PERCUTANEOUS TRANS-SPLENIC PORTAL VENOGRAPHY—Applications and Hazards

Trans-splenic percutaneous portavenography is a useful and relatively simple roentgen examination. Although infrequent, splenic hemorrhage and delayed splenic rupture sometimes do occur after splenic puncture. Hence the procedure should be used only with provision for immediate operation in case of hemorrhage.The method is invaluable in the demonstration of intrahepatic and extrahepatic portal obstruction, gastric and esophageal varices. With it, the size of the portasplenic veins and the degree of portal hypertension can be estimated.     

Effect of portal hypertension on splenic blood flow,intrasplenic extravasation and systemic blood pressure

We have previously shown that intrasplenic fluid extravasation is important in controlling blood volume. We proposed that, because the splenic vein flows in the portal vein, portal hypertension would increase splenic venous pressure and thus increase intrasplenic microvascular pressure and fluid extravasation. Given that the rat spleen has no capacity to store/release blood, intrasplenic fluid extravasation can be estimated by measuring the difference between splenic arterial inflow and venous outflow. In anesthetized rats, partial ligation of the portal vein rostral to the junction with the splenic vein caused portal venous pressure to rise from 4.5 +/- 0.5 to 12.0 +/- 0.9 mmHg (n = 6); there was no change in portal venous pressure downstream of the ligation, although blood flow in the liver fell. Splenic arterial flow did not change, but the arteriovenous flow differential increased from 0.8 +/- 0.3 to 1.2 +/- 0.1 ml/min (n = 6), and splenic venous hematocrit rose. Mean arterial pressure fell (101 +/- 5.5 to 95 +/- 4 mmHg). Splenic afferent nerve activity increased (5.6 +/- 0.9 to 16.2 +/- 0.7 spikes/s, n = 5). Contrary to our hypothesis, partial ligation of the portal vein caudal to the junction with the splenic vein (same increase in portal venous pressure but no increase in splenic venous pressure) also caused the splenic arteriovenous flow differential to increase (0.6 +/- 0.1 to 1.0 +/- 0.2 ml/min; n = 8). The increase in intrasplenic fluid efflux and the fall in mean arterial pressure after rostral portal vein ligation were abolished by splenic denervation. We propose there to be an intestinal/hepatic/splenic reflex pathway, through which is mediated the changes in intrasplenic extravasation and systemic blood pressure observed during portal hypertension.     

Influence of acute hemorrhage on erythrodieresis

Influence of acute hemorrhage on peritoneal and splenic macrophages function and NO production was studied. Interaction of peritoneal and splenic macrophages with autologous erythrocytes was examined the day after the hemorrhage. Concentration of nitrate ions: the stable metabolites of nitric oxide, was measured in peritoneal lavage, splenic cells suspension, blood, as well as in supernatant of peritoneal and splenic macrophages before and after hemorrhage. The data obtained suggest that splenic macrophages of intact rats are more active than peritoneal ones. After hemorrhage peritoneal macrophages activity increases, whereas splenic macrophages remain unchanged. Concentration of nitrate ions is significantly reduced after hemorrhage.     

Pancreatic glucagon secretion during a short period of hemorrhage in anesthetized dogs

Glucagon has been implicated in the hormonal metabolic response to hemorrhage. However, evidence for this has been obtained largely from observations of circulating plasma glucagon concentration. A clear increase in the pancreatic glucagon secretion remains to be demonstrated. Plasma concentrations of pancreatic immunoreactive glucagon (IRG) and insulin (IRI) were determined in portal venous and aortic blood, and plasma glucose in aortic blood. Dogs were bled (approximately 15 mL/kg) until aortic systolic blood pressure dropped to approximately 50% (70.5 +/- 8.1 mmHg, n = 7) (1 mmHg = 133.32 Pa) of its control value (135 +/- 7.1 mmHg, n = 7), and the hemorrhagic hypotension was maintained for 10 min. The net portal venous IRG delivery rate rose significantly and continued to increase during the hemorrhagic hypotension despite a significant fall in the portal venous blood flow. Aortic IRG increased significantly along with the increase in portal venous IRG delivery rate (r = 0.838, n = 42, p less than 0.01). The portal venous delivery rate of IRI decreased significantly in response to hemorrhage. The aortic IRG/IRI concentration ratio increased significantly during the hemorrhage-induced hypotension. Aortic glucose concentration increased significantly 5 min after hemorrhage and continued to rise until the end of the hemorrhagic hypotension. The present study demonstrates that the secretion of pancreatic glucagon actually increases during the early phase of hemorrhage. The results also indicate that the increase in aortic IRG during the hemorrhagic hypotension is due to the increased pancreatic glucagon secretion. It is suggested that the pancreatic glucagon may be involved in the early hyperglycemic response to hemorrhage.     

