed by a significant increase (four- to sixfold) in the amount of hydroxyproline and the level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and perivascular fibrosis with incipient formation of septa was seen. After reduction of the portal blood flow, these effects were significantly less pronounced. These operative techniques represent an excellent small animal model for studying the mechanism of liver regeneration and the genesis of fibrosis in liver and vessel tissue. The presenting findings indicate that the negative effects of "overarterialization" may be largely avoided by reducing portal blood flow. This implies that permanent PVA in clinical liver transplantation should be performed only in conjunction with a down-regulation of portal flow.

Beneficial effects of arterialization of the portal vein on extended hepatectomy.

Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.

Change in portal flow after liver transplantation: Effect on hepatic arterial resistance indices and role of spleen size

Information on changes in splanchnic hemodynamics after liver transplantation is incomplete. In particular, data on long-term changes are lacking, and the relationship between changes in arterial and portal parameters is still under debate. The effect of liver transplantation on splanchnic hemodynamics was analyzed with echo-Doppler in 41 patients with cirrhosis who were followed for up to 4 years. Doppler parameters were also evaluated in 7 patients transplanted for acute liver failure and in 35 controls. In cirrhotics, portal blood velocity and flow increased immediately after transplantation (from 9.1 ± 3.7 cm/sec to 38.3 ± 14.6 and from 808 ± 479 mL/min to 2,817 ± 1,153, respectively, P < .001). Hepatic arterial resistance index (pulsatility index) also augmented (from 1.36 ± 0.32 to 2.34 ± 1.29, P < .001) and was correlated with portal blood velocity and flow. The early changes in these parameters were related, in agreement with the hepatic buffer response theory. Portal flow returned to normal values after 2 years. Superior mesenteric artery flow normalized after 3 to 6 months. Splenomegaly persisted after 4 years, when spleen size was related to portal blood flow. In 7 patients transplanted for acute liver failure, portal flow, and hepatic arterial resistance index were normal after transplantation. In conclusion, a high portal flow was present in cirrhotics until 2 years after transplantation, probably because of maintenance of elevated splenic flow. An early increase in hepatic arterial resistance indices is a common finding, but it is transient and is related to the increase in portal blood flow. A normal time course of portal-hepatic hemodynamics was detected in patients transplanted for acute liver failure. (HEPATOLOGY 2002;35:601-608.)

Changes in esophageal variceal pressure after transcatheter arterial embolization for hepatocellular carcinoma.

The aim of this study was to investigate the influence of transcatheter arterial embolization on esophageal variceal pressure and portal hemodynamics. Out of 18 cirrhotic patients with hepatocellular carcinoma, 12 underwent transcatheter arterial embolization and the remaining six patients underwent angiography alone as a control. We examined esophageal variceal pressure with an endoscopic pneumatic pressure sensor and portal blood flow with Doppler ultrasonography immediately before and 3 days after transcatheter arterial embolization or angiography. Angiography alone did not influence esophageal variceal pressure or portal blood flow. Transcatheter arterial embolization resulted in an increase in variceal pressure in five (42%) of the 12 patients and in a marked increase in portal blood flow in eight (88.9%) of nine patients, although no change in the endoscopic variceal findings was observed after transcatheter arterial embolization. The change in esophageal variceal pressure did not correlate with the change in portal blood flow. We could not find predictive factors for the elevation of variceal pressure after transcatheter arterial embolization. Our study demonstrated that transcatheter arterial embolization resulted in an increase in esophageal variceal pressure in about half of the patients, bearing little relation to portal hemodynamic parameters.

Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation

Background. Altered intestinal blood flow during systemic inflammation leads to organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We hypothesized that separate mechanisms are active in the large resistance and small mucosal microvessels to account for this dichotomy. Methods. Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours after a single inoculation of bacterium or 24 hours after a second inoculation (ie, 72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10−9 to 10−5 mol/L) in resistance (A1) and premucosal (A3) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from dose response curves for each animal. Results. Vasodilator sensitivity to acetylcholine in A1 arterioles was significantly decreased at 24 hours, and these changes persisted up to 72 hours after a single bacterial inoculation. There was no change in the dilator sensitivity of A3 arterioles after a single inoculation. When there was a challenge with a second bacterial inoculation, there was a reversal of the A1 dilator response and an increase in A3 sensitivity. Conclusions. An initial septic event results in a decrease in dilator reactivity in the resistance A1 arterioles that persists for at least 72 hours. A sustained septic challenge results in increased dilator reactivity in both A1 and A3 vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic approach to preservation of intestinal blood flow will be necessary. (Surgery 2000;128:513-9.)

Complications of cirrhosis. I. Portal hypertension

Increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension, and is mainly determined by the morphological changes occurring in chronic liver diseases. This is aggravated by a dynamic component, due to the active — reversible — contraction of different elements of the porto-hepatic bed. A decreased synthesis of NO in the intrahepatic circulation is the main determinant of this dynamic component. This provides a rationale for the use of vasodilators to reduce intrahepatic resistance and portal pressure. Another factor contributing to aggravate the portal hypertension is a significant increase in portal blood flow, caused by arteriolar splanchnic vasodilation and hyperkinetic circulation. Splanchnic arteriolar vasodilation is a multifactorial phenomenon, which may involve local (endothelial) mechanisms as well as neurogenic and humoral pathways. Most pharmacological treatments have been aimed at correcting the increased portal blood inflow by the use of splanchnic vasoconstrictors, such as beta-blockers, vasopressin derivatives and somatostatin. Several studies have demonstrated that changes in the hepatic venous pressure gradient (HVPG) during maintenance therapy are useful to identify those patients who are going to have a variceal bleeding or rebleeding. The wide individual variation in the HVPG response to pharmacological treatment makes it desirable to schedule follow-up measurements of HVPG during pharmacological therapy. A priority for research in the forthcoming years is to develop accurate non-invasive methods to assess prognosis, which can be used to substitute or as surrogate indicators of the HVPG response. In the clinical management of portal hypertension, beta-blockers are at present the only accepted treatment for the prevention of variceal bleeding. Whether the association of isosorbide-5-mononitrate will improve the high efficacy of beta-blockers is questionable. The efficacy of more aggressive techniques, such as endoscopic band ligation, should be further tested against beta-blockers in patients with a high risk of bleeding. In the treatment of acute variceal bleeding, administration of somatostatin or terlipressin is an established therapy. It may be used alone or, preferably, as an initial treatment before sclerotherapy or endoscopic band ligation. No more than two sessions of endoscopic treatment should be used to control the bleeding. If the bleeding is not easily controlled, other alternatives such as transjugular intrahepatic portosystemic shunts (TIPS) or derivative surgery should be considered, the former being the best in patients with poor liver function. Recent studies suggest that early measurement of HVPG during variceal bleeding may be used as a guide for therapeutic decisions in the treatment of patients with acute variceal bleeding. Those patients with a high HVPG have a high risk of poor evolution, and may be candidates for more intensive and aggressive therapy, such as surgery or TIPS. Those with lower HVPG have a very high probability of an uneventful evolution, and may thus be managed more conservatively using medical and endoscopic treatments. Pharmacological agents (propranolol or nadolol), endoscopic treatment (preferably banding ligation) or surgery can be used to prevent rebleeding. A pending task for the new millennium is to assess whether the early treatment of asymptomatic, compensated cirrhotic patients with portal pressure reducing agents can prevent the development of esophageal varices and of other complications of portal hypertension.