Longitudinal prostaglandin E(2) generation in various organs during evolution of experimental portal hypertension

It has been suggested that the arteriolar vasodilatation and hyperdynamic circulation observed in rats with partial portal vein ligation (PPVL) is caused by increased splanchnic and systemic delivery of vasodilator substances. The aims of our study were to determine organ-specific generation of prostaglandin E(2) (PGE(2)) in rats with PPVL during the evolution of portal hypertension. Rats with PPVL and sham-operated (S) rats were studied in the first, third, fourth and 14th postoperative days. They were anesthetized and splenic pulp pressure and blood pressure were measured. Spleen, colon and lungs were removed and the splenic, pulmonary and mucosal colonic PGE(2) were determined. All PPVL rats developed sequential hemodynamic changes compatible with evolving portal hypertension. Splenic pulp pressure was higher in PPVL rats compared with S rats during all days of the study. Within the group of PPVL the splenic pulp pressure was higher in the first postoperative day and decreased in the ensuing days. No changes in splenic and colonic PGE(2) generation were noted during the study period. Pulmonary PGE(2) generation increased significantly in the first postoperative day in PPVL rats compared with S rats. However, similar increase was observed on the third postoperative day in S rats. PGE(2) probably has no role in splanchnic hemodynamic changes during evolution of portal hypertension. Pulmonary PGE(2) generation may increase as a response to increased portal pressure, or to abdominal surgery.     

Pancreatic adenocarcinoma presenting as sinistral portal hypertension: an unusual presentation of pancreatic cancer

A rare syndrome, sinistral (left-sided) portal hypertension resulting from splenic vein thrombosis secondary to pancreatic adenocarcinoma of the tail is presented here. Pancreatic cancer is notorious for presenting with vague and nonspecific symptoms, including but not exclusively weight loss, abdominal pain, and anorexia with or without jaundice. However, physicians should be aware that in the presence of splenic vein thrombosis, this finding alone puts pancreatic cancer high on the differential diagnosis.     

Cardiopulmonary effects of hemorrhagic shock in splenic autotransplanted pigs: a new surgical model

The spleen is an important organ for hemodynamic compensation during hemorrhagic shock. The aim of the study was to compare the hemodynamic and metabolic responses of sham-operated pigs with intact spleen, splenectomized pigs, and splenic autotransplanted pigs during hemorrhagic shock. Hemorrhagic shock was induced by 30% total blood volume bleed in sham-operated, splenectomized and splenic autotransplanted pigs (n = 20). Cardiopulmonary and metabolic variables were measured before, immediately after, and at 20, 60 and 100 minutes after hemorrhage. Upon hemorrhagic shock induction, body temperature, mean arterial pressure, mean pulmonary arterial pressure, cardiac output, cardiac index and oxygen delivery decreased, while lactate and shock index increased. Hemoglobin and hematocrit were significantly lower in the splenectomized and splenic autotransplant groups as compared with the control group at 60 and 100 minutes after hemorrhage (p < 0.05). Unlike intact spleen, splenic autotransplant could not improve hemodynamic parameters in hemorrhagic shock in pigs. In comparison to mice, rats or dogs, this species could be an interesting investigation model to test new surgical procedures during splenic related hemorrhagic shock, with potential applications in human medicine.     

Evidence for a migratory capability of rat Kupffer cells to portal tracts and hepatic lymph nodes

The present study concerns the migratory ability of Kupffer cells in the rat. Phagocytic cells were labeled with colloidal carbon or gold, these markers being administered intravenously either into a tail vein, which resulted in generalized reticuloendothelial uptake, or in low dose into the portal vein, which produced uptake by Kupffer cells alone. Cells containing marker were observed in the portal tracts and in hepatic lymph nodes from 1 to 3 days after injection into the portal vein. The direct movement of single marker particles to the portal tracts could be excluded. Since injection of marker into the portal vein labeled Kupffer cells exclusively, whereas blood cells, splenic and bone marrow macrophages remained unlabeled, the labeled cells in the portal tracts and hepatic lymph nodes appeared to be former Kupffer cells migrating which had migrated to these sites.     

Metabolic effects of long-term arterialization of portal blood

In nine splenectomized male dogs a splenic artery, -splenic vein shunt was made. Before splenectomy and 3, 6 and 18 months after arterialization of portal blood, different metabolic and endocrine parameters were estimated. Long-term arterialization of portal blood was followed by only insignificant increase of portal vein pressure but a significant drop of pCO2 and increase of pO2 in portal blood was recorded. Simultaneously, a significant decrease of the erythrocyte count, hematocrit value, serum cholesterol and uric acid levels, and a shortening of the T1/2 of insulin and glucagon were found. In contrast, long-term arterialization of portal blood was followed by a significant increase of serum triglycerides, alpha2-globulins, plasma renin activity, cortisol, gastrin and 25-hydroxyvitamin D, and by slight carbohydrate intolerance. No morphological abnormalities in the liver and kidney tissue were found. Data presented in this paper suggest usefulness of a splenic artery-splenic vein shunt in the treatment of some metabolic disorders and of the failing hepatocytes.     

Inflammation: a way to understanding the evolution of portal hypertension

Background

Portal hypertension is a clinical syndrome that manifests as ascites, portosystemic encephalopathy and variceal hemorrhage, and these alterations often lead to death.

Hypothesis

Splanchnic and/or systemic responses to portal hypertension could have pathophysiological mechanisms similar to those involved in the post-traumatic inflammatory response. The splanchnic and systemic impairments produced throughout the evolution of experimental prehepatic portal hypertension could be considered to have an inflammatory origin. In portal vein ligated rats, portal hypertensive enteropathy, hepatic steatosis and portal hypertensive encephalopathy show phenotypes during their development that can be considered inflammatory, such as: ischemia-reperfusion (vasodilatory response), infiltration by inflammatory cells (mast cells) and bacteria (intestinal translocation of endotoxins and bacteria) and lastly, angiogenesis. Similar inflammatory phenotypes, worsened by chronic liver disease (with anti-oxidant and anti-enzymatic ability reduction) characterize the evolution of portal hypertension and its complications (hepatorenal syndrome, ascites and esophageal variceal hemorrhage) in humans.

Conclusion

Low-grade inflammation, related to prehepatic portal hypertension, switches to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease.     

The Warren Shunt in Treating Bleeding Esophageal Varices

In patients who have impaired hepatic reserve, the Warren shunt has been proposed as an effective operation because it decompresses the esophageal varices without disturbing portal perfusion of the liver. However, early reports of high operative mortality and technical difficulties have impeded acceptance of the procedure.The operation was done in a series of 17 patients. All patients in whom elective variceal decompression with a patent splenic vein was required and without clinical ascites were candidates for this operation. Follow-up ranged from 2 to 48 months. Six patients had alcoholic cirrhosis, two had primary biliary cirrhosis and seven had postnecrotic cirrhosis; in two the cause of the liver disease was unknown. Five patients were categorized as Child''s class A, nine as class B and three as class C. No intraoperative or early postoperative deaths owing to hemorrhage occurred. However, there was one death two weeks postoperatively from pulmonary sepsis and one death five weeks postoperatively due to antigen-positive hepatitis. Two patients died from hepatic failure six weeks and five months after operation, respectively; in the first of these, chronic active hepatitis was diagnosed at the time of operation. In one patient hemorrhage recurred and transfusion was required. Although ascites, which eventually resolved, developed in eight patients after operation, the results in 76 percent of patients have been good without new episodes of hemorrhage or encephalopathy. We conclude that the Warren shunt is a safe and effective elective operation for the treatment of patients in whom hemorrhage from esophageal varices has occurred.     

Splenic baroreceptors control splenic afferent nerve activity

Stenosis of either the portal or splenic vein increases splenic afferent nerve activity (SANA), which, through the splenorenal reflex, reduces renal blood flow. Because these maneuvers not only raise splenic venous pressure but also reduce splenic venous outflow, the question remained as to whether it is increased intrasplenic postcapillary pressure and/or reduced intrasplenic blood flow, which stimulates SANA. In anesthetized rats, we measured the changes in SANA in response to partial occlusion of either the splenic artery or vein. Splenic venous and arterial pressures and flows were simultaneously monitored. Splenic vein occlusion increased splenic venous pressure (9.5 +/- 0.5 to 22.9 +/- 0.8 mmHg, n = 6), reduced splenic arterial blood flow (1.7 +/- 0.1 to 0.9 +/- 0.1 ml/min, n = 6) and splenic venous blood flow (1.3 +/- 0.1 to 0.6 +/- 0.1 ml/min, n = 6), and increased SANA (1.7 +/- 0.4 to 2.2 +/- 0.5 spikes/s, n = 6). During splenic artery occlusion, we matched the reduction in either splenic arterial blood flow (1.7 +/- 0.1 to 0.7 +/- 0.05, n = 6) or splenic venous blood flow (1.2 +/- 0.1 to 0.5 +/- 0.04, n = 5) with that seen during splenic vein occlusion. In neither case was there any change in either splenic venous pressure (-0.4 +/- 0.9 mmHg, n = 6 and +0.1 +/- 0.3 mmHg, n = 5) or SANA (-0.11 +/- 0.15 spikes/s, n = 6 and -0.05 +/- 0.08 spikes/s, n = 5), respectively. Furthermore, there was a linear relationship between SANA and splenic venous pressure (r = 0.619, P = 0.008, n = 17). There was no such relationship with splenic venous (r = 0.371, P = 0.236, n = 12) or arterial (r = 0.275, P = 0.413, n = 11) blood flow. We conclude that it is splenic venous pressure, not flow, which stimulates splenic afferent nerve activity and activates the splenorenal reflex in portal and splenic venous hypertension.     

Disordered central cardiovascular regulation in portal hypertensive and cirrhotic rats

Portal hypertension due to either prehepatic portal hypertension or cirrhosis is associated with cardiovascular derangement. We aimed to delineate regulatory mechanisms in the brain stem cardiovascular nuclei in rat models of prehepatic portal hypertension and cirrhosis. Neuronal activation in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM) were assessed by immunohistochemical staining for the immediate-early gene product Fos. In the same sections, catecholaminergic neurons were counted by tyrosine hydroxylase (TH) staining. Ninety minutes after hypotensive hemorrhage (or no volume challenge), the animals were killed for Fos and TH medullary staining. These protocols were repeated after capsaicin administration. The NTS of unchallenged sham-operated rats had scant Fos-positive cells (3.6 +/- 0.4 cells/section), whereas hemorrhage significantly increased Fos staining (91.8 +/- 14). In contrast, the unchallenged portal hypertensive and cirrhotic groups showed increased Fos staining (14.3 +/- 5.8 and 32.8 +/- 2.8, respectively), which hemorrhage did not alter significantly. The numbers of TH-positive cells were similar in the three unchallenged groups; double labeling revealed that approximately 50% of TH-positive cells were activated by hemorrhage in the sham and cirrhotic rats but not the portal hypertensive rats. Similar patterns of Fos and TH staining were observed in the VLM. Capsaicin treatment not only significantly reduced the Fos-positive neuron numbers in portal hypertensive and cirrhotic rats but also attenuated hemorrhage-induced Fos and double-positive cells in both NTS and VLM. These results suggest that disordered trafficking in capsaicin-sensitive nerves and central dysregulation contribute to blunted cardiovascular responsiveness in cirrhosis and prehepatic portal hypertension.     

Portal hypertension complicating myelofibrosis: reversal following splenectomy.

Portal hypertension occurs in approximately 10% of patients with myelofibrosis. Increased portal blood flow secondary to splenomegaly has been proposed to explain its development. In a 60-year-old woman with proven myelofibrosis of 10 years'' duration and gross splenomegaly, portal hypertension developed with esophageal varices and ascites. There was no demonstrable obstruction to portal blood flow. Following splenectomy the ascites and esophageal varices disappeared. Despite the presence of splenic myeloid metaplasia, splenectomy did not impair the patient''s hematologic status. Portal hypertension complicating myelofibrosis has a poor prognosis, so careful attention should be given to its detection. Splenectomy may be preferable to portal-systemic shunting in the management of this complication.     

Enhancement of Aflatoxin B1 induced liver carcinogenesis by portal diversion in the rat

Conflicting results have been reported on the influence of portacaval anastomosis on liver carcinogenesis. The purpose of this investigation was to study the effect of portal diversion on liver carcinogenesis induced in the rat by a potent chemical liver carcinogen, Aflatoxin B1 (AFB1). Liver tumors appeared earlier and were significantly bigger in rats with shunts than in sham-operated controls. Portal diversion also induced in rats fed AFB1 a splenic atrophy with nearly complete disappearance of Malpighian corpuscles suggesting a profound immunodepression. This might be responsible for the enhancement of liver cancer by portacaval anastomosis in the rats fed AFB1. Thus, the influence of portal diversion on liver cancers appears to be multifactorial.     

Effects of repeated praziquantel treatment on schistosomiasis mekongi morbidity as detected by ultrasonography

Schistosomiasis mekongi is endemic in the Mekong River basin; about 80,000 people are at risk of infection in Cambodia. We conducted ultrasonographic studies of patients with schistosomiasis mekongi in Kratie province, Cambodia, focusing especially on the relationship between the frequency of praziquantel treatment and findings of ultrasonographic imaging. The frequency of praziquantel treatment in the period from 1995 to 2002 was classified into four groups: 1–2, 3–4, 5–6, and 7–8 times. Ultrasonographic images were examined to determine the presence of thickening of the portal vein wall and formation of meandering collateral circulation of the splenic vein. We selected these parameters because they are unaffected by interobserver bias. The results showed that thickening of the portal vein wall may have potential to improve with frequent praziquantel treatment. On the other hand, established hard splenomegaly and meandering collateral circulation of the splenic vein, improved very little with praziquantel treatment.     

Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut ischemia.

The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in two groups of anesthetized dogs before and after induction of splanchnic ischemia by way of hemorrhage. During the first portion of the experiment, both groups received fenoldopam (1.5 microg x kg(-1) x min(-1)) for 45 min followed by a 45-min washout. During the second portion, hemorrhage (10 ml/kg) was induced, followed by no intervention in group I (controls) and restarting of the fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite portal blood flow by 33% (P < 0.01). After hemorrhage-induced splanchnic ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal PCO(2). DA-1 receptor stimulation increased portal blood flow and redistributed blood flow away from the serosal layer in favor of the mucosa during basal conditions and after hemorrhage, suggesting a more concentrated distribution of splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam maintained splanchnic blood flow during hypoperfusion and attenuated the splanchnic vasoconstrictive response to hemorrhage.     

A non-hemolytic, group B Streptococcus infection of cultured bullfrogs, Rana catesbeiana, in Brazil

A systemic streptococcal infection in cultured bullfrogs in Brazil was characterized by necrotizing splenitis and hepatitis with hepatic and renal hemorrhage. A non-hemolytic Group B Streptococcus appeared to be the cause of the lesions, and the stimulus for the splenic reticuloendothelial hyperplasia observed in the animals. Stress may have been a factor in the development of the pathological condition.     

Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity

A portal venous injection of allogeneic donor cells is known to prolong the survival of subsequently transplanted allografts. In this study, we investigated the role of liver sinusoidal endothelial cells (LSECs) in immunosuppressive effects induced by a portal injection of allogeneic cells on T cells with indirect allospecificity. To eliminate the direct CD4+ T cell response, C57BL/6 (B6) MHC class II-deficient C2tatm1Ccum (C2D) mice were used as donors. After portal injection of irradiated B6 C2D splenocytes into BALB/c mice, the host LSECs that endocytosed the irradiated allogeneic splenocytes showed enhanced expression of MHC class II molecules, CD80, and Fas ligand (FasL). Due to transmigration across the LSECs from BALB/c mice treated with a portal injection of B6 C2D splenocytes, the naive BALB/c CD4+ T cells lost their responsiveness to stimulus of BALB/c splenic APCs that endocytose donor-type B6 C2D alloantigens, while maintaining a normal response to stimulus of BALB/c splenic APCs that endocytose third-party C3H alloantigens. Similar results were not observed for naive BALB/c CD4+ T cells that transmigrated across the LSECs from BALB/c FasL-deficient mice treated with a portal injection of B6 C2D splenocytes. Adaptive transfer of BALB/c LSECs that had endocytosed B6 C2D splenocytes into BALB/c mice via the portal vein prolonged the survival of subsequently transplanted B6 C2D hearts; however, a similar effect was not observed for BALB/c FasL-deficient LSECs. These findings indicate that LSECs that had endocytosed allogeneic splenocytes have immunosuppressive effects on T cells with indirect allospecificity, at least partially via the Fas/FasL pathway